This document provides updates on several topics in pediatrics from the past 6 months, as determined by editors and authors to be particularly notable. It includes: 1) Updated recommendations for the diagnosis and treatment of head lice from the American Academy of Pediatrics. 2) A warning from the FDA about potential health risks of over-the-counter homeopathic treatments for asthma. 3) Evidence that head circumference standards may vary between countries/ethnic groups, and local standards may be preferable to WHO standards in some cases.

1. What's new in pediatrics
Authors
Alison G Hoppin, MD
Melanie S Kim, MD
Elizabeth TePas,MD, MS
Mary M Torchia, MD
Carrie Armsby, MD, MPH
All topics are updated as new evidence becomesavailable and our peer
review process is complete.
Literaturereview currentthrough: May 2015. | This topic last
updated: Jun 01, 2015.
The following representadditions to UpToDate from the past six months
that were considered bythe editors and authors to be of particular interest.
The most recent What's New entries are at the top of each subsection.
GENERAL PEDIATRICS AND ADOLESCENT MEDICINE
Updated recommendations for pediatric head lice (May 2015)
Pediculosis capitis is a commoncondition that can lead to physical
discomfortand social stigmatization. An update to the 2010 clinical report
on head lice published by the American Academyof Pediatrics
incorporates new therapies (spinosad and topical ivermectin), clarifies
diagnosis and treatment protocols,and provides guidance for the
management of children with pediculosis capitis inthe schoolsetting [1].
Examples of major points in the update include recommendations that no
child should be excluded from schoolbecause of head lice or nits and that
pyrethroids remain reasonable first-line therapies for primary treatment of
pediculosis capitis in communities where resistance to pyrethroids is
unproven. (See "Pediculosis capitis",sectionon 'Pediculicide selection'.)
Warning aboutuse of non-prescription asthmatreatments (April 2015)
The US Food and Drug Administration (FDA) released a consumerwarning
about the potential health risks of over-the-counter (OTC) homeopathic
products for asthma [2]. The efficacyand safety of OTC products are not

2. evaluated by the FDA. In addition, there is evidence that some non-
prescriptiontherapies, such as racemic epinephrine inhaler (sold as
Asthmanefrin) and systemic ephedrine (sold as Bronkaid and Primatene
tablets), are less effective than standard therapies for asthma and have a
higher rate of side effects.Thus, OTC products are not recommendedfor
the routine care of asthma, particularly acute asthma symptoms.These
warnings are an important reminder for clinicians to ask their patients about
use of OTC products. (See "Asthma in children younger than 12 years:
Rescue treatment for acute symptoms",sectionon 'Nonstandard
therapies' and "Alternative and experimental agents for the treatment of
asthma", section on 'Risks associated with inhaled
epinephrine' and "Alternative and experimental agents for the treatment of
asthma", section on 'Homeopathic agents' and "Homeopathy",sectionon
'Specific diseases'.)
National and ethnic variability in head circumferencestandards
(March2015)
The World Health Organization (WHO) Child Growth Standards were
developedwith data from the WHO Multicenter Growth ReferenceStudy
(MGRS) to describe normal growth in children younger than five years of
age. However, it may be inappropriate to use a single head circumference
standard for children from differentcountries or ethnic groups. A systematic
review compared the mean head circumferences from the WHO MGRS
with the mean head circumferences from a variety of studies in 55
countries or ethnic groups [3]. The mean head circumferencesin some
groups were sufficientlydifferentfrom those of the MGRS that use of the
WHO growth standards would result in misclassificationof microcephaly or
macrocephaly. When available, local head circumference standards may
be preferable to the WHO growth standards. (See "Microcephaly in infants
and children: Etiology and evaluation", section on 'Head circumference
charts' and "Macrocephaly in infants and children: Etiology and evaluation",
sectionon 'Head circumferencecharts'.)

3. Light-emitting e-readers delay normalcircadian rhythmsand interfere
with sleep (February 2015)
Prolonged use of portable light-emitting devices (laptops,tablets,
smartphones)before bedtime can have a negative impact on melatonin
secretion,circadian rhythms, and sleep.One study compared the effects of
reading an electronic bookon a light-emitting device (LE-ebook)versus a
printed book (by reflected light) for four hours prior to bedtime for five
consecutive nights [4]. Subjects in the LE-ebookgroup had suppressed
melatonin concentrations in the early part of the night, a delayed
endogenous circadian melatonin phase, felt less sleepybefore bed,took
longer to fall asleep,and reported feeling sleepierthe following morning.
These observations suggestthat evening use of light-emitting devices may
contribute to phase-delays in the circadian clock and difficulty initiating
sleep. (See "Physiologyand available preparations of melatonin", section
on 'Effects of drugs or light'.)
Bronchodilatorsnot routinely recommended for bronchiolitis in
infants and children (January 2015)
In November2014,the American Academyof Pediatrics released updated
guidelines for the diagnosis, management, and prevention of bronchiolitis
[5]. The 2014 guideline recommendsagainst the administration of inhaled
albuterol or epinephrine in the treatment of bronchiolitis; the previous
guideline (2006)included a trial of bronchodilators as an option. We agree
that bronchodilators should not be used routinely in the treatment of
bronchiolitis and no longer suggesta trial of bronchodilators. Although
bronchodilators may provide modestshort-term clinical improvement,they
do not affectoverall outcome,may have adverse effects,and increase the
costof care.
While we no longer routinely suggestinhaled bronchodilators for infants
and children with bronchiolitis, a one-time trial of inhaled bronchodilators

4. may be warranted for infants and children with bronchiolitis and severe
disease (eg, nasal flaring; retractions; grunting; respiratory rate >70 breaths
per minute; dyspnea; or cyanosis) or respiratory failure. (See "Bronchiolitis
in infants and children: Treatment; outcome;and prevention", sectionon
'Inhaled bronchodilators'.)
NEONATOLOGY
Endotrachealsuctioningmay not benefitnonvigorous neonates with
meconium-stainedamniotic fluid (May 2015)
Current guidelines recommend intubation and tracheal suctioning
(endotracheal suctioning) of residual meconium for nonvigorous
(depressed) infants (ie, absent or depressed respirations,decreased
muscle tone, or heart rate less than 100 beats/minute) with meconium-
stained amniotic fluid (MSAF), although supportive data are limited. In a
recent randomized clinical trial of 122 nonvigorous term infants with MSAF
in India, there was no additional benefitto endotracheal suctioning
compared with no intubation and suctioning [6]. Specifically,there were no
differences betweenthe two groups in the incidence of meconium
aspiration syndrome (33 versus 31 percent), need for mechanical
ventilation (23 versus 25 percent), survival at nine months of age (70
versus 72 percent), and mental and motor developmental status at nine
months of age. Although these results suggestthat endotracheal
suctioning may not be needed in all infants with MSAF regardless of the
level of activity, additional confirmatory evidence with larger clinical trials is
needed before we recommend achange in practice for nonvigorous infants
with MSAF. (See "Prevention and management of meconium aspiration
syndrome",sectionon 'Neonatal care'.)
Valganciclovir for treatmentof symptomatic congenitalCMV
infections (April 2015)

