Expert panel on integrated guidelines for cardiovascular disease in children
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Expert panel on integrated guidelines for cardiovascular disease in children Document Transcript

  • 1. PEDIATRICSOFFICIAL JOURNAL OF THE AMERICAN ACADEMY OF PEDIATRICSDECEMBER 2011 • VOLUME 128 • SUPPLEMENT 5A SUPPLEMENT TO PEDIATRICSExpert Panel on Integrated Guidelines for CardiovascularHealth and Risk Reduction in Children and Adolescents:Summary ReportRae-Ellen W. Kavey, MD, MPH, Denise G. Simons-Morton, MD, MH, PhD,and Janet M. de Jesus, MS, RD, Supplement EditorsSponsored by the National Heart, Lung, and Blood Institute,National Institutes of HealthThese guidelines have been endorsed by the American Academy ofPediatrics. Statements and opinions expressed in this supplementare those of the authors and not necessarily those of Pediatricsor the Editor or Editorial Board of Pediatrics.PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). Copyright © 2011 by theAmerican Academy of Pediatrics
  • 2. SUPPLEMENT TO PEDIATRICSCONTENTS S•••• 1. Introduction S•••• 2. State of the Science: Cardiovascular Risk Factors and the Development of Atherosclerosis in Childhood S••••• 3. Integrated Cardiovascular Health Schedule S•••• 4. Family History of Early Atherosclerotic CVD S•••• 5. Nutrition and Diet S•••• 6. Physical Activity S•••• 7. Tobacco Exposure S•••• 8. High BP S•••• 9. Lipids and Lipoproteins S•••• 10. Overweight and Obesity S•••• 11. DM and Other Conditions Predisposing to the Development of Accelerated Atherosclerosis S•••• 12. Risk-Factor Clustering and the Metabolic Syndrome S•••• 13. Perinatal Factors doi:10.1542/peds.2009-2107Awww.pediatrics.org A3
  • 3. Expert Panel Members Stephen R. Daniels, MD, PhD, Panel Chair University of Colorado School of Medicine Denver, CO Irwin Benuck, MD, PhD Northwestern University Feinberg School of Medicine Chicago, IL Dimitri A. Christakis, MD, MPH University of Washington Seattle, WA Barbara A. Dennison, MD New York State Department of Health Albany, NY Samuel S. Gidding, MD Alfred I du Pont Hospital for Children Wilmington, DE Matthew W. Gillman, MD, MS Harvard Pilgrim Health Care Boston, MA Mary Margaret Gottesman, PhD, RN, CPNP Ohio State University-College of Nursing Columbus, OH Peter O. Kwiterovich, MD Johns Hopkins University School of Medicine Baltimore, MD Patrick E. McBride, MD, MPH University of Wisconsin School of Medicine and Public Health Madison, WI Brian W. McCrindle, MD, MPH Hospital for Sick Children Toronto, Ontario, Canada Albert P. Rocchini, MD C. S. Mott Children’s Hospital Ann Arbor, MI Elaine M. Urbina, MD Cincinnati Children’s Hospital Medical Center Cincinnati, OH Linda V. Van Horn, PhD, RD Northwestern University-Feinberg School of Medicine Chicago, IL Reginald L. Washington, MD Rocky Mountain Hospital for Children Denver, CO NHLBI Staff Rae-Ellen W. Kavey, MD, MPH Panel Coordinator National Heart, Lung, and Blood Institute Bethesda, MDA4
  • 4. Christopher J. O’Donnell, MD, MPHNational Heart, Lung, and Blood InstituteFramingham, MAKaren A. Donato, SMNational Heart, Lung, and Blood InstituteBethesda, MDRobinson Fulwood, PhD, MSPHNational Heart, Lung, and Blood InstituteBethesda, MDJanet M. de Jesus, MS, RDNational Heart, Lung, and Blood InstituteBethesda, MDDenise G. Simons-Morton, MD, MPH, PhDNational Heart, Lung, and Blood InstituteBethesda, MDContract StaffThe Lewin Group, Falls Church, VAClifford Goodman, MS, PhDChristel M. Villarivera, MSCharlene Chen, MHSErin Karnes, MHSAyodola Anise, MHSdoi:10.1542/peds.2009-2107B A5
  • 5. SUPPLEMENT ARTICLESExpert Panel on Integrated Guidelines forCardiovascular Health and Risk Reduction in Childrenand Adolescents: Summary ReportEXPERT PANEL ON INTEGRATED GUIDELINES FOR Atherosclerotic cardiovascular disease (CVD) remains the leadingCARDIOVASCULAR HEALTH AND RISK REDUCTION IN cause of death in North Americans, but manifest disease in childhoodCHILDREN AND ADOLESCENTS and adolescence is rare. By contrast, risk factors and risk behaviorsABBREVIATIONS that accelerate the development of atherosclerosis begin in childhood,CVD—cardiovascular diseaseNHLBI—National Heart, Lung, and Blood Institute and there is increasing evidence that risk reduction delays progres-RCT—randomized controlled trial sion toward clinical disease. In response, the former director of thePDAY—Pathobiological Determinants of Atherosclerosis in National Heart, Lung, and Blood Institute (NHLBI), Dr Elizabeth Nabel,YouthBP—blood pressure initiated development of cardiovascular health guidelines for pediatricHDL—high-density lipoprotein care providers based on a formal evidence review of the science withDM—diabetes mellitus an integrated format addressing all the major cardiovascular riskCIMT—carotid intima-media thicknessLDL—low-density lipoprotein factors simultaneously. An expert panel was appointed to develop theT1DM—type 1 diabetes mellitus guidelines in the fall of 2006.T2DM—type 2 diabetes mellitusTC—total cholesterol The goal of the expert panel was to develop comprehensive evidence-AAP—American Academy of Pediatrics based guidelines that address the known risk factors for CVD (TableDGA—Dietary Guidelines for Americans 1-1) to assist all primary pediatric care providers in both the promo-NCEP—National Cholesterol Education ProgramDASH—Dietary Approaches to Stop Hypertension tion of cardiovascular health and the identification and management ofCHILD—Cardiovascular Health Integrated Lifestyle Die specific risk factors from infancy into young adult life. An innovativeFLP—fasting lipid profile approach was needed, because a focus on cardiovascular risk reduc-CDC—Centers for Disease Control and Prevention tion in children and adolescents addresses a disease process (athero-AMA—American Medical AssociationMCHB—Maternal and Child Health Bureau sclerosis) in which the clinical end point of manifest CVD is remote. TheFDA—Food and Drug Administration recommendations, therefore, need to address 2 different goals:AHA—American Heart Association the prevention of risk-factor development (primordial prevention) andwww.pediatrics.org/cgi/doi/10.1542/peds.2009-2107C the prevention of future CVD by effective management of identified riskdoi:10.1542/peds.2009-2107C factors (primary prevention).Accepted for publication Aug 4, 2009 The evidence review also required an innovative approach. Most sys-Address correspondence to Janet M. de Jesus, MS, RD, 31Center Dr, Building 31, Room 4A17, MSC 2480, Bethesda, MD tematic evidence reviews include 1 or, at most, a small number of finite20892. E-mail: dejesusjm@nhlbi.nih.gov questions that address the impact of specific interventions on specificPEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). health outcomes, and a rigorous literature review often results in onlyCopyright © 2011 by the American Academy of Pediatrics a handful of in-scope articles for inclusion. Typically, evidence is limitedFINANCIAL DISCLOSURE: Dr Daniels has served as a consultant to randomized controlled trials (RCTs), systematic reviews, and meta-for Abbott Laboratories, Merck, and Schering-Plough and has analyses published over a defined time period. There is a defined for-received funding/grant support for research from the National mat for abstracting studies, grading the evidence, and presenting ofInstitutes of Health (NIH); Dr Gidding has served as a consultantfor Merck and Schering-Plough and has received funding/grant results. The results of the review lead to the conclusions, independentsupport for research from GlaxoSmithKline; Dr Gillman has of interpretation.given invited talks for Nestle Nutrition Institute and Danone andhas received funding/grant support for research from Mead By contrast, given the scope of the charge to the expert panel, thisJohnson, Sanofi-Aventis, and the NIH; Dr Gottesman has servedon the Health Advisory Board, Child Development Council of evidence review needed to address a broad array of questions con-Franklin County, was a consultant to Early Head Start for Region cerning the development, progression, and management of multiple5B, has written for iVillage and taught classes through Garrison risk factors extending from birth through 21 years of age, including (Continued on last page) studies with follow-up into later adult life. The time frame extended back to 1985, ϳ5 years before the review for the last NHLBI guideline addressing lipids in children published in 1992.1 This evidence is largely available in the form of epidemiologic observational studies PEDIATRICS Volume 128, Supplement 6, December 2011 S1
  • 6. TABLE 1-1 Evaluated Risk Factors TABLE 1-2 Evidence Grading System: Quality GradesFamily history Grade EvidenceAge A Well-designed RCTs or diagnostic studies performed on a population similar to the guideline’sGender target populationNutrition/diet B RCTs or diagnostic studies with minor limitations; genetic natural history studies;Physical inactivity overwhelmingly consistent evidence from observational studiesTobacco exposure C Observational studies (case-control and cohort design)BP D Expert opinion, case reports, or reasoning from first principles (bench research or animalLipid levels studies)Overweight/obesity Adapted from American Academy of Pediatrics, Steering Committee on Quality Improvement and Management. Pediatrics.Diabetes mellitus 2004;114(3):874 – 877.Predisposing conditionsMetabolic syndromeInflammatory markersPerinatal factors titioners, physician assistants, and dations. The summary report will be registered dietitians. The full report released simultaneously with online contains complete background infor- availability of the full report with refer-(rather than RCTs) that, therefore, mation on the state of the science, ences for each section and the evidencemust be included in the review. In ad- methodology of the evidence review tables at www.nhlbi.nih.gov/guidelines/dition, the review required critical ap- and the guideline-development pro- cvd_ped/index.htm.praisal of the body of evidence that ad- cess, summaries of the evidence re- It is the hope of the NHLBI and the expertdresses the impact of managing risk views according to risk factor, discus- panel that these recommendations will befactors in childhood on the develop- sion of the expert panel’s rationale for useful for all those who provide cardiovas-ment and progression of atherosclero- recommendations, and Ͼ1000 cita- cular health care to children.sis. Because of known gaps in the evi- tions from the published literature anddence base relating risk factors and is available at www.nhlbi.nih.gov/ 2. STATE OF THE SCIENCE:risk reduction in childhood to clinical guidelines/cvd_ped/index.htm. The CARDIOVASCULAR RISK FACTORSevents in adult life, the review must in- complete evidence tables will be avail- AND THE DEVELOPMENT OFclude the available evidence that justi- able as a direct link from that site. This ATHEROSCLEROSIS IN CHILDHOODfies evaluation and treatment of risk summary report presents the expertfactors in childhood. The process of Atherosclerosis begins in youth, and this panel’s recommendations for patientidentifying, assembling, and organiz- process, from its earliest phases, is re- care relative to cardiovascular healthing the evidence was extensive, the re- and risk-factor detection and manage- lated to the presence and intensity of theview process was complex, and the ment with only the references cited in known cardiovascular risk factorsconclusions could only be developed the text provided. It begins with a state- shown in Table 1-1. Clinical events suchby interpretation of the body of evi- of-the-science synopsis of the evi- as myocardial infarction, stroke, pe-dence. Even with inclusion of every rel- dence, which indicates that athero- ripheral arterial disease, and rup-evant study from the evidence review, sclerosis begins in childhood, and the tured aortic aneurysm are the culmi-there were important areas in which extent of atherosclerosis is linked di- nation of the lifelong vascular processthe evidence was inadequate. When rectly to the presence and intensity of of atherosclerosis. Pathologically, thethis occurred, recommendations were known risk factors. This is followed by process begins with the accumulationmade on the basis of a consensus of a cardiovascular health schedule (Sec- of abnormal lipids in the vascular in-the expert panel. The schema used in tion 3), which summarizes the expert tima, a reversible stage, progresses tograding the evidence appears in Ta- panel’s age-based recommendations an advanced stage in which a core ofbles 1-2 and 1-3; expert consensus according to risk factor in a 1-page pe- extracellular lipid is covered by a fibro-opinions are identified as grade D. riodic table. Risk factor specific sec- muscular cap, and culminates inThe NHLBI expert panel integrated tions follow, with the graded conclu- thrombosis, vascular rupture, or acuteguidelines for cardiovascular health sions of the evidence review, normative ischemic syndromes.and risk reduction in children and ad- tables, and age-specific recommenda-olescents contain recommendations tions. These recommendations are often Evidence Linking Risk Factors inbased on the evidence review and are accompanied by supportive actions, Childhood to Atherosclerosis atdirected toward all primary pediatric which represent expert consensus sug- Autopsycare providers: pediatricians, family gestions from the panel provided to sup- Atherosclerosis at a young age waspractitioners, nurses and nurse prac- port implementation of the recommen- first identified in Korean and VietnamS2 EXPERT PANEL
  • 7. SUPPLEMENT ARTICLESTABLE 1-3 Evidence Grading System: Strength of Recommendations Statement Type Definition ImplicationStrong recommendation The expert panel believes that the benefits of the recommended approach Clinicians should follow a strong recommendation clearly exceed the harms and that the quality of the supporting unless a clear and compelling rationale for an evidence is excellent (grade A or B). In some clearly defined alternative approach is present. circumstances, strong recommendations may be made on the basis of lesser evidence when high-quality evidence is impossible to obtain and the anticipated benefits clearly outweigh the harms.Recommendation The expert panel feels that the benefits exceed the harms but that the Clinicians should generally follow a quality of the evidence is not as strong (grade B or C). In some clearly recommendation but remain alert to new defined circumstances, recommendations may be made on the basis of information and sensitive to patient lesser evidence when high-quality evidence is impossible to obtain and preferences. when the anticipated benefits clearly outweigh the harms.Optional Either the quality of the evidence that exists is suspect (grade D) or well- Clinicians should be flexible in their decision- performed studies (grade A, B, or C) have found little clear advantage making regarding appropriate practice, to one approach versus another. although they may set boundaries on alternatives; patient and family preference should have a substantial influencing role.No recommendation There is both a lack of pertinent evidence (grade D) and an unclear Clinicians should not be constrained in their balance between benefits and harms. decision-making and be alert to new published evidence that clarifies the balance of benefit versus harm; patient and family preference should have a substantial influencing role.Adapted from American Academy of Pediatrics, Steering Committee on Quality Improvement and Management. Pediatrics. 2004;114(3):874 – 877.War casualties. Two major contempo- (determined by renal artery thick- young people with severe abnormali-rary studies, the Pathobiological De- ness), tobacco use (thiocyanate con- ties of individual risk factors:terminants of Atherosclerosis in Youth centration), diabetes mellitus (DM) ● In adolescents with a marked eleva-(PDAY) study2 and the Bogalusa Heart (glycohemoglobin), and (in men) obe- tion of low-density lipoprotein (LDL)Study,3 subsequently evaluated the ex- sity. There was a striking increase in cholesterol level caused by familialtent of atherosclerosis in children, ad- both severity and extent as age and the heterozygous hypercholesterol-olescents, and young adults who died number of risk factors increased. By emia, abnormal levels of coronaryaccidentally. The Bogalusa study3 mea- contrast, the absence of risk factors calcium, increased CIMT, and im-sured cardiovascular risk factors was shown to be associated with a vir- paired endothelial function have(lipid levels, blood pressure [BP], BMI, tual absence of advanced atheroscle- been found.and tobacco use) as part of a compre- rotic lesions, even in the oldest sub-hensive school-based epidemiologic jects in the study. ● Children with hypertension havestudy in a biracial community. These been shown to have increased CIMT,results were related to atherosclero- Evidence Linking Risk Factors in increased left ventricular mass, andsis measured at autopsy after acciden- Childhood to Atherosclerosis eccentric left ventricular geometry.tal death. Strong correlations were Assessed Noninvasively ● Children with type 1 DM (T1DM) haveshown between the presence and in- Over the last decade, measures of sub- significantly abnormal endothelialtensity of risk factors and the extent clinical atherosclerosis have devel- function and, in some studies, in-and severity of atherosclerosis. In the oped, including the demonstration of creased CIMT.PDAY study,2 risk factors and surro- coronary calcium on electron beam ● Children and young adults with agate measures of risk factors were computed tomography imaging, in- family history of myocardial infarc-measured after death in 15- to 34-year creased carotid intima-media thick-olds who died accidentally of external ness (CIMT) assessed with ultrasound, tion have increased CIMT, highercauses. Strong relationships were endothelial dysfunction (reduced arte- prevalence of coronary calcium,found between atherosclerotic sever- rial dilation) with brachial ultrasound and endothelial dysfunction.ity and extent, and age, non– imaging, and increased left ventricular ● Endothelial dysfunction has beenhigh-density lipoprotein (HDL) choles- mass with cardiac ultrasound. These shown by ultrasound and plethys-terol, HDL cholesterol, hypertension measures have been assessed in mography in association with ciga- PEDIATRICS Volume 128, Supplement 6, December 2011 S3
  • 8. rette smoking (passive and active) in non-HDL cholesterol level was asso- gard to tobacco-use rates, obesity and obesity. In obese children, im- ciated with a visible incremental in- prevalence, hypertension, and dyslipi- provement in endothelial function crease in the extent and severity of demia. Low socioeconomic status in occurs with regular exercise. atherosclerosis. In natural-history and of itself confers substantial risk.● Left ventricular hypertrophy at lev- studies of DM, early CVD mortality is so However, evidence is not adequate for els associated with excess mortality consistently observed that the pres- the recommendations provided in this in adults has been found in children ence of DM is considered evidence of report to be specific to racial or ethnic with severe obesity. vascular disease in adults. Consonant groups or socioeconomic status. with this evidence, in 15- to 19-yearFour longitudinal studies have found The Impact of Risk-Factor olds in the PDAY study, the presence ofrelationships of risk factors measured Clustering in Childhood on the hyperglycemia was associated within youth (specifically LDL cholesterol, Development of Atherosclerosis the demonstration of advanced ath-non-HDL cholesterol and serum apoli- erosclerotic lesions of the coronary From a population standpoint, cluster-poproteins, obesity, hypertension, to- arteries. In the PDAY study, there was ing of multiple risk factors is the mostbacco use, and DM) with measures of also a strong relationship between ab- common association with prematuresubclinical atherosclerosis in adult- dominal aortic atherosclerosis and to- atherosclerosis. The pathologic stud-hood. In many of these studies, risk bacco use. Finally, in a 25-year follow- ies reviewed above clearly showedfactors measured in childhood and ad- up, the presence of the metabolic that the presence of multiple risk fac-olescence were better predictors of syndrome risk-factor cluster in child- tors is associated with striking evi-the severity of adult atherosclerosis hood predicted clinical CVD in adult dence of an accelerated atheroscle-than were risk factors measured at subjects at 30 to 48 years of age.4 rotic process. Among the mostthe time of the subclinical atheroscle- prevalent multiple-risk combinationsrosis study. The Impact of Racial/Ethnic are the use of tobacco with 1 other risk Background and Socioeconomic factor and the development of obesity,Evidence Linking Risk Factors in Status in Childhood on the which is often associated with insulinChildhood to Clinical CVD Development of Atherosclerosis resistance, elevated triglyceride lev-The most important evidence relating CVD has been observed in diverse geo- els, reduced HDL cholesterol levels,risk in youth to clinical CVD is the ob- graphic areas and all racial and ethnic and elevated BP, a combination knownserved association of risk factors for backgrounds. Cross-sectional re- in adults as the metabolic syndrome.atherosclerosis to clinically manifest search in children has found differ- There is ample evidence from bothcardiovascular conditions. Genetic dis- ences according to race and ethnicity cross-sectional and longitudinal stud-orders related to high cholesterol are and according to geography for preva- ies that the increasing prevalence ofthe biological model for risk-factor im- lence of cardiovascular risk factors; obesity in childhood is associated withpact on the atherosclerotic process. these differences are often partially the same obesity-related risk-factorWith homozygous hypercholesterol- explained by differences in socioeco- clustering seen in adults and that itemia, in which LDL cholesterol levels nomic status. No group within the continues into adult life. This high-riskexceed 800 mg/dL beginning in infancy, United States is without a significant combination is among the reasonscoronary events begin in the first de- prevalence of risk. Several longitudi- that the current obesity epidemic withcade of life and life span is severely nal cohort studies referenced exten- its relationship to future CVD and DM isshortened. With heterozygous hyper- sively in this report (Bogalusa Heart considered one of the most importantcholesterolemia, in which LDL choles- Study,3 the PDAY study,2 and the Coro- public health challenges in contempo-terol levels are minimally 160 mg/dL nary Artery Risk Development in Young rary society. One other prevalentand typically Ͼ200 mg/dL and total Adults [CARDIA] study5) have included multiple-risk combination is the asso-cholesterol (TC) levels exceed 250 racially diverse populations, and other ciation of low cardiorespiratory fit-mg/dL beginning in infancy, 50% of studies have been conducted outside ness (identified in 33.6% of adoles-men and 25% of women experience the United States. However, longitudi- cents in the National Health andclinical coronary events by the age of nal data on Hispanic, Native American, Nutrition Examination Surveys [NHANES]50. By contrast, genetic traits associ- and Asian children are lacking. Clini- from 1999 to 20026) with overweightated with low cholesterol are associ- cally important differences in preva- and obesity, elevated TC level and sys-ated with longer life expectancy. In the lence of risk factors exist according to tolic BP, and a reduced HDL cholesterolPDAY study,2 every 30 mg/dL increase race and gender, particularly with re- level.S4 EXPERT PANEL
