This document discusses hypertension in newborns and children. It begins by defining hypertension in neonates and outlining objectives for identifying and characterizing it. Common causes of neonatal hypertension are then reviewed, including renovascular, renal parenchymal, cardiac, endocrine, and iatrogenic factors. The evaluation, management, and long-term outcomes of hypertension in newborns are also described. The document then discusses hypertension in children, defining pediatric hypertension and outlining an approach to diagnosis, evaluation, and treatment. Risk factors and management of pre-hypertensive and stages I and II hypertension in children are also reviewed.
3. Objectives
1. A standardized protocol for identifying hypertension in the
neonate.
2. Characterize the relationship of blood pressure with
gestational age, postconceptual age, and birthweight.
3. Characterize the need for blood pressure measurement in
neonates who have left neonatal intensive care units.
4. List the causes of most cases of neonatal hypertension.
5. Describe potential complications related to specific
antihypertensive agents or too-rapid reduction in blood
pressure.
4. • Defining hypertension or even normotension in the
neonate is difficult.
• The initial step is to ensure that the blood pressure (BP) is
being measured accurately.
• In both term and preterm infants, normal BP increases
with gestational age, postconceptual age, and birth weight.
5. Incidence
• The incidence of neonatal hypertension is low.
• In the general NICU population, one study found that 0.08% (26/3,179) of
infants had hypertension.
• Another study found that hypertension accompanied 2% (20/988) of NICU
admissions.
• Some subpopulations, such as those who have bronchopulmonary dysplasia,
patent ductus arteriosus, and intraventricular hemorrhage, had a greater risk
of being diagnosed with this abnormality.
• Although infrequent, hypertension always is abnormal and, thus, merits
further attention.
• Hypertension may not be diagnosed in some infants until after discharge from
the NICU.
6. Causes
• Medical disease, anatomic anomalies, and iatrogenic conditions all may
contribute to hypertension.
• Most cases of neonatal hypertension are due to renovascular or renal
causes.
• In the past, much attention has been placed on umbilical artery
catheters as theoretical sources of thromboembolic events that cause
areas of infarction and increased renin release.
• Thrombi have been demonstrated to be present on 25% to 81% of
catheters studied.
8. • Other renovascular conditions may cause neonatal hypertension.
• The classic presentation of renal vein thrombosis is hypertension,
gross hematuria, and an abdominal mass.
• Fibromuscular dysplasia may be present, causing renal artery stenosis.
• When renal artery stenosis is present, there also may be a mid-aortic
coarctation and cerebral vascular stenosis.
• Also in the differential diagnosis is mechanical compression of the
renal vessels by tumors, hydronephrotic kidneys, or other abdominal
masses.
9. • Renal parenchymal abnormalities also may cause hypertension.
• Autosomal dominant and autosomal recessive polycystic kidney disease (PKD)
may present in the neonatal period with enlarged kidneys and hypertension.
• The hypertension may progress even to the degree that the patient may
develop congestive heart failure, necessitating bilateral nephrectomies.
• An infant who has unilateral multicystic dysplastic kidney also may present
with hypertension, although this is poorly understood because such kidneys
are believed to be entirely nonfunctional.
• Unilateral renal hypoplasia also may have this finding, although this is
uncommon.
• Additional renal parenchymal diseases that may be found in the evaluation of
hypertension are congenital ureteropelvic junction obstruction or ureteral
obstruction by other abdominal processes.
10. • Acquired renal parenchymal disease in the newborn period may cause
significant hypertension.
• Acute tubular necrosis, interstitial nephritis, or cortical necrosis all
may have this finding, usually because of volume overload or
hyperreninemia.
• An especially difficult to manage hypertension can be found in
hemolytic-uremic syndrome, which has been described in both term
and preterm infants.
• Infants who have bronchopulmonary dysplasia are at particularly
increased risk for the development of hypertension.
• Studies have shown that 13% to 43% of affected infants develop
systemic hypertension.
• The source of the hypertension is unclear, although chronic hypoxia is
believed to play a role.
11. • Cardiac, endocrine, and neurologic disorders also may
contribute to the development of hypertension and should be
included in the differential diagnosis.
• The most common cardiac lesion is coarctation of the thoracic
aorta.
