NEWS FROM THE CURRENT CLINICAL LITERATURE
From Current Clinical Pediatrics 2008, presented April 21-25, 2008, by Boston University School of Medicine
Howard Bauchner, MD, Professor of Pediatrics and Public Health, and Director, Division of General Pediatrics, Boston
University School of Medicine, Boston, MA
Educational Objectives
| The goal of this program is to improve patient care by providing the physician with an update on evidence-based advances
in pediatrics. After hearing and assimilating this program, the clinician will be better able to:
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 | 1. Manage neonates with elevated bilirubin levels and evidence of hemolysis.
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| 2. Choose appropriate therapy for children with musculoskeletal pain.
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| 3. Assess the efficacy of antimicrobial prophylaxis for preventing urinary tract infections.
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| 4. Describe new recommendations from the American Academy of Pediatrics for the routine care of children.
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| 5. Evaluate strategies for preventing development of atopic disease.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the
planning committee to disclose relevant financial relationships within the past 12 months that might create any personal
conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes
quality in health care and not a proprietary business or commercial interest. For this program, Dr. Bauchner and the
planning committee reported nothing to disclose.
Acknowledgments
Dr. Bauchner was recorded at Current Clinical Pediatrics 2008, presented April 21-25, 2008, at Hilton Head Island,
SC, by Boston University School of Medicine. The Audio-Digest Foundation thanks Dr. Bauchner and Boston University
School of Medicine for their cooperation in the production of this program.
| Neurodevelopmental consequences of high bilirubin (Newman, 2006): concern kernicterus; 82 term or
near-term infants with total serum bilirubin (BR) levels ≥25 mg/dL (511 µmol/L) compared to 168 controls; 2 infants
with high BR received exchange transfusions and 80 had phototherapy; at ages 2 and 5 yr, no differences found between
infants with high BR levels and controls on IQ tests, visual motor integration (VMI), visual perception, or motor
coordination; parental reports of behavior similar; gestational age and degree or duration of high BR did not affect outcomes;
findings—9 of 82 children had hemolysis (based on direct antiglobulin [Coombs] test) and substantially lower
IQ scores than 61 children with negative tests (absolute differences 18 points for verbal IQ, 12 for performance, and
17.8 for full scale); comment—if patient has high BR level, and evidence of hemolysis present, follow more closely (if
present, speaker uses light therapy 6 or 12 hr more to decrease BR level to 10 or 12 mg/dL); results reassuring; however,
more aggressive therapy may be warranted when infants with hyperbilirubinemia show evidence of hemolysis
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| Circumcision and sexually transmitted diseases (STDs)
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| Fergusson, 2007: birth cohort study; 510 boys followed to age 25 (154 circumcised; controls not circumcised); study
looked at self-reported chlamydia, genital warts, genital herpes, and gonorrhea; findings—at ages 18 to 21, and 21
to 25, uncircumcised men 3.19 times more likely than circumcised men to report history of STD (absolute differences
8.5% of uncircumcised men vs 3.4% of circumcised men reported sexually transmitted infection [STI] at ages
21-25); difference in relative risk almost 50%
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| Randomized clinical trials (RCTs) by Gray and Newell, 2007: 53% (Kenya) and 48% (Uganda) reduction in number
of HIV-negative men relative to uncircumcised men; findings may be less relevant to patients in United States
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| Study from Australia, 2008: 499 boys and young men; 201 circumcised men followed to age 32 (control group uncircumcised);
percentage who developed STIs same in each group (23.4% vs 23.5%); findings raise doubt about
whether circumcision protects against STDs
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| Other benefits of circumcision: urinary tract infection (UTI) rare in patients >3 yr of age; rate of penile cancer reduced
from 2 in 100,000 to 1 in 100,000
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| New therapy for colic (Savino, 2006): unblinded RCT; 90 breast-fed infants 21 to 90 days old, with colic ≤6 days
before enrollment; median crying time at baseline 197 min/day; Lactobacillus reuteri probiotic available in United