  • 9. SUPPLEMENT ARTICLESRisk-Factor Tracking From bariatric surgery, but the long-term out- have less atherosclerosis and will col-Childhood Into Adult Life come of those with T2DM diagnosed in lectively have lower CVD rates. ThisTracking studies from childhood to childhood is not known. concept is supported by research thatadulthood have been performed for all ● As already discussed, risk-factor has found that (1) societies with lowthe major risk factors. clusters such as those seen with levels of cardiovascular risk factors obesity and the metabolic syndrome have low CVD rates and that changes● Obesity tracks more strongly than have been shown to track from in risk in those societies are associ- any other risk factor; among many childhood into adulthood. ated with a change in CVD rates, (2) reports from studies that have dem- in adults, control of risk factors onstrated this fact, one of the most CVD Prevention Beginning in Youth leads to a decline in morbidity and recent is from the Bogalusa study,7 The rationale for these guidelines mortality from CVD, and (3) those in which Ͼ2000 children were fol- comes from the following evidence. without childhood risk have minimal lowed from initial evaluation at 5 to atherosclerosis at 30 to 34 years of 14 years of age to adult follow-up at ● Atherosclerosis, the pathologic ba- age, absence of subclinical athero- a mean age of 27 years. On the basis sis for clinical CVD, originates in childhood. sclerosis as young adults, extended of BMI percentiles derived from the life expectancy, and a better quality study population, 84% of those with ● Risk factors for the development of of life free from CVD. a BMI in the 95th to 99th percentile atherosclerosis can be identified in as children were obese as adults, childhood. The Pathway to Recommending and all of those with a BMI at the ● Development and progression of Clinical Practice-Based Prevention Ͼ99th percentile were obese in atherosclerosis clearly relates to adulthood. Increased correlation is The most direct means of establishing the number and intensity of cardio- seen with increasing age at which evidence for active CVD prevention be- vascular risk factors, which begin in the elevated BMI occurs. ginning at a young age would be to ran- childhood. domly assign young people with● For cholesterol and BP, tracking ● Risk factors track from childhood defined risks to treatment of cardio- correlation coefficients in the range into adult life. vascular risk factors or to no treat- of 0.4 have been reported consis- ● Interventions exist for the manage- ment and follow both groups over tently from many studies, correlat- ment of identified risk factors. sufficient time to determine if cardio- ing these measures in children 5 to The evidence for the first 4 bullet vascular events are prevented without 10 years of age with results 20 to 30 points is reviewed in this section, and undue increase in morbidity arising years later. These data suggest that the evidence surrounding interven- from treatment. This direct approach having cholesterol or BP levels in tions for identified risk factors is ad- is intellectually attractive, because the upper portion of the pediatric dressed in the risk-factor–specific atherosclerosis prevention would be- distribution makes having them as sections of the guideline to follow. gin at the earliest stage of the disease adult risk factors likely but not cer- process and thereby maximize the tain. Those who develop obesity It is important to distinguish between benefit. However, this approach is as have been shown to be more likely the goals of prevention at a young age unachievable as it is attractive, pri- to develop hypertension or dyslipi- and those at older ages in which ath- marily because such studies would be demia as adults. erosclerosis is well established, mor- extremely expensive and would be sev-● Tracking data on physical fitness bidity may already exist, and the pro- cess is only minimally reversible. At a eral decades in duration, a time period are more limited. Physical activity in which changes in environment and levels do track but not as strongly young age, there have historically been 2 goals of prevention: (1) prevent the medical practice would diminish the as other risk factors. relevance of the results. development of risk factors (primor-● By its addictive nature, tobacco use dial prevention); and (2) recognize and The recognition that evidence from persists into adulthood, although manage those children and adoles- this direct pathway is unlikely to be ϳ50% of those who have ever cents who are at increased risk as a achieved requires an alternative step- smoked eventually quit. result of the presence of identified risk wise approach in which segments of● T1DM is a lifelong condition. factors (primary prevention). It is well an evidence chain are linked in a man-● The insulin resistance of T2DM can be established that a population that en- ner that serves as a sufficiently rigor- alleviated by exercise, weight loss, and ters adulthood with lower risk will ous proxy for the causal inference of a PEDIATRICS Volume 128, Supplement 6, December 2011 S5
  • 10. clinical trial. The evidence reviewed in This document provides recommenda- studies have found that a family his-this section provides the critical ratio- tions for preventing the development tory of premature coronary heart dis-nale for cardiovascular prevention be- of risk factors and optimizing cardio- ease in a first-degree relative (heartginning in childhood: atherosclerosis vascular health, beginning in infancy, attack, treated angina, percutaneousbegins in youth; the atherosclerotic that are based on the results of the coronary catheter interventional pro-process relates to risk factors that can evidence review. Pediatric care provid- cedure, coronary artery bypass sur-be identified in childhood; and the ers (pediatricians, family practitio- gery, stroke, or sudden cardiac deathpresence of these risk factors in a ners, nurses, nurse practitioners, in a male parent or sibling before thegiven child predicts an adult with risk physician assistants, registered dieti- age of 55 years or a female parent orif no intervention occurs. The remain- tians) are ideally positioned to rein- sibling before the age of 65 years) is aning evidence links pertain to the dem- force cardiovascular health behaviors important independent risk factor foronstration that interventions to lower as part of routine care. The guideline future CVD. The process of atheroscle-risk will have a health benefit and that also offers specific guidance on pri- rosis is complex and involves many ge-the risk and cost of interventions to mary prevention with age-specific, netic loci and multiple environmentalimprove risk are outweighed by the re- evidence-based recommendations for and personal risk factors. Nonethe-duction in CVD morbidity and mortal- individual risk-factor detection. Man- less, the presence of a positive paren-ity. These issues are captured in the agement algorithms provide staged tal history has been consistently foundevidence reviews of each risk factor. care recommendations for risk reduc- to significantly increase baseline riskThe recommendations reflect a com- tion within the pediatric care setting for CVD. The risk for CVD in offspring isplex decision process that integrates and identify risk-factor levels that re- strongly inversely related to the age ofthe strength of the evidence with quire specialist referral. The guide- the parent at the time of the indexknowledge of the natural history of lines also identify specific medical con- event. The association of a positiveatherosclerotic vascular disease, esti- ditions such as DM and chronic kidney family history with increased cardio-mates of intervention risk, and the phy- disease that are associated with in- vascular risk has been confirmed forsician’s responsibility to provide both creased risk for accelerated athero- men, women, and siblings and in dif-health education and effective disease sclerosis. Recommendations for ferent racial and ethnic groups. The ev-treatment. These recommendations ongoing cardiovascular health man- idence review identified all RCTs, sys-for those caring for children will be agement for children and adolescents tematic reviews, meta-analyses, andmost effective when complemented by with these diagnoses are provided. observational studies that addresseda broader public health strategy. A cornerstone of pediatric care is the family history of premature athero- provision of health education. In the US sclerotic disease and the developmentThe Childhood Medical Office Visit health care system, physicians and and progression of atherosclerosisas the Setting for Cardiovascular nurses are perceived as credible mes- from childhood into young adult life.Health Management sengers for health information. The childhood health maintenance visit Conclusions and Grading of theOne cornerstone of pediatric care is provides an ideal context for effective Evidence Review for the Role ofplacing clinical recommendations in a delivery of the cardiovascular health Family History in Cardiovasculardevelopmental context. Those who message. Pediatric care providers Healthmake pediatric recommendationsmust consider not only the relation of provide an effective team educated to ● Evidence from observational stud-age to disease expression but the abil- initiate behavior change to diminish ies strongly supports inclusion of aity of the patient and family to under- risk of CVD and promote lifelong car- positive family history of early coro-stand and implement medical advice. diovascular health in their patients nary heart disease in identifyingFor each risk factor, recommenda- from infancy into young adult life. children at risk for accelerated ath-tions must be specific to age and devel- erosclerosis and for the presence ofopmental stage. The Bright Futures 4. FAMILY HISTORY OF EARLY an abnormal risk profile (grade B).concept of the American Academy of ATHEROSCLEROTIC CVD ● For adults, a positive family historyPediatrics8 (AAP) is used to provide a A family history of CVD represents the is defined as a parent and/or siblingframework for these guidelines with net effect of shared genetic, biochemi- with a history of treated angina,cardiovascular risk-reduction recom- cal, behavioral, and environmental myocardial infarction, percutane-mendations for each age group. components. In adults, epidemiologic ous coronary catheter interven-S6 EXPERT PANEL
  • 11. SUPPLEMENT ARTICLES tional procedure, coronary artery risk. Evidence relative to diet and the specific nutrition area with grades are bypass grafting, stroke, or sudden development of atherosclerosis in summarized. Where the evidence is in- cardiac death before 55 years in childhood and adolescence was identi- adequate yet nutrition guidance is men or 65 years in women. Because fied by the evidence review for this needed, recommendations for pediat- the parents and siblings of children guideline and, collectively, provides ric care providers are based on a con- and adolescents are usually young the rationale for new dietary preven- sensus of the expert panel (grade D). themselves, it was the panel con- tion efforts initiated early in life. The age- and evidence-based recom- sensus that when evaluating family This new pediatric cardiovascular mendations of the expert panel follow. history of a child, history should guideline not only builds on the recom- also be ascertained for the occur- mendations for achieving nutrient ad- In accordance with the Surgeon Gen- rence of CVD in grandparents, equacy in growing children as stated eral’s Office, the World Health Organi- aunts, and uncles, although the evi- zation, the AAP, and the American in the 2010 DGA but also adds evidence dence supporting this recommen- Academy of Family Physicians, exclu- regarding the efficacy of specific di- dation is insufficient to date (grade sive breastfeeding is recommended etary changes in reducing cardiovas- D). for the first 6 months of life. Contin- cular risk from the current evidence● Identification of a positive family ued breastfeeding is recommended review for use by pediatric care pro- history for cardiovascular disease to at least 12 months of age with the viders in the care of their patients. Be- and/or cardiovascular risk fac- addition of complementary foods. If cause the focus of these guidelines is tors should lead to evaluation of breastfeeding per se is not possible, on cardiovascular risk reduction, the all family members, especially feeding human milk by bottle is sec- evidence review specifically evaluated parents, for cardiovascular risk ond best, and formula-feeding is the dietary fatty acid and energy compo- factors (grade B). third choice. nents as major contributors to hyper-● Family history evolves as a child ma- cholesterolemia and obesity, as well tures, so regular updates are a nec- as dietary composition and micronu- ● Long-term follow-up studies have essary part of routine pediatric trients as they affect hypertension. found that subjects who were care (grade D). New evidence from multiple dietary tri- breastfed have sustained cardio- als that addressed cardiovascular risk vascular health benefits, including● Education about the importance of reduction in children has provided lower cholesterol levels, lower accurate and complete family important information for these BMI, reduced prevalence of type 2 health information should be part of recommendations. DM, and lower CIMT in adulthood routine care for children and ado- (grade B). lescents. As genetic sophistication increases, linking family history to Conclusions and Grading of the ● Ongoing nutrition counseling has specific genetic abnormalities will Evidence Review for Diet and been effective in assisting children provide important new knowledge Nutrition in Cardiovascular Risk and families to adopt and sustain about the atherosclerotic process Reduction recommended diets for both nutri- (grade D). The expert panel concluded that there ent adequacy and reducing cardio-Recommendations for the use of fam- is strong and consistent evidence that vascular risk (grade A).ily history in cardiovascular health good nutrition beginning at birth has ● Within appropriate age- and gender-promotion are listed in Table 4-1. profound health benefits and the po- based requirements for growth and tential to decrease future risk for CVD. nutrition, in normal children and in5. NUTRITION AND DIET The expert panel accepts the 2010 DGA8 children with hypercholesterolemiaThe 2010 Dietary Guidelines for Ameri- as containing appropriate recommen- intake of total fat can be safely lim-cans (DGA)8 include important recom- dations for diet and nutrition in chil- ited to 30% of total calories, satu-mendations for the population aged 2 dren aged 2 years and older. The rec- rated fat intake limited to 7% to 10%years and older. In 1992, the National ommendations in these guidelines are of calories, and dietary cholesterolCholesterol Education Program (NCEP) intended for pediatric care providers limited to 300 mg/day. Under thePediatric Panel report1 provided di- to use with their patients to address guidance of qualified nutritionists,etary recommendations for all chil- cardiovascular risk reduction. The this dietary composition has beendren as part of a population-based ap- conclusions of the expert panel’s re- shown to result in lower TC and LDLproach to reducing cardiovascular view of the entire body of evidence in a cholesterol levels, less obesity, and PEDIATRICS Volume 128, Supplement 6, December 2011 S7
  • 12. less insulin resistance (grade A). tervention should be tailored to activity. Calorie intake needs to Under similar conditions and with each specific child’s needs. match growth demands and physi- ongoing follow-up, these levels of fat ● Optimal intakes of total protein and cal activity needs (grade A). Esti- intake might have similar effects total carbohydrate in children were mated calorie requirements ac- starting in infancy (grade B). Fats not specifically addressed, but with cording to gender and age group at are important to infant diets be- a recommended total fat intake of 3 levels of physical activity from the cause of their role in brain and cog- 30% of energy, the expert panel rec- dietary guidelines are shown in Ta- nitive development. Fat intake for in- ommends that the remaining 70% of ble 5-2. For children of normal fants younger than 12 months calories include 15% to 20% from weight whose activity is minimal, should not be restricted without protein and 50% to 55% from carbo- most calories are needed to meet medical indication. hydrate sources (no grade). These nutritional requirements, which● The remaining 20% of fat intake leaves only ϳ5% to 15% of calorie recommended ranges fall within should comprise a combination of intake from extra calories. These the acceptable macronutrient dis- monosaturated and polyunsatu- calories can be derived from fat or tribution range specified by the rated fats (grade D). Intake of trans sugar added to nutrient-dense 2010 DGA: 10% to 30% of calories fats should be limited as much as foods to allow their consumption as from protein and 45% to 65% of cal- possible (grade D). sweets, desserts, or snack foods ories from carbohydrate for chil- (grade D).● For adults, the current NCEP guide- dren aged 4 to 18 years. ● Dietary fiber intake is inversely as- lines9 recommend that adults con- ● Sodium intake was not addressed sociated with energy density and in- sume 25% to 35% of calories from by the evidence review for this sec- creased levels of body fat and is pos- fat. The 2010 DGA supports the Insti- tion on nutrition and diet. From the itively associated with nutrient tute of Medicine recommendations evidence review for the “High BP” density (grade B); a daily total di- for 30% to 40% of calories from fat section, lower sodium intake is as- etary fiber intake from food sources for ages 1 to 3 years, 25% to 35% of sociated with lower systolic and di- of at least age plus 5 g for young calories from fat for ages 4 to 18 astolic BP in infants, children, and children up to 14 g/1000 kcal for years, and 20% to 35% of calories adolescents. older children and adolescents is from fat for adults. For growing chil- ● Plant-based foods are important recommended (grade D). dren, milk provides essential nutri- low-calorie sources of nutrients in- ents, including protein, calcium, ● The expert panel supports the 2008 cluding vitamins and fiber in the di- AAP recommendation for vitamin D magnesium, and vitamin D, that are ets of children; increasing access to supplementation with 400 IU/day for not readily available elsewhere in fruits and vegetables has been all infants and children.10 No other the diet. Consumption of fat-free shown to increase their intake vitamin, mineral, or dietary supple- milk in childhood after 2 years of (grade A). However, increasing fruit ments are recommended (grade D). age and through adolescence opti- and vegetable intake is an ongoing The new recommended daily allow- mizes these benefits without com- challenge. ance for vitamin D for those aged 1 promising nutrient quality while avoiding excess saturated fat and ● Reduced intake of sugar-sweetened to 70 years is 600 IU/day. calorie intake (grade A). Between beverages is associated with de- ● Use of dietary patterns modeled on the ages of 1 and 2 years, as chil- creased obesity measures (grade those shown to be beneficial for dren transition from breast milk or B). Specific information about fruit adults (eg, Dietary Approaches to formula, reduced-fat milk (ranging juice intake is too limited for an Stop Hypertension [DASH] pattern) from 2% milk to fat-free milk) can be evidence-based recommendation. is a promising approach to improv- used on the basis of the child’s Recommendations for intake of ing nutrition and decreasing cardio- growth, appetite, intake of other 100% fruit juice by infants was vascular risk (grade B). nutrient-dense foods, intake of made by a consensus of the expert ● All diet recommendations must be other sources of fat, and risk for panel (grade D) and are in agree- interpreted for each child and fam- obesity and CVD. Milk with reduced ment with those of the AAP. ily to address individual diet pat- fat should be used only in the con- ● Per the 2010 DGA, energy intake terns and patient sensitivities such text of an overall diet that supplies should not exceed energy needed as lactose intolerance and food al- 30% of calories from fat. Dietary in- for adequate growth and physical lergies (grade D).S8 EXPERT PANEL
  • 13. 3. INTEGRATED CARDIOVASCULAR HEALTH SCHEDULE Risk Factor Age Birth to 12 mo 1–4 y 5–9 y 9–11 y 12–17 y 18–21 y Family — At 3 y, evaluate family history for Update at each nonurgent health Reevaluate family history for early Update at each nonurgent health Repeat family-history evaluation with history of early CVD: parents, grand- encounter CVD in parents, grandparents, encounter patient early CVD parents, aunts/uncles, men aunts/uncles, men Յ55 y old, Յ55 y old, women Յ65 y old; women Յ65 y old review with parents and refer as needed; positive family history identifies children for intensive CVD RF attention Tobacco Advise smoke-free home; Continue active antismoking Obtain smoke exposure history Assess smoking status of child; Continue active antismoking Reinforce strong antismoking message; exposure offer smoking-cessation advice with parents; offer from child Begin active active antismoking counseling counseling with patient; offer offer smoking-cessation assistance or assistance or referral smoking-cessation assistance antismoking advice with child or referral as needed smoking-cessation assistance or referral as needed to parents and referral as needed referral as needed Nutrition/diet Support breastfeeding as At age 12–24 mo, may change to Reinforce CHILD-1 diet messages Reinforce CHILD-1 diet messages Obtain diet information from child Review healthy diet with patient optimal to 12 mo of age cow’s milk with 2% as needed and use to reinforce healthy diet if possible; add formula percentage of fat decided by and limitations and provide if breastfeeding family and pediatric care counseling as needed decreases or stops provider; after 2 y of age, before 12 mo of age fat-free milk for all; juice Յ4 oz/d; transition to CHILD-1 diet by the age of 2 y Growth, Review family history for Chart height/weight/BMI; Chart height/weight/BMI and Chart height/weight/BMI and Chart height/weight/BMI and review Review height/weight/BMI and norms for overweight/ obesity; discuss weight- classify weight-by BMI from review with parent; BMI Ն review with parent and child; with child and parent; BMI Ն85th health with patient; BMI Ն 85th obesity for-height tracking, age 2 y; review with parent 85th percentile, crossing BMI Ն 85th percentile, percentile, crossing percentiles: percentile, crossing percentiles: growth chart, and percentiles: Intensify diet/ crossing percentiles: Intensify intensify diet/activity focus for 6 intensify diet/activity focus for 6 mo; healthy diet activity focus for 6 mo; if no diet/activity focus for 6 mo; if mo; if no change: RD referral, if no change: RD referral, manage per change: RD referral, manage no change: RD referral, manage per obesity algorithms; obesity algorithms; BMI Ն 95th per obesity algorithms manage per obesity BMI Ն 95th percentile, manage percentile, manage per obesity BMI Ն 95th percentile, manage algorithms; BMI Ն 95th per obesity algorithms algorithms per obesity algorithms percentile: manage per obesity algorithms Lipids No routine lipid screening Obtain FLP only if family history Obtain FLP only if family history Obtain universal lipid screen with Obtain FLP if family history newly Measure 1 nonfasting non–HDL or FLP in for CVD is positive, parent has for CVD is positive, parent nonfasting non-HDL ϭ TC Ϫ positive, parent has all: review with patient; manage with dyslipidemia, child has any has dyslipidemia, child has HDL, or FLP: manage per lipid dyslipidemia, child has any other lipid algorithms per ATP as needed other RFs or high-risk any other RFs or high-risk algorithms as needed RFs or high-risk condition; condition condition manage per lipid algorithms as needed BP Measure BP in infants with Measure BP annually in all from Check BP annually and chart for Check BP annually and chart for Check BP annually and chart for Measure BP: review with patient; renal/urologic/cardiac the age of 3 y; chart for age/ age/gender/height: review age/gender/height: review with age/gender/height: review with evaluate and treat per JNC guidelines diagnosis or history of gender/height percentile and with parent; workup and/or parent, workup and/or adolescent and parent, workup neonatal ICU review with parent management per BP management per BP algorithm and/or management per BP algorithm as needed as needed algorithm as needed Physical Encourage parents to Encourage active play; limit Recommend MVPA of Ն1 h/d; Obtain activity history from child: Use activity history with adolescent Discuss lifelong activity, sedentary time activity model routine activity; sedentary/screen time to Յ2 limit screen/sedentary time recommend MVPA of Ն1 h/d to reinforce MVPA of Ն1 h/d and limits with patient no screen time before h/d; no TV in bedroom to Յ2 h/d and screen/sedentary time of leisure screen time of Յ2 h/d the age of 2 y Յ2 h/d Diabetes — — — Measure fasting glucose level per Measure fasting glucose level per Obtain fasting glucose level if indicated; ADA guidelines; refer to ADA guidelines; refer to refer to endocrinologist as needed endocrinologist as needed endocrinologist as neededPEDIATRICS Volume 128, Supplement 6, December 2011 All algorithms and guidelines in this schedule are included in this summary report. RF indicates risk factor; RD, registered dietitian; ATP, Adult Treatment Panel III (“Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults”); JNC, Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; MVPA, moderate-to-vigorous physical activity; ADA, American Diabetes Association. SUPPLEMENT ARTICLESS9 The full and summary reports of the Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents can also be found on the NHLBI Web site (www.nhlbi.nih.gov).