• Early repair improves the long-term outcome, although
hypertension may persist even after the surgical repair.
• Congenital adrenal hyperplasia, hyperaldosteronism, and
hyperthyroidism are accompanied by hypertension, and
seizures and increased intracranial pressure are common
causes of episodic hypertension.
12. • Of particular importance in any differential
diagnosis are iatrogenic causes.
• Prolonged total parenteral nutrition may lead to
either salt and water overload or hypercalcemia,
both of which can result in hypertension.
• Also included in the iatrogenic category is the
undertreatment of pain. Adequate analgesia may be
the only antihypertensive needed in these cases.
13. • Among the maternal causes of neonatal hypertension are
cocaine use, which can harm the developing kidneys and lead to
hypertension in the neonatal period.
• Hypertension also has been reported with neonatal withdrawal
from maternal heroin use.
• Neoplasms are rare in the neonatal period, but they should be
considered in the complete differential diagnosis of
ypertension.
• Neuroblastoma, Wilms tumor, and mesoblastic nephroma have
been reported to cause neonatal hypertension, either from
compression of the renal vessels or ureters or through
production of vasoactive substances.
14. Evaluation
• Hypertension may be noted during the routine monitoring of vital signs or it
may be found during the evaluation of an ill neonate.
• Life-threatening presentations of hypertension include congestive heart failure
and cardiogenic shock.
• Less ill infants may present with feeding difficulties, unexplained tachypnea,
lethargy, apnea, irritability, mottling of the skin, or seizures due to
hypertension.
• When hypertension is present, obtaining a focused history is the first priority.
• Prenatal exposures such as heroin and cocaine should be noted.
• Concurrent predisposing conditions such as bronchopulmonary dysplasia,
central nervous system disorders, patent ductus arteriosus, and hypervolemia
(eg, after blood transfusion) should be identified.
15. • The physical examination should focus specifically on the cardiac and
abdominal evaluations.
• A careful set of four extremity BPs may rule out coarctation of the
aorta.
• When BP in the lower extremities is lower than in the upper
extremities or if the femoral pulses are not palpable, the evaluation
should proceed with a cardiac consultation and an echocardiogram.
• Dysmorphic features may indicate the diagnosis of congenital adrenal
hyperplasia or Turner syndrome (which is associated with aortic
coarctation).
• The presence of a flank mass may indicate ureteropelvic junction
obstruction, and an epigastric bruit suggests renal artery stenosis.
16. • Appropriate initial laboratory studies include urinalysis, complete
blood count, electrolytes, blood urea nitrogen, creatinine, and calcium.
• A urine culture is indicated if infection is suspected.
• A plasma renin level also should be obtained, although at present there
are few data on what constitutes a normal value in neonates.
• Usually, a significantly elevated renin level indicates the presence of
renovascular disease, although this is not always true.
• Common NICU medications, such as aminophylline, may cause a falsely
elevated renin level.
• Nephrology consultation may be needed to help interpret the results
in perplexing cases.
17. • Depending on findings of the history and physical examination,
additional tests that may be appropriate to obtain are thyroid
studies and evaluations of urine vanillylmandelic
acid/homovanillic acid, aldosterone, and cortisol.
• A chest radiograph and echocardiogram may be useful if there is
concern for congestive heart failure.
• Ultrasonography imaging of the genitourinary tract is a
relatively inexpensive, noninvasive, and rapid study that should
be performed in all hypertensive infants.
• Surgically correctible cases of hypertension, such as
ureteropelvic junction obstruction, will be readily apparent.
18. • Ultrasonography also is the modality of choice for identifying
renal venous thrombosis.
• Additional imaging studies may include abdominal/pelvic
ultrasonography, voiding cystourethrography, or aortography.
• Because this final test may be technically difficult in the neonate,
it should be obtained only in experienced centers.
• Nuclear scanning has been recommended by some, but it is
difficult to obtain accurate, interpretable results in this age
group.
19. Management
• In general, easily correctible causes of hypertension should be addressed initially.
• Pain should be treated, volume overload corrected, and inotropic infusions weaned
before considering the administration of any antihypertensive medications.
• Attempts should be made to choose a suitable agent for the specific clinical situation.
• For most acutely ill infants, continuous intravenous infusions are most appropriate.