5. Congenital cytomegalovirus (CMV) infectionis a leading cause of hearing
loss in children and can cause other serious long-term neurodevelopmental
disabilities. An earlier study found that in infants with congenital CMV
involving the central nervous system (CNS), six weeks of ganciclovir was
associated with improved audiologic outcomes.Subsequentstudies found
that valganciclovir (the orally available prodrug of ganciclovir) achieved
similar clinical effectiveness.A recent multicenter randomized controlled
trial compared six months with six weeks of valganciclovir therapy in infants
with symptomatic congenital CMV (including infants without neurologic
involvement) [7]. Infants who received six months of therapy had improved
hearing and language developmentat 24 months compared with those who
received six weeks of therapy. Based on these findings we now treat all
infants with symptomatic congenital CMV infection(not just those with
isolated CNS infection) with six months of antiviral therapy.
(See "Congenital cytomegalovirus infection: Management and outcome",
sectionon 'Whom to treat'.)
Ibuprofenversus indomethacinfor PDA closure in preterm infants
(March2015)
Although randomized clinical trials have shown that the
cyclooxygenase (COX)inhibitors ibuprofenand indomethacin are both
effective in the pharmacologic closing of patent ductus arteriosus (PDA) in
preterm infants, it has beenuncertain which should be the preferred
agent. A recent systematic review of trials demonstrated that ibuprofenwas
as effective as indomethacin in closing PDA in preterm infants and was
associated with fewer significant adverse effects,including lower risks of
necrotizing enterocolitis and transient renal insufficiency,and a shorter
duration of mechanical ventilation [8]. These results confirm our
recommendationthat ibuprofenis the COX inhibitor of choice when it is
decided to close a clinically significant PDA in preterm infants by
pharmacologic intervention. (See "Management of patent ductus arteriosus
in premature infants", sectionon 'Ibuprofen'.)

6. Early follow-up for newborns with shortbirth hospitalizations (March
2015)
In the United States (US) and other developedcountries, a follow-up visit
within 48 hours of discharge has been recommendedfor newborns with
birth hospitalizations that are less than 48 hours. Support foran early
follow-up visit was provided by a recent study using data from a large
healthcare system in the US that showed early follow-up visits (within 72
hours of discharge) reduced the rate of rehospitalizations compared with
later visits [9]. As a result, we recommend an early follow-up visit (in the
home or the office/clinic) for newborn infants with a birth hospitalization that
is less than 48 hours. (See"Overviewof the routine management of the
healthy newborn infant", sectionon 'Follow-up visit'.)
Mortality decreasing for extremelypreterm infants (January2015)
Although infants born extremely premature have the highest mortality rate,
mortality has decreasedwith advances in prenatal and neonatal care. This
was illustrated in a large prospective study of 22,248 extremelypremature
infants (defined as gestational age between22 and 28 6/7 weeks)
conducted by the National Institute of Child Health and Human
DevelopmentNeonatal ResearchNetwork that compared mortality across
three time periods (2000 to 2003,2004 to 2007,and 2008 to 2011)[10]. In
this analysis, mortality was lowest in the third time period (2008 to 2011)
due to decreased rates of deaths related to pulmonary causes (neonatal
respiratory distress syndrome and bronchopulmonary dysplasia),
immaturity, infection, and central nervous system injury. The study also
documented improved prenatal care among mothers of these preterm
infants, as the percentage of women who received prenatal care increased
throughout the three study periods including higher rates of prenatal
glucocorticoidadministration. (See "Incidenceand mortality of the
premature infant", sectionon 'Extremely preterm infants'.)

7. Low Apgar scores:Predictors of neonataland infant deaths
(November 2014)
Although not used to guide resuscitation, Apgar scores,firstintroduced in
1953,have beenused as a measure of the newborn's overall clinical status
and response to resuscitation during the first minutes after delivery.
The accurate predictability of low Apgar scores formortality was confirmed
by a study that reviewed discharge and mortality data for all births in
Scotland between 1992 and 2010 [11]. Linear regressionanalysis showed
Apgar scores ≤3 at five minutes, compared with normal scores (between7
and 10), were associated with 300-fold increased risk of early neonatal
death (birth to seven days of life), 30-fold increased risk of late neonatal
death (7 to 28 days of life), and 50-fold increased infant death (up to one
year of age). (See "Neonatal resuscitation in the delivery room",section on
'Apgar scores'.)
ALLERGY, IMMUNOLOGY,AND RHEUMATOLOGY
Early introduction of peanuts in high-riskinfants (March2015)
Previous guidelines recommended delayed introduction of highly allergenic
solid foods(eg, eggs,peanuts, tree nuts, dairy products other than cow's
milk, fish, and shellfish) for the purpose of preventing allergic disease in
high-risk infants. However, evidence from observational studies suggested
this practice was not effective and may lead to an increased incidence of
food allergies.The Learning Early about Peanut Allergy (LEAP)trial is the
first randomized trial to show benefitof early introduction of a major food
allergen [12]. In this study, introduction of peanut at 4 to 11 months of age
rather than avoidance until 60 months of age in children at high risk for
peanut allergy due to severe eczema and/or egg allergy decreased the risk
of developing peanut allergy. The rate of peanut allergy in the consumption
group compared with the avoidance group was 1.9 versus 13.7 percent
in children who were skin prick test-negative, and 10.6 versus 35.3 percent

8. in children who were skin prick test-positive (wheal 1 to 4 mm). Exclusion
criteria included a skin prick test wheal >4 mm or a positive baseline oral
food challenge to peanut. These findings indicate that past
recommendations to delay introduction of highly allergenic foods were
appropriately rescinded. (See "Introducing formula and solid foods to
infants at risk for allergic disease",sectionon 'Introduction of solid foods to
high-risk infants'.)
Sensitivity to nonsteroidalantiinflammatorydrugsin children with
chronic urticaria (February 2015)
In many patients with chronic spontaneous urticaria (CSU), nonsteroidal
antiinflammatory drugs (NSAIDs) exacerbate symptoms.NSAID
sensitivity has been demonstrated in 20 to 40 percentof adults with CSU
and typically presents as an increase in urticaria lesions appearing one
to four hours after ingestion. However, data in children have been
limited. In a new study of 68 children with CSU and no history of previous
reactions to NSAIDs,subjects underwent single-blind challenge with
aspirin, and 10 to 24 percent developedincreased symptoms, with the
majority experiencing isolated lip angioedema[13]. Clinicians should inform
patients with CSU (and their caretakers) about potential sensitivity to
NSAIDs.(See "Chronic urticaria: Standard management and patient
education", sectionon 'Avoidance of exacerbating factors'.)
2014 Food allergy practice parameter update (December2014)
The American Academyof Allergy, Asthma & Immunology,the American
College of Allergy, Asthma & Immunology,and the Joint Council of Allergy,
Asthma & Immunologyhave updated their practice parameter for
food allergy that covers multiple aspects of patient care [14].
Recommendations are largely consistent with those presented in
UpToDate.One area highlighted was the utility of component-resolved
diagnostic testing for peanut allergy. (See "Componenttesting for pollen-