  • 14. TABLE 4-1 Evidence-Based Recommendations for Use of Family History in Cardiovascular review focused on the effects of activ- Health Promotion ity on cardiovascular health, becauseBirth to 18 y Take detailed family history of CVD at initial encounter and/or at 3, Grade B physical inactivity has been identified 9–11, and 18 ya Recommend as an independent risk factor for cor- If positive family history identified, evaluate patient for other onary heart disease in adults. Over the cardiovascular risk factors, including dyslipidemia, hypertension, last several decades, there has been a DM, obesity, history of smoking, and sedentary lifestyle steady decrease in the amount of time If positive family history and/or cardiovascular risk factors identified, Grade B that children spend being physically evaluate family, especially parents, for cardiovascular risk factors Recommend active and an accompanying increase Update family history at each nonurgent health encounter Grade D in time spent in sedentary activities. The Recommend evidence review identified many studies in youth ranging in age from 4 to 21 years Use family history to stratify risk for CVD risk as risk profile evolves Grade D that strongly linked increased time Recommend spent in sedentary activities with re- Supportive action: educate parents about the importance of family duced overall activity levels, disadvanta- history in estimating future health risks for all family members geous lipid profiles, higher systolic BP,18 to 21 y Review family history of heart disease with young adult patient Grade B higher levels of obesity, and higher levels Strongly recommend of all the obesity-related cardiovascular Supportive action: educate patient about family/personal risk for risk factors including hypertension, in- early heart disease, including the need for evaluation for all cardiovascular risk factors sulin resistance, and type 2 DM.Grades reflect the findings of the evidence review; recommendation levels reflect the consensus opinion of the expert panel;and supportive actions represent expert consensus suggestions from the expert panel provided to support implementation Conclusions and Grading of theof the recommendations (they are not graded). Evidence Review for Physicala “Family” includes parent, grandparent, aunt, uncle, or sibling with heart attack, treated angina, coronary artery bypassgraft/stent/angioplasty, stroke, or sudden cardiac death at Ͻ55 y in males and Ͻ65 y in females. Activity The expert panel felt that the evidence strongly supports the role of physicalGraded, age-specific recommenda- bles. This diet has been modified for activity in optimizing cardiovasculartions for pediatric care providers to use in children aged 4 years and older health in children and adolescents.use in optimizing cardiovascular on the basis of daily energy needs ac- ● There is reasonably good evidencehealth in their patients are summa- cording to food group and is shown in that physical activity patterns es-rized in Table 5-1. The Cardiovascular Table 5-3 as an example of a heart- tablished in childhood are carriedHealth Integrated Lifestyle Diet healthy eating plan using CHILD-1 forward into adulthood (grade(CHILD-1) is the first stage in dietary recommendations. C).change for children with identified dys-lipidemia, overweight and obesity, 6. PHYSICAL ACTIVITY ● There is strong evidence that in-risk-factor clustering, and high-risk Physical activity is any bodily move- creases in moderate-to-vigorousmedical conditions that might ulti- ment produced by contraction of skel- physical activity are associated withmately require more intensive dietary etal muscle that increases energy ex- lower systolic and diastolic BP, de-change. CHILD-1 is also the recom- penditure above a basal level. Physical creased measures of body fat, de-mended diet for children with a posi- activity can be focused on strengthen- creased BMI, improved fitness mea-tive family history of early cardiovas- ing muscles, bones, and joints, but be- sures, lower TC level, lower LDLcular disease, dyslipidemia, obesity, cause these guidelines address car- cholesterol level, lower triglycerideprimary hypertension, DM, or expo- diovascular health, the evidence level, higher HDL cholesterol level,sure to smoking in the home. Any di- review concentrated on aerobic activ- and decreased insulin resistance inetary modification must provide nutri- ity and on the opposite of activity: sed- childhood and adolescence (gradeents and calories needed for optimal entary behavior. There is strong evi- A).growth and development (Table 5-2). dence for beneficial effects of physical ● There is limited but strong and con-Recommended intakes are adequately activity and disadvantageous effects of sistent evidence that physical exer-met by a DASH-style eating plan, which a sedentary lifestyle on the overall cise interventions improve subclini-emphasizes fat-free/low-fat dairy and health of children and adolescents cal measures of atherosclerosisincreased intake of fruits and vegeta- across a broad array of domains. Our (grade B).S10 EXPERT PANEL
  • 15. SUPPLEMENT ARTICLESTABLE 5-1 Evidence-Based Recommendations for Diet and Nutrition: CHILD-1Birth to 6 mo Infants should be exclusively breastfed (no supplemental formula or other foods) until the age of 6 moa Grade B Strongly recommend6 to 12 mo Continue breastfeeding until at least 12 mo of age while gradually adding solids; transition to iron- Grade B fortified formula until 12 mo if reducing breastfeedinga Strongly recommend Fat intake in infants Ͻ12 mo of age should not be restricted without medical indication Grade D Recommend Limit other drinks to 100% fruit juice (Յ4 oz/d); no sweetened beverages; encourage water Grade D recommend12 to 24 mo Transition to reduced-fatb (2% to fat-free) unflavored cow’s milkc (see supportive actions) Grade B Recommend Limit/avoid sugar-sweetened beverage intake; encourage water Grade B Strongly recommend Transition to table food with: Total fat 30% of daily kcal/EERd Grade B Recommend Saturated fat 8%–10% of daily kcal/EER Grade B Recommend Avoid trans fat as much as possible Grade D Strongly recommend Monounsaturated and polyunsaturated fat up to 20% of daily kcal/EER Grade D recommend Cholesterol Ͻ 300 mg/d Grade B Strongly recommend Supportive actions The fat content of cow’s milk to introduce at 12–24 mo of age should be decided together by parents and health care providers on the basis of the child’s growth, appetite, intake of other nutrient-dense foods, intake of other sources of fat, and potential risk for obesity and CVD 100% fruit juice (from a cup), no more than 4 oz/d Limit sodium intake Consider DASH-type diet rich in fruits, vegetables, whole grains, and low-fat/fat-free milk and milk products and lower in sugar (Table 5-3)2 to 10 y Primary beverage: fat-free unflavored milk Grade A Strongly recommend Limit/avoid sugar-sweetened beverages; encourage water Grade B Recommend Fat content: Total fat 25%–30% of daily kcal/EER Grade A Strongly recommend Saturated fat 8%–10% of daily kcal/EER Grade A Strongly recommend Avoid trans fats as much as possible Grade D, recommend Monounsaturated and polyunsaturated fat up to 20% of daily kcal/EER Grade D Recommend Cholesterol Ͻ 300 mg/d Grade A Strongly Recommend Encourage high dietary fiber intake from foodse Grade B recommend Supportive actions: Teach portions based on EER for age/gender/age (Table 5-2) Encourage moderately increased energy intake during periods of rapid growth and/or regular moderate-to-vigorous physical activity Encourage dietary fiber from foods: age ϩ 5 g/de Limit naturally sweetened juice (no added sugar) to 4 oz/d Limit sodium intake Support DASH-style eating plan (Table 5-3)11 to 21 y Primary beverage: fat-free unflavored milk Grade A Strongly recommend Limit/avoid sugar-sweetened beverages; encourage water Grade B Recommend PEDIATRICS Volume 128, Supplement 6, December 2011 S11
  • 16. TABLE 5-1 Continued Fat content: Total fat 25%–30% of daily kcal/EERd Grade A Strongly recommend Saturated fat 8%–10% of daily kcal/EER Grade A Strongly recommend Avoid trans fat as much as possible Grade D Recommend Monounsaturated and polyunsaturated fat up to 20% of daily kcal/EER Grade D Recommend Cholesterol Ͻ 300 mg/d Grade A Strongly recommend Encourage high dietary fiber intake from foodse Grade B Recommend Supportive actions: Teach portions based on EER for age/gender/activity (Table 5-2) Encourage moderately increased energy intake during periods of rapid growth and/or regular moderate-to-vigorous physical activity Advocate dietary fiber: goal of 14 g/1000 kcale Limit naturally sweetened juice (no added sugar) to 4–6 oz/d Limit sodium intake Encourage healthy eating habits: breakfast every day, eating meals as a family, limiting fast-food meals Support DASH-style eating plan (Table 5-3)Grades reflect the findings of the evidence review; recommendation levels reflect the consensus opinion of the expert panel. Supportive actions represent expert consensus suggestionsfrom the expert panel provided to support implementation of the recommendations; they are not graded. EER indicates estimated energy requirement.a Infants who cannot be fed directly at the breast should be fed expressed milk. Infants for whom expressed milk is not available should be fed iron-fortified infant formula.b For toddlers 12 to 24 mo of age with a family history of obesity, heart disease, or high cholesterol, parents should discuss transition to reduced-fat milk with pediatric care provider after12 months of age.c Continued breastfeeding is still appropriate and nutritionally superior to cow’s milk. Reduced-fat milk should be used only in the context of an overall diet that supplies 30% of calories from fat.d Estimated energy requirements per day for age/gender (Table 5-2).e Naturally fiber-rich foods are recommended (fruits, vegetables, whole grains); fiber supplements are not advised. Limit refined carbohydrates (sugars, white rice, and white bread). ● Physical activity patterns, dietary choices, and smoking behaviorsTABLE 5-2 Estimated Calorie Needs per Day by Age, Gender, and Physical Activity Levela cluster together (grade C).Gender Age Calorie Requirements (kcals) by Activity Levelb ● There is no evidence of harm asso- (Years) Sedentary Moderately Active ciated with increased physical activ- Active ity or limitation of sedentary activityChild 2–3 1000–1200 1000–1400c 1000–1400c in healthy children (grade A).Femaled 4–8 1200–1400 1400–1600 1400–1800 9–13 1400–1600 1600–2000 1800–2200 ● There is strong evidence that physi- 14–18 1800 2000 2400 cal activity should be promoted in 19–30 1800–2000 2000–2200 2400Male 4–8 1200–1400 1400–1600 1600–2000 schools (grade A). 9–13 1600–2000 1800–2200 2000–2600 There is less specific information on 14–18 2000–2400 2400–2800 2800–3200 19–30 2400–2600 2600–2800 3000 the type and amount of physical exer-Estimated amounts of calories needed to maintain caloric balance for various gender and age groups at three different cise required for optimum cardiovas-levels of physical activity. The estimates are rounded to the nearest 200 calories. An individual’s calorie needs may be higher cular health. Reported activity inter-or lower than these average estimates.a Based on Estimated Energy Requirements (EER) equations, using reference heights (average) and reference weights ventions ranged from 20 to 60 minutes,(health) for each age/gender group. For children and adolescents, reference height and weight vary. For adults, the 2 to 5 times per week in children agedreference man is 5 feet 10 inches tall and weighs 154 pounds. The reference woman is 5 feet 4 inches tall and weighs 126pounds. EER equations are from the Institute of Medicine. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, 3 to 17 years and included a wide vari-Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington (DC): The National Academies Press; 2002. ety of dynamic and isometric exer-b Sedentary means a lifestyle that includes only the light physical activity associated with typical day-to-day life. Moderately cises. Extrapolating from theseactive means a lifestyle that includes physical activity equivalent to walking ϳ1.5 to 3 miles per day at 3 to 4 miles per hour,in addition to the light physical activity associated with typical day-to-day life. Active means a lifestyle that includes physical interventions, which occurred in su-activity equivalent to walking Ͼ3 miles per day at 3 to 4 miles per hour, in addition to the light physical activity associated pervised settings, to the real world ofwith typical day-to-day life.c The calorie ranges shown are to accommodate needs of different ages within the group. For children and adolescents, childhood and adolescence, the ex-more calories are needed at older ages. For adults, fewer calories are needed at older ages. pert panel recommends at least 1d Estimates for females do not include women who are pregnant or breastfeeding.Reproduced with permission from Institute of Medicine. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, hour of moderate-to-vigorous activ-Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: National Academies Press; 2002:175–182. ity every day of the week for childrenS12 EXPERT PANEL
  • 17. SUPPLEMENT ARTICLESTABLE 5-3 DASH Eating Plan: Servings per Day According to Food Group and Total Energy Intake Food Group No. of Servings Serving Size Examples and Notes Significance of Each Food Group to the 1200 1400 1600 1800 2000 2600 DASH Eating Plan cal cal cal cal cal calGrainsa 4–5/d 5–6/d 6/d 6/d 6–8/d 10–11/d 1 slice bread; 1 oz dry Whole-wheat bread and rolls, Major sources of energy cerealb; 1⁄2 cup whole-wheat pasta, and fiber cooked rice, pasta, English muffin, pita bread, or cerealb bagel, cereals, grits, oatmeal, brown rice, unsalted pretzels and popcornVegetables 3–4/d 3–4/d 3–4/d 4–5/d 4–5/d 5–6/d 1 cup raw leafy Broccoli, carrots, collards, Rich sources of vegetable; 1⁄2 cup green beans, green peas, potassium, cut-up raw or kale, lima beans, potatoes, magnesium, and fiber cooked vegetable; spinach, squash, sweet 1⁄2 cup vegetable potatoes, tomatoes juiceFruits 3–4/d 4/d 4/d 4–5/d 4–5/d 5–6/d 1 medium fruit; 1⁄4 cup Apples, apricots, bananas, Important sources of dried fruit; 1⁄2 cup dates, grapes, oranges, potassium, fresh, frozen, or grapefruit, grapefruit magnesium, and fiber canned fruit; 1⁄2 cup juice, mangoes, melons, fruit juice peaches, pineapples, raisins, strawberries, tangerinesFat-free or low- 2–3/d 2–3/d 2–3/d 2–3/d 2–3/d 3/d 1 cup milk or yogurt; Fat-free milk or buttermilk, Major sources of fat milk and 11⁄2 oz cheese fat-free, low-fat, or calcium and protein milk products reduced-fat cheese, fat- free/low-fat regular or frozen yogurtLean meats, Յ3/d Յ3–4/d Յ3–4/d Յ6/d Յ6/d Յ6/d 1 oz cooked meats, Select only lean; trim away Rich sources of protein poultry, and poultry, or fish; 1 visible fats; broil, roast, or and magnesium fish eggc poach; remove skin from poultryNuts, seeds, and 3/wk 3/wk 3–4/wk 4/wk 4–5/wk 1/d 13 ⁄ cup or 11⁄2 oz nuts; Almonds, filberts, mixed nuts, Rich sources of energy, legumes 2 tbsp peanut peanuts, walnuts, magnesium, protein, butter; 2 tbsp or 1⁄2 sunflower seeds, peanut and fiber oz seeds; 1⁄2 cup butter, kidney beans, cooked legumes lentils, split peas (dry beans and peas)Fats and oilsd 1/d 1/d 2/d 2–3/d 2–3/d 3/d 1 tsp soft margarine; Soft margarine, vegetable oil The DASH study had 27% 1 tsp vegetable oil; (such as canola, corn, of calories as fat, 1 tbsp mayonnaise; olive, or safflower), low-fat including fat in or 2 tbsp salad mayonnaise, light salad added to foods dressing dressingSweets and Յ3/wk Յ3/wk Յ3/wk Յ5/wk Յ5/wk Յ2/d 1 tbsp sugar; 1 tbsp Fruit-flavored gelatin, fruit Sweets should be low in added sugars jelly or jam; 1⁄2 cup punch, hard candy, jelly, fat sorbet, gelatin; 1 maple syrup, sorbet and cup lemonade ices, sugarTable 5-2 provides estimated energy requirements according to age, gender, and activity level for use with this table. The FDA and the Environmental Protection Agency advise women ofchildbearing age who may become pregnant, pregnant women, nursing mothers, and young children to avoid some types of fish and shellfish and eat fish and shellfish that are low inmercury. For more information, call the FDA’s food information line toll free at 1[hyphen]888-SAFEFOOD or visit www.cfsan.fda.gov/~dms/admehg3.html.a Whole grains are recommended for most grain servings as a good source of fiber and nutrients.b Serving sizes vary between a 1⁄2 and 11⁄4 cups, depending on cereal type. Check the product’s nutrition-facts label.c Because eggs are high in cholesterol, limit egg yolk intake to no more than 4 per week; 2 egg whites have the same protein content as 1 oz of meat.d Fat content changes serving amount for fats and oils. For example, 1 tbsp of regular salad dressing ϭ 1 serving; 1 tbsp of low-fat dressing ϭ 1⁄2 serving; 1 tbsp fat-free dressing ϭ 0 servings. PEDIATRICS Volume 128, Supplement 6, December 2011 S13
  • 18. older than 5 years (Table 6-1). In lished in May 200812 systematically re- ate success, although long-term re-agreement with the “Physical Activity viewed almost 9000 publications and sults are limited (grade B).Guidelines Advisory Committee Re- concluded that smoking prevention ● Practice-based interventions to achieveport, 2008”11 from the Department of and cessation interventions are effec- smoking cessation in adolescents haveHealth and Human Services, the ex- tive in adults. These same methods had moderate success with limitedpert panel recommends that activity should be safely applicable in child- long-term follow-up (grade B).be vigorous on 3 days/week (www. hood and adolescence, because behav- ● School-based smoking-preventionhealth.gov/paguidelines). In working ioral interventions to alter smoking be- programs have been moderatelywith children and families, the ex- haviors have little if any morbidity and successful with limited long-termpert panel suggested that moderate- because morbidity with pharmaco- follow-up (grade B).to-vigorous activity could be com- logic treatment is limited. Physicians Although the evidence base for effec-pared with jogging or playing who care for children are well posi- tive office-based approaches to to-baseball and that vigorous physical tioned to provide prevention and treat- bacco interventions is moderate andactivity could be compared with ment interventions for their patients. mixed, the evidence that cigarette userunning, playing singles tennis, or Youth interventions must target par- is harmful and addictive is unequivo-playing soccer. Similarly, reducing ents as well as children, because pa- cal. The need to reduce tobacco expo-sedentary time is convincingly asso- rental smoking is both a risk factor for sure is so compelling that a role forciated with a favorable cardiovascu- child smoking and provides second- pediatric health care providers is es-lar profile, and the expert panel hand smoke exposure to fetuses and sential. The lack of harm associatedagreed with the AAP recommenda- children. The evidence review as- with such interventions and the impor-tion for limiting leisure screen time sessed prevention and treatment in- tance of communicating the messageto Ͻ2 hours/day. terventions in each of these areas. of risk associated with tobacco pro- vides the rationale for “strongly rec-7. TOBACCO EXPOSURE Conclusions and Grading of the ommend” despite the lack of conclu-Tobacco dependence is responsible for Evidence on Preventing Tobacco sive evidence that office-basedϳ4 million deaths worldwide annually, Exposure interventions reliably reduce tobaccoand in utero exposure to tobacco prod- initiation or smoking cessation. Physi- Among all the known risk factors foructs, involuntary tobacco smoke expo- cians and nurses who care for chil- CVD, the dichotomy between known ben-sure (secondhand smoke), and tobacco dren are well positioned to provide in- efits of risk elimination and the paucityuse directly impair health in fetuses, in- tervention to patients who smoke. The of evidence for effective interventions tofants, children, and adolescents. On the expert panel feels that such providers achieve risk reduction in pediatric carebasis of an analysis of published causes should routinely identify patients who provider settings is greatest for tobaccoof death, tobacco use is the leading ac- smoke by using the medical history exposure. The quality of the evidence re-tual cause of death in the United States. (Table 7-1). Patients should be explic- garding the harm of smoking and theThe evidence that cigarette use is harm- itly informed about the addictive and benefits of avoiding passive smoke expo-ful and addictive is unequivocal. In child- adverse health effects of tobacco use. sure, smoking prevention, and smokinghood, nicotine is highly addicting; By using the 5 A’s (ask, advise, assess, cessation is uniformly grade A. That evi-symptoms of tobacco dependence assist, and arrange), providers can as- dence grades in the recommendationshave been found after brief intermit- sess readiness to quit and assist intent use. Cigarette use among high are less than grade A reflects the lack of providing resources to supportschool students declined from 1997 to existing evidence on interventions that smoking-cessation efforts. Informa-2003. Rates were stable from 2003 to impact smoking behaviors in specific pe- tion about telephone quit lines (eg,2007 with Ͼ20% of high school stu- diatric age groups as opposed to the col- 1-800-QUIT-NOW), community cessationdents reporting daily smoking. From a lective evidence. programs, and pharmacotherapypublic health standpoint, the need to ● Good-quality interventions in pediatric should also be made available.reduce tobacco exposure is compel- care settings to decrease children’s en- As described, practice-based interven-ling, and a role for pediatric health vironmental smoke exposure have had tions to decrease environmentalcare providers is essential. mixed results (grade B). smoke exposure have had mixed re-A clinical practice guideline update ● Intervention studies to prevent sults. Nonetheless, the expert panelfrom the US Public Health Service pub- smoking initiation have had moder- believes that pediatric care providersS14 EXPERT PANEL
  • 19. SUPPLEMENT ARTICLESTABLE 6-1 Evidence-Based Activity Recommendations for Cardiovascular Health should identify parents and otherNewborn to Parents should create an environment that promotes and models Grade D caregivers who smoke and explicitly 12 mo physical activity and limits sedentary time Recommend recommend that children not be ex- Supportive actions: Discourage TV viewing altogether posed to tobacco smoke in the home,1 to 4 y Allow unlimited active playtime in safe, supportive environments Grade D in automobiles, or in any other space Recommend where exposure can occur. For the Limit sedentary time, especially TV/video Grade D Recommend parent who smokes, information pro- Supportive actions: vided should include statements about Limit total media time to no more than 1-2 hours of quality health benefits to the individual, child, programming per day and/or fetus and referral to smoking- For children Յ2 y old, discourage TV viewing altogether No TV in child’s bedroom cessation care providers. Encourage family activity at least once per week Counsel routine activity for parents as role models for children 8. HIGH BP5 to 10 y Moderate-to-vigorous physical activity every daya Grade A Strongly recommend In 2004, an NHLBI task force published Limit daily leisure screen time (TV/video/computer) Grade B “The Fourth Report on the Diagnosis, Strongly recommend Evaluation, and Treatment of High Supportive actions: Blood Pressure in Children and Adoles- Prescribe moderate-to-vigorous activity 1 h/da with vigorous- intensity physical activity 3 d/wkb cents.”13 This report included a com- Limit total media time to no more than 1–2 h/d of quality plete review of the current evidence on programming this subject and detailed recommen- No TV in child’s bedroom Take activity and screen-time history from child once per year dations for managing BP throughout Match physical activity recommendations with energy intake childhood. These recommendations Recommend appropriate safety equipment relative to each were used as the basis for these guide- sport Support recommendations for daily physical education in lines, considered complete until 2003 schools when the review for the report ended.11 to 17 y Moderate-to-vigorous physical activity every daya Grade A Therefore, this evidence review for BP Strongly recommend for these guidelines was limited to stud- Limit leisure time TV/video/computer use Grade B Strongly recommend ies published between January 1, 2003, Supportive actions: and June 30, 2007, with the addition of Encourage adolescents to aim for 1 h/d of moderate-to-vigorous selected studies through June 30, 2008, daily activitya with vigorous intense physical activityb 3 d/wk Encourage no TV in bedroom identified by the expert panel as having Limit total media time to no more than 1–2 h/d of quality met all the criteria for inclusion. Repeat- programming ing the review performed by the task Match activity recommendations with energy intake Take activity and screen-time history from adolescent at health force was not felt to be necessary, given supervision visits the short time since publication of that Encourage involvement in year-round physical activities report, or a judicious use of the re- Support continued family activity once per week and/or family sources available for development of support of adolescent’s physical activity program Endorse appropriate safety equipment relative to each sport these guidelines. Recommendations re-18 to 21 y Moderate-to-vigorous physical activity every daya Grade A garding BP are all graded as expert opin- Strongly recommend ion (grade D), because they are based on Limit leisure time TV/video/computer Grade B Strongly recommend the expert consensus conclusions of this Supportive actions: NHLBI task force. Support goal of 1 h/d of moderate-to-vigorous activity with vigorous intense physical activity 3 d/wk Conclusions of the Evidence-Review Recommend that combined leisure screen time not exceed 2 h/d Update for High BP (2003–2008) Activity and screen-time history at health supervision visits Encourage involvement in year-round, lifelong physical activities ● The evidence review for the definedGrades reflect the findings of the evidence review; recommendation levels reflect the consensus opinion of the expert panel; time period resulted in no majorand supportive actions represent expert consensus suggestions from the expert panel provided to support implementationof the recommendations (they are not graded). changes in the approach to BP eval-a Examples of moderate-to-vigorous physical activities are jogging and playing baseball. uation and management.b Examples of vigorous physical activities are running, playing singles tennis, and playing soccer. ● According to epidemiologic surveys of children and adolescents over PEDIATRICS Volume 128, Supplement 6, December 2011 S15