• Severe hypertension is treated best in this manner because of the wide fluctuations in BP
frequently associated with intermittently administered agents.
• Preterm infants who have immature periventricular circulation are at increased risk for
cerebral ischemia and hemorrhage from rapidly falling BPs, so care should be taken to
correct the hypertension slowly.
• Continuous infusions allow for titration to this desired effect.
20. • Published experience indicates that nicardipine, labetalol,
and nitroprusside are effective continuously infused
medicines in this population.
• During infusions, BP should be monitored by an indwelling
arterial catheter or by frequently repeated (every 10 to 15
min) cuff measurements, so the dose can be adjusted to
prevent profound hypotension or inadequately treated
hypertension.
21. • Mild hypertension may be treated with intermittent intravenous
agents in some infants who are not yet ready for oral medicines.
Hydralazine and labetalol have been shown to be effective.
• These must be administered carefully, though, because in some
infants, even doses at the lower end of the recommended range
may cause significant hypotension.
• An especially risky agent in this regard is intravenous
enalaprilat, which should be avoided because of its
unpredictable antihypertensive efficacy and potential to cause
oligoanuria via blockade of the renin-angiotensin axis.
22. • Oral antihypertensive agents may be considered when the
hypertension is less severe or when the infant is ready to be weaned
from intravenous therapy.
• Captopril has proven to be effective, although infants should be
monitored for profound decreases in their BP when therapy with this
agent is initiated.
• When captopril alone is not effective, the addition of a diuretic often
yields the desired blood pressure reduction.
• Such an addition is particularly encouraged in infants who have chronic
lung disease.
• Beta blockers should be avoided.
• Other recommended oral agents are amlodipine, hydralazine, and
isradipine. Isradipine is especially recommended because it takes effect
quickly and can be compounded into a stable suspension that can be
dosed accurately in even the tiniest infants.
24. • Some hypertension occasionally can be corrected surgically.
• Ureteral obstruction and aortic coarctation are especially
amenable to surgical correction.
• Those who have renal artery stenosis may require medical
management until they have grown sufficiently to allow for
vascular repair.
• As noted previously, nephrectomies may be necessary in some
infants who have polycystic kidney disease.
• Surgery after chemotherapy frequently is indicated when a
Wilms tumor or neuroblastoma is the cause of hypertension.
• Some recommend the removal of multicystic dysplastic and
polycystic kidneys when they are causing hypertension.
25. Long term outcome and prognosis
• The long-term prognosis for infants who have hypertension depends on the
cause of the disorder.
• Often the hypertension resolves over time.
• Some infants may require frequent adjustments of their antihypertensive
regimen as their weight increases; others may be weaned from their medicines
as they grow out of their dose.
• Home BP monitoring is crucial and should be established for any infant
discharged from the NICU on antihypertensive medications.
• Some hypertension persists as the infant grows. Polycystic kidneys and other
forms of renal parenchymal disease may continue to cause hypertension.
Hypertension due to renal vein thrombosis may persist sufficiently
• to require nephrectomy. The reappearance of hypertension after repair of renal
artery stenosis or thoracic coarctation repair should lead to a search for
restenosis.
27. Objectives
1. Define hypertension in children, and be familiar with the approach to
the diagnosis of hypertension.
2. Recognize important signs and symptoms associated with hypertension
and its sequelae, and formulate an appropriate differential when
presented with a hypertensive child or adolescent.
3. Initiate an appropriate evaluation, and know when to refer to
subspecialty care.
4. Prescribe both non-pharmacologic and pharmacologic antihypertensive
therapy to hypertensive children, and be familiar with the various
classes of antihypertensive medications available.
28. • HTN in the pediatric age group is on the rise, now affecting
almost 5% of all children.
• One possible explanation for this striking increase in
prevalence over the past several decades is the concurrent
rise in pediatric obesity, which currently affects 17% of the
pediatric population.
29. Hypertension
• Pediatric HTN is defined as the sustained elevation of
either the systolic or diastolic BP at or above the 95th
percentile of BP for a child’s age, gender, and height
percentile.
30. • Normal BP: Both systolic and diastolic BPs are less than the
90th percentile or less than 120/80 mmHg, whichever is lower.