9. related, plant-derived food allergies",sectionon 'Peanut testing
approach' and "Componenttesting for pollen-related,plant-derived food
allergies", sectionon 'Overview'.)
DERMATOLOGY
Pimecrolimus for atopic dermatitis in infants and young children (May
2015)
Topicalcalcineurin inhibitors have been approved in the United States as
second-line therapies for the treatment of mild to moderate atopic
dermatitis (AD) in adults and children ≥2 years. However, they have been
used off-labelas first-line treatment for AD in younger children and infants,
in the absence of long-term studies evaluating their efficacyand safety. A
five-year randomized, open-labeltrial evaluated the safety and long-term
efficacyof pimecrolimus 1% cream compared with low or mid-potency
topical corticosteroids in over 2400 infants with mild to moderate
AD [15]. Afterfive years, overall treatment success was achieved in
approximately 90 percent of children in both groups.Growth, immune
function, and cancer rates were similar in the two groups,as were overall
rates of adverse events. However, episodes ofbronchitis, infected eczema,
impetigo,and nasopharyngitis were slightly more frequent in the
pimecrolimus group,and the rates of cutaneous adverse events (eg, skin
irritation, atrophy, telangiectasias) were not reported.Thus, the advantage
of using pimecrolimus rather than low to mid-potencytopical corticosteroids
in this age group remains unclear. (See "Treatment of atopic dermatitis
(eczema)", sectionon 'Off-labeluse in infants'.)
Serum potassium monitoring during spironolactone therapy for acne
(March2015)
Spironolactone is an androgen receptorantagonist that is effective forthe
treatment of acne in females.Although periodic monitoring of serum
potassium levels is often performed during treatment with spironolactone,

10. there is uncertainty about the need for monitoring in young, healthy acne
patients. A large retrospective study comparing the rate of hyperkalemia
during treatment with spironolactone with baseline rates of hyperkalemia in
women with acne (ages 18 to 45) did not find increased rates of
hyperkalemia during spironolactone therapy, suggesting that periodic
monitoring of serum potassium in healthy women is not necessary[16].
These results cannot be applied to patients who may be at increased risk
for hyperkalemia due to heart failure, renal disease,concomitant medical
therapy, or other conditions. (See "Hormonal therapy for women with acne
vulgaris", section on 'Side effects'.)
Propranololfor infantile hemangiomas (March 2015)
Although propranolol is widely accepted as a first line therapy for infantile
hemangiomas, the optimal dose and duration of treatment have not been
established.In a large industry-sponsored randomized trial, 456 infants
aged five weeks to five months with a proliferating hemangioma of at least
1.5 cm received placebo or propranolol (1 or 3 mg/kg per day) for three or
six months [17]. Complete or near-complete resolution of the
target hemangiomas, as assessed bycentralized blinded evaluation of
digital photographs, was observed in60 percent of patients treated with
propranolol 3 mg/kg per day for six months and 4 percent of those treated
with placebo,and therapy was well tolerated. A limitation of this study is the
lack of a group treated with propranolol 2 mg/kg per day, the dose most
frequently used in clinical practice. (See "Management of infantile
hemangiomas",section on 'Efficacy'.)
Safety of calcineurin inhibitorsfor treatmentof atopic dermatitis in
children (February2015)
Topicalcalcineurin inhibitors can be used as an alternative to topical
corticosteroids forthe treatment of mild to moderate atopic dermatitis. In
2005,based upon case reports, animal studies, and the known risks with

11. systemic calcineurin inhibitors, the US Food and Drug Administration (FDA)
issued boxed warnings about a possiblelink betweenthe topical
calcineurin inhibitors and cancer. An analysis of data from 7500 children
enrolled between2004 and 2014 in the Pediatric Eczema Elective Registry
(PEER), an ongoing post-marketing cohort study, found a trend toward
increased risk for lymphoma and leukemia that was not statistically
significant compared with incidence in the general population based on the
SEER database [18]. The small sample size and wide confidence intervals
for these data may not exclude all risk. While awaiting data from a larger
study, it seems prudentto use topical calcineurin inhibitors only as second-
line therapy for the management of atopic dermatitis in areas at high risk
for skin atrophy when treated with topical corticosteroids.(See "Treatment
of atopic dermatitis (eczema)", sectionon 'Long-term safety concerns'.)
DEVELOPMENTAL AND BEHAVIORAL PROBLEMS
Sleep problemsin children with ADHD (March 2015)
Attention deficithyperactivity disorder(ADHD) is associated with sleep
problems,particularly initiating and maintaining sleep.A randomized trial
suggests that ADHD symptoms improve with treatment of comorbid sleep
problems [19]. Children with ADHD and a moderate to severe sleep
disorderwere assigned to usual care or two sleep consultations and a
follow-up phone call with a trained clinician; most of the children were
receiving ADHD medications (predominantly methylphenidate). At the
three- and six-month follow-up, children in the intervention group had
modestimprovements in ADHD symptoms and teacher-reported behavior.
These findings highlight the importance of treating coexisting sleep
problems in children with ADHD. (See "Attention deficithyperactivity
disorderin children and adolescents:Overview of treatment and
prognosis",sectionon 'Treatment of coexisting conditions'.)

12. Family-based interpersonal psychotherapyfor depressed children
(March2015)
Although efficacious psychotherapies have been developedforpediatric
unipolar depression,moststudies have enrolled adolescents.A new
therapy called family-based interpersonal psychotherapyhas been
developedspecificallyfor preadolescents;the therapy focusesupon current
peer relationship problems and also involves the family to address parent-
child conflicts.Evidence forthe efficacyof this treatment includes a 14-
week randomized trial that compared family-based interpersonal
psychotherapy with child-centered therapy (which resembles supportive
therapy) in 38 preadolescentchildren with a depressive syndrome [20].
Remissionoccurred in more patients who received family-based
interpersonal psychotherapy than child-centered therapy (64 versus 31
percent). In addition, anxiety and interpersonal impairment improved more
with family-based interpersonal psychotherapy. (See "Pediatric unipolar
depression:Psychotherapy",section on 'Family-based interpersonal
psychotherapy'.)
No change to recommendations for pain medicineuse in pregnancy
(January 2015)
Studies of pain medicine use by pregnant women have suggested
associations between prescriptionnonsteroidalantiinflammatory drugs
(NSAIDs)and the risk of miscarriage,the use of acetaminophen and
subsequentchildhood attention deficithyperactivity disorder(ADHD), and
the use of opioids and the developmentof fetal neural tube defects. A 2015
US Food and Drug Administration (FDA) Drug Safety Communication
has found methodologic limitations to these studies and inconclusive
results regarding NSAIDs and acetaminophen use [21]. Further
investigation is needed regarding maternal opioid use and the risk of fetal
neural tube defects. It is always advisable for pregnant women to avoid
medications that are not clearly needed.However, specific