  • 20. TABLE 7-1 Evidence-Based Recommendations to Prevent Tobacco ExposurePrenatal Obtain smoking history from mothers; provide explicit smoking-cessation message before Grade A and during pregnancy Strongly recommend Supportive actions: Identify resources to support maternal smoking-cessation efforts. Advocate for school and community-based smoke-free interventions See “Perinatal Factors” section0 to 4 y Smoke-free home environment Grade B Strongly recommend Reinforce this message at every encounter, including urgent visits for respiratory problems Grade C Recommend Supportive actions: Provide information about health benefits of a smoke-free home to parents and children Advocate for school- and community-based smoke-free interventions5 to 10 y Obtain smoke-exposure history from child, including personal history of tobacco use Grade C Recommend Counsel patients strongly about not smoking, including providing explicit information about Grade C the addictive and adverse health effects of smoking Recommend11 to 21 y Obtain personal smoking history at every nonurgent health encounter Grade B Strongly recommend Explicitly recommend against smoking Grade B Strongly recommend Provide specific smoking-cessation guidance Grade B Strongly recommend Supportive actions: Use 5 A questions to assess readiness to quit Establish your health care practice as a resource for smoking cessation Provide quit-line phone number Identify community cessation resources Provide information about pharmacotherapy for cessation Advocate for school and community-based smoke-free interventionsGrades reflect the findings of the evidence review; recommendation levels reflect the consensus opinion of the expert panel; and supportive actions represent expert consensus suggestionsfrom the expert panel provided to support implementation of the recommendations (they are not graded). the past 20 years, BP levels have the DASH eating plan described in in late childhood. This potential risk been increasing, and the prevalence “Diet and Nutrition” is an appropriate should be considered when such diets of hypertension and prehyperten- diet for children that meets the DASH are selected in the clinical setting. sion are also increasing, explained study and 2010 DGA nutrient goals. ● In another study, transcendental partially by the rise in obesity rates. ● Lower dietary sodium intake is as- meditation effectively lowered BP in● Prehypertension progresses to hy- sociated with lower BP levels in in- nonhypertensive adolescents. pertension at a rate of ϳ7% per fants, children, and adolescents. year; hypertension persists in al- Recommendations ● Losartan, amlodipine, felodipine, fosi- most one-third of boys and one- nopril, lisinopril, metoprolol, and val- In “The Fourth Report on the Diagnosis, fourth of girls on 2-year longitudinal sartan can be added to the list of med- Evaluation, and Treatment of High follow-up. ications that are tolerated over short Blood Pressure in Children and Adoles-● Breastfeeding and supplementation cents,”13 an NHLBI task force provided periods and can reduce BP in children of formula with polyunsaturated an algorithm and flow diagram to as- from ages 6 to 17 years but are pre- fatty acids in infancy are both asso- sist clinicians in identifying hyperten- dominantly effective in adolescents. ciated with lower BP at follow-up. sion in children. For these guidelines, For black children, greater doses of● A DASH-style diet, which is rich in fosinopril might be needed for effec- the task force’s recommendations are fruits, vegetables, low-fat or fat-free tive BP control. Medications are stratified here to provide an age- dairy products, whole grains, fish, appropriate approach congruent with shown in Table 8-5. poultry, beans, seeds, and nuts and other risk-factor recommendations in lower in sweets and added sugars, ●In 1 study of small-for-gestational- other sections, and this is also re- fats, and red meats than the typical age infants, a nutrient-enriched diet flected in a series of revised algo- American diet, is associated with that promoted rapid weight gain was rithms (Table 8-1 and Figs 8-1 and 8-2). lower BP. The CHILD-1 combined with associated with higher BP on follow-up Conditions under which childrenS16 EXPERT PANEL
  • 21. SUPPLEMENT ARTICLESTABLE 8-1 Age-Specific Recommendations for BP Measurement and Diagnosis of get organ disease; this testing should Hypertension be performed for patients with stage 2Birth to 3 y No routine BP measurement Measure BP if history (ϩ) for neonatal complications, congenital heart disease, urinary/ hypertension and those with persis- renal abnormality, solid-organ transplant, malignancy, drug prescription, or tent stage 1 hypertension. Elevated left condition known to raise BP or increase intracranial pressure (Table 8-2) ventricular mass might be useful in es- If BP Ն90th percentile by oscillometry, confirm by auscultation ¡ If BP confirmed Ն90th percentile, initiate evaluation for etiology and treatment per algorithm (Figure tablishing the need for pharmacologic 8-2) treatment of hypertension. In Table 8-5,3 to 11 y Annual BP measurement in all, interpreted for age/gender/height per Tables 8-3 and 8-4 the medications used to achieve BP If BP Ͻ90th percentile, repeat in 1 y If BP Ն90th percentile: control in children and adolescents Repeat BP ϫ 2 by auscultation are listed. At present, there are no data Average replicate measurements and reevaluate BP category (Fig 8-1) If BP confirmed Ͼ90th percentile, Ͻ95th percentile ϭ prehypertension (HTN): to support the use of specific antihy- Recommend weight management if indicated pertensive agents for specific age Repeat BP in 6 mo If BP Ն95th percentile, Ͻ99th percentile ϩ 5 mm Hg: groups. Repeat BP in 1–2 wk, average all BP measurements and reevaluate BP category (Fig 8-1) 9. LIPIDS AND LIPOPROTEINS If BP confirmed Ͼ95th percentile, Ͻ99th percentile ϩ 5 mm Hg ϭ stage 1 HTN: Basic work-up per Fig 8-2 Since the last NHLBI guidelines for lipid If BP Ն99th percentile ϩ 5 mm Hg management in children and adoles- Repeat BP by auscultation ϫ 3 at that visit, average all BP measurements and reevaluate BP category cents were published in 1992,1 both the If BP confirmed Ͼ99th percentile ϩ 5 mm Hg ϭ stage 2 HTN: knowledge base surrounding dyslipi- Refer to pediatric HTN expert within 1 wk OR demia in childhood and the clinical pic- Begin BP treatment and initiate basic work-up, per Fig 8-212 to 17 y Annual BP measurement in all, interpreted for age/gender/height per Tables 8-3 and 8-4 ture have changed. A series of critical If BP Ͻ90th percentile, counsel on CHILD-1 diet, activity recommendations, and repeat BP observational studies have found a in 1 y clear correlation between lipoprotein If BP Ն90th percentile or Ն120/80 mm Hg: Repeat BP ϫ 2 by auscultation disorders and the onset and severity of Average replicate measurements and reevaluate BP category (Fig 8-1) atherosclerosis in children, adoles- If BP confirmed Ͼ90th percentile, Ͻ 95th percentile or Ͼ120/80 ϭ pre-HTN: cents, and young adults. A major in- CHILD-1 diet, activity recommendations, weight management if indicated Repeat BP in 6 mo crease in the prevalence of obesity has If BP Ն95th percentile, Ͻ99th percentile ϩ 5 mm Hg led to a much larger population of chil- Repeat BP in 1–2 wk, average all BP measurements and reevaluate BP category (Fig dren with dyslipidemia. At the time of 8-1) If BP confirmed Ն95th percentile, Ͻ99th percentile ϩ 5 mm Hg ϭ stage 1 HTN: the original guidelines, the focus was Basic workup per Fig 2 almost exclusively on identification of If BP Ն99th percentile ϩ 5 mm Hg: children with an elevated LDL choles- Repeat BP by auscultation ϫ 3 at that visit, average all BP measurements and reevaluate BP category terol level. Since then, the predomi- If BP confirmed Ͼ99th percentile ϩ 5 mm Hg ϭ stage 2 HTN: nant dyslipidemic pattern in childhood Refer to pediatric HTN expert within 1 wk OR is a combined pattern associated with Begin BP treatment and initiate work-up per Fig 8-218 to 21 y Measure BP at all health care visits obesity, moderate-to-severe elevation BP Ն120/80 to 139/89 ϭ pre-HTN in triglyceride level, normal-to-mild el- BP Ն140/90 to 159/99 ϭ stage 1 HTN evation in LDL cholesterol level, and a BP Ն160/100 ϭ stage 2 HTN reduced HDL cholesterol level. BothBP recommendations are based on the NHLBI’s “The Fourth Report on the Diagnosis, Evaluation and Treatment of High BloodPressure in Children and Adolescents” with the evidence review updated from 2003. Recommendations are all graded as dyslipidemic patterns have beenexpert opinion (grade D) because they are based on the expert consensus conclusions of the Fourth Report. shown to be associated with initiation and progression of atherosclerotic le- sions in children and adolescents asyounger than 3 years should have BP birth to 12 months are provided in the demonstrated by pathology and imag-measured are shown in Table 8-2. The “Report of the Fourth Task Force on ing studies. Identification of childrenBP norms for age, gender, and height Blood Pressure Control in Children.” with dyslipidemias, which place themare shown in Tables 8-3 and 8-4 and For all age groups the assessment of at increased risk for accelerated earlywere taken directly from the NHLBI left ventricular mass by echocardiog- atherosclerosis, must include a com-task force’s report. Age-specific per- raphy is recommended as the best prehensive assessment of serum lipidcentiles of BP measurements from method of assessing hypertensive tar- and lipoprotein levels. PEDIATRICS Volume 128, Supplement 6, December 2011 S17
  • 22. TABLE 8-2 Conditions Under Which Children <3 Years Old Should Have BP Measured of the presence of atherosclerosis,History of prematurity, very low birth weight, or other neonatal complication requiring intensive care as powerful as any other lipoproteinCongenital heart disease (repaired or unrepaired) cholesterol measure in childrenRecurrent urinary tract infections, hematuria, or proteinuriaKnown renal disease or urologic malformations and adolescents. For both childrenFamily history of congenital renal disease and adults, non-HDL cholesterolSolid-organ transplant level seems to be more predictive ofMalignancy or bone marrow transplantTreatment with drugs known to raise BP persistent dyslipidemia and, there-Other systemic illnesses associated with hypertension (neurofibromatosis, tuberous sclerosis, etc) fore, atherosclerosis and futureEvidence of increased intracranial pressure events than TC, LDL cholesterol, orReproduced with permission from High Blood Pressure Education Program Working Group on High Blood Pressure inChildren and Adolescents. Pediatrics. 2004;114(2 suppl 4th report):556. HDL cholesterol levels alone. A ma- jor advantage of non-HDL choles- terol is that it can be accurately cal- culated in a nonfasting state and isThe evidence review for lipids and lipo- also demonstrated significant therefore practical to obtain in clin-proteins addressed the association tracking of elevated lipid levels from ical practice. The expert panel feltbetween dyslipidemia and atheroscle- childhood into adulthood. Lipid and that non-HDL cholesterol should berosis in childhood, lipid assessment in lipoprotein results in childhood are added as a screening tool for iden-childhood and adolescence with tables predictive of future adult lipopro- tification of a dyslipidemic state inof normative results provided, the dys- tein profiles; the strongest statisti- childhood (grade B).lipidemias, dietary treatment of dyslip- cal correlation occurs between re-idemia, and medication therapy. ● In terms of other lipid measure- sults in late childhood and in the third and fourth decades of life ments, (1) most but not all studiesConclusions and Grading of the have found that measurement of (grade B).Evidence Review for Lipid apolipoprotein B and apolipopro-Assessment in Childhood and ● TC and LDL cholesterol levels de- tein A-1 for universal screening pro-Adolescence crease as much as 10% to 20% or vides no additional advantage over more during puberty (grade B). On the● Combined evidence from autopsy measuring non-HDL cholesterol, LDL studies, vascular studies, and co- basis of this normal pattern of change cholesterol, and HDL cholesterol lev- hort studies strongly indicates that in lipid and lipoprotein levels with els, (2) measurement of lipopro- abnormal lipid levels in childhood growth and maturation, 10 years of tein(a) is useful in the assessment are associated with increased evi- age (range: 9 –11 years) is a stable of children with both hemorrhagic dence of atherosclerosis (grade B). time for lipid assessment in children and ischemic stroke, (3) in offspring (grade D). For most children, this age of a parent with premature CVD and● The evidence review supports the range will precede the onset of no other identifiable risk factors, el- concept that early identification and puberty. evations of apolipoprotein B, apoli- control of dyslipidemia throughout youth and into adulthood will sub- ● Significant evidence exists to indicate poprotein A-1, and lipoprotein(a) stantially reduce clinical CVD risk that using family history of premature have been noted, and (4) measure- beginning in young adult life. Pre- CVD or cholesterol disorders as the ment of lipoprotein subclasses and liminary evidence in children with primary factor in determining lipid their sizes by advanced lipoprotein heterozygous familial hypercholes- screening for children misses ϳ30% testing has not been found to have terolemia with markedly elevated to 60% of children with dyslipidemias, sufficient clinical utility in children LDL cholesterol levels indicates that and accurate and reliable measures at this time (grade B). earlier treatment is associated with of family history are not available ● Obesity is commonly associated reduced subclinical evidence of ath- (grade B). In the absence of a clinical with a combined dyslipidemia pat- erosclerosis (grade B). or historic marker, identification of tern with mild elevation in TC and● Multiple prospective screening co- children with lipid disorders that pre- LDL cholesterol levels, moderate-to- hort studies have demonstrated the dispose them to accelerated athero- severe elevation in triglyceride normal lipid and lipoprotein distri- sclerosis requires universal lipid as- level, and a low HDL cholesterol butions in childhood, adolescence, sessment (grade B). level. This is the most common dys- and young adult life (Tables 9-1 and ● Non-HDL cholesterol level has been lipidemic pattern seen in childhood, 9-2) (grade B). Cohort studies have identified as a significant predictor and lipid assessment in overweightS18 EXPERT PANEL
  • 23. SUPPLEMENT ARTICLESTABLE 8-3 BP Norms for Boys by Age and Height Percentile and obese children identifies an im-Age, BP %ile SBP, mm Hg DBP, mm Hg portant proportion of those with y significant lipid abnormalities Percentile of Height Percentile of Height 5th 10th 25th 50th 75th 90th 95th 5th 10th 25th 50th 75th 90th 95th (grade B). 1 50th 80 81 83 85 87 88 89 34 35 36 37 38 39 39 ● Dyslipidemias can be acquired ge- 90th 94 95 97 99 100 102 103 49 50 51 52 53 53 54 95th 98 99 101 103 104 106 106 54 54 55 56 57 58 58 netically but also secondary to spe- 99th 105 106 108 110 112 113 114 61 62 63 64 65 66 66 cific conditions such as DM, ne- 2 50th 84 85 87 88 90 92 92 39 40 41 42 43 44 44 90th 97 99 100 102 104 105 106 54 55 56 57 58 58 59 phrotic syndrome, chronic renal 95th 101 102 104 106 108 109 110 59 59 60 61 62 63 63 disease, postorthotopic heart trans- 99th 109 110 111 113 115 117 117 66 67 68 69 70 71 71 3 50th 86 87 89 91 93 94 95 44 44 45 46 47 48 48 plant, history of Kawasaki disease 90th 100 101 103 105 107 108 109 59 59 60 61 62 63 63 95th 104 105 107 109 110 112 113 63 63 64 65 66 67 67 with persistent coronary involve- 99th 111 112 114 116 118 119 120 71 71 72 73 74 75 75 ment, chronic inflammatory dis- 4 50th 88 89 91 93 95 96 97 47 48 49 50 51 51 52 90th 102 103 105 107 109 110 111 62 63 64 65 66 66 67 ease, hypothyroidism, and other 95th 106 107 109 111 112 114 115 66 67 68 69 70 71 71 causes, as outlined in Table 9-3. 99th 113 114 116 118 120 121 122 74 75 76 77 78 78 79 5 50th 90 91 93 95 96 98 98 50 51 52 53 54 55 55 There is impressive evidence for 90th 104 105 106 108 110 111 112 65 66 67 68 69 69 70 accelerated atherosclerosis both 95th 108 109 110 112 114 115 116 69 70 71 72 73 74 74 99th 115 116 118 120 121 123 123 77 78 79 80 81 81 82 clinically and as assessed with 6 50th 91 92 94 96 98 99 100 53 53 54 55 56 57 57 noninvasive methods in some of 90th 105 106 108 110 111 113 113 68 68 69 70 71 72 72 95th 109 110 112 114 115 117 117 72 72 73 74 75 76 76 these conditions, which have been 99th 116 117 119 121 123 124 125 80 80 81 82 83 84 84 7 50th 92 94 95 97 99 100 101 55 55 56 57 58 59 59 designated accordingly as special 90th 106 107 109 111 113 114 115 70 70 71 72 73 74 74 risk diagnoses for accelerated 95th 110 111 113 115 117 118 119 74 74 75 76 77 78 78 99th 117 118 120 122 124 125 126 82 82 83 84 85 86 86 atherosclerosis (Table 9-7); 8 50th 94 95 97 99 100 102 102 56 57 58 59 60 60 61 management of these conditions 90th 107 109 110 112 114 115 116 71 72 72 73 74 75 76 95th 111 112 114 116 118 119 120 75 76 77 78 79 79 80 is described in “DM and Other 99th 119 120 122 123 125 127 127 83 84 85 86 87 87 88 Conditions Predisposing to the De- 9 50th 95 96 98 100 102 103 104 57 58 59 60 61 61 62 90th 109 110 112 114 115 117 118 72 73 74 75 76 76 77 velopment of Accelerated Athero- 95th 113 114 116 118 119 121 121 76 77 78 79 80 81 81 sclerosis.” Lipid evaluation for 99th 120 121 123 125 127 128 129 84 85 86 87 88 88 89 10 50th 97 98 100 102 103 105 106 58 59 60 61 61 62 63 these patients contributes to risk 90th 111 112 114 115 117 119 119 73 73 74 75 76 77 78 95th 115 116 117 119 121 122 123 77 78 79 80 81 81 82 assessment and identifies an im- 99th 122 123 125 127 128 130 130 85 86 86 88 88 89 90 portant proportion of those with 11 50th 99 100 102 104 105 107 107 59 59 60 61 62 63 63 90th 113 114 115 117 119 120 121 74 74 75 76 77 78 78 dyslipidemia (grade B). 95th 117 118 119 121 123 124 125 78 78 79 80 81 82 82 99th 124 125 127 129 130 132 132 86 86 87 88 89 90 90 ● The complete phenotypic expres- 12 50th 101 102 104 106 108 109 110 59 60 61 62 63 63 64 sion of some inherited disorders 90th 115 116 118 120 121 123 123 74 75 75 76 77 78 79 95th 119 120 122 123 125 127 127 78 79 80 81 82 82 83 such as familial combined hyperlip- 99th 126 127 129 131 133 134 135 86 87 88 89 90 90 91 idemia may be delayed until adult- 13 50th 104 105 106 108 110 111 112 60 60 61 62 63 64 64 90th 117 118 120 122 124 125 126 75 75 76 77 78 79 79 hood. Therefore, evaluation of 95th 121 122 124 126 128 129 130 79 79 80 81 82 83 83 children and adolescents from high- 99th 128 130 131 133 135 136 137 87 87 88 89 90 91 91 14 50th 106 107 109 111 113 114 115 60 61 62 63 64 65 65 risk families with familial combined 90th 120 121 123 125 126 128 128 75 76 77 78 79 79 80 hyperlipidemia (Table 9-4) should 95th 124 125 127 128 130 132 132 80 80 81 82 83 84 84 99th 131 132 134 136 138 139 140 87 88 89 90 91 92 92 begin in childhood and continue 15 50th 109 110 112 113 115 117 117 61 62 63 64 65 66 66 90th 122 124 125 127 129 130 131 76 77 78 79 80 80 81 through adulthood (per NCEP adult 95th 126 127 129 131 133 134 135 81 81 82 83 84 85 85 treatment guidelines) and will lead 99th 134 135 136 138 140 142 142 88 89 90 91 92 93 93 16 50th 111 112 114 116 118 119 120 63 63 64 65 66 67 67 to early detection of those with ab- 90th 125 126 128 130 131 133 134 78 78 79 80 81 82 82 normalities (grade B). 95th 129 130 132 134 135 137 137 82 83 83 84 85 86 87 99th 136 137 139 141 143 144 145 90 90 91 92 93 94 94 Age-specific recommendations for 17 50th 114 115 116 118 120 121 122 65 66 66 67 68 69 70 90th 127 128 130 132 134 135 136 80 80 81 82 83 84 84 lipid assessment are outlined in Table 95th 131 132 134 136 138 139 140 84 85 86 87 87 88 89 9-5. Specific management for children 99th 139 140 141 143 145 146 147 92 93 93 94 95 96 97The 90th percentile is 1.28 SD, the 95th percentile is 1.645 SD, and the 99th percentile is 2.326 SD over the mean. with identified dyslipidemia is outlinedReproduced with permission from High Blood Pressure Education Program Working Group on High Blood Pressure in in the algorithms in Figs 9-1 and 9-2.Children and Adolescents. Pediatrics. 2004;114(2 suppl 4th report):558. Definitions of the risk factors and spe- PEDIATRICS Volume 128, Supplement 6, December 2011 S19
  • 24. TABLE 8-4 BP Norms for Girls by Age and Height Percentile cial risk conditions for use with theAge, BP %ile SBP, mm Hg DBP, mm Hg recommendations and in the algo- y rithms appear in Tables 9-6 and 9-7. Percentile of Height Percentile of Height 5th 10th 25th 50th 75th 90th 95th 5th 10th 25th 50th 75th 90th 95th The first step proposed for manage- 1 50th 83 84 85 86 88 89 90 38 39 39 40 41 41 42 ment of children with identified lipid 90th 97 97 98 100 101 102 103 52 53 53 54 55 55 56 abnormalities is a focused interven- 95th 100 101 102 104 105 106 107 56 57 57 58 59 59 60 99th 108 108 109 111 112 113 114 64 64 65 65 66 67 67 tion on diet and physical activity. 2 50th 85 85 87 88 89 91 91 43 44 44 45 46 46 47 90th 98 99 100 101 103 104 105 57 58 58 59 60 61 61 95th 102 103 104 105 107 108 109 61 62 62 63 64 65 65 Conclusions and Grading of the 99th 109 110 111 112 114 115 116 69 69 70 70 71 72 72 3 50th 86 87 88 89 91 92 93 47 48 48 49 50 50 51 Evidence Review for Dietary 90th 100 100 102 103 104 106 106 61 62 62 63 64 64 65 Management of Dyslipidemia 95th 104 104 105 107 108 109 110 65 66 66 67 68 68 69 99th 111 111 113 114 115 116 117 73 73 74 74 75 76 76 ● A diet with total fat at 25% to 30% of 4 50th 88 88 90 91 92 94 94 50 50 51 52 52 53 54 90th 101 102 103 104 106 107 108 64 64 65 66 67 67 68 calories, saturated fat at Ͻ10% of 95th 105 106 107 108 110 111 112 68 68 69 70 71 71 72 calories, and cholesterol intake at 99th 112 113 114 115 117 118 119 76 76 76 77 78 79 79 5 50th 89 90 91 93 94 95 96 52 53 53 54 55 55 56 Ͻ300 mg/day, as recommended by 90th 103 103 105 106 107 109 109 66 67 67 68 69 69 70 the original NCEP Pediatric Panel,1 95th 107 107 108 110 111 112 113 70 71 71 72 73 73 74 99th 114 114 116 117 118 120 120 78 78 79 79 80 81 81 has been shown to safely and effec- 6 50th 91 92 93 94 96 97 98 54 54 55 56 56 57 58 tively reduce the levels of TC and LDL 90th 104 105 106 108 109 110 111 68 68 69 70 70 71 72 95th 108 109 110 111 113 114 115 72 72 73 74 74 75 76 cholesterol in healthy children 99th 115 116 117 119 120 121 122 80 80 80 81 82 83 83 7 50th 93 93 95 96 97 99 99 55 56 56 57 58 58 59 (grade A). There is some evidence 90th 106 107 108 109 111 112 113 69 70 70 71 72 72 73 that this is also the case when the 95th 110 111 112 113 115 116 116 73 74 74 75 76 76 77 99th 117 118 119 120 122 123 124 81 81 82 82 83 84 84 diet begins in infancy and is sus- 8 50th 95 95 96 98 99 100 101 57 57 57 58 59 60 60 tained throughout childhood and 90th 108 109 110 111 113 114 114 71 71 71 72 73 74 74 95th 112 112 114 115 116 118 118 75 75 75 76 77 78 78 into adolescence (grade B). The 99th 119 120 121 122 123 125 125 82 82 83 83 84 85 86 CHILD-1, described in “Nutrition and 9 50th 96 97 98 100 101 102 103 58 58 58 59 60 61 61 90th 110 110 112 113 114 116 116 72 72 72 73 74 75 75 Diet,” has this composition. 95th 114 114 115 117 118 119 120 76 76 76 77 78 79 79 99th 121 121 123 124 125 127 127 83 83 84 84 85 86 87 ● In children with identified hypercho- 10 50th 98 99 100 102 103 104 105 59 59 59 60 61 62 62 lesterolemia and an elevated LDL 90th 112 112 114 115 116 118 118 73 73 73 74 75 76 76 95th 116 116 117 119 120 121 122 77 77 77 78 79 80 80 cholesterol level, a more stringent 11 99th 50th 123 123 125 126 127 129 129 84 84 100 101 102 103 105 106 107 60 60 85 60 86 61 86 62 87 63 88 63 diet with saturated fat at Յ7% of 90th 114 114 116 117 118 119 120 74 74 74 75 76 77 77 calories and dietary cholesterol lim- 95th 118 118 119 121 122 123 124 78 78 78 79 80 81 81 99th 125 125 126 128 129 130 131 85 85 86 87 87 88 89 ited to 200 mg/day has been shown 12 50th 102 103 104 105 107 108 109 61 61 61 62 63 64 64 to be safe and modestly effective in 90th 116 116 117 119 120 121 122 75 75 75 76 77 78 78 95th 119 120 121 123 124 125 126 79 79 79 80 81 82 82 lowering the LDL cholesterol level 99th 127 127 128 130 131 132 133 86 86 87 88 88 89 90 (grade A) (CHILD-2–LDL; Table 9-8). 13 50th 104 105 106 107 109 110 110 62 62 62 63 64 65 65 90th 117 118 119 121 122 123 124 76 76 76 77 78 79 79 ● The use of dietary adjuncts such as 95th 121 122 123 124 126 127 128 80 80 80 81 82 83 83 99th 128 129 130 132 133 134 135 87 87 88 89 89 90 91 plant sterol or stanol esters up to 14 50th 106 106 107 109 110 111 112 63 63 63 64 65 66 66 20 g/day can safely enhance LDL 90th 119 120 121 122 124 125 125 77 77 77 78 79 80 80 95th 123 123 125 126 127 129 129 81 81 81 82 83 84 84 cholesterol–lowering effects short- 99th 130 131 132 133 135 136 136 88 88 89 90 90 91 92 term in children with familial 15 50th 107 108 109 110 111 113 113 64 64 64 65 66 67 67 90th 120 121 122 123 125 126 127 78 78 78 79 80 81 81 hypercholesterolemia (grade A). 95th 124 125 126 127 129 130 131 82 82 82 83 84 85 85 99th 131 132 133 134 136 137 138 89 89 90 91 91 92 93 However, long-term studies on the 16 50th 108 108 110 111 112 114 114 64 64 65 66 66 67 68 safety and effectiveness of plant ste- 90th 121 122 123 124 126 127 128 78 78 79 80 81 81 82 95th 125 126 127 128 130 131 132 82 82 83 84 85 85 86 rol and stanol esters have not been 99th 132 133 134 135 137 138 139 90 90 90 91 92 93 93 completed. Their use, therefore, is 17 50th 108 109 110 111 113 114 115 64 65 65 66 67 67 68 90th 122 122 123 125 126 127 128 78 79 79 80 81 81 82 usually reserved for children with 95th 125 126 127 129 130 131 132 82 83 83 84 85 85 86 primary elevations of their LDL cho- 99th 133 133 134 136 137 138 139 90 90 91 91 92 93 93The 90th percentile is 1.28 SD, the 95th percentile is 1.645 SD, and the 99th percentile is 2.326 SD over the mean. lesterol level who do not achieve LDLReproduced with permission from High Blood Pressure Education Program Working Group on High Blood Pressure in cholesterol goals with dietary treat-Children and Adolescents. Pediatrics. 2004;114(2 suppl 4th report):559. ment alone. Such an approachS20 EXPERT PANEL