• Pre-Hypertension: Systolic or diastolic BP is between the 90th
percentile and the 95th percentile, or between 120/ 80 mmHg
and the 95th percentile, if 120/80 mmHg happen to be higher
than the reported 90th percentile for the individual child based
on his or her age, gender, and height percentile.
• Stage I HTN: Systolic or diastolic BP between the 95th
percentile and the 99th percentile +/- 5 mmHg.
• Stage II HTN: Systolic or diastolic BP above the 99th percentile
+/- 5 mmHg.
31. • All children age 3 years and older should have their BP
measured during each physician visit, whether the visit is
for health supervision care, urgent care, or emergency care,
at a minimum of once yearly.
• In addition, children younger than age 3 years should also
have their BP measured at each visit if they have a
comorbid condition that places them at increased risk for
HTN
32. • Particular attention should be given to children who have
conditions such as diabetes mellitus, chronic kidney
disease, a history of Kawasaki disease (with or without
current coronary artery aneurysms), kidney or heart
transplantation, chronic inflammatory diseases, human
immunodeficiency virus infection, and nephrotic
syndrome, because they are at increased cardiovascular
risk.
• In addition to regular BP measurement, these children
should have additional cardiovascular risk factor
assessment conducted at health care encounters.
33. Pre-hypertensive
• These children should be considered prehypertensive and
should be followed closely because of their increased risk
of developing sustained HTN.
• They should be counseled on weight management, if
indicated, and should be given activity and the
Cardiovascular Health Integrated Lifestyle Diet
recommendations.
34. Stage I hypertension
• If the child is asymptomatic, have him or her return
for repeat BP measurements on two additional
occasions, 1 to 2 weeks apart.
• If stage I HTN is confirmed by averaging all BP
measurements obtained, perform evaluation within
1 month.
• If the child is symptomatic, more immediate referral
to a pediatric HTN specialist for initiation of
evaluation and treatment is indicated.
35. Stage II hypertension
• If the child is asymptomatic, he or she should undergo evaluation and
treatment within 1 week.
• If symptomatic, the child should be referred immediately to the
emergency department or an inpatient facility for care.
• Pediatric HTN is largely asymptomatic; however, children may present
initially in hypertensive crisis with severely elevated BP and symptoms
ranging from nausea and vomiting to ataxia, mental status changes,
seizures, and coma, or with symptoms related to the underlying cause
of their HTN.
36. • In addition, some children may experience anxiety during evaluations,
which may cause elevate BPs that are in the hypertensive range; yet,
when monitored in their home environment, the children have BP
measurements in the normal range.
• This phenomenon of “white coat” HTN can be diagnosed with a 24-
hour ambulatory BP monitor that obtains many BP measurements
taken in a child’s home environment.
37. • Children who manifest white coat HTN also should be
considered at increased risk for the development of
sustained HTN and therefore should be followed every 6
months.
39. Initial evaluation
• All children diagnosed as having HTN should undergo an
evaluation to investigate for secondary causes of HTN.
• Although primary HTN is on the rise, and is the most
common cause of HTN among adolescents, secondary
HTN is common enough to warrant investigation,
particularly in younger children and those with stage II
HTN at presentation.
• The initial evaluation should start with a focused history
and physical examination. In addition to obtaining a
complete review of systems to help narrow the diffe
rential diagnosis (Table 3 below), particular attention
should be paid to the pastmedical history (including
birth history), current medications, family history, and
social history.
40. • current medications, family history, and social history.
• When obtaining the past medical history, it is important
to inquire about any previous diagnosis or treatment of
HTN. Any recent discontinuation of antihypertensive
• medications, such as b-blockers and a-adrenergic
• agonists,[
• can cause severe rebound HTN if discontinued abruptly.
41. It is important also to determine if the child has any of the
following comorbid conditions or syndromes associated with
HTN:
Comorbid conditions
• Diabetes mellitus
• Thyroid disease
• Cushing syndrome
• Systemic lupus erythematosus
• Other rheumatologic disorder
Syndromes
• Williams syndrome (associated with
supravalvular aortic
• stenosis, midaortic syndrome, renal artery
stenosis,
• renal anomalies)
• Turner syndrome (associated with
coarctation of the
• aorta, renal anomalies, idiopathic HTN)
• Tuberous sclerosis (associated with
coarctation of the
• aorta, renal artery stenosis, brain tumors)
• Neurofibromatosis (associated with
essential and renovascular
• HTN)
• Polycystic kidney disease, both autosomal
recessive and
• autosomal dominant variants
42. • A previous history of urinary tract infections or unexplained fevers
may suggest chronic pyelonephritis and renal cortical scars or reflux
nephropathy.