13. recommendations regarding analgesic use need not change based on this
current analysis. (See "Initial prenatal assessmentand first trimester
prenatal care", sectionon 'Treatment of pain and fever'.)
EMERGENCY MEDICINE
Post-resuscitationtherapeutic hypothermia notbetter than targeted
normothermia in children(May 2015)
Therapeutic hypothermia to maintain core body temperature below normal
(typically 32 to 34°C)has been proposed afterresuscitation from pediatric
cardiac arrest based upon evidence for improved neurologic outcome in
neonates and selected adults. In a multicenter trial involving children who
were resuscitated from an out-of-hospital cardiac arrest, 260 patients (48
hours to 18 years of age) were randomized to either therapeutic
hypothermia with a target core body temperature of 33°C or therapeutic
normothermia to maintain a temperature of 36.8°C.One-year survival with
good neurologic function was not significantly differentin patients
undergoing therapeutic hypothermia compared with therapeutic
normothermia (20 versus 12 percent,respectively,relative likelihood 1.54,
95% CI 0.86-2.76)[22]. Of note, the number of patients randomized was
insufficientto exclude an important benefitor harm from therapeutic
hypothermia. Further study is needed to determine the role of therapeutic
hypothermia after resuscitation from pediatric cardiac arrest; current
practice is to provide targeted temperature management to prevent fever
(core bodytemperature >38°C). (See "Guidelines for pediatric advanced
life support",section on 'Early postresuscitationmanagement'.)
Diagnostic accuracy of serialultrasounds for pediatric appendicitis
(April 2015)
In pediatric patients whose initial ultrasound is equivocal for the diagnosis
of appendicitis and who have persistentfindings, repeat physical
examination and a second ultrasound has good diagnostic accuracy and

14. can markedly reduce the use of computed tomography (CT). A prospective
observational study of 294 children undergoing acute evaluation for
abdominal pain (38 percent with appendicitis)evaluated a protocol
stratifying children into three paths: serial physical examination, surgical
consultation, and repeat ultrasound if the initial ultrasound was equivocal;
discharge home if the initial ultrasound showed a normal appendix; and
surgical consultation if the initial ultrasound was positive for appendicitis
[23]. This strategy, consistentwith our approach, achieved a sensitivity of
97 percentand a specificityof 91 percent; CT was performed in four
patients. (See "Acute appendicitis in children: Diagnostic imaging", section
on 'Imaging approach'.)
Risk of intracranialinjury in young childrenwith isolated linear skull
fractures(April 2015)
Linear skull fractures account for approximately 75 percent of all skull
fractures in children, and hospitalization for this condition is frequently
performed.In a prospective,multicenter observational study of 350 children
(median age 10 months) with isolated linear skull fractures and
no additional injury identified on initial computed tomography,no
patient required neurosurgical intervention on follow-up ranging from 7 to
90 days (95% CI 0 to 1 percent), although 201 patients were hospitalized
after initial evaluation [24]. These findings suggestthat neurologically
normal children with isolated linear skull fractures have a low risk for
intracranial injury requiring neurosurgical intervention and may safely
undergo discharge home to a reliable caretaker after emergency
department evaluation. (See "Skull fractures in children", sectionon
'Isolated skull fractures'.)
Headacheafter minor head trauma in children (March2015)
Headache is a frequentcomplaint after minor blunt head trauma in children.
When presentwith other symptoms,headache modestlyincreases the risk

15. of clinically important traumatic brain injury (ciTBI)and is of particular
concern if it is persistent or worsening over time. When isolated, however,
headache is not associated with ciTBI.As an example, in a prospective
multicenter cohort of almost 28,000 verbal children with minor head trauma,
none of the 2,462 patients with an isolated headache (defined by history
and physical examination features, including a normal scalp) had ciTBI
compared with 1.6 percentof the 10,105 patients with headache and other
symptoms [25]. (See "Minor head trauma in infants and children:
Evaluation", section on 'Headache'.)
Utility of abdominalexamination findingsafter blunt pediatric trauma
(February2015)
Children with significant blunt abdominal trauma warrant a complete
physical examination as part of the secondarysurvey and consistentwith
the principles of Advanced Trauma Life Support. In a prospective,
multicenter observational study of more than 12,000 children undergoing
evaluation for blunt torso trauma, four abdominal exam findings were
associated with an increased risk of intraabdominal injury (IAI)
compared with a baseline risk of 5 percentfor patients without abdominal
pain or tenderness:peritoneal irritation (44 percent), abdominal distension
(31 percent), any abdominal tenderness (13 percent),and absent bowel
sounds (8 percent) [26]. Serial examinations are necessaryin children with
abdominal trauma because serious IAI may not be apparent during the
initial examination. (See "Overview of blunt abdominal trauma in children",
sectionon 'Abdomen'.)
Strict cognitive restassociatedwith more symptomsin children with
concussions(February 2015)
Strict cognitive rest, including avoidance of reading, video games,loud
music, and screen time (computer, tablet, television, or smart phone),
limitation of social activities, and absence from school, has been advocated

16. as a primary treatment for pediatric concussion.However, evidence for this
approach is sparse. In a trial of 99 patients aged 11 to 22 years who were
diagnosed with a concussionafter pediatric emergencydepartment
evaluation (36 percentwith loss of consciousness),all subjects reduced
physical activity and one group was assigned to strict cognitive rest forfive
days while the other was assigned to usual care (one to two days of rest
followed by gradual return to full cognitive activities) [27]. Strict cognitive
rest was associated with significantly more daily reported postconcussive
symptoms during the 10 days of follow-up, while there were no
differences inneurocognitive function or balance outcomes at three and 10
days after injury. Thus, strict cognitive rest was harmful in this trial. We
suggestan individualized approach to cognitive rest, in which patients are
instructed to avoid mental activities that worsen symptoms and are followed
closelyby a clinician with expertise in managing concussions.
(See "Concussionin children and adolescents:Management", sectionon
'Cognitive rest'.)
Caustic ingestionsmimicking anaphylaxis in young children
(February2015)
Accidentalingestion of caustic liquids by young children may be mistaken
for anaphylaxis because both may presentwith nausea, vomiting, difficulty
swallowing, and swelling of the lips, tongue, or pharynx. In a report of
two cases and review of the literature, clinical clues to the diagnosis of
caustic ingestion include the lack of a history of food allergy or other
allergic disease and failure to respond to treatment for anaphylaxis [28].
Caretakers may not have witnessed the ingestion, or may not report it for
fear of reprisal. Careful visualization of the affected areas with endoscopy
or microlaryngoscopycan distinguish caustic ingestion from anaphylaxis
by identifying ulceration and mucosaldamage to the upper airway and
esophagus.Preparations should be in place to intubate, if necessary,when
manipulating a compromised airway. (See "Differentialdiagnosis of