  • 25. SUPPLEMENT ARTICLESTABLE 8-5 Antihypertensive Medications With Pediatric Experience Class Drug Initial Dosea Maximal Dose Dosing Evidenceb FDAc Commentsd IntervalACE inhibitors Benazepril 0.2 mg/kg per d up to 0.6 mg/kg per d up QD RCT Yes 1. All ACE inhibitors are contraindicated 10 mg/d to 40 mg/d in pregnancy; women of childbearing age should use reliable contraception Captopril 0.3–0.5 mg/kg per 6 mg/kg per d TID RCT, CS No 2. Check serum potassium and creatinine dose (Ͼ12 mo) periodically to monitor for hyperkalemia and azotemia 3. Cough and angioedema are reportedly less common with newer members of this class than with captopril Fosinoprile Children Ͼ50 kg: 40 mg/d QD RCT Yes 4. Benazepril, enalapril, and lisinopril 5–10 mg/d labels contain information on the preparation of a suspension; captopril may also be compounded into a suspension Lisinoprile 0.07 mg/kg per d up 0.6 mg/kg per d up QD RCT Yes 5. FDA approval for ACE inhibitors with to 5 mg/d to 40 mg/d pediatric labeling is limited to children Ն6 y of age and to children with creatinine clearance rate of Ն30 mL/ min per 1.73 m2 Quinapril 5–10 mg/d 80 mg/d QD RCT, EO No 6. Initial dose of fosinopril of 0.1 mg/kg per d may be effective, although black patients might require a higher doseARBs Irbesartan 6–12 y: 75–150 mg/d; 300 mg/d QD CS Yes 1. All ARBs are contraindicated in Ն13 y: 150–300 pregnancy; women of childbearing age mg/d should use reliable contraception Losartane 0.7 mg/kg per d up to 1.4 mg/kg per d up QD–BID RCT Yes 2. Check serum potassium and creatinine 50 mg/d to 100 mg/d levels periodically to monitor for hyperkalemia and azotemia Valsartane 5–10 mg/d; 0.4 mg/kg 40–80 mg/d; 3.4 QD RCT No 3. Losartan label contains information on per d mg/kg per d the preparation of a suspension 4. FDA approval for ARBs is limited to children Ն6 y of age and to children with creatinine clearance rate of Ն30 mL/min per 1.73 m2␣- and Labetalol 1–3 mg/kg per d 10–12 mg/kg per d BID CS, EO No 1. Asthma and overt heart failure are ␤-antagonist up to 1200 mg/d relative contraindications 2. Heart rate is dose-limiting 3. May impair athletic performance in athletes 4. Should not be used in insulin- dependent diabetic patients␤-antagonists Atenolol 0.5–1 mg/kg per d 2 mg/kg per d up QD–BID CS No 1. Noncardioselective agents to 100 mg/d (propranolol) are contraindicated in asthma and heart failure Bisoprolol/ 2.5–6.25 mg/d 10/6.25 mg/d QD RCT No 2. Heart rate is dose-limiting hydrochlorothiazide Metoprolole Children Ͼ6 y: 1 mg/ 2 mg/kg per d up BID CS Yesf 3. May impair athletic performance in kg per d (12.5–50 to 200 mg/d athletes mg/d) Propranolol 1–2 mg/kg per d 4 mg/kg per d up BID–TID RCT, EO Yes 4. Should not be used in insulin- to 640 mg/d dependent diabetic patients 5. A sustained-release, once-daily formulation of propranolol is availableCalcium-channel Amlodipinee Children 6–17 y: 2.5 5 mg/d QD RCT Yes 1. Amlodipine and isradipine can be blockers mg/d compounded into stable extemporaneous suspensions Felodipine 2.5 mg/d 10 mg/d QD RCT, EO No 2. Felodipine and extended-release nifedipine tablets must be swallowed whole PEDIATRICS Volume 128, Supplement 6, December 2011 S21
  • 26. TABLE 8-5 Continued Class Drug Initial Dosea Maximal Dose Dosing Evidenceb FDAc Commentsd Interval Isradipine 0.15–0.2 mg/kg per d 0.8 mg/kg per d up TID–QID CS, EO No 3. Isradipine is available in both to 20 mg/d immediate- and sustained-release formulations; sustained release form is dosed QD or BID Extended-release 0.25–0.5 mg/kg per d 3 mg/kg per d up QD–BID CS, EO No 4. May cause tachycardia nifedipine to 120 mg/d 5. Doses up to 10 mg of amlodipine have been evaluated in children 6. Contraindicated for children Ͻ1 y of ageCentral ␣-agonist Clonidine Children Ն12 y: 0.2 2.4 mg/d BID EO Yes 1. May cause dry mouth and/or sedation mg/d 2. Transdermal preparation is available 3. Sudden cessation of therapy can lead to severe rebound hypertensionDiuretics Hydrochlorothiazide 1 mg/kg per d 3 mg/kg per d up QD EO Yes 1. All patients treated with diuretics to 50 mg/d should have their electrolytes monitored shortly after initiating therapy and periodically thereafter Chlorthalidone 0.3 mg/kg per d 2 mg/kg per d up QD EO No 2. Useful as add-on therapy in patients to 50 mg/d being treated with drugs from other drug classes Furosemide 0.5–2.0 mg/kg per 6 mg/kg per d QD–BID EO No 3. Potassium-sparing diuretics dose (spironolactone, triamterene, amiloride) may cause severe hyperkalemia, especially if given with an ACE inhibitor or ARB Spironolactone 1 mg/kg per d 3.3 mg/kg per d up QD–BID EO No 4. Furosemide is labeled only for to 100 mg/d treatment of edema but may be useful as add-on therapy in children with resistant hypertension, particularly in children with renal disease Triamterene 1–2 mg/kg per d 3–4 mg/kg per d BID EO No 5. Chlorthalidone may precipitate up to 300 mg/d azotemia in patients with renal diseases and should be used with caution in those with severe renal impairment Amiloride 0.4–0.625 mg/kg per 20 mg/d QD EO No dPeripheral Doxazosin 1 mg/d 4 mg/d QD EO No 1. May cause first-dose hypotension ␣-antagonists Prazosin 0.05–0.1 mg/kg per 0.5 mg/kg per d TID EO No day Terazosin 1 mg/d 20 mg/d QD EO NoVasodilators Hydralazine 0.75 mg/kg per d 7.5 mg/kg per d up QID EO Yes 1. Tachycardia and fluid retention are to 200 mg/d common adverse effects Minoxidil Children Ͻ12 y: 0.2 Children Ͻ12 y: 50 QD–TID CS, EO Yes 2. Hydralazine can cause a lupus-like mg/kg per d; mg/d; children syndrome in slow acetylators children Ͼ12 y: 5 Ն12 y: 100 3. Prolonged use of minoxidil can cause mg/d mg/d hypertrichosis 4. Minoxidil is usually reserved for patients with hypertension that is resistant to multiple drugsACE indicates angiotensin-converting enzyme; QD, every day; BID, 2 times daily; TID, 3 times daily; QID, 4 times daily; CS, case series; EO, expert opinion; ARB, angiotensin-receptor blocker.a The maximal recommended adult dose should not be exceeded in routine clinical practice.b Level of evidence on which recommendations are based.c FDA-approved pediatric labeling information is available for treatment of hypertension. Recommended doses for agents with FDA-approved pediatric labels contained in this table are thedoses contained in the approved labels. Even when pediatric labeling information is not available, the FDA-approved label should be consulted for additional safety information.d Comments apply to all members of each drug class except where otherwise stated.e Indicates drug added since “The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents” (2004).f Study did not reach the primary end point (dose response for reduction in systolic BP). Some prespecified secondary end points demonstrated effectiveness.Adapted from High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. Pediatrics. 2004;114(2 suppl 4th report):555–576.S22 EXPERT PANEL
  • 27. SUPPLEMENT ARTICLESTABLE 9-1 Acceptable, Borderline-High, and High Plasma Lipid, Lipoprotein, and TABLE 9-3 Causes of Secondary Apolipoprotein Concentrations for Children and Adolescents Dyslipidemia Category Low, mg/dL a Acceptable, mg/dL Borderline-High, mg/dL High, mg/dL a ExogenousTC — Ͻ170 170–199 Ն200 AlcoholLDL cholesterol — Ͻ110 110–129 Ն130 Drug therapy: corticosteroidsNon-HDL cholesterol — Ͻ120 120–144 Ն145 IsoretinoinApolipoprotein B — Ͻ90 90–109 Ն110 ␤-blockersTriglycerides Some oral contraceptives 0–9 y — Ͻ75 75–99 Ն100 Select chemotherapeutic agents 10–19 y — Ͻ90 90–129 Ն130 Select antiretroviral agentsHDL cholesterol Ͻ40 Ͼ45 40–45 — Endocrine/metabolicApolipoprotein A-1 Ͻ115 Ͼ120 115–120 — Hypothyroidism/hypopituitarism T1DM and T2DMValues for plasma lipid and lipoprotein levels are from the NCEP Expert Panel on Cholesterol Levels in Children. Non-HDLcholesterol values from the Bogalusa Heart Study are equivalent to the NCEP Pediatric Panel cut points for LDL cholesterol. PregnancyValues for plasma apolipoprotein B and apolipoprotein A-1 are from the National Health and Nutrition Examination Survey Polycystic ovary syndromeIII. Note that values shown are in mg/dL; to convert to SI units, divide the results for TC, LDL cholesterol, HDL cholesterol, and Lipodystrophynon-HDL cholesterol by 38.6; for triglycerides, divide by 88.6. Acute intermittent porphyriaa Low cut points for HDL cholesterol and apolipoprotein A-1 represent approximately the 10th percentile. The cut points for Renalhigh and borderline-high represent approximately the 95th and 75th percentiles, respectively. Chronic renal disease Hemolytic uremic syndrome Nephrotic syndromeTABLE 9-2 Recommended Cut Points for Lipid and Lipoprotein Levels in Young Adults Infectious Category Low, mg/dL Borderline-Low, Acceptable, Borderline-High, High, mg/dL Acute viral/bacterial infectiona mg/dL mg/dL mg/dL HIVTC — — Ͻ190 190–224 Ն225 HepatitisLDL cholesterol — — Ͻ120 120–159 Ն160 HepaticNon-HDL cholesterol — — Ͻ150 150–189 Ն190 Obstructive liver disease/cholestatic conditionsTriglycerides — — Ͻ115 115–149 Ն150 Biliary cirrhosisHDL cholesterol Ͻ40 40–44 Ͼ45 — — Alagille syndrome Inflammatory diseaseValues provided are from the Lipid Research Clinics Prevalence Study. The cut points for TC, LDL cholesterol, and non-HDLcholesterol represent the 95th percentile for 20- to 24-year-old subjects and are not identical with the cut points used in the Systemic lupus erythematosismost recent NHLBI adult guidelines, Adult Treatment Panel III (“Third Report of the Expert Panel on Detection, Evaluation, and Juvenile rheumatoid arthritisTreatment of High Blood Cholesterol in Adults”), which are derived from combined data on adults of all ages. The age-specific Storage diseasecut points given here are provided for pediatric care providers to use in managing this young adult age group. For TC, LDL Glycogen-storage diseasecholesterol, and non-HDL cholesterol, borderline-high values are between the 75th and 94th percentiles, whereas accept- Gaucher diseaseable value are at the Ͻ75th percentile. The high triglyceride cut point represents approximately the 90th percentile; Cystine-storage diseaseborderline-high values are between the 75th and 89th percentiles, and acceptable values are at the Ͻ75th percentile. The Juvenile Tay-Sachs diseaselow HDL cholesterol cut point represents approximately the 25th percentile; borderline-low values are between the 26th and Niemann-Pick disease50th percentiles, and acceptable values are at the Ͼ50th percentile. Other Kawasaki disease Anorexia nervosa might lower the LDL cholesterol sociated with increased intake of Post–solid organ transplantation level sufficiently to avoid the neces- complex carbohydrates and reduced Childhood cancer survivor Progeria sity of drug treatment. Food prod- saturated-fat intake. When triglycer- Idiopathic hypercalcemia ucts that contain plant stanol es- ide elevation is associated with obe- Klinefelter syndrome ters, such as some margarines, are sity, decreased calorie intake and in- Werner syndrome marketed directly to the general creased activity levels are of a Delay measurement until Ն3 weeks after infection. public. In 2 short-term trials, they paramount importance. The CHILD- have been shown to be safe and 2–TG (shown in Table 9-8) is recom- NCEP Pediatric Panel recommenda- have minimal LDL-lowering effects mended as the primary diet therapy tions.1 For all children with identified in healthy children (grade B). in this setting. dyslipidemia in whom the response● Evidence for the use of other dietary ● A behavioral approach that engages to a low-fat/low-saturated-fat/low- supplements is insufficient for any the child and family delivered by a cholesterol diet has not been evalu- recommendation (no grade). registered dietitian has been shown ated, the CHILD-1 (described in “Nutri-● In children with an elevated triglycer- to be the most consistently effective tion and Diet”) is recommended as the ide level, reduction of simple carbohy- approach for achieving dietary first step; implementation should be drate intake and weight loss are asso- change (grade B). guided by a registered dietitian. ciated with decreased triglyceride For obese children with identified levels (grade B). Reduction of simple The approach to management of dys- dyslipidemia, additional age- and BMI- carbohydrate intake needs to be as- lipidemias is staged, as in the original specific recommendations that PEDIATRICS Volume 128, Supplement 6, December 2011 S23
  • 28. FIGURE 8-1BP measurement and categorization. HT indicates height; WT, weight; HTN, hypertension; %ile, percentile. a See Table 8-2; b see “Nutrition and Diet”Table5-1; c see “Physical Activity”; c see “Overweight and Obesity.” Adapted from High Blood Pressure Education Program Working Group on High Blood Pressurein Children and Adolescents. Pediatrics. 2004;114(2 suppl 4th report):555–576.address calorie restriction and in- ily. Note that, in the following section, ter a 6-month trial of lifestylecreased activity appear in “Overweight values given are in mg/dL; to convert to management (CHILD-1 ¡ CHILD-and Obesity.” If, after a 3-month trial of SI units, divide the results for TC, LDL 2–LDL) for children aged 10 yearsthe CHILD-1/lifestyle management, cholesterol, HDL cholesterol, and non- or older.fasting-lipid-profile (FLP) findings ex- HDL cholesterol by 38.6; for triglycer- ● LDL cholesterol 160 to 189 mg/dLceed the therapeutic goals listed in Ta- ides, divide by 88.6. after a 6-month trial of lifestyle/bles 9-1 and 9-2, then the lipid ● Decisions regarding the need for diet management (CHILD-1 ¡parameter-specific diet changes out- medication therapy should be CHILD-2–LDL) in a child aged 10lined in Table 9-8 are recommended. based on the average of results years or older with a positiveDyslipidemia management is also out- from at least 2 FLPs obtained at family history of premature CVD/lined in the algorithms in Figs 9-1 and least 2 weeks but no more than 3 events in first-degree relatives9-2. months apart (grade C) (Fig 9-1). (Table 9-6) or at least 1 high-levelConclusions and Grading of the ● The cut points used to define the risk factor or risk condition or atEvidence Review for Use of level at which drug therapy should least 2 moderate-level risk fac-Medication to Treat Dyslipidemia be considered from the 1992 NCEP tors or risk conditions (TablesWhen medication is recommended, pediatric guidelines1 have been 9-6, 9-7, and 9-12; Fig 9-1).it should always be in the context of used as the basis for multiple drug ● LDL cholesterol 130 to 190 mg/dLthe complete cardiovascular risk safety and efficacy trials in dyslipi- in a child aged 10 years or olderprofile of the patient and in consul- demic children (grade B): with a negative family history oftation with the patient and the fam- ● LDL cholesterol Ն 190 mg/dL af- premature CVD in first-degreeS24 EXPERT PANEL
  • 29. SUPPLEMENT ARTICLESFIGURE 8-2BP management according to category. HTN indicates hypertension; CV, cardiovascular; Hx, history; PEx, physical examination; CBC, complete bloodcount; U/A, urinalysis; U/S, ultrasound; Ped, pediatric; LVH, left ventricular hypertrophy; Q, every; Rx, prescription; 2°, secondary; W/U, workup; TOD, targetorgan damage; s/p, status post; CKD, chronic kidney disease; %ile, percentile. a Workup for target organ damage/left ventricular hypertrophy if obese orpositive for other cardiovascular risk factors; b see “Nutrition and Diet”; c see “Physical Activity”; d see “Overweight and Obesity.” Adapted from High BloodPressure Education Program Working Group on High Blood Pressure in Children and Adolescents. Pediatrics. 2004;114(2 suppl 4th report):555–576. relatives and no high- or levels (Ͼ500 mg/dL) have under- disposing to the Development of Ac- moderate-level risk factor or risk gone effective LDL-lowering ther- celerated Atherosclerosis”). condition: management should apy with biweekly LDL apheresis ● Bile acid sequestrants are medica- continue to focus on lifestyle under the care of lipid specialists tions that bind bile salts within the changes (CHILD-1 ¡ CHILD-2– in academic medical centers intestinal lumen and prevent their LDL) based on lipid-profile find- (grade C). enterohepatic reuptake in the ter- ings (Fig 9-1) plus weight man- ● Multiple cohort studies have found minal ileum, which results in a de- agement if the BMI is at the that the benefits of LDL-lowering pletion of bile salts in the liver and Ն85th percentile. therapy in children at high risk for signals for increased production. ● The goal of LDL-lowering therapy accelerated atherosclerosis (such Because bile salts are synthesized in childhood and adolescence is as those with chronic kidney dis- from intracellular cholesterol in the to decrease the LDL cholesterol ease, T1DM or T2DM, Kawasaki dis- liver, the intracellular pool of cho- level to the Ͻ95th percentile ease with coronary aneurysms, lesterol becomes depleted, which (Յ130 mg/dL). or post– cardiac transplantation) signals increased production of LDL● Children with homozygous familial should be considered for initiation receptors and increased clearance hypercholesterolemia and ex- of medication therapy (grade C) of circulating LDL cholesterol to re- tremely elevated LDL cholesterol (see “DM and Other Conditions Pre- plenish the intracellular cholesterol PEDIATRICS Volume 128, Supplement 6, December 2011 S25
  • 30. TABLE 9-4 Summary of Major Lipid Disorders in Children and Adolescents doses and interacting drugs; the lat- Primary Lipid Disorders Lipid/Lipoprotein Abnormality ter occurs primarily with drugs thatFamilial hypercholesterolemia are metabolized by the cytochrome Homozygous 11 LDL cholesterol P-450 system, which is the primary Heterozygous 1 LDL cholesterolaFamilial defective apolipoprotein B 1 LDL cholesterol mode of metabolism for the major-Familial combined hyperlipidemiaa ity of statins. Drugs that potentially Type IIa 1 LDL cholesterol interact with statins include fi- Type IV 1 VLDL cholesterol, 1 triglycerides Type IIb 1 LDL cholesterol, 1 VLDL cholesterol, 1 brates, azole antifungal agents, triglycerides macrolide antibiotics, antiarrhyth- Types IIb and IV 2 HDL cholesterol (often) mic agents, and protease inhibitorsPolygenic hypercholesterolemia 1 LDL cholesterol (grade A).Familial hypertriglyceridemia (200–1000 mg/dL) 1 VLDL cholesterol, 1 triglyceridesSevere hypertriglyceridemia (Ն1000 mg/dL) 1 chylomicrons, 1 VLDL cholesterol, 11 ● Bile acid– binding sequestrants may triglyceridesFamilial hypoalphalipoproteinemia 2 HDL cholesterol be used in combination with a statinDysbetalipoproteinemia (TC: 250–500 mg/dL; 1 IDL cholesterol, 1 chylomicron remnants for patients who fail to meet LDL cho- triglycerides: 250–600 mg/dL) lesterol target levels with either med-1 indicates increased; 2, decreased; IDL indicates intermediate-density lipoprotein; VLDL, very low density lipoprotein. ication alone. One pediatric study as-a These are the 2 lipid and lipoprotein disorders seen most frequently in childhood and adolescence; familial combinedhyperlipidemia most often manifests with obesity. sessed this combination and found no increase in adverse effects. The effi- cacy of the 2 agents together seems to be additive (grade B). pool for increased production of junction with a family history of ele- bile salts. Studies of bile acid se- vated LDL cholesterol and/or ath- ● There is limited published experi- questrants in children and adoles- erosclerosis or CAD) when used ence in children of use of niacin and cents aged 6 to 18 years with LDL from 8 weeks to 2 years for children fibrates, which have been useful in cholesterol levels from 131 to 190 aged 8 to 18 years. The lower LDL treating adult patients with com- mg/dL have resulted in TC reduction cholesterol level for eligibility into bined dyslipidemias. Efficacy and of 7% to 17% and reduction of LDL the statin trials was Ն190 or Ն160 safety data are limited, and no data cholesterol of 10% to 20%, some- mg/dL with Ն2 additional risk fac- are available regarding newer for- times with a modest elevation in tri- mulations. In adults, cholesterol ab- tors after a trial period on diet. Trial glyceride level. Bile acid seques- sorption inhibitors have been advo- subjects were monitored carefully trants commonly cause adverse cated as an adjunct to statin throughout treatment; adverse ef- gastrointestinal effects that can sig- therapy for patients who do not fects on growth, development, or nificantly affect compliance. How- reach LDL cholesterol therapeutic sexual maturation were not seen, ever, they are safe and moderately targets. Because their action is in- and adverse-event profiles and effi- effective (grade A). dependent of and complementary to cacy were similar to those in stud- that of statins, the LDL cholesterol–● Statin medications inhibit hydroxy- ies of adults (grade A). methylglutaryl coenzyme A reduc- lowering effect is additive. No pedi- ● Adverse effects from statins are atric studies of monotherapy with tase, which is a rate-limiting enzyme in the endogenous cholesterol- rare at standard doses but include cholesterol absorption inhibitors synthesis pathway. This inhibition myopathy and hepatic enzyme ele- had been published during the time results in a decrease in the intracel- vation. In a meta-analysis of statin period for this evidence review. The lular pool of cholesterol, which sig- use in children, evidence of hepatic use of niacin, fibrates, and choles- nals upregulation of LDL receptors enzyme elevation and muscle toxic- terol absorption inhibitors should and increased clearance of circulat- ity did not differ between the statin be instituted only in consultation ing LDL cholesterol. As a group, st- and placebo groups. Routine moni- with a lipid specialist (grade C). atins have been shown to reduce toring of hepatic enzymes and clini- ● Medication therapy is rarely needed LDL cholesterol in children and ado- cal assessment for muscle toxicity for children with elevated triglycer- lescents with marked LDL choles- are strongly recommended for chil- ide levels that respond well to terol elevation or familial hypercho- dren and adolescents on statin ther- weight loss and lifestyle changes lesterolemia (defined as elevated apy (Table 9-12). The risk of adverse (grade B) (Fig 9-2; Table 9-8). When LDL cholesterol in the child in con- events increases with use of higher triglyceride levels exceed 500 mg/S26 EXPERT PANEL
  • 31. SUPPLEMENT ARTICLESTABLE 9-5 Evidence-Based Recommendations for Lipid AssessmentBirth to 2 y No lipid screening Grade C Recommend2 to 8 y No routine lipid screening Grade B Recommend Measure fasting lipid profile twice,a average results if: Parent, grandparent, aunt/uncle, or sibling with Grade B MI, angina, stroke, CABG/stent/angioplasty at Ͻ55 y in males, Ͻ65 y in females Strongly recommend Parent with TC Ն 240 mg/dL or known dyslipidemia Grade B Parent with TC Ն 240 mg/dL or known dyslipidemia Strongly recommend Child has diabetes, hypertension, BMI Ն 95th percentile or smokes cigarettes Grade B Strongly recommend Child has a moderate- or high-risk medical condition (Table 5-2) Grade B Strongly recommend Use Table 9-1 for interpretation of results, algorithms in Figs 9-1 and 9-2 for management.9 to 11 y Universal screening Grade B Strongly recommend Non-FLP: Calculate non–HDL cholesterol: Non–HDL cholesterol ‫ ؍‬TC ؊ HDL cholesterol If non-HDL Ն 145 mg/dL Ϯ HDL Ͻ 40 mg/dLb: Obtain FLP twice,a average results OR FLP: If LDL cholesterol Ն 130 mg/dL Ϯ non-HDL cholesterol Ն 145 mg/dL Ϯ HDL cholesterol Ͻ 40 mg/dL Ϯ triglycerides Ն 100 mg/dL if Ͻ10 y, Ն130 mg/dL if Ն10 y: Repeat FLP, average results Use Table 9-1 for interpretation of results, algorithms in Figs 9-1 and 9-2 for management.12 to 16 y No routine screeningc Grade B Recommend Measure FLP twice,a average results, if new knowledge of: Parent, grandparent with MI, angina, stroke, CABG/stent/angioplasty, sudden death at Ͻ55 y in male, Ͻ65 y in female Grade B Strongly recommend Parent with TC Ն 240 mg/dL or known dyslipidemia Grade B Strongly recommend Patient has diabetes, hypertension, BMI Ն 85th percentile or smokes cigarettes Grade B Strongly recommend Patient has a moderate- or high-risk medical condition (Table 5-2) Grade B Strongly recommend Use Table 9-1 for interpretation of results, algorithms in Figs 9-1 and 9-2 for management.17 to 21 y Universal screening once in this time period: Grade B Recommend Non-FLP: Calculate non–HDL cholesterol: Non–HDL cholesterol ‫ ؍‬TC ؊ HDL cholesterol* 17–19 y: If non–HDL cholesterol Ն145 mg/dL Ϯ HDL cholesterol Ͻ 40 mg/dLb Measure FLP twice,a average results OR FLP: If LDL cholesterol Ն 130 mg/dL Ϯ non–HDL cholesterol Ն 145 mg/dL Ϯ HDL cholesterol Ͻ 40 mg/dL Ϯ triglycerides Ն 130 mg/dL Repeat FLP, average results Use Table 9-1 for interpretation of results, algorithms in Figs 9-1 and 9-2 for management. 20–21 y: Non–HDL cholesterol Ն 190 mg/dL Ϯ HDL cholesterol Ͻ 40 mg/dL Measure FLP twice, average results OR FLP: If LDL cholesterol Ն 160 mg/dL Ϯ non–HDL cholesterol Ն 190 mg/dL Ϯ HDL cholesterol Ͻ 40 mg/dL Ϯ triglycerides Ն 150 mg/dL Repeat FLP, average results Use Table 9-2 for interpretation of results, Adult Treatment Panel (ATP III) algorithm for management.Grades reflect the findings of the evidence review, recommendation levels reflect the consensus opinion of the expert panel. Note that the values given are in mg/dL. To convert to SI units,divide the results for TC, LDL cholesterol, HDL cholesterol, and non-HDL cholesterol by 38.6; for triglycerides, divide by 88.6. MI indicates myocardial infarction; CABG, coronary artery bypassgraft; ATP III, Adult Treatment Panel III.a Interval between FLP measurements: after 2 weeks but within 3 months.b Use Table 9-1 for interpretation of results; use lipid algorithms in Figs 9-1 and 9.2 for management of results.c Disregard triglyceride and LDL cholesterol levels in nonfasting sample.d Lipid screening is not recommended for those aged 12 to 16 years because of significantly decreased sensitivity and specificity for predicting adult LDL cholesterol levels and significantlyincreased false-negative results in this age group. Selective screening is recommended for those with the clinical indications outlined.e Use Table 9-1 for interpretation of results of 7- to 19-year-olds and lipid algorithms in Figs 9-1 and 9-2 for management. Use Table 17 for interpretation of results of 20- to 21-year-olds andATP III algorithms for management. PEDIATRICS Volume 128, Supplement 6, December 2011 S27