• A recent or relatively remote streptococcal infection of the pharynx or
skin, or exposure to enterohemorrhagic Escherichia coli, may indicate a
resolving or resolved postinfectious glomerulonephritis or hemolytic
uremic syndrome, respectively.
• Henoch- Schönlein purpura can be associated with persistent renal
• manifestations, including HTN, even after initial complete resolution of
symptoms. Previous hospitalizations may reveal information on
systemic illnesses, exposure to nephrotoxic medications, or evidence of
renal injury. Recent injuries should be assessed, because renal or
neurologic trauma can lead to HTN as well as associated pain.
43. • Because prematurity and low birthweight are associated
with decreased nephron endowment and HTN, and
umbilical catheter placement can lead to renal artery
stenosis and renal vein thrombosis, a detailed birth history
also should be obtained.
44. A thorough review of both prescribed and over-thecounter
medications may reveal the following possible
causes for elevated BP:
• Corticosteroids
• Decongestants/cold preparations
• Nonsteroidal anti-inflammatory medications
• Herbal medications/supplements
• Oral contraceptive pills
• Antihypertensive medications (recent discontinuation
of these medications)
• b-Adrenergic agonists/theophylline
• Erythropoietin
• Cyclosporine/tacrolimus
• Attention deficit disorder medications
45. • The family history can be helpful in determining the cause of HTN,
particularly for children who have monogenic forms of HTN (such as
Liddle syndrome, Gordon syndrome, and apparent mineralocorticoid
excess) and renal disease, and can help also with risk stratification.
• As described in the recent Expert Panel on Integrated Guidelines for
Cardiovascular Health and Risk Reduction in Children and Adolescents,
This risk is inversely related to the age at the time of event. Children
who have this family history should be considered at increased
cardiovascular risk.
46. • Social history should focus on the following: sexual activity (pregnancy,
pre-eclampsia); diet (consumption of caffeine, licorice, sodium,
nutritional supplements); smoking/drinking/illicit drug history
(nicotine, cocaine, amphetamines, anabolic steroids, hencyclidine,
methylenedioxymethamphetamine [“ecstasy”]); level of physical
activity (obesity); sleep history (snoring, daytime somnolence,
difficulty awakening, which may be suggestive of obstructive sleep
apnea); and psychosocial history(stress, anxiety).
47. • After eliciting a detailed history, the evaluation should then
progress to a detailed physical examination, paying
particularly close attention to findings suggestive of
underlying causes
51. • If the results of this
• initial evaluation are negative in an older child who
has
• stage I HTN, particularly if the average BP is close to
• the 95th percentile, the child can be given a
diagnosis
• of primary HTN. Younger children and those with
• more markedly elevated BP (stage II HTN) should
undergo
• further testing if the initial evaluation is unrevealing
• to exclude secondary causes for HTN
53. Treatment
• Once a child is diagnosed as having HTN and has
undergone an evaluation, antihypertensive therapy
should be initiated. This therapy should include
guidance on lifestyle modification and
nonpharmacologic therapy. All children should be
counseled on the following heart-healthy lifestyle:
• 1. Weight loss if overweight 2. For children age 5
years or older: participate in at least 1 hour of
moderate-to-vigorous exercise jogging, baseball)
every day of the week, and vigorous activity (eg,
running, singles tennis, soccer) on 3 days per week.