17. anaphylaxis in children and adults", section on 'Caustic ingestion (young
children)' and "Caustic esophagealinjury in children".)
Seat belt sign and intraabdominalinjury in children (February 2015)
The seat belt sign consists of abdominal wall bruising in a linear pattern
across the abdomenin restrained children who are injured in a motor
vehicle collision. In a prospective observationalstudy of 1864 children
injured in a motorvehicle collisionwho underwent definitive determination
of the presence of an intraabdominal injury (IAI), these injuries occurred
more frequently in children demonstrating a seat belt sign than in those
who did not (19 versus 12 percent) [29]. The seat belt sign
was independently associated with IAI after adjustment for several other
physical findings,including abdominal or costal margin pain. In addition,
among all patients with normal or near-normal mental status and no
abdominal pain, IAI was found in 6 percentof children with a seat belt sign
compared with 2 percent of patients without it. Thus, the seat belt sign is an
important indicator of IAI in children with blunt abdominal
trauma. (See "Overview of blunt abdominal trauma in children", sectionon
'Seat belt sign'.)
ENDOCRINOLOGY
Glycemic controland mortality in type 1 diabetes mellitus (January
2015)
In a report from the Diabetes Control and Complications Trial (DCCT)and
follow-up Epidemiologyof Diabetes Interventions and Complications
Study (EDIC),representing a mean follow-up period of 27 years (1429
patients), there was a modestreductionin all-cause mortality in patients
with type 1 diabetes initially assigned to intensive insulin therapy (43
deaths in the intensive therapy group versus 64 in the conventional group)
[30]. The median A1C values for the intensive therapy and conventional
therapy groups during the 6.5 year DCCT were 7.2 and 9.1 percent,

18. respectively.However, the A1C levels equalized during the subsequent
EDIC study. Thus, compared with conventional therapy, intensive insulin
therapy for 6.5 years during the DCCT reduced the risk of mortality over at
least the next 20 years, despite an absence of a difference in A1C values
during the post-DCCT period. (See "Glycemic control and vascular
complications in type 1 diabetes mellitus", section on 'Mortality'.)
Genetic defects associated with gigantism and acromegaly
(December 2014)
Microduplications in the Xp26.3 region that include the GPR101 (G protein-
coupled receptor101)gene are associated with gigantism due to an
excess of growth hormone, termed X-linked acrogigantism (X-LAG) [31]. All
patients identified with this microduplicationhad disease onsetbefore five
years of age. The G protein-coupled receptorwas overexpressed in the
patients' pituitary lesions.A recurrent mutation in GPR101is found in some
adults with acromegaly. (See "Pituitary gigantism" and "Causes and clinical
manifestations of acromegaly", sectionon 'Causes' and "Sex chromosome
abnormalities", sectionon 'Xp26.3 microduplication'.)
GASTROENTEROLOGY,HEPATOLOGY,AND NUTRITION
Azithromycinand infantile pyloric stenosis (March2015)
Treatment with erythromycin during the first few weeks of life is an
established risk factor for developing infantile hypertrophic pyloric stenosis
(IHPS). A large study further defines the magnitude of that risk, and reveals
that azithromycin also is a risk factor for IHPS. In a retrospective cohort of
more than one million infants, the risk of developing IHPS was increased
more than ten-fold for exposure to erythromycin or azithromycin during the
first two weeks of life, and more than three-fold for exposure between two
and six weeks of age [32]. Exposure after six weeks of age was not
associated with IHPS risk. (See "Infantile hypertrophic pyloric stenosis",
sectionon 'Macrolide antibiotics'.)

19. Oat cerealfor thickeninginfantbottle feeds (February 2015)
For healthy infants with problematic gastroesophagealreflux who are
bottle-fed,thickening feedswith infant cereal slightly improves symptoms.
Although rice cereal has traditionally been used for this purpose,oat cereal
is now preferred because of concerns about possiblecontamination of rice
cereal with arsenic [33-35].The US Food and Drug Administration (FDA) is
investigating to determine if there are clinically significant traces of arsenic
in rice cereal. (See "Gastroesophagealreflux in infants", sectionon
'Thickening feeds'.)
GENETICS AND PEDIATRIC METABOLISM
False positive Down syndromescreening tests(April 2015)
Noninvasive prenatal Down syndrome screening using cell free
DNA results in lower false positive and false negative
rates than conventional aneuploidy screening tests. In a recent study of
Down syndrome screening in an unselected population including almost
16,000 women, the false positive rates of cell free DNA and conventional
screening were 0.1 and 5 percent, respectively,and false negative rates
were 0 and 21 percent,respectively[36]. False positive results can be due
to factors such as maternal mosaicism,maternal tumors, maternal copy
number variants, vanishing twins, confined placental mosaicism,or a failure
of the complexbioinformatics necessaryto generate a result [37-44].
Despite the low false positive rate with cell free DNA screening,
confirmatory diagnostic testing (genetic amniocentesis or chorionic
villus sampling) is mandatory after a screenpositive
result. (See "Noninvasive prenatal testing using cell-free nucleic acids in
maternal blood",sectionon 'Trisomy21, 18, 13'.)
HEMATOLOGY AND ONCOLOGY

20. Rapid test for complement-mediated thrombotic microangiopathy
(April 2015)
Primary thrombotic microangiopathies (TMAs) are rare, potentially life-
threatening conditions that cause microangiopathic hemolytic anemia,
thrombocytopenia,and variable degreesof renal failure and other organ
damage. A critical assessmentmust be made between thrombotic
thrombocytopenic purpura(TTP) and complement-mediatedTMA, because
appropriate therapy for TTP involves urgent plasma exchange, and therapy
for complement-mediated TMA involves the therapeutic antibody
eculizumab. Both of these therapies are costly and have significant
toxicities, and generally they cannot be given concurrently. A rapid test
using complement-sensitive cells has been developed,and in a small
cohort of adult patients with known diagnoses of TTP or complement-
mediated TMA, this testing was effective in correctly identifying
the diagnosis [45]. Further study is required to establish the usefulness of
this testing in the evaluation of patients with a suspectedTMA.
(See "Diagnosis of thrombotic thrombocytopenic purpura-hemolytic uremic
syndrome in adults", sectionon 'Evaluation'.)
Underuseof hydroxyureain sickle cell disease(April 2015)
Hydroxyurea is a mainstay of therapy for individuals with sickle cell
disease.Despite the clear clinical benefits,studies suggestthat many
patients do not receive this therapy. A large United States database review
identified 2086 adults with sickle cell disease and frequent painful
episodes,and found that only one-fourth were prescribed hydroxyurea [46].
These data highlight the underuse of appropriate therapy in sickle cell
disease.Potential contributing factors include patient-
, parent/family/caregiver-, provider-, and system-level
barriers. (See "Hydroxyurea and other disease-modifying therapies in sickle
cell disease",sectionon 'Indications'.)