  • 32. TABLE 9-6 Risk-Factor Definitions for Dyslipidemia Algorithms causes of hyperlipidemia, addi-Positive family history: myocardial infarction, angina, coronary artery bypass graft/stent/angioplasty, tional risk factors, and risk condi- sudden cardiac death in parent, grandparent, aunt, or uncle at Ͻ55 y for males, Ͻ65 y for females tions (grade C) (Tables 9-3, 9-6, andHigh-level RFs Hypertension that requires drug therapy (BP Ն 99th percentile ϩ 5 mm Hg) 9-7). Current cigarette smoker ● Children with lipid abnormalities BMI at the Ն97th percentile Presence of high-risk conditions (Table 9-7) (other than an LDL cholesterol level (DM is also a high-level RF, but it is classified here as a high-risk condition to correspond with Adult of Ն250 mg/dL or triglyceride level Treatment Panel III recommendations for adults that DM be considered a CVD equivalent.) of Ͼ500 mg/dL) should be managedModerate-level RFs Hypertension that does not require drug therapy initially for 3 to 6 months with diet BMI at the Ն95th percentile, Ͻ97th percentile changes (CHILD-1 ¡ CHILD-2–LDL or HDL cholesterol Ͻ 40 mg/dL CHILD-2–TG) (Table 9-8) on the basis Presence of moderate-risk conditions (Table 9-7) of specific lipid profile findings (FigsRF indicates risk factor. 9-1 and 9-2); if the BMI is at the Ն85th percentile, add increasedTABLE 9-7 Special Risk Conditions physical activity, reduced screenHigh risk time, and calorie restriction. As- T1DM and T2DM Chronic kidney disease/end-stage renal disease/post–renal transplant sessment for associated secondary Post–orthotopic heart transplant causes (Table 9-3), additional risk Kawasaki disease with current aneurysms factors, or high-risk conditions (Ta-Moderate risk Kawasaki disease with regressed coronary aneurysms bles 9-6 and 9-7) is recommended. Chronic inflammatory disease (systemic lupus erythematosus, juvenile rheumatoid arthritis) Children at high risk who are un- HIV infection likely to achieve lipid targets with Nephrotic syndrome this strategy alone (severe primary dyslipidemia, post– cardiac trans- plantation) should concomitantly be dL, patients are at risk for pancre- condition that is associated with se- considered for initiation of medica- atitis and require care in consulta- rious medical morbidity (homozy- tion therapy (grade C) (see “DM and tion with a lipid specialist (grade B). gous hypercholesterolemia/LDL Other Conditions Predisposing to In adults, use of ␻-3 fish oil has been cholesterol level of Ն400 mg/dL; the Development of Accelerated shown to lower the triglyceride level primary hypertriglyceridemia with Atherosclerosis”). by 30% to 40% and to raise the HDL a triglyceride level of Ն500 mg/dL; Treatment for children with severe el- level by 6% to 17%. Experience with evident CVD in the first 2 decades of evation of LDL cholesterol is based on fish oil in children has been limited life; post– cardiac transplantation) assessment of lipid levels and associ- to small case series, and no safety (grade C). ated risk factors or risk conditions (Ta- concerns identified; there have bles 9-6 and 9-7; Figs 9-1 and 9-2): been no RCTs of fish oil in children Children Aged 10 to 21 Years ● Decisions regarding the need for ● Children with an average LDL cho- (grade D). medication therapy should be lesterol level of Ն250 mg/dL shouldAge-Based Recommendations for based on the average of results be referred directly to a lipid spe-Medication Therapy of Children from at least 2 FLPs obtained at cialist (grade B).with Dyslipidemia least 2 weeks but no more than 3 ● If the LDL cholesterol level remainsThe age-specific recommendations months apart (grade C) (Fig 9-1). Ն190 mg/dL after a 6-month trial offor pharmacologic management of ● Children with an average LDL cho- lifestyle/diet management (CHILD-1dyslipidemia are summarized in lesterol level of Ն250 mg/dL or av- ¡ CHILD-2–LDL) for children agedTable 9-9. Children Younger Than 10 erage triglyceride level of Ն500 10 years and older, statin therapyYears mg/dL should be referred directly to should be considered (grade A) (Fig● Children younger than 10 years a lipid specialist (grade B). 9-1; Table 9-11 and 9-12). should not be treated with a medi- ● Children with lipid abnormalities ● If the LDL cholesterol level remains cation unless they have a severe pri- should have a detailed family his- Ն130 to Ͻ190 mg/dL in a child aged mary hyperlipidemia or a high-risk tory taken and be assessed for 10 years or older with a negativeS28 EXPERT PANEL
  • 33. SUPPLEMENT ARTICLES or at least 1 high-level risk factor or FLP x 2a, average TG > 500 mg/dL, LDL-C > 250 mg/dL risk condition together with at least Consult lipid Consult lipid 2 moderate-level risk factors or risk specialist specialist conditions (Tables 21 and 22), then LDL-C > 130, < 250 mg/dL b** Target LDL-C statin therapy should be considered TG > 100, < 500 mg/dL, < 10 y Target TG > 130, < 500 mg/dL, 10-19 yy 10–19 (grade C) (Fig 9-1; Table 9-12). (see TG algorithm, Figure 9-2) (see TG algorithm, Fig 9-2) ● For children aged 8 or 9 years with Exclude secondary causes. Evaluate for other RFs. an LDL cholesterol level persistently Start CHILD-1 CHILD-2–LDL (Table 9-8) + lifestyle change x 6 moc Ն190 mg/dL after a trial of lifestyle/ diet management (CHILD-1 ¡ CHILD- FLP 2–LDL), together with multiple first- LDL-C < 130 mg/dL degree family members with Continue CHILD-2–LDL Repeat FLP every 12 mo premature CVD/events, or the pres- ence of at least 1 high-level risk fac- tor or risk condition or the presence of at least 2 moderate-level risk fac- LDL-C > 160 to -189 mg/dL LDL-C > 130 to -159 mg/dL + LDL-C > 130 to -189 mg/dL LDL-C > 190 mg/dL FHx (+) or 2 high-level RFs or tors or risk conditions (Fig 9-1) (Ta- FHx (-) 1 high-level RF or 1 high-level + > 2 moderate- No other RFs > 2 moderate-level RFs level RFs OR clinical CVD bles 9-6 and 9-7), statin therapy Continue CHILD-2–LDL, Follow every 6 mo with FLP, Initiate statin therapy Initiate statin therapy Initiate statin therapy might be considered (grade B) (Ta- (Tables 9-1 and 9-12) (Tables 9-11 and 9-12) (Tables 9-11 and 9-12) FHx/RF update ble 9-12)). ● Statin use should begin with the Follow with FLPs, related chemistries per Table 9-12 lowest available dose given once daily. If LDL cholesterol target levels LDL-C still > 130 mg/dL, TG < 200 mg/dL, refer to lipid specialist for addition of second lipid-lowering agent; monitor per Table 9-12 are not achieved with at least 3 In high LDL-C patients, if non–HDL-C > 145 mg/dL after effective LDL-C treatment, Target TG (Fig 9-2) months of compliant use, then the dose may be increased by 1 incre-FIGURE 9-1Dyslipidemia algorithm: target LDL cholesterol. Values given are in mg/dL. To convert to SI units, ment (usually 10 mg). If LDL choles-divide results for TC, LDL cholesterol, HDL cholesterol, and non-HDL cholesterol by 38.6; for triglycer- terol target levels are still notides, divide by 88.6. TG indicates triglycerides; C, cholesterol; RF, risk factor; FHx, family history; a achieved with at least 3 months ofObtain FLPs at least 2 weeks but no more than 3 months apart. b Per Table 9-9, use of drug therapy islimited to children aged 10 years and older with defined risk profiles. c In a child with an LDL compliant use, then the dose may becholesterol level of Ͼ190 mg/dL and other risk factors, a trial of the CHILD-2–LDL may be abbreviated. further increased by 1 increment. The risk and effectiveness of dose escalation have been explored in family history of premature CVD in lifestyle/diet management (CHILD-1 several of the clinical trials of st- first-degree relatives and no high- ¡ CHILD-2–LDL) in a child aged 10 atins in children, and no additional or moderate-level risk factor or risk years or older with a positive family safety issues have been identified condition (Tables 9-6 and 9-7), man- history of premature CVD/events in (grade B). Alternatively, a second agement should continue to be fo- first-degree relatives (Table 9-6) or agent such as a bile acid seques- cused on diet changes (CHILD-2– at least 1 high-level risk factor or trant or cholesterol absorption in- LDL) on the basis of lipid profile risk condition or at least 2 hibitor may be added under the di- findings (Fig 9-1) plus weight man- moderate-level risk factors or risk rection of a lipid specialist (grade B) agement if BMI is at the Ն85th per- conditions (Tables 9-6 and 9-7), then (Table 9-12). centile. Pharmacologic therapy is statin therapy should be considered ● Children taking a statin should have not generally indicated, but treat- (grade B) (Fig 3; Table 27). routine clinical monitoring for ment with bile acid sequestrants ● If the LDL cholesterol level remains symptoms of muscle toxicity and as- might be considered, the latter in Ն130 to 159 mg/dL after a trial of sessment of hepatic transaminases consultation with a lipid specialist lifestyle/diet management (CHILD-1 and creatine kinase (grade A) (Ta- (grade B). ¡ CHILD-2–LDL) in a child aged 10 ble 9-12).● If the LDL cholesterol level remains years or older with at least 2 high- ● Pediatric care providers should be Ն160 to 189 mg/dL after a trial of level risk factors or risk conditions on the alert for, and children and PEDIATRICS Volume 128, Supplement 6, December 2011 S29
  • 34. ered for further intensification of FLP x 2a, average results TG > 500 mg/dL, LDL-C > 250 mg/dL statin therapy or additional therapy Consult lipid Consult lipid specialist specialist with a fibrate or niacin in conjunc- tion with referral to a lipid specialist LDL-C > 130, < 250 mg/dL ** Target LDL-C (see (see LDL algorithm, Fig 9-1) LDL algorithm, Figure 9-1) (grade D) (Fig 9-1) (Tables 9-10 and TG > 100, < 500 mg/dL, < 10 y Target TG 9-11). > 130, < 500 mg/dL, 10-19 y 10–19 y ● Children with severe or complex TARGET TGs TGs --> Cardiovascular Health Integrated TARGET CHILD-1 CHILD-2–TG diet (Table 9-8) + mixed dyslipidemias, particularly lifestyle modification with WT-loss goal as TG diet (Table 9– Lifestyle Diet (CHILD 1) CHILD 2 needed × 6 mo when multiple medications are be- needed × 6 months ing considered, should be referred for consultation with a lipid special- FLP ist (grade D) (Figs 9-1 and 9-2). 10. OVERWEIGHT AND OBESITY The dramatic increases in childhood TG < 100 mg/dL <10 y, TG > 100, < 200 mg/dL, <10 y TG > 200–499 mg/dL overweight and obesity in the United < 130 mg/dL, 10–19 y > 130, < 200 mg/dL, 10–19y If LDL-C target achieved and non-HDL States since 1980 are an important Continue CHILD-2–TG Intensify CHILD-2–TG + WT loss > 145 mg/dL lipid specialist for drug + lifestyle change Increase dietary fish contentb therapy (statin±fibrate±nicotinic acid) public health focus. Despite efforts Reassess q 12 mo Repeat FLP in 6 mo Consider ω-3 fish-oil therapy over the last decade to prevent andFIGURE 9-2 control obesity, recent reports fromDyslipidemia algorithm: target triglycerides. Values given are in mg/dL. To convert to SI units, divideresults for TC, LDL cholesterol, HDL cholesterol, and non-HDL cholesterol by 38.6; for triglycerides, the National Health and Nutrition Ex-divide by 88.6. C indicates cholesterol; a Obtain FLPs at least 2 weeks but no more than 3 months apart. amination Survey14 show sustainedb The FDA and the Environmental Protection Agency advise women of childbearing age who may high prevalence; 17% of children andbecome pregnant, pregnant women, nursing mothers, and young children to avoid some types of fishand shellfish and to eat fish and shellfish that are lower in mercury. For more information, call the adolescents have a BMI at the Ͼ95thFDA’s food information line toll-free at 1-888-SAFEFOOD or visit ϳdms/admehg3.html;/Border [0 0 percentile for age and gender. The0]?Ͼwww.cfsan.fda.gov/ϳdms/admehg3.html. presence of obesity in childhood and adolescence is associated with in- creased evidence of atherosclerosis their families should be counseled or niacin to prevent pancreatitis at autopsy and of subclinical mea- about, potential medication interac- should be considered (grade D) (Fig sures of atherosclerosis on vascular tions (grade D) (Table 9-12). 9-2) (Tables 9-10 and 9-11). imaging. Because of its strong asso-● Females taking a statin should be ● Children with fasting triglyceride ciation with many of the other estab- counseled about risks associated levels of Ն200 to 499 mg/dL after a lished risk factors for cardiovascu- with pregnancy and appropriate trial of lifestyle/diet management lar disease, obesity is even more contraception strategies if indi- with CHILD-1 ¡ CHILD-2–TG (Table powerfully correlated with athero- cated. Use of oral contraceptives in 9-8) should have non-HDL recalcu- sclerosis; this association has been combination with statins is not con- lated and be managed to a goal level shown for BP, dyslipidemia, and insu- traindicated (grade D) (Table 9-12). of Ͻ145 mg/dL (grade D). lin resistance in each of the majorChildren with elevated triglyceride or ● Children with fasting triglyceride pediatric epidemiologic studies. Ofnon-HDL cholesterol after control of levels of Ն200 to 499 mg/dL, non- all the risk factors, obesity tracksLDL cholesterol are managed on the HDL levels of Ͼ145 mg/dL, after a most strongly from childhood intobasis of lipid levels (Fig 9-2): trial of lifestyle/diet management adult life. Improvement in weight sta-● Children with average fasting tri- with CHILD-1 ¡ CHILD-2–TG (Table tus and decrease in body fatness glyceride levels of Ն500 mg/dL or 9-8) and increased fish intake, may have been shown to be associated any single measurement of Ն1000 be considered for fish-oil supple- with improvement in all the obesity- mg/dL related to a primary hypertri- mentation (grade D) (Table 9-10). related risk factors and in subclini- glyceridemia should be treated in ● Children aged 10 years or older with cal vascular changes. Higher BMI conjunction with a lipid specialist; non-HDL cholesterol levels of Ն145 during childhood is directly associ- the CHILD-2–TG (Table 9-8) should be mg/dL after the LDL cholesterol goal ated with increased coronary heart started, and use of fish oil, fibrate, has been achieved may be consid- disease in adult life. ExtrapolationS30 EXPERT PANEL
  • 35. SUPPLEMENT ARTICLESTABLE 9-8 Evidence-Based Recommendations for Dietary Management of Elevated LDL distribution derived from measure- Cholesterol, Non-HDL Cholesterol, and Triglyceride Levels ments taken during several National2 to 21 y Elevated LDL cholesterol: CHILD-2–LDL Health and Nutrition Examination Sur- Refer to a registered dietitian for family medical nutrition therapy Grade B Strongly veys as points of reference. Although recommend the charts were published in 2000, they 25%–30% of calories from fat, Յ7% from saturated fat, ϳ10% Grade A include selected data from the 1963 from monounsaturated fat; Ͻ200 mg/d of cholesterol; Recommend avoid trans fats as much as possible through 1980 surveys and, thus, are Supportive actions: not representative of the US popula- Plant sterol esters and/or plant stanol estersa up to 2 g/d as tion in 2000. These BMI percentile replacement for usual fat sources can be used after 2 y of age in children with familial hypercholesterolemia growth charts provide the best refer- Plant stanol esters as part of a regular diet are marketed ence data available for describing nor- directly to the public; short-term studies have found no mal growth in US children. They are, harmful effects in healthy children The water-soluble fiber psyllium can be added to a low-fat, low- however, a screening tool and not an saturated-fat diet as cereal enriched with psyllium at a instrument for the diagnosis of over- dose of 6 g/d for children 2–12 y of age and 12 g/d for weight and obesity. those Ն12 y of age As for all children, 1 h/d of moderate-to-vigorous physical An expert committee jointly convened activity and Ͻ2 h/d of sedentary screen time are by the American Medical Association recommended. (AMA), the CDC, and the Maternal and Elevated triglycerides or non-HDL cholesterol: CHILD-2–TG Child Health Bureau (MCHB) of the Refer to a registered dietitian for family medical nutrition Grade B Health Resources and Services Admin- therapyb Strongly recommend istration (US Department of Health and 25%–30% of calories from fat, Յ7% from saturated fat, ϳ10% Grade A Human Services)16 recently recom- from monounsaturated fat; Ͻ200 mg/d of cholesterol; Recommend mended that BMI be used to assess avoid trans fats as much as possible Decrease sugar intake Grade B weight-for-height relationships in chil- Recommend dren. This conclusion was reached be- Replace simple with complex carbohydrates cause BMI can be easily calculated No sugar-sweetened beverages Increase dietary fish to increase ␻-3 fatty acidsc Grade D from height and weight, correlates Recommend strongly with direct measures of bodyGrades reflect the findings of the evidence review; recommendation levels reflect the consensus opinion of the expert panel; fat (especially at higher BMI values),and supportive actions represent expert consensus suggestions from the expert panel provided to support implementation associates only weakly with height,of the recommendations (they are not graded). Values given are in mg/dL. To convert to SI units, divide the results for TC, LDLcholesterol, HDL cholesterol, and non-HDL cholesterol by 38.6; for triglycerides, divide by 88.6. and identifies those with the highesta Can be found added to some foods, such as some margarines.b If the child is obese, nutrition therapy should include calorie restriction, and increased activity (beyond that recommended body fat correctly with acceptable ac-for all children) should be prescribed. See “Overweight and Obesity” for additional age-specific recommendations. curacy, particularly above the 85th BMIc The FDA and the Environmental Protection Agency advise women of childbearing age who may become pregnant, pregnant percentile. Pediatric care providerswomen, nursing mothers, and young children to avoid some types of fish and shellfish and eat fish and shellfish that are lowin mercury. For more information, call the FDA’s food information line toll-free at 1[hyphen]888-SAFEFOOD or visit ϳdms/ need a feasible standard for identify-admehg3.html;/Border [0 0 0]?Ͼwww.cfsan.fda.gov/ϳdms/admehg3.html. ing overweight and obesity in their pa- tients, because parents recognize afrom current data suggests that ad- Identification of Overweight and child’s overweight status in fewer thanolescent obesity will likely increase Obese Children and Adolescents half of the cases. The AMA/CDC/MCHBadult coronary heart disease by 5% expert committee16 defined a BMI at theto 16% over the next 25 years with To identify overweight and obesity in Ն95th percentile as obese and a BMI be-Ͼ100 000 excess cases of coronary children living in the United States, BMI tween the 85th and 94th percentiles asheart disease attributable to in- percentile distributions relative to overweight; children in the latter BMIcreased obesity in childhood. The gender and age on the Centers for Dis- category have a great deal of variationevidence review included RCTs, sys- ease Control and Prevention (CDC) with respect to prediction of future risk.tematic reviews, meta-analyses, and 2000 growth charts15 are now the pre- The expert panel for these guidelinesobservational studies that assessed ferred reference. The CDC growth concluded that BMI is a sufficient mea-the prevention and treatment of charts were not developed as a health- sure for screening children and adoles-overweight and obesity in childhood related standard. Instead, the growth cents to identify those who need evalua-and adolescence. charts present percentiles of the BMI tion for cardiovascular risk factors PEDIATRICS Volume 128, Supplement 6, December 2011 S31
  • 36. TABLE 9-9 Evidence-Based Recommendations for Pharmacologic Treatment of DyslipidemiaBirth to 10 Pharmacologic treatment is limited to children with severe primary hyperlipidemia (homozygous familial Grade C Recommend y hypercholesterolemia, primary hypertriglyceridemia [triglycerides Ն 500 mg/dL]), a high-risk condition (Tables 9-6 and 9-7), or evident cardiovascular disease, all under the care of a lipid specialistՆ10 to 21 y Detailed family history and RF assessment required before initiation of drug therapya (high- to moderate-level RFs Grade C Strongly recommend and RCs are listed in Tables 9-6 and 9-7) LDL cholesterol If average LDL cholesterol Ն 250 mg/dLa, consult lipid specialist Grade B Strongly recommend If average LDL cholesterol Ն 130–250 mg/dL, or non-HDL Ն 145 mg/dL: Refer to dietitian for medical nutrition therapy with CHILD-1 ¡ CHILD-2–LDL (Table 9-8) for 6 mo; repeat Grade A Strongly recommend FLP Repeat FLP LDL cholesterol Ͻ 130 mg/dL, continue CHILD-2–LDL, reevaluate in 12 mo Grade A Strongly recommend LDL cholesterol Ն 190 mg/dL,b consider initiation of statin therapy per Tables 9-11 and 9-12 Grade A Strongly recommend LDL cholesterol Ն 130–189 mg/dL, negative family history, no other RF or RC, continue CHILD-2–LDL, Grade B Recommend reevaluate every 6 mo LDL cholesterol ϭ 160–189 mg/dL ϩ positive family history or Ն1 high-level RF/RC or Ն2 moderate-level Grade B Recommend RFs/RCs, consider statin therapy per Tables 9-11 and 9-12 LDL cholesterol Ն 130–159 mg/dL ϩ Ն2 high-level RFs/RCs or 1 high-level ϩ 2 moderate-level RFs/RCs, Grade B Recommend consider statin therapy per Tables 9-11 and 9-12 Children on statin therapy should be counseled and carefully monitored per Table 9-12 Grade A Strongly recommendՆ10 to 21 y Detailed family history and RF/RC assessment required before initiation of drug therapya (high- and moderate- Grade C Strongly recommend level RFs/RCs in Tables 9-6 and 9-7c) Triglycerides If average triglycerides Ն 500 mg/dL, consult lipid specialist Grade B Recommend If average triglycerides Ն 100 mg/dL in a child aged Ͻ10 y, Ն130 mg/dL in a child aged 10–19 y, or Ͻ500 mg/dL: Refer to dietitian for medical nutrition therapy with CHILD-1 ¡ CHILD-2–TG (Table 9-8) for 6 mo Grade B Strongly recommend Repeat FLP Triglycerides Ͻ 100 (130) mg/dL, continue CHILD-2–TG, monitor every 6–12 mo Grade B Strongly recommend Triglycerides Ͼ 100 (130) mg/dL, reconsult dietitian for intensified CHILD-2–TG diet counseling Grade C Recommend Triglycerides Ն 200–499 mg/dL, non-HDL Ն 145 mg/dL, consider fish oil Ϯ consult lipid specialist Grade D Recommend Non-HDL cholesterol Children aged Ն10 y with non-HDL cholesterol Ն 145 mg/dL after LDL cholesterol goal is achieved may be Grade D Optional considered for additional treatment with statins, fibrates, or niacin in conjunction with a lipid specialist consultationGrades reflect the findings of the evidence review, and recommendation levels reflect the consensus opinion of the expert panel. When medication is recommended, it should always be inthe context of the complete cardiovascular risk profile of the patient and in consultation with the patient and the family. Values given are in mg/dL. To convert to SI units, divide the resultsfor TC, LDL cholesterol, HDL cholesterol, and non-HDL cholesterol by 38.6; for triglycerides, divide by 88.6. RF indicates risk factor; RC, risk condition.a Consideration of drug therapy is based on the average of Ն2 FLPs, obtained at least 2 weeks but no more than 3 months apart.b If average LDL cholesterol Ն 190 mg/dL after CHILD-2–LDL and child is 8 to 9 years old with a positive family history or Ն1 high-level risk factor/risk condition or Ն2 moderate-level riskfactors/risk conditions, statin therapy may be considered.c If the child is obese, nutrition therapy should include calorie restriction and increased activity beyond that recommended for all children. See “Overweight and Obesity” for additionalage-specific recommendations.associated with body adiposity. The ex- growth chart should be used to express sidered on an individual basis in decid-pert panel also concluded that the scien- concern regarding weight-for-height dis- ing how best to convey the seriousnesstific evidence linking elevated BMI to car- proportion. It is important to follow the of this issue and to develop managementdiovascular risk factors and morbidity is pattern of growth over time by using plans.strong and well supported. these cut points to identify children whoThe expert panel therefore recom- require more frequent follow-up and fur- Conclusions of the Evidencemends that children and adolescents ther assessment rather than to assign a Review on Prevention ofaged 2 to 18 years with a BMI at the diagnosis. Some might feel that “obese” Overweight and Obesity With DietՆ95th percentile be described as is an unacceptable term for children and or Combined Diet and Physical“obese” and identified as needing as- parents, so as with all health conditions, Activity Interventionssessment for cardiovascular risk fac- the practitioner is encouraged to use de- The expert panel concluded that theretors. For children with a BMI that falls scriptive terminology that is appropriate is good evidence that the dietary be-between the 85th and 95th percentiles, for each child and family and to provide a havior of children can safely be im-the term “overweight” should be used, thorough explanation and discussion. proved with interventions that resultand the position of the child’s BMI on the Each patient and family should be con- in lower saturated fat intake, reducedS32 EXPERT PANEL
  • 37. SUPPLEMENT ARTICLESTABLE 9-10 Medications for Managing Hyperlipidemia Type of Mechanism of Action Major Effects Examples Adverse Reactions FDA Approval in Youths (as of Medication This Writing)HMG-CoA reductase Inhibits cholesterol synthesis Mainly lowers LDL Atorvastatin, fluvastatin, Raised hepatic enzymes, All statins listed are approved as inhibitors in hepatic cells; decreases cholesterol; some lovastatin, raised creatine kinase, an adjunct to diet to lower LDL (statins) cholesterol pool, resulting decrease in pravastatin, myopathy possibly cholesterol in adolescent boys in upregulation of LDL triglycerides and rosuvastatin, progressing to and postmenarcheal girls aged receptors modest increase in simvastatin rhabdomyolysis 10–18 y (Ն8 y for pravastatin) HDL cholesterol with heFH and LDL cholesterol Ն190 mg/dL, or Ն160 mg/dL with family history of premature CVD and Ն2 CVD risk factors in the pediatric patientBile acid Binds intestinal bile acids, Lowers LDL cholesterol; Cholestyramine, Limited to gastrointestinal No pediatric indication listed for sequestrants interrupting enterohepatic small increase in colestipol, tract: gas, bloating, cholestyramine or colestipol; recirculation; more HDL cholesterol; colesevelam constipation, cramps colesevelam indicated as cholesterol converted into raises triglycerides monotherapy or with statin for bile acids; decreases LDL cholesterol reduction in hepatic cholesterol pool; boys and postmenarcheal girls upregulates LDL receptors aged 10–17 y with family history after diet trial if LDL cholesterol Ն 190 mg/dL or if LDL cholesterol Ն 160 mg/dL with family history of premature CVD or Ն2 CVD risk factors in the pediatric patientCholesterol Inhibits intestinal absorption Mainly lowers LDL Ezetimibe Myopathy, gastrointestinal Not approved absorption of cholesterol and plant cholesterol; some upset, headache inhibitors sterols; decreases hepatic decrease in cholesterol pool; triglycerides and upregulates LDL receptors small increase in HDL cholesterolFibric acid Agonist for PPAR-␣ nuclear Mainly lowers Fenofibrate, gemfibrozil Dyspepsia, constipation, Not approved derivatives receptors that upregulate triglycerides and myositis, anemia LPL and downregulate raises HDL apolipoprotein C-III, both cholesterol; little increasing degradation of effect on LDL VLDL cholesterol and cholesterol triglycerides; hepatic synthesis of VLDL cholesterol may also be decreasedNicotinic acid Inhibits release of FFA from Lowers triglycerides Niacin, extended release Flushing, hepatic toxicity, Use not recommended in (extended adipose tissue; decreases and LDL cholesterol can increase fasting children Ͻ2 y old release) VLDL and LDL cholesterol and raises HDL blood glucose, uric production and HDL cholesterol; can acid; can cause cholesterol degradation decrease hyperacidity lipoprotein(a)␻-3 fish oil Decreases hepatic FA and Lowers triglycerides; ␻-3 acid ethyl esters Occasional adverse Only 1 fish-oil preparation is triglycerides synthesis raises HDL gastrointestinal effects FDA-approved for adults, but while enhancing FA cholesterol; increases but no adverse effect many generic fish-oil capsules degradation/oxidation, LDL cholesterol and on glucose levels or are commercially available with subsequent reduced LDL cholesterol muscle or liver VLDL cholesterol release particle size enzymes or bleedingHMG-CoA indicates hydroxymethylglutaryl coenzyme A; heFH, heterozygous hypercholesterolemia; PPAR-␣, peroxisome proliferator-activated receptor; LPL, lipoprotein lipase; VLDL, very lowdensity lipoprotein; FFA, free fatty acid; FA, fatty acid.Adapted from McCrindle BW, Urbina EM, Dennison BA, et al; American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee; American Heart Association, Councilof Cardiovascular Disease in the Young; American Heart Association, Council on Cardiovascular Nursing. Circulation. 2007;115(14):1948 –1967.intake of sweetened beverages, and in- these changes were associated with Most studies also had specific inter-creased fruit and vegetable consump- lower BMI. No evidence that diets of ventions aimed at changing physicaltion. In a small number of studies, this kind are harmful was identified. activity behaviors, so it is difficult to PEDIATRICS Volume 128, Supplement 6, December 2011 S33