54. • Decrease sedentary activities such as television watching
• and playing video and computer games to less than
• 2 hours per day
• 4. Institute several dietary changes according to the Cardiovascular
• Health Integrated Lifestyle diet and Dietary
• Approaches to Stop HTN eating plan (1) such as:
• a. Increase intake of fresh vegetables, fruits, and lowfat
• dairy foods
• b. Reduce carbohydrate, fat, and processed sugar intake
• i. For 4- to 18-year-olds: aim for 10% to 30% of total
• calories to come from protein, 45% to 65%
• from carbohydrate, 25% to 30% from fat
• c. Limit or avoid sugar-sweetened beverages
• d. Encourage foods with high dietary fiber content
• (age þ 5 ¼ number of grams per day)
55. • Salt restriction
• a. Initially recommend “no added salt,” with the
ultimate
• goal of achieving the current recommendation
• of 1.2 g/day total for 4- to 8-year-olds and 1.5
g/
• day total for children age 9 years and older(2)
• 6. Smoking cessation, if applicable
56. • Children who have not experienced normalization of their BP
with the above interventions after 6 months should be started
on antihypertensive medications. In addition, children who
present initially with secondary HTN, symptomatic HTN, left
ventricular hypertrophy, or hypertensive retinopathy, or who
have diabetes mellitus, should be started on antihypertensive
medications at
• the time of diagnosis, while implementing the same lifestyle
interventions. The pharmacologic agent chosen
• should be targeted to the underlying diagnosis, with attention
being paid to existing comorbidities.
58. • Unless contraindicated, initial therapy with either a calcium channel
blocker or an angiotensin-converting enzyme inhibitor could be
considered, because these medications are well-tolerated, have a
minimal adverse effect profile, and can be dosed once daily. b-Blockers,
angiotensin receptor blockers, and diuretics also are acceptable first-
line agents for the treatment of HTN in children.
 The lowest dose should be started, titrating to effect until the
maximum recommended dose is achieved or until the patient
experiences adverse effects. At this point, if the BP is not controlled, an
additional agent from
59. Goal of therapy
• The goal of antihypertensive therapy is achievement of
normotension, defined as persistent systolic and diastolic BPs
below the 95th percentile.
• In children at increased ardiovascular risk (those with chronic
kidney disease, diabetes mellitus, post-heart or kidney
transplantation, history of Kawasaki disease, chronic
inflammatory disease, human immunodeficiency virus infection,
or nephrotic yndrome) or end-organ damage (left ventricular
hypertrophy or hypertensive retinopathy), the antihypertensive
goal is lower.
• These children should be treated to achievesystolic and diastolic
BPs below either the 90th percentile or 120/80 mmHg.
60. Prognosis
• Children who have HTN should be followed closely to
evaluate the effectiveness of prescribed antihypertensive
therapy, and to reinforce medication adherence and
heart-healthy behaviors.
• If available, BP measurements obtained by a school
nurse can be useful in titrating medication dosages
between clinic appointments and in monitoring therapy.
• Hypertensive children also should be screened
intermittently for the development of end-organ damage
in the form of left ventricular hypertrophy, hypertensive
retinopathy, and microalbuminuria.
61. • Children who have left ventricular hypertrophy at diagnosis should
have a repeat echocardiography completed 6 to 12 months after
starting antihypertensive medications to ensure that their left
ventricular mass has decreased with therapy.
• Children without evidence of left ventricular hypertrophy at diagnosis
also should undergo follow-up echocardiography, because left
ventricular hypertrophy can develop relatively quickly, can be seen in
children who have presumably good BP control, and cannot be
predicted by the severity of a child’s BP elevation.
• Although often clinically silent in childhood, these forms of end organ
damage are associated with significant morbidity and mortality in
adulthood.
• The presence of any one of these entities signifies increased
cardiovascular risk and the need for intensified antihypertensive
treatment to reverse these findings and prevent worsening
cardiovascular disease.
62. • Some children will require long-term antihypertensive therapy
into adulthood to maintain normotension. However, successful
implementation of lifestyle modifications has been shown to be
effective in lowering BP in both children and adults, and can
allow some children to avoid or discontinue pharmacologic
treatment.
• Children who have primary, obesity-related HTN, in particular,
may be able avoid or discontinue antihypertensive medications
with lifestyle
• modifications. Obese children have been shown to experience
significant BP reductions with salt restriction, and weight loss is
particularly effective at lowering BP.
63. • Children who have secondary HTN may
experience normalization of BP as their
underlying disease process resolves, allowing
them to discontinue medical therapy.
• However, when a chronic underlying condition
has led to a child’s HTN, complete
normalization of BP is less likely and
management may require long-term
antihypertensive therapy and monitoring.