21. Response-based treatmentmodificationin children with Hodgkin
lymphoma (December2014)
Most children and adolescents with intermediate risk Hodgkin lymphoma
(HL) have a good prognosis following intensive combination chemotherapy
plus low-dose involved-field radiation therapy (IFRT). A randomized trial
of more than 1700 children and adolescents with newly diagnosed
intermediate risk HL evaluated whether treatment may be escalated or
deescalated based on the results of interim imaging studies [47]. The
addition of IFRT did not improve outcomes among patients with a rapid
early response that subsequentlyattained a complete remissionafter four
cycles of chemotherapy. In contrast, intensification of the chemotherapy
regimen in those without a rapid early response improved event-free
survival. These results supportthe omissionof IFRT in rapid early
responders who achieve PET-negative complete remissionafter four cycles
of ABVE-PC.They also support the escalation of therapy in slow early
responders with PET positive disease. (See "Overview of Hodgkin
lymphoma in children and adolescents",sectionon 'Intermediate risk
disease'.)
INFECTIOUS DISEASES AND IMMUNIZATIONS
Reduced HPV vaccination rate amongwomen who have sex with
women (May 2015)
Prior researchhas suggestedthat women who have sex with women
(WSW)may be less likely to initiate human papillomavirus (HPV)
vaccination than their age-matched heterosexual peers. One possible
reason for this discrepancyis that both WSW and their healthcare
providers may erroneously believe that WSW are not at risk for HPV
infection or cervical cancer. In one study of over 12,000 United States
women from 2006 to 2010,of women who were aware of the HPV vaccine,
only 8 percent of lesbian women had initiated vaccination compared with

22. 28 percentof heterosexual women and 32 percent of bisexual women [48].
This study highlights the need for healthcare providers to discuss HPV
vaccination with all patients. The American Academyof Pediatrics and the
American College of Obstetricians and Gynecologistsrecommend
vaccination for females and males ages 11 or 12 years of age, up to age
26. (See "Medical care of women who have sex with women", sectionon
'Prevention of sexually transmitted diseases'.)
Effectiveness ofpertussis vaccinein infants (May 2015)
Infants younger than 12 months have the highest incidence of pertussis
and pertussis-related complications,including death. In a large case-control
study, having received ≥1 dose of pertussis vaccine was associated with a
72 percentreduction in the risk of death and a 31 percent reduction in the
risk of hospitalization in infants ≥6 weeks of age (the minimum age for the
first dose of pertussis vaccine) [49]. However, 64 percentof the deaths
occurred in infants younger than six weeks. These findings highlight the
importance of timely pertussis immunization for infants, as well as maternal
immunization during pregnancy and immunization of the infant’s close
contacts, as recommendedby the Global Pertussis Initiative [50].
(See "Diphtheria, tetanus, and pertussis immunization in infants and
children 0 through 6 years of age", sectionon 'Efficacyand
effectiveness' and "Immunizations during pregnancy", sectionon 'Tetanus,
diphtheria, and pertussis vaccination' and "Bordetellapertussis infection in
adolescents and adults: Treatment and prevention", section on 'Tdap
booster'.)
Aerosolized measles vaccine inferiorto subcutaneous vaccine with
respectto seropositivity rate (April 2015)
Measles vaccine is usually given by subcutaneous injection; an aerosolized
vaccine could be administered by individuals with less training and would
not require sterile needles or syringes. In a study including 2004 infants

23. aged 9.0 to 11.9 months in India randomized to receive measles vaccine
either by aerosolinhalation or subcutaneous injection, aerosolized vaccine
was found to be immunogenic but inferior to the subcutaneous vaccine with
respectto seropositivityrate [51]. Follow-up was completedfor1560
children (775 children in the aerosolized vaccine group and 785 children in
the subcutaneous vaccine group); seropositivity rates at day 91 were 85.4
and 94.6 percent, respectively.Subcutaneous administration of the
measles vaccine remains the standard of care. (See "Prevention and
treatment of measles",sectionon 'Types of vaccines'.)
Measles outbreak in United States (April 2015,MODIFIED April2015)
The United States has experienced a record number of measles cases
during 2014 to 2015.In 2014,644 cases were reported from 27 states [52].
Between January 1 and May 1, 2015,169 cases have beenreported.Most
cases have occurred among individuals who were unvaccinated. Children
living in or traveling to areas where there is a measles outbreak (defined as
≥3 cases linked in time and space) and children traveling outside the
United States should receive measles-mumps-rubellavaccine earlier than it
is routinely recommended.(See "Epidemiologyand transmission of
measles",sectionon 'United States'.)
Choice of influenza vaccineformulation in patients with egg allergy
(March2015)
Most influenza vaccines are produced in an egg-based system,which has
been a concern in patients with egg allergy. A number of observational
studies have shown that administration of injectable inactivated influenza
vaccine (IIV) containing up to 0.7 mcg ovalbumin per 0.5 mL dose is safe in
patients with egg allergy. Two new observational studies have
demonstrated safe administration of the intranasal live attenuated influenza
vaccine (LAIV)containing <0.24 mcg ovalbumin per 0.2 mL dose in
patients with egg allergy [53,54].Influenza vaccine ovalbumin content is

24. shown in the table (table 1). About 40 percentof patients in these studies
had a history of anaphylaxis to egg and around 60 to 70 percent had
asthma.
Based upon these findings and accumulating unpublished
clinical experience,we recommend that all patients with egg allergy ≥6
months of age, including those with a history of anaphylaxis, receive annual
immunization with an influenza vaccine according to the indications for all
other patients without egg allergy. We would administer any age-
appropriate, approved influenza vaccine (table 1), including the LAIV, in
these patients according to the indications and contraindications outlined in
the tables (table 2 and table 3). The vaccine is administered in a single
dose rather than in two or more doses as a graded challenge. A 30 minute
observation period is still suggested forpatients with egg allergy who
receive an egg-based influenza vaccine. This observation period is not
necessaryfor those receiving an egg-free influenza
vaccine. (See "Influenza vaccination in individuals with egg allergy", section
on 'Safety of vaccines in patients with egg allergy' and "Influenza
vaccination in individuals with egg allergy", sectionon 'Our approach'.)
Circulating influenza A H3N2 viruses and influenza vaccine
effectiveness in the United States (December 2014,MODIFIEDMarch
2015)
In December2014,the United States Centers for Disease Control and
Prevention (CDC) released a health advisory stating that more than half of
influenza A H3N2 viruses collected and analyzed in the United States in
Octoberand November2014 were antigenically different(drifted)from the
H3N2 antigen included in this season's influenza vaccines [55]. Most
isolated influenza viruses to date have been H3N2 strains. During previous
seasons in which influenza A H3N2 viruses have predominated,higher
hospitalization and mortality rates have been reported among older people,
very young children, and individuals with certain medicalconditions. In