  • 38. TABLE 9-11 Clinical Trials of Lipid-Lowering Medication Therapy in Children and Adolescents Study Authors, Type, Medication No. of Subjects, Gender, Condition Daily Dose Effect on Lipid Profile, % and Duration TC LDL HDL Triglycerides Cholesterol CholesterolBile acid–binding resins Tonstad et al, RCT, 1 y Cholestyramine 72, male and female, FH (LDL Ն 190 mg/dL 8g Ϫ12 Ϫ17 8 NA without family history of premature CVD or LDL Ն 160 with family history after 1-y diet; ages 6–11 y) McCrindle et al, RCT Cholestyramine 40, male and female, FH (1 parent with FH; 8g Ϫ7 to Ϫ11 Ϫ10 to Ϫ15 2 to 4 6 to 9 crossover, 2 ϫ 8 LDL cholesterol Ն 131 mg/dL; on diet; wk ages 10–18 y) Tonstad et al, RCT, 8 Colestipol 66, male and female, FH (TC Ն 239 mg/dL 2–12 g Ϫ17 Ϫ20 Ϫ7 Ϫ13 wk; open label, and triglycerides Յ 115 mg/dL; ages 44–52 wk 10–16 y) McCrindle et al, RCT Colestipol 36, male and female, FH/FCHL (LDL Ն 160 10 g Ϫ7 Ϫ10 2 12 crossover, 2 ϫ 18 mg/dL after 6 mo of diet counseling; wk ages 8–18 y) Stein et al , RCT, 8 wk; Colesevelam 191, male and female, FH (LDL Ն 190 mg/ 1.87 g Ϫ3 Ϫ6 5 6 open label, 18 wk dL or LDL Ն plus 2 additional risk factors after 6 mo of diet counseling; 3.75 g Ϫ7 Ϫ13 8 5 ages 10–17 yHMG-CoA reductase inhibitors (statins) McCrindle et al, RCT; Atorvastatin 187, male and female, FH/severe 10–20 mg Ϫ30 Ϫ40 6 Ϫ13 open label, 26 wk hyperlipidemia (LDL cholesterol Ն 190 mg/dL or LDL cholesterol Ն 160 mg/dL with family history; triglycerides Ͻ 400 mg/dL; ages 10 – 17 y) Van der Graaf et al, Fluvastatin 85, male and female, FH (LDL cholesterol 80 mg Ϫ27 Ϫ34 5 Ϫ5 open label, 2 y Ն 190 mg/dL or LDL cholesterol Ն 160 mg/dL and Ն1 risk factor or LDL receptor mutation; ages 10–16 y) Lambert et al, RCT, 8 Lovastatin 69, male, FH (LDL cholesterol Ͼ 95th 10 mg Ϫ17 Ϫ21 9 Ϫ18 wk percentile, family history of 20 mg Ϫ19 Ϫ24 2 9 atherosclerosis and hyperlipidemia; on 30 mg Ϫ21 Ϫ27 11 3 diet; mean age: 13 y) 40 mg Ϫ29 Ϫ36 3 Ϫ9 Stein et al, RCT, 48 wk Lovastatin 132, male, FH (LDL 189–503 mg/dL ϩ 10 mg Ϫ13 Ϫ17 4 4 family history of high LDL; or 220–503 20 mg Ϫ19 Ϫ24 4 8 mg/dL ϩ family history of CAD death; 40 mg Ϫ21 Ϫ27 5 6 AHA diet Ն4 mo; ages 10–17 y) Clauss et al, RCT, 24 Lovastatin 54, female, FH (family history of FH; LDL 40 mg Ϫ22 Ϫ27 3 Ϫ23 wk 160–400 mg/dL and triglycerides Ͻ 350 mg/dL; 4-wk diet placebo run-in and 20-wk treatment; ages 10–17 y, postmenarcheal) Knipscheer et al, RCT, Pravastatin 72, male and female, FH (family history 5 mg Ϫ18 Ϫ23 4 2 12 wk hypercholesterolemia or premature 10 mg Ϫ17 Ϫ24 6 7 atherosclerosis; LDL Ͼ 95th percentile; 20 mg Ϫ25 Ϫ33 11 3 diet for 8 wk; ages 8–16 y) Wiegman et al, RCT, 2 Pravastatin 214, male and female, FH (LDL cholesterol 20–40 mg Ϫ19 Ϫ24 6 Ϫ17 y Ն 155 mg/dL and triglycerides Յ 350 mg/dL; diet for 3 mo; ages 8–18 y) Rodenburg et al, Pravastatin 186, male and female, FH (LDL cholesterol 20 mg (ages Ϫ23 Ϫ29 3 Ϫ2 open-label, 2-y RCT; Ն 154 mg/dL and triglycerides Ͻ 154 Ͻ14 y) or 4.5-y open-label mg/dL; diet for 3 mo; ages 8–18 y) 40 mg follow-up (ages Ն 14 y) de Jongh et al, RCT, Simvastatin 173, male and female, FH (LDL cholesterol 10–40 mg Ϫ31 Ϫ41 3 Ϫ9 48 wk ϭ 158–397 mg/dL; ages 10–17 y) de Jongh et al, RCT, Simvastatin 50, male and female, FH (LDL cholesterol 40 mg Ϫ30 Ϫ40 5 Ϫ17 28 wk Ͼ 95th percentile, family history of hyperlipidemia, or LDL receptor mutation; ages 9–18 y)S34 EXPERT PANEL
  • 39. SUPPLEMENT ARTICLESTABLE 9-11 Continued Study Authors, Type, Medication No. of Subjects, Gender, Condition Daily Dose Effect on Lipid Profile, % and Duration TC LDL HDL Triglycerides Cholesterol Cholesterol Avis et al, RCT, 12 wk; Rosuvastatin 177, male and female, FH (LDL cholesterol Ն 5 mg Ϫ30 Ϫ38 4 Ϫ13 then, 40-wk open- 190 mg/dL or LDL cholesterol Ͼ 160 mg/ 10 mg Ϫ34 Ϫ45 10 Ϫ15 label follow-up dL plus positive family history of early 20 mg Ϫ39 Ϫ50 9 Ϫ16 CVD or Ն2 other risk factors for CVD)Other agents Wheeler et al, RCT, 26 Bezafibrate 14, male and female, FH (TC Ͼ 269 mg/dL, 10–20 mg Ϫ22 NC 15 Ϫ23 wk normal triglycerides ϩ family history of FH or premature CAD; ages 4–15 y) Colletti et al, open Niacin 21, male and female, FH (mean LDL ϭ 500–2200 Ϫ13 Ϫ17 4 13 label, 1–19 mo 243 Ϯ 45 mg/dL on low-fat diet; mean mg triglycerides ϭ 87 Ϯ 39 mg/dL; ages 4–14 y) McCrindle et al, RCT Pravastatin and 36, male and female, FH/FCHL (LDL Ͼ 160 Pravastatin, Ϫ13 Ϫ17 4 8 crossover, 2 ϫ 18 colestipol mg/dL ϩ family history of FH or 10 mg wk premature CAD; triglycerides Ͼ 177 (with mg/dL in 10 of the 36; ages 10–18 y) colestipol, 5g) van der Graaf et al, Simvastatin and 248, male and female, FH (LDL Ͼ 159 mg/ Simvastatin Ϫ38 Ϫ49 7 Ϫ17 RCT, 6 and 27 wk; ezetimibe dL ϩ genotype-confirmed FH or ϩ 10–40 mg open label to 53 parental genotype-confirmed FH or ϩ (with wk parental LDL Ͼ 210 mg/dL or ϩ ezetimibe, tendinous xanthomas or LDL Ͼ 189 10 mg) mg/dL ϩ family history of hypercholesterolemia; ages 10–17 y)Addendum Goldberg et al, ␻-3 ␻-3 fish oils (1 g — 1–4 g/d NC 17 to 31 6 to 17 Ϫ30 to Ϫ40 fatty acid review in per capsule)a adults; no RCTs in childrenFH indicates heterozygous familial hypercholesterolemia; NA, not available; FCHL, familial combined hyperlipidemia; HMG-CoA, hydroxymethylglutaryl coenzyme A; CAD, coronary arterydisease; NC, not calculated.a There is only one FDA-approved fish-oil preparation, but there are many generic forms of fish-oil capsules that are commercially available. The University of Wisconsin maintains apreventive cardiology patient education Web site (www.heartdecision.org). The fish-oil section includes information about the content of various preparations. The Web site is updated every6 months (www.heartdecision.org/chdrisk/v_hd/patient_edu_docs/Fish_Oil_11[hyphen]2007.pdf).Adapted from McCrindle BW, Urbina EM, Dennison BA, et al; American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee; American Heart Association, Councilof Cardiovascular Disease in the Young; American Heart Association, Council on Cardiovascular Nursing. Circulation. 2007;115(14):1948 –1967.separate benefits related to diet ing energy intake to growth and and/or sedentary behavior on preven-change alone. Although calorie bal- expenditure. For healthy children, im- tion of overweight and obesity. In aance is generally seen as a key issue plementation of the CHILD-1 dietary rec- small number of these studies, the in-for weight control, intervention stud- ommendations with monitoring of BMI tervention was effective. It should beies that addressed both diet and phys- and dietary intake over time should be noted that these successful interven-ical activity had mixed results, per- all that is needed from a nutritional tions often addressed reduction inhaps because most of them offered standpoint to prevent obesity. No addi- sedentary behavior rather than at-relatively weak interventions at the tional recommendations are indicated tempts to increase physical activity. Incommunity level rather than targeting on the basis of this evidence review. a majority of the studies there was noindividual at-risk youths. significant difference in body-size mea-The guideline recommendations for Conclusions of the Evidence sures. Sample sizes were often small,diet and nutrition for children at ele- Review on Prevention of and follow-up was often short (fre-vated cardiovascular risk (CHILD-1) Overweight and Obesity With quently Ͻ6 months). It is suggested(Table 5-1; “Nutrition and Diet”) specif- Physical Activity that gender-specific programs mightically address optimizing the diet in A moderate number of RCTs have eval- be more successful in changing ac-each of these areas as well as increas- uated the effect of interventions that tivity behavior. Overall, the experting intake of whole grains and match- addressed only physical activity panel concluded that on the basis of PEDIATRICS Volume 128, Supplement 6, December 2011 S35
  • 40. TABLE 9-12 Recommendations for Use of 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Inhibitors (Statins) in Children and AdolescentsPatient selection 1. Use algorithm (Fig 9-1) and risk-factor categories (Tables 9-6 and 9-7) to select statin therapy for patients. 2. Include preferences of patient and family in decision-making. 3. In general, do not start treatment with statins before the age of 10 y (patients with high-risk family history, high-risk conditions, or multiple risk factors [Tables 9-6 and 9-7] might be considered for medication initiation at age Յ10 y). 4. Precaution/contraindication with potentially interactive medications (cyclosporine, niacin, fibric acid derivatives, erythromycin, azole antifungal agents, nefazodone, many HIV protease inhibitors); check for potential interaction with all current medications at baseline. 5. Conduct baseline hepatic panel and CK before initiating treatment.Initiation and titration 1. Choice of particular statin is a matter of preference. Clinicians are encouraged to develop familiarity and experience with one of the statins, including dosage regimen and potential drug-drug interactions. 2. Start with the lowest dose once daily, usually at bedtime. Atorvastatin and rosuvastatin can be taken in the morning or evening because of their long half-lives. 3. Measure baseline CK, ALT, and AST. 4. Instruct the patient to report all potential adverse effects, especially muscle cramps, weakness, asthenia, and more diffuse symptoms suggestive of myopathy. 5. Advise female patients about concerns with pregnancy and the need for appropriate contraception. 6. Advise about potential future medication interactions, especially cyclosporine, niacin, fibric acid derivatives, erythromycin, azole antifungal agents, nefazodone, and HIV protease inhibitors. Check for potential interaction whenever any new medication is initiated. 1. Whenever potential myopathy symptoms are present, stop medication and assess CK; determine relation to recent physical activity. The threshold for worrisome level of CK is 10 times above the upper limit of reported normal, considering the impact of physical activity. Monitor the patient for resolution of myopathy symptoms and any associated increase in CK level. Consideration can be given to restarting the medication once symptoms and laboratory abnormalities have resolved. 2. After 4 wk, measure FLP, ALT, and AST and compare with laboratory-specific reported normal values. The threshold for worrisome levels of ALT or AST is Ն3 times the upper limit of reported normal. Target levels for LDL cholesterol: minimal, Ͻ130 mg/dL; ideal, Ͻ110 mg/dL. 3. If target LDL cholesterol levels are achieved and there are no potential myopathy symptoms or laboratory abnormalities, continue therapy and recheck FLP, ALT, and AST in 8 wk and then in 3 mo. 4. If laboratory abnormalities are noted or symptoms are reported, temporarily withhold the medication and repeat the blood work in 2 wk. When abnormalities resolve, the medication may be restarted with close monitoring. 5. If target LDL cholesterol levels are not achieved, increase the dose by 1 increment (usually 10 mg) and repeat the blood work in 4 wk. If target LDL cholesterol levels are still not achieved, dose may be further increased by 1 increment, or another agent (bile acid sequestrant or cholesterol absorption inhibitor) may be added under the direction of a lipid specialist.Maintenance monitoring 1. Monitor growth (height, weight, and BMI relative to normal growth charts), sexual maturation, and development. 2. Whenever potential myopathy symptoms present, stop medication and assess CK. 3. Monitor FLP, ALT, and AST every 3–4 mo in the first year, every 6 mo in the second year and beyond, and whenever clinically indicated. 4. Monitor and encourage compliance with lipid-lowering dietary and medication therapy. Serially assess and counsel for other risk factors such as weight gain, smoking, and inactivity. 5. Counsel adolescent girls about statin contraindications in pregnancy and the need for abstinence or use of appropriate contraceptive measures. Use of oral contraceptives is not contraindicated if medically appropriate. Seek referral to an adolescent medicine or gynecologic specialist as appropriate.CK indicates creatine kinase; ALT, alanine aminotransferase; AST, aspartate aminotransferase.the evidence review, increasing ac- tions in “Physical Activity.” On the ba- at greater risk; however, research istivity in isolation is of little benefit in sis of this evidence review, no addi- lacking regarding an appropriate inter-preventing obesity. By contrast, the tional specific recommendations vention. Despite that fact, epidemiologicreview suggests that reducing sed- addressing physical activity in pre- associations suggest that primary careentary behavior might be beneficial venting obesity are indicated. providers should be alert to increasingin preventing the development of BMI trends and excessive weight gain be-obesity. The activity recommenda- Summary of the Evidence Review yond what is anticipated for height in-tions in the guideline specifically ad- of Children at Increased Risk for crease when dealing with these childrendress limiting sedentary behavior Overweight and Obesity and consider intervention before theand increasing physical activity in all Certain populations of children who are child becomes overweight.children. Guidance on amounts and of normal weight are at risk for develop-intensity of physical activity and lim- ing overweight and obesity as they grow Observational studies have identifieditations on sedentary screen time older. Observational studies have identi- sample populations that are at specialare provided in the recommenda- fied risk factors that put these children risk for obesity:S36 EXPERT PANEL
  • 41. SUPPLEMENT ARTICLES● children with a BMI between the bidities (grade A). However, such pro- ● Behavior-change programs that 85th and 95th percentiles; grams have been effective primarily involved peers resulted in more● children in whom there is a positive in a comprehensive weight-loss pro- sustained weight loss (grade B). family history of obesity in 1 or both gram or in research settings; only a ● In overweight and obese youth, the parents; small number have been shown to be combination of diet and a specific● early onset of increasing weight beyond effective in primary care settings. physical activity intervention that that appropriate for increase in height, ● No data were identified on weight- reduced sedentary activity and/or which can be identified early (beginning loss programs for children younger increased physical activity was uni- in the first year of life); than 6 years. versally more effective at achieving● excessive increase in weight during ● No single negative-energy diet plan decreases in weight and BMI as well adolescence, particularly in black was identified from the evidence re- as decreases in body fat compared girls; and view. Dietary plans should be deter- with an isolated diet intervention:● children who have been very active mined for each child on the basis of ● In both children and adolescents, and then become inactive or adoles- baseline body size, energy require- exercise training improved weight cents who are inactive in general ments for growth, and physical activity loss and body composition (de- (an example would be a child who level (grade D). creasing fat mass and reducing previously participated in organized ● Increasing dietary fiber from corn visceral fat), decreased insulin re- sports and has stopped, particu- bran, wheat flour, wheat bran, oat sistance, reduced BP, normalized larly in adolescence). flakes, corn germ meal, or gluco- dyslipidemia, and normalized sub-No RCTs that addressed these popula- mannan does not significantly im- clinical measures of atherosclero-tions were identified. Despite this fact, prove weight loss (grade A). sis (grade A).the expert panel believes that lifestyle ● Various diets, including low-glycemic- ● In children aged 7 to 12 years, re-recommendations with a goal of pre- load diets, low-carbohydrate diets, fi- duction in sedentary activity inde-vention of excessive weight gain are ber supplements, and protein- pendent of increasing physicalneeded for normal-weight children sparing modified fasts, have not activity produced weight losswith characteristics consistent with been adequately studied as to their ef- (grade B). In this age group, re-special risk for development of over- fects on obesity in children andweight and obesity. The diet and activ- ductions in sedentary activity adolescents. were effectively accomplished byity recommendations proposed for ● For children aged 6 to 12 years: rewarding children for timechildren at elevated cardiovascular ● Family-based programs in re- spent being physically active withrisk (“Nutrition and Diet”; “Physical Ac-tivity”) should be vigorously reinforced search settings that addressed TV-viewing time (grade B). both diet and activity have beenin these children. In any child, the de- ● Girls did not respond as well asvelopment of a BMI between the 85th shown to be effective at initiat- boys to combined treatmentsand 95th percentile should be taken as ing and sustaining weight loss that both reduced sedentary be-a sign that increased attention to diet over a follow-up of 10 years haviors and increased physicaland activity as well as BMI-specific (grade A). activity (grade B).follow-up is indicated. ● The greatest weight loss is achieved ● For adolescents with or without sig- when parents are the focus of the in-Conclusions and Grading of the nificant comorbidities and a BMI at tervention (grade A).Evidence Review on Treatment of the Ͼ95th percentile and for ado-Obesity ● For adolescents: lescents with a BMI of Ͼ35 who ● Comprehensive programs in re- have failed to lose weight in a com-● There is good evidence for the effec- tiveness of combined weight-loss pro- search settings were effective at prehensive lifestyle weight-loss pro- grams that included behavior-change achieving weight loss in the gram, addition of medication under counseling, negative energy balance short-term (grade A). the care of a physician experienced through diet, and increased physical ● The greatest weight change was in managing weight loss with medi- activity in addressing obesity in chil- achieved when the adolescent cation can be safe and effective in dren older than 6 years with a BMI at was the primary focus of the in- achieving weight loss with follow-up the Ն95th percentile and no comor- tervention (grade B). of 4 to 12 months. However, long- PEDIATRICS Volume 128, Supplement 6, December 2011 S37
  • 42. term safety and efficacy data are allowing normal growth and devel- ages of 10 and 15 years. If not treated not available: opment. For those with a BMI at the adequately, the degree of hyperglyce- ● In adolescents with severe obe- Ͼ95th percentile without comor- mia is severe, and patients are highly sity and insulin resistance, the bidities, both the AMA/CDC/MCHB symptomatic. By contrast, with T2DM, addition of metformin to a com- expert committee and the AAP16 rec- the majority of patients present in prehensive lifestyle weight-loss ommend weight maintenance re- adult life, but a small and growing program improved fasting insu- sulting in decreasing BMI as age in- number present in adolescence, and lin levels and significantly re- creases. With a BMI at the Ͼ95th most are relatively asymptomatic with duced weight and BMI (grade B). percentile with comorbidities, the only mild-to-moderate hyperglycemia (Metformin is currently approved AMA/CDC/MCHB expert committee in combination with obesity. Regard- by the US Food and Drug Adminis- and the AAP16 recommend gradual less of these differences, children with tration [FDA] for pediatric pa- weight loss not to exceed 1 lb/ DM, type 1 or 2, are at significantly in- tients aged 10 years or older with month in children aged 2 to 11 years creased risk for accelerated athero- T2DM but is not approved for or 2 lb/week in adolescents (no sclerosis and early CVD. weight loss for either children or grade). In certain other pediatric disease adults.) ● For adolescents with a BMI far states, the process of atherosclerosis ● For obese adolescents older than above 35 and associated comorbidi- is dramatically accelerated with clini- 12 years, the addition of orlistat ties, bariatric surgery on a research cal coronary events occurring in child- to a comprehensive lifestyle protocol in conjunction with a com- hood and very early adult life. These weight-loss program improved prehensive lifestyle weight-loss pro- conditions were the subject of a recent weight loss and BMI (grade A); gram improved weight loss, BMI, guideline from the American Heart As- however, use of this medication and other outcomes such as insulin sociation (AHA).17 The expert panel had a high rate of adverse gastro- resistance, glucose tolerance, and elected to use the AHA guideline as a intestinal effects. (Orlistat [under cardiovascular measures in small template for developing recommenda- the trade name Xenical (Roche case series (grade D). tions for children with conditions such Pharmaceuticals, Nutley, NJ)] is The recommendations for manage- as DM that predispose them to very ac- approved by the FDA for weight ment of overweight and obesity are celerated atherosclerosis, because loss in pediatric patients 12 years listed in Table 10-1. the evidence review identified only a of age and older in conjunction small number of studies that ad- with a reduced-calorie diet. In Au- 11. DM AND OTHER CONDITIONS dressed these conditions in an RCT. gust 2009, the FDA released an PREDISPOSING TO THE early communication about an DEVELOPMENT OF ACCELERATED Conclusions of the Evidence ongoing safety review regarding ATHEROSCLEROSIS Review for DM and Other reports of liver-related adverse Predisposing Conditions DM is an established risk factor for events in some patients taking or- early CVD. Metabolically, DM is charac- Children with DM, T1DM or T2DM, rep- listat. In May 2010, the orlistat la- terized by hyperglycemia caused by resent the prototype of the child at beling was updated to incorpo- defects in insulin secretion (T1DM) special risk for accelerated athero- rate safety information and insulin function and/or secretion sclerosis and early clinical CVD. To pertaining to the occurrence of maximize identification of T2DM in (T2DM). Both T1DM and T2DM are asso- rare postmarketing cases of se- childhood and adolescence, the ciated with vascular disease. Results vere liver injury, including he- screening algorithm from the Ameri- of autopsy and noninvasive imaging patic failure that resulted in can Diabetes Association18 is recom- studies suggest that the extent of vas- liver transplant or death.) mended for screening in all children cular involvement reflects the dura-● Dropout rates are substantial for all tion of the disease and the severity of (Table 11-1). weight-treatment programs. the chronic metabolic derangement. Limited high-quality studies that ad-● No studies defining an appropriate The epidemiologies of the 2 types differ dressed cardiovascular risk reduction rate for weight loss in any age group significantly. T1DM presents at a in children with conditions predispos- were identified by the guidelines ev- younger age; 25% of patients are diag- ing them to accelerated atherosclero- idence review. The 2010 DGA8 recom- nosed between the ages of 5 and 10 sis were found, so the expert panel mends slowing weight gain while years and another 40% between the elected to modify the recommenda-S38 EXPERT PANEL