25. seasons where predominant circulating influenza viruses have antigenically
drifted,decreased vaccine effectivenesshas beenobserved.Nevertheless,
vaccination typically provides some cross-protectionagainst drifted viruses
and should still reduce hospitalization and death. As of late February 2015,
overall vaccine effectiveness was only 19 percentand vaccine
effectivenessagainst influenza A H3N2 was only 18 percent[56]. Influenza
vaccination is still highly recommended [55]. The CDC health advisory was
issued to reemphasize the importance of the use of neuraminidase
inhibitors (eg, oseltamivir, zanamivir) when indicated for the treatment and
prevention of influenza infection as an adjunct to vaccination.
(See "Seasonalinfluenza vaccination in adults", section on 'Drifted H3N2
viruses during the 2014 to 2015 influenza season' and "Seasonal influenza
in children: Prevention with vaccines", sectionon 'Drifted H3N2 viruses
during the 2014 to 2015 influenza season'.)
Isoniazid and rifapentinefor treatmentof latent tuberculosis infection
in children (February 2015)
Isoniazid (INH) is the regimenof choice for the treatment of latent
tuberculosis infection in children, but full adherence throughout the nine-
month course can be challenging. A study among 1058 children ages 2 to
17 years demonstrated that directly observed treatment with three months
of INH and rifapentine (RPT) was as effective as nine months of
unsupervised INH alone forprevention of tuberculosis [57]. Treatment
related adverse events were uncommonand similar with the two regimens.
Directly observed treatment with INH-RPT is a reasonable regimenfor
children aged 2 to 17 years when the circumstances make completionof
nine months of daily INH difficult.(See "Latent tuberculosis infectionin
children", section on 'Isoniazid and rifapentine'.)
New human papillomavirus (HPV) vaccine targets nine HPV types
(February2015)

26. Infectionwith human papillomavirus (HPV) types 16, 18, 31, 33, 45, 52,
and 58 is implicated in approximately 90 percent of invasive cervical
cancers. The US Food and Drug Administration has approved Gardasil 9, a
9-valent HPV vaccine that targets those seven HPV types in addition to the
two types associated with genital warts (6 and 11), for the prevention of
HPV-related disease [58]. In a trial that included approximately 14,000
females randomly assigned to receive the 9-valent or quadrivalent HPV
vaccine, immune responses with the two vaccines were comparable for the
HPV types targeted by both (6, 11, 16, and 18). Additionally, the 9-valent
HPV vaccine was 97 percent effective for preventing precancerous and
cancerous lesions of the cervix, vagina, and vulva associated with the other
targeted HPV types (31, 33, 45, 52, and 58). Safety profiles were overall
similar. We favor the 9-valent HPV vaccine for its broader HPV type
coverage.
Routine immunization should be offeredto boys and girls aged 11 to 12,
but can be administered as early as nine years of age. Catch-up
vaccination should be offeredformales between the ages of 13 to 21 and
females between13 to 26 years who have not been previously vaccinated.
Repeatvaccination with the 9-valent vaccine is likely not warranted for
individuals who have completed a series with a differentHPV vaccine.
(See "Recommendations forthe use of human papillomavirus vaccines",
sectionon 'Available vaccines'.)
No association between HPV vaccinationand multiple sclerosis
(January 2015)
Although anecdotal and sporadic case reports had fueled concerns about a
potential causal relationship betweenhuman papillomavirus (HPV)
vaccination and developmentof multiple sclerosis and other demyelinating
disorders,larger studies have refuted this. In a study of nearly four million
Swedish and Danish females aged 10 to 44 years, receipt of the

27. quadrivalent HPV vaccine was not associated with demyelinating diseases,
including multiple sclerosis,optic neuritis, transverse myelitis, and acute
disseminated encephalomyelitis [59].This study adds to the abundance
of data demonstrating the overall safety of HPV
vaccination. (See "Recommendations forthe use of human papillomavirus
vaccines", sectionon 'Postlicensure data'.)
Rapid nucleic acid amplification test for seasonalinfluenza(January
2015)
A rapid nucleic acid amplification test for influenza, the Alere i influenza A &
B test, is available in several countries in Europe.In January 2015,the US
Food and Drug Administration allowed use of the test in non-traditional
laboratory sites, including physicians' offices,emergencyrooms,health
department clinics, and other healthcare facilities [60]. This test uses a
nasal swab sample and provides results (reports influenza A or B, but not
subtypes)in as few as 15 minutes. It is performedon a small proprietary
machine. Nucleic acid amplification tests are generally more sensitive than
antigen and immunofluorescencetechniques,which most other rapid
influenza tests utilize. (See "Diagnosis of seasonal influenza in adults",
sectionon 'Nucleic acid tests' and "Seasonal influenza in children: Clinical
features and diagnosis",sectionon 'Approachto testing'.)
Multistate outbreakof listeriosis associatedwith caramelapples
(December 2014)
A multistate outbreak of listeriosis associated with commerciallyproduced
prepackaged caramel apples was reported in the United States in
December2014 [61]. Updated case counts, a list of states in which cases
have beenreported, and guidance from the United States Centers for
Disease Control and Prevention (CDC) can be found on the CDC’s
website. (See "Epidemiologyand pathogenesis of Listeria monocytogenes
infection", sectionon 'Food epidemiologyand outbreaks'.)

28. NEPHROLOGY AND UROLOGY
Hypotonic versus isotonic parenteralmaintenance fluids in
hospitalizedchildren (April 2015)
Previous systematic reviews have demonstrated that the use of parenteral
hypotonic solution for maintenance fluid therapy in hospitalized
children increased the risk of hyponatremia compared with isotonic
solution. The largest clinical trial to date of 690 hospitalized children, which
was subsequently published, reconfirmed that the administration of
hypotonic (sodium concentration of 77 mEq/L)versus isotonic maintenance
fluid (sodium concentration of 140 mEq/L) increased the risk of developing
hyponatremia [62]. As a result, in hospitalized children requiring parenteral
fluid therapy, we recommend that isotonic solution be used as maintenance
therapy. (See "Maintenance fluid therapy in children", sectionon
'Hospitalized children'.)
Duration of initial steroid therapy in childrenwith idiopathic nephrotic
syndrome(January2015)
Children with idiopathic nephrotic syndrome (NS) are usually responsive to
an initial empirical course of corticosteroid therapy. However, the optimal
duration of initial therapy to reduce the risk and frequency of subsequent
relapses remains uncertain. Previous systematic reviews showed that initial
prednisone therapy of at least three to seven months, compared to shorter
courses,reduced the risk of relapses.But, two recent randomized
trials report prolonged initial prednisolone therapy (six months)
did not reduce the frequencyof later relapses compared to shorter course
(two to three months) [63,64].Of note, there are no trials that directly
compare prednisone and prednisolone as first-line treatment for NS, and it
is unknown whether the dosing used for these studies was equivalent. Our
current approach, when corticosteroid therapyis initiated to treat
children with NS, is to administer therapy for at least two to three

29. months. (See "Treatment of idiopathic nephrotic syndrome in children",
sectionon 'Length of therapy and risk of relapse'.)
Genetic testing for sporadic steroid-resistantnephrotic syndrome
(January 2015)
Genetic testing may be useful in children with sporadic steroid-resistant
nephrotic syndrome (SRNS) who do not have a family history of SRNS or
evidence of syndromic nephrotic syndrome due to a genetic mutation (eg,
Denys-Drash syndrome and WT1 mutation). This was illustrated in two
studies that reported that a third of patients with sporadic SRNS were
identified as having a genetic condition associated with SRNS that is not
responsive to immunosuppressive therapy [65,66]. As a result, we suggest
genetic testing in patients who do not respond to steroid therapy and in
whom renal biopsyfindings are consistentwith a diagnosis of idiopathic NS
(eg, minimal change disease or focalsegmental glomerulosclerosis).
Genetic screening for this selective group of patients who have a high
likelihood of a genetic condition would avoid unnecessary exposure to
other immunosuppressive agents for those with an underlying genetic
condition. (See "Steroid-resistant idiopathic nephrotic syndrome in
children", section on 'Genetic testing'.)
NEUROLOGY
Etiologic evaluation in childrenwith infantile spasms(April 2015)
Infantile spasms (IS)is a rare form of epilepsywith a wide range of
underlying etiologies.Approximatelytwo-thirds of patients will have an
etiologic diagnosis established after clinical examination and brain
magnetic resonance imaging (MRI); metabolic and genetic testing can
establish an etiologyin an additional 10 to 15 percentof patients. This was
demonstrated by a prospective multicenter study of 251 patients with newly
diagnosed IS,in which 55 percent of patients had an obvious cause for
IS identified by an initial evaluation that included MRI [67]. In the remaining

30. patients, array comparative genomic hybridization and epilepsygene panel
testing had the highest diagnostic yield; these and other tests established a
diagnosis in 23 additional patients. These results supportour practice
of performing metabolic and genetic testing in patients with IS who do not
have a cause identified by the initial evaluation. (See "Clinical features and
diagnosis of infantile spasms",sectionon 'Other studies'.)
Acute flaccid myelitis in children (January 2015)
A polio-like illness of unknown etiology termed acute flaccid myelitis (AFM)
was first reported in the United States in 2014.A recent study provides
more details about the clinical and radiographic features of AFM in 12
children from Colorado with a median age of 11.5 years [68]. MRI revealed
longitudinally extensive spinal cord lesions of the central gray matter,
spanning a median of 17 vertebral segments, with predominant anterior
horn cell involvement and brainstem lesions. Nasopharyngeal specimens
were positive for enterovirus D68 in 5 of 11 children; however, polymerase
chain reaction (PCR) testing for enterovirus of cerebrospinalfluid, blood,
and rectal swabs were negative. All children who presented with limb
weakness had incomplete recoverywith persistentmotor deficits.
(See "Polio and infectious diseases of the anterior horn", sectionon 'Acute
flaccid myelitis'.)
Vigabatrin-inducedvisualfield defects in children (January2015)
Children treated with the anticonvulsant vigabatrin for infantile spasms (IS)
can develop irreversible visual field constriction, but the frequencyof this
complicationhas been difficultto estimate due to poor reliability of visual
field testing in young children. In the largest study to date that included 32
school-aged children with IS treated with vigabatrin in infancy, the
prevalence of visual field defects was 34 percent, similar to that in adults
treated with vigabatrin [69]. The frequencyand severity of defects
increased with treatment duration and cumulative dose.These data

31. reinforce the importance of ophthalmologic monitoring in patients with IS
treated with vigabatrin, for whom few effective alternative therapies exist.
(See "Management and prognosis of infantile spasms",sectionon 'Side
effects and monitoring'.)
PULMONOLOGY
Ivacaftor for children two years and older with cystic fibrosis (March
2015)
Ivacaftor is a drug that restores the functioning of the mutant protein in
patients with G551D or nine similar cystic fibrosis transmembrane regulator
(CFTR)mutations. It has beenrecommended forchildren six years and
older with one of these specific mutations.Now, ivacaftor has been
approved by the US Food and Drug Administration for use in children two
years and older [70]. The approval was based upon a small open-label trial
in children two to less than six years, which demonstrated that the safety of
ivacaftor was similar to that in older age groups. (See "Cystic fibrosis:
Overview of the treatment of lung disease",sectionon 'CFTR modulators'.)
Morphineis not more effective than ibuprofen for post-tonsillectomy
pain in children (March 2015)
There is growing evidence that opioid medicationshould not be used as
first-line analgesic therapy for post-tonsillectomypain, particularly in
children with underlying obstructive sleep apnea (OSA). A randomized
trial found ibuprofenand acetaminophen to be as effective as morphine
and acetaminophen for postoperative pain management in children
undergoing tonsillectomyfor OSA [71]. In addition, children treated with
morphine had increased episodes ofpostoperative desaturation compared
with baseline, whereas those who received ibuprofenhad improvementin
oxygen saturation postoperatively. Caution should be used in prescribing
opioids post-tonsillectomyin patients with underlying OSA.

32. (See "Tonsillectomy(with or without adenoidectomy)in children:
Postoperative care and complications",sectionon 'Pain'.)
Ivacaftor for patients with cystic fibrosis and an R117H mutation
(January 2015)
A phase 3 randomized double-blind clinical study shows clinical efficacyof
ivacaftor in subjects age six and older with cystic fibrosis (CF) and an
R117Hmutation [72]. On the basis of this trial, the R117H mutation was
approved as an indication for ivacaftor for patients with cystic fibrosis in the
United States [70] and an approval application is pending with the
European Medicines Agency [72]. Because the R117H mutation is
responsible forabout 3 percent of cases of cystic fibrosis, this expands by
approximately 650 the number of CF patients age six and olderwho are
eligible for ivacaftor in the United States. Ivacaftor was previously approved
for patients with cystic fibrosis and a G551D mutation, or any one of eight
other "gating" mutations (G178R,S549N,S549R,G551S,G1244E,
S1251N,S1255P,or G1349D). (See "Cystic fibrosis:Overview of the
treatment of lung disease",sectionon 'CFTR modulators'.)