  • 43. SUPPLEMENT ARTICLESTABLE 11-1 American Diabetes Association (ADA) Screening Recommendations for Type 2 phrotic syndrome, these 2 conditions DM in Childhood have been added to the selected dis-Criteria: ease settings in the moderate-risk cat-● Overweight, defined by: –BMI Ն 85th percentile for age and gender, or egory. Patients in the high-risk cate- –Weight for height Ն 85th percentile, or gory require intensive management –Weight Ͼ 120% of ideal for height with more aggressive goals for ther-Plus any two of the following risk factors:● Family history of type 2 DM in first- or second-degree relative apy than those in the moderate-risk● Race/ethnicity (Native American, African-American, Latino, Asian-American, Pacific Islander) category, as outlined in the algorithm.● Signs of insulin resistance or conditions associated with insulin resistance (acanthosis nigricans, hypertension, dyslipidemia, or polycystic ovary syndrome)Screening procedure: 12. RISK-FACTOR CLUSTERING ANDAge of initiation: THE METABOLIC SYNDROMEՆ10 y, or at onset of puberty, if puberty occurs at a younger ageFrequency: Traditional cardiovascular risk factorsEvery 2 y such as obesity, hypertension, and dys-Test: lipidemia demonstrate clustering inFasting plasma glucose youth. Risk behaviors such as smok-Reproduced with permission from American Diabetes Association. Diabetes Care. 2000;23(3):386. ing, suboptimal diet, and sedentary be-TABLE 11-2 Special Risk Pediatric Conditions: Stratification by Risk Category havior also demonstrate clustering, asHigh risk do advantageous diet and exercise Manifest coronary artery disease at Յ30 y of age: clinical evidence habits. Becoming obese increases the T1DM or T2DM prevalence of the risk-factor cluster in Chronic kidney disease/end-stage renal disease/post–renal transplant Post–orthotopic heart transplantation adults called the metabolic syndrome. Kawasaki disease with current coronary aneurysms The metabolic syndrome is defined asModerate risk Ն3 of the following risk factors: elevated Accelerated atherosclerosis: pathophysiologic evidence Kawasaki disease with regressed coronary aneurysms waist circumference, triglyceride levels, Chronic inflammatory disease (systemic lupus erythematosus, juvenile rheumatoid arthritis) BP, and/or fasting glucose level and re- HIV infection duced HDL cholesterol level. In the United Nephrotic syndrome States, the metabolic syndrome is said toAdapted from Kavey RE, Allada V, Daniels SR, et al; American Heart Association, Expert Panel on Population and PreventionScience; American Heart Association, Council on Cardiovascular Disease in the Young; American Heart Association, Council affect between 34% and 39% of adults,on Epidemiology and Prevention; American Heart Association, Council on Nutrition, Physical Activity and Metabolism; including 7% of men and 6% of women inAmerican Heart Association, Council on High Blood Pressure Research; American Heart Association, Council on Cardiovas-cular Nursing; American Heart Association, Council on the Kidney in Heart Disease; Interdisciplinary Working Group on the 20- to 30-year-old age group. The ex-Quality of Care and Outcomes Research. Circulation. 2006;114(24):2710 –2738. pert panel reviewed all the RCTs, system- atic reviews, meta-analyses, and obser-tions of an expert pediatric panel con- moderate-risk category, the disease vational studies that addressed thevened by the AHA that published its process has been shown to be associ- childhood association between the risk-recommendations for risk-factor man- ated with pathologic, physiologic, or factor cluster known as the metabolicagement in 2006; these recommenda- subclinical evidence of accelerated syndrome and the development of ath-tions have been endorsed by the AAP atherosclerosis. erosclerosis, and the identification andand are included in the guideline data- management of the cluster in children The expert panel believes that thesebase for these guidelines.17 and adolescents. recommendations should be used forThe authors of the AHA statement rec- the management of children and ado- There is a lack of consensus on how toommended specific risk identification lescents with DM and other predispos- define metabolic syndrome in youth,and management stratified according ing conditions as outlined in the algo- which has led to widely varying esti-to risk on the basis of defined other rithm in Fig 11-1 and in Tables 11-2 and mates of its frequency. A recent analysisconditions that parallel the recom- 11-3. With the growing evidence of vas- of National Health and Nutrition Examina-mendations for adults with DM or cular disease in children with T2DM, tion Survey data from 1999 to 200219other CVD equivalents. For those in the the expert panel felt that it was pru- yielded prevalence estimates for allhigh-risk category (Table 11-2), the dis- dent to include both T1DM and T2DM in teens from 2.0% to 9.4% and for obeseease process has been associated the high-risk category. With increasing teens from 12.4% to 44.2%. Regardless ofwith clinical coronary disease before evidence of vascular dysfunction in the definition used, the prevalence of the30 years of age. For those in the children with HIV infection and ne- metabolic syndrome risk-factor cluster PEDIATRICS Volume 128, Supplement 6, December 2011 S39
  • 44. Tier I: High Risk Tier II: Moderate Risk Step 1. T1DM and T2DM Kawasaki disease with regressed RISK Chronic kidney disease/end stage coronary aneurysms STRATIFICATION renal disease/ post–kidney transplant Chronic inflammatory disease BY DISEASE Post–heart transplant HIV PROCESS Kawasaki disease with current Nephrotic syndrome coronary artery aneurysms CV RISK FACTORS/ COMORBIDITIES Step 2. Family history of early CVD in expanded first-degree pedigree (♂ ≤55 y; ASSESS ♀ ≤65 y) FLP CV RFs Smoking history (> 2 RFs BP (3 separate occasions), interpreted for age/gender/HT percentile (%ile) Move to tier 1) HT, WT, BMI FG Diet, physical activity/exercise history Yes No Step 3. Tier 1: High Risk Tier II: Moderate Risk TIER- BMI < 85th%ile for age/gender. BMI ≤ 90%ile for age/gender SPECIFIC CUT BP < 90th %ile for age/gender/HT%ile BP ≤ 95%ile for age/gender/HT%ile POINTS/ Lipids (mg/dL): LDL-C < 100, Lipids (mg/dL): LDL-C ≤ 130, TREATMENT TG < 90, non–HDL-C < 120 TG < 130, non–HDL-C < 140 FG < 100 mg/dL, HgbA1c < 7% FG < 100 mg/dL, HgbA1c < 7% GOALS Step 4: Intensive lifestyle management Intensive lifestyle management LIFESTYLE CHILD-1a, Activity Rxb CHILD-1a, Activity Rxb CHANGE WT loss as neededc Weight loss as neededc PLUS Step 5: If goals not met, consider Condition-specific DRUG medication per risk-specific management – Table 11-3 THERAPY guideline recommendations Directions: Step 1: Risk stratification by disease process (Table 11-2). Step 2: Assess all cardiovascular risk factors. If there are >2 comorbidities, move tier II patient to tier I for subsequent management. Step 3: Tier-specific treatment goals/cut points defined. Step 4: Initial therapy: For tier I, initial management is therapeutic lifestyle change PLUS disease-specific management (Table 11-3). For tier II, initial management is therapeutic lifestyle change.FIGURE 11-1Risk stratification and management for children with conditions predisposing to accelerated atherosclerosis and early CVD. CV indicatescardiovascular; RF, risk factor; HT, height; WT, weight; TG, triglycerides; %ile, percentile; C, cholesterol; FG, fasting glucose; Rx, recommendation. a See“Nutrition and Diet”; b see “Physical Activity”; c see “Overweight and Obesity.” Adapted from Kavey RE, Allada V, Daniels SR, et al; American Heart Association,Expert Panel on Population and Prevention Science; American Heart Association, Council on Cardiovascular Disease in the Young; American HeartAssociation, Council on Epidemiology and Prevention; American Heart Association, Council on Nutrition, Physical Activity and Metabolism; American HeartAssociation, Council on High Blood Pressure Research; American Heart Association, Council on Cardiovascular Nursing; American Heart Association, Councilon the Kidney in Heart Disease; Interdisciplinary Working Group on Quality of Care and Outcomes Research. Circulation. 2006;114(24):2710 –2738.is higher in older (12- to 14-year-old) sulin resistance. Longitudinal studies of hypertension in early childhood and sub-compared with younger (8- to 11-year- cohorts in which the metabolic syn- sequent development of the metabolicold) children. The specific etiology of drome cluster was present in childhood syndrome constellation in adulthood hasmetabolic syndrome is unknown; how- identified an increased incidence of both been consistently demonstrated. Treat-ever, it is most likely caused by the ex- T2DM and clinical cardiovascular events ment of cardiovascular risk-factor clus-pression of various genotypes modified over a follow-up period of 25 years.4 A tering in youth has not been thoroughlyby environmental interactions and medi- strong association between obesity with evaluated, but maintenance of low levelsated through abdominal obesity and in- or without elevated insulin levels and/or of cardiovascular risk factors starting inS40 EXPERT PANEL
  • 45. SUPPLEMENT ARTICLESTABLE 11-3 Condition-Specific Treatment Recommendations for High-Risk Conditions sis on lifestyle modification to addressRigorous age-appropriate education in diet, activity, smoking cessation for all individual metabolic syndrome risk-Specific therapy as needed to achieve BP, LDL cholesterol, glucose, and HbA1c goals indicated for each factor levels. tier, as outlined in algorithm; timing individualized for each patient and diagnosisDM regardless of type: ● The presence of obesity should For T1DM, intensive glucose management per endocrinologist with frequent glucose monitoring/insulin prompt specific evaluation for all titration to maintain optimal plasma glucose and HbA1c levels for age other cardiovascular risk factors in- For T2DM, intensive weight management and glucose control in consultation with an endocrinologist as needed to maintain optimal plasma glucose and HbA1c levels for age cluding family history of premature Assess BMI and fasting lipid levels: step 4 lifestyle management of weight and lipid levels for 6 mo CVD, hypertension, dyslipidemia, If LDL goals are not achieved, consider statin therapy if age is Ն10 y to achieve tier 1 treatment goals DM, and tobacco exposure. for LDL cholesterol Initial BP Ն 90th percentile: step 4 lifestyle management plus no added salt, increased activity for 6 mo ● The coexistence of obesity with any If BP is consistently at the Ն95th percentile for age/gender/height, initiate angiotensin-converting other major cardiovascular risk fac- enzyme inhibitor therapy with a BP goal of Ͻ90th percentile for gender/height or Ͻ120/80 mm Hg, whichever is lower tor should be recognized by clini-Chronic kidney disease/end-stage renal disease/post–renal transplant: cians as a setting in which: Optimization of renal-failure management with dialysis/transplantation per nephrology Assess BMI, BP, and lipid and FG levels: step 4 lifestyle management for 6 mo ● intensive weight reduction If LDL goals are not achieved, consider statin therapy if age is Ն10 y to achieve tier 1 treatment goals should be undertaken per the for LDL cholesterol recommendations in “Overweight If BP is consistently at the Ն95th percentile for age/gender/height, initiate angiotensin-converting enzyme inhibitor therapy with a BP goal of Ͻ90th percentile for gender/height or Ͻ120/80 mm Hg, and Obesity,” along with manage- whichever is lower ment of identified risk factorsAfter heart transplantation: including initiation of pharmaco- Optimization of antirejection therapy, treatment for cytomegalovirus infection, routine evaluation by angiography/perfusion imaging per transplant physician logic therapy, per the risk-factor– Assess BMI, BP, and lipid and FG levels: initiate step 5 therapy, including statins, immediately for all specific sections in these guide- patients aged Ն1 y to achieve tier 1 treatment goals lines (“High BP”; “Lipids andKawasaki disease with current coronary aneurysms: Antithrombotic therapy, activity restriction, ongoing myocardial perfusion evaluation per cardiologist Lipoproteins”; “DM and Other Assess BMI, BP, and lipid and FG levels: step 4 lifestyle management for 6 mo Conditions Predisposing to the If goals are not achieved, consider pharmacologic therapy for LDL cholesterol and BP if age is Ն10 y to Development of Accelerated Ath- achieve tier 1 treatment goals erosclerosis”; “Tobacco Expo-FG indicates fasting glucose.Adapted from Kavey RE, Allada V, Daniels SR, et al; American Heart Association, Expert Panel on Population and Prevention sure”); andScience; American Heart Association, Council on Cardiovascular Disease in the Young; American Heart Association, Councilon Epidemiology and Prevention; American Heart Association, Council on Nutrition, Physical Activity and Metabolism; ● prompt evaluation for DM, liver-American Heart Association, Council on High Blood Pressure Research; American Heart Association, Council on Cardiovas- function abnormalities, left ven-cular Nursing; American Heart Association, Council on the Kidney in Heart Disease; Interdisciplinary Working Group onQuality of Care and Outcomes Research. Circulation. 2006;114(24):2710 –2738. tricular hypertrophy, and sleep apnea should be undertaken. These recommendations are sup-childhood is associated with a lower risk factor in childhood and adoles- ported by the knowledge that cardio-prevalence of CVD and increased longev- cence. Prevention of obesity is the most vascular morbidity has a continuousity in adult life. important strategy for lowering the relationship across the risk- prevalence of metabolic syndrome inRECOMMENDATIONS FOR distribution spectrum and that a youth adults, and this seems strongly applica-MANAGEMENT OF RISK-FACTOR with multiple borderline risk factors ble in childhood (see “Overweight andCLUSTERING AND THE METABOLIC might, in fact, have risk equivalent to aSYNDROME Obesity”). Given the strong relationship person with extreme abnormality of a of obesity and physical inactivity to theThe metabolic-syndrome concept is im- single major risk factor. A presenta- metabolic syndrome and insulin resis-portant, because it identifies a common tion such as this should lead to intense tance, the expert panel makes the follow-multiple cardiovascular-risk phenotype nutrition and exercise management ing recommendations. Because of the with close follow-up, and if lifestyle in-in pediatrics. However, the absence of a paucity of evidence available, the recom- tervention is unsuccessful, consider-defined etiology, the lack of consensus mendations are a consensus of the ex- ation should be given to endocrine re-on definition, and the paucity of high- pert panel (grade D). ferral. Table 12-1 provides definitionslevel evidence addressing managementin childhood led the expert panel to con- ● The presence of any combination of of component risk-factor levels forclude that the metabolic syndrome multiple risk factors should prompt in- evaluating children with multiple car-should not be considered as a separate tensification of therapy with an empha- diovascular risk factors. PEDIATRICS Volume 128, Supplement 6, December 2011 S41
  • 46. TABLE 12-1 Metabolic Syndrome Component Levels for Evaluation of Children With Multiple Conclusions and Grading of the Cardiovascular Risk Factors Evidence Review on Maternal Risk Factor Cut Point Reference Smoking CessationObesity, percentile BMI Ն85th to Ͻ95th CDC growth charts ● The expert panel found that strong Waist circumference Ն90th to Ͻ95th NHANES evidence supports a benefit for in-BP, percentile Ն90th to Ͻ95th “The Fourth Report on the Diagnosis, terventions directed at maternal Evaluation and Treatment of High Blood Pressure in Children and smoking cessation during preg- Adolescents” nancy (grade A). Weaker evidenceDyslipidemia, mg/dL See “Lipids and Lipoproteins” for suggests that these interventions normative values HDL cholesterol Ն40 to Յ45 do not prevent relapse after deliv- Triglycerides ery. Trials of cessation in the post- 0–9 y Ն75 to Ͻ100 partum period, which would be Ն10 y Ն90 to Ͻ130 the most applicable to pediatric Non-HDL cholesterol Ն120 to Ͻ144Glycemia, mg/dL ADA screening recommendations providers, have been limited in Fasting glucose Ն100 to Ͻ126 number and suggest that for ma- Fasting insulin Elevated fasting insulin level, above ternal smoking cessation to be normal for gender, race, and pubertal status, is considered sustained, specific continued sup- evidence of insulin resistance port in the pediatric care settingNHANES indicates National Health and Nutrition Examination Survey; ADA, American Diabetes Association. is required.TABLE 13-1 Evidence-Based Recommendations for Maternal Smoking Cessation ● No smoking-cessation interventionsSmoking-cessation guidance during pregnancy is strongly advised Grade A, strongly recommend have resulted in any reported ad-Supportive action: verse effects related to the interven- Pediatric care providers should be provided with appropriate training and materials to deliver, or refer to, a smoking- tions (no grade). cessation program in the postpartum period for all smoking ● The expert panel believes that pedi- women of childbearing age atric care providers can play a role This intervention should be directly linked to ongoing smoke- free home recommendations directed at all young mothers and in helping mothers to remain fathers as described in the “Tobacco Exposure” section smoke-free or to quit smoking in theGrades reflect the findings of the evidence review; recommendation levels reflect the consensus opinion of the expert panel; interpregnancy interval. For mostand supportive actions represent expert consensus suggestions from the expert panel provided to support implementationof the recommendations (they are not graded). women, this interval will extend to the early first trimester of any sub- sequent pregnancy. The pediatric13. PERINATAL FACTORS could not identify any prepregnancy well-child schedule calls for ϳ10Increasing evidence links prenatal or postpartum studies that ad- visits in the first 2 years of life, andexposures to adverse health out- dressed maternal obesity in a pedi- mothers attend most of those visits,comes. Perinatal risk reduction is an atric care setting, and more general so the pediatric care provider usu-area in which pediatric care provid- ally sees women in this period more approaches to preventing or treatingers can potentially be effective, be- than any other health care profes- obesity in women of reproductivecause they are often the only physi- sional. Pediatric care providers of- age are beyond the scope of this re- ten have a sustained relationshipcians whom a mother sees between port. A detailed discussion of child- with the mother and her infant, andpregnancies. The expert panel identi- hood obesity itself is the subject of many already advocate for parentalfied 3 potential areas for consider- “Overweight and Obesity.” With re- smoking cessation in their efforts toation: maternal obesity; choice ofneonatal feeding method; and mater- gard to choice of neonatal feeding promote a smoke-free environmentnal smoking cessation. Maternal method, the cardiovascular advan- for children. Pediatric providersobesity is associated with gesta- tages of breastfeeding as the pri- and/or their staff need to be trainedtional DM, higher birth weight, child- mary source of nutrition for infants to either deliver or refer to a long-hood obesity measured by increased are emphasized in “Nutrition and term maternal smoking-cessationBMI, and increased risk of the meta- Diet.” Therefore, the evidence review program (no grade).bolic syndrome and T2DM in off- for this section is focused on mater- Recommendations for maternal smok-spring. However, the expert panel nal smoking cessation. ing cessation are listed in Table 13-1.S42 EXPERT PANEL
  • 47. SUPPLEMENT ARTICLESTABLE 10-1 Evidence-Based Recommendations for Management of Overweight and ObesityBirth to 24 mo No weight-for-height–specific recommendations CHILD-1 diet is recommended for pediatric care providers to use with their child and adolescent patients to reduce cardiovascular risk2 to 5 y Identify children at high risk for obesity because of parental obesity and excessive BMI increase Grade B Recommend Focused CHILD-1 diet and physical activity education BMI percentile stable: reinforce current program, follow-up in 6 mo Increasing BMI percentile: RD counseling for energy-balanced diet, intensify physical activity change; 6-mo follow-up BMI ϭ 85th–95th percentile Excess weight-gain prevention with parents as focus for energy-balanced diet; reinforce physical activity Grade D recommendations for 6 mo Recommend Improvement in BMI percentile: continue current program Increasing BMI percentile: RD counseling for energy-balanced diet; intensify physical activity recommendations; 6-mo follow-up BMI Ն 95th percentile Specific assessment for comorbiditiesa Grade B Strongly recommend Family-based weight-gain prevention with parents as focus; RD counseling and follow-up for energy-balanced diet; Grade B Recommend MVPA prescription; limit sedentary screen time; 3-mo follow-up6 to 11 y Identify children at increased risk for obesity because of parental obesity, change in physical activity Ϯ excessive gain in Grade B BMI for focused CHILD-1 diet/physical activity education Recommend BMI percentile stable: reinforce current program, 6-mo follow-up Increasing BMI percentile: RD counseling for energy-balanced CHILD-1 diet, intensified physical activity, 3 mo follow-up BMI ϭ 85th–95th percentile Excessive weight-gain prevention with parents as focus for energy-balanced diet; reinforce physical activity Grade D recommendations, 6-mo follow-up Recommend Stable/improving BMI percentile: reinforce current program, 6-mo follow-up Increasing BMI percentile: RD counseling for energy-balanced CHILD-1 diet, intensified physical activity recommendations, 3-mo follow-up BMI Ն 95th percentile Specific assessment for comorbiditiesa Grade B Strongly recommend BMI Ն 95th percentile with no comorbidities Office-based weight-loss plan: family-centered program with parents as focus for behavior modification, (Ϫ) Grade A energy-balanced diet, counseling by RD, prescription for increased MVPA, decreased sedentary time for 6 mo Strongly recommend Improvement in BMI percentile/comorbidities: continue current plan No improvement in BMI percentile: refer to comprehensive multidisciplinary lifestyle weight-loss program BMI Ն 95th percentile with comorbidities, BMI Ͼ 97th percentile, or progressive rise in BMI despite therapy Grade A Refer to comprehensive multidisciplinary weight-loss program for intensive management for 6 mo Strongly recommend Improvement in BMI percentile: continue current program No improvement in BMI percentile: consider referral to another comprehensive multidisciplinary weight-loss program12 to 21 y Identify adolescents at increased risk for obesity because of parental obesity, change in physical activity Ϯ excess gain Grade B in BMI for focused diet/physical activity education for 6 mo Recommend BMI/BMI percentile stable: reinforce current program, 6-mo follow-up Increasing BMI/BMI percentile: RD counseling for energy-balanced CHILD-1 diet, intensified physical activity for 3 mo BMI ϭ 85th–95th percentile Excess weight-gain prevention with adolescent as change agent for energy-balanced CHILD-1 diet, reinforced physical Grade B activity recommendations for 6 mo Recommend Improvement in BMI percentile: continue current program Increasing BMI percentile: RD counseling for energy-balanced weight-control diet, intensified physical activity, 3-mo follow-up BMI Ն 95th percentile Specific assessment for comorbiditiesa Grade B BMI Ն 95th percentile with no comorbidities Strongly recommend Office-based weight-loss plan: family-centered with adolescent as change agent for behavior-modification Grade B counseling, RD counseling for (Ϫ) energy-balanced diet, prescription for increased MVPA, decreased Strongly recommend sedentary time for 6 mo Improvement in BMI/BMI percentile: continue current program No improvement in BMI/BMI percentile: refer to comprehensive multidisciplinary weight-loss program with peers No improvement in BMI/BMI percentile: consider initiation of medication (orlistat) under care of experienced clinician for 6–12 mo BMI Ն 95th percentile with comorbidities or BMI Ͼ 35 Refer to comprehensive lifestyle weight-loss program for intensive management for 6–12 mo Grade A Improvement in BMI/BMI percentile: continue current program Strongly recommend No improvement in BMI/BMI percentile: consider initiation of orlistat under care of experienced clinician for 6–12 mo If BMI is far above 35 and comorbidities unresponsive to lifestyle therapy for Ͼ1 y, consider bariatric surgery/referral to center with experience/expertise in proceduresGrades reflect the findings of the evidence review, and recommendation levels reflect the consensus opinion of the expert panel. RD indicates registered dietitian; MVPA, moderate-to-vigorous physical activity.a Comorbidities: hypertension, dyslipidemia, and T2DM.REFERENCES 1. NCEP Expert Panel of Blood Cholesterol Levels lesterol Levels in Children and Adolescents. adolescents and young adults: implications in Children and Adolescents. National Choles- Pediatrics. 1992;89(3):495–501 for prevention from the Pathobiological De- terol Education Program (NCEP): highlights of 2. Strong JP, Malcom GT, McMahan CA, et al; terminants of Atherosclerosis in Youth the report of the Expert Panel on Blood Cho- Prevalence and extent of atherosclerosis in Study. JAMA. 1999;281(3):495–501 PEDIATRICS Volume 128, Supplement 6, December 2011 S43
  • 48. 3. Berenson GS, Srinivasan SR, Bao W, New- Adults. Executive summary of the Third Re- obesity: summary report. Pediatrics. 2007; man WP III, Tracy RE, Wattigney WA. Associ- port of the National Cholesterol Education 120(suppl 4):S164 –S192 ation between multiple cardiovascular risk Program (NCEP) Expert Panel on Detection, 17. Kavey RE, Allada V, Daniels SR, et al; Ameri- factors and atherosclerosis in children and Evaluation, and Treatment of High Blood can Heart Association Expert Panel on Pop- young adults. The Bogalusa Heart Study. N Cholesterol in Adults (Adult Treatment ulation and Prevention Science; American Engl J Med. 1998;338(23):1650 –1656 Panel III). JAMA. 2001;285(19):2486 –2497 Heart Association Council on Cardiovascu- 4. Morrison JA, Friedman LA, Gray-McGuire C. 10. Abrams SA. Dietary guidelines for calcium lar Disease in the Young; American Heart Metabolic syndrome in childhood predicts and vitamin D: a new era. 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Adv Data. 2000;314: 1–27 19. Cook S; Auinger P; Li C; Ford ES. Metabolic Washington, DC: US Government Printing 16. Barlow SE; Expert Committee. Expert com- syndrome rates in United States adoles- Office; 2011 mittee recommendations regarding the cents, from the National Health and Nutri- 9. Expert Panel on Detection, Evaluation, and prevention, assessment, and treatment of tion Examination Survey, 1999 –2002. J Pedi- Treatment of High Blood Cholesterol in child and adolescent overweight and atr. 2008;152(2):165–170(Continued from first page)Associates for the State of Ohio, Bureau of Early Intervention Services and Help Me Grow program, and has received funding/grant support for research from theNIH; Dr Kwiterovich has served as a consultant or advisory board member for Merck, Schering-Plough, Pfizer, Sankyo, LipoScience, and Astra Zeneca, has servedon speaker’s bureaus for Merck, Schering-Plough, Pfizer, Sankyo, Kos, and Astra Zeneca, and has received funding/grant support for research from Pfizer,Merck, GlaxoSmithKline, Sankyo, and Schering-Plough; Dr McBride has served as a consultant or advisory board member for Bristol-Myers Squibb and Merckand has served on speaker’s bureaus for Kos, Merck, and Pfizer but declares no relevant relationships since July 2007; Dr McCrindle has been a consultant forAbbott, Bristol-Myers Squibb, Daichii Sankyo, and Roche, owns stock in CellAegis and reports funding/grant support for research from Astra Zeneca, Sankyo,Merck, Schering-Plough, and the NIH; Dr Urbina reports funding/grant support for research from Merck, Schering-Plough, Sankyo, and the NIH; and Dr VanHornhas provided advice to Chartwells School Food Service and has received funding/grant support for research from General Mills and the NIH. Drs Benuck,Christakis, Dennison, O’Donnell, Rocchini, and Washington have indicated they have no financial relationships relevant to this article to disclose.Funded by the National Institutes of Health (NIH).S44 EXPERT PANEL