States (one group received 5 drops once per day 30 min after feeding); other group received simethicone (60 mg/day
as 15 drops bid after feeding); mothers asked to adopt cow’s milk-free diet; primary outcome that average crying time
reduced from baseline to <3 hr/day on day 28; findings—cure rate with probiotic 95%, compared to 7% with simethicone;
at day 21, average crying time in probiotic group 76 min/day (in simethicone group, average time 161 min/day)
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| Relief of musculoskeletal pain (Clark, 2007): in double-blind RCT, 300 children 6 to 17 yr of age with musculoskeletal
injury in previous 48 hr received acetaminophen (15 mg/kg), ibuprofen (10 mg/kg), or codeine (1 mg/kg); at
60 min after dosing, decline in visual analog scale (VAS) greatest with ibuprofen (24 mm) vs acetaminophen (11 mm)
or codeine (12 mm); ibuprofen group significantly more likely to achieve adequate pain control, defined as VAS rating
<30 mm; rate of success with ibuprofen 52% (compared to 36% and 40% for acetaminophen and codeine, respectively);
for relief of pain due to musculoskeletal injuries, ibuprofen better than acetaminophen or codeine in acute setting
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| Acquired undescended testes (UDT)
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| Previous assumption: UDT congenital and occurs in ≈1% of population
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| Pettersson, 2007: risk for testicular cancer greater if surgery for UDT performed after 13 yr of age
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| Hack, 2007: position of testes in school boys determined at 6, 9, and 13 yr of age (all had descended testes at age 1 yr);
rate of acquired UDT—in 6-yr-olds, 1.2% (25 of 2042); 9-yr-olds (2.2%; 23 of 1038); 13-yr-olds (1.1%; 4 of 353);
rate of congenital UDT 1.0% (33 of 3443); examination of testes should be part of routine surveillance, even as
child ages
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| New therapy for bronchiolitis (Kuzik, 2007): double-blind RCT in Canada and United Arab Emirates; 96 infants
<18 mo of age (mean age 4.5 mo) admitted to hospital with moderate-to-severe disease (<94% SaO2 ); intervention—4
mL of 3% hypertonic saline q2h for 3 doses, followed by q4h for 6 doses, then q6h until discharge; control group received
normal saline; findings—length of stay reduced by ≈1 day in hypertonic saline group, compared to controls
(3.5 days vs 2.6 days); no adverse effects noted; caveat—some infants received other therapies (eg, albuterol or racemic
epinephrine); results promising, but more data needed
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| Thimerosal and neuropsychologic development (Thompson, 2007): multisite study examined relationship
between early immunization and neurocognitive outcome in 1047 children 7 to 10 yr of age; infant and maternal
records reviewed; median cumulative exposure to mercury 113.5 µg (range 0-188 µg) between birth and 7 mo of age;
study found no consistent relationship between mercury levels and 42 neurocognitive measures; results similar for
mercury exposure during pregnancy and during first 28 days after birth; results reassuring of no relationship between
early exposure to mercury and autism
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| Artificial food additives and attention-deficit/hyperactivity disorder (ADHD; McCann, 2007): investigators
conducted 6-wk double-blind placebo-controlled crossover RCT; 153 children 3 yr of age and 144 children 8 or
9 yr of age received 2 different fruit drink mixes with additives (mix A and mix B) and placebo (fruit drink) for 1 wk
each; both mixes contained sodium benzoate preservative, but kinds and amounts of artificial food coloring (AFC) differed;
younger children received 300 mL/day (older children, 625 mL/day); findings—based on weekly parent and
teacher ratings and computerized test of attention in older children, mix A determined to have significant negative effect
on behavior of younger children, compared to placebo; mix B had significant negative effect on behavior of older
children; caveat—children not followed long enough to determine whether AFCs increased risk for ADHD; results
will fuel increased debate about role of AFCs in hyperactivity
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| Caffeine for apnea of prematurity (AOP; Schmidt, 2007): multisite RCT; 2000 infants with birth weights of
500 to 1250 g (gestational age 25-26 wk or 30-31 wk); patients received caffeine or saline placebo until AOP resolved
(generally, before 35 wk postmenstrual age); findings—at corrected age of 18 to 21 mo, every outcome (eg, less cerebral
palsy [CP], blindness, severe hearing loss, and cognitive delay) favored caffeine group (54% compared to ≈60%);
specific reductions included 35% reduction in CP (4.4% vs 7.3%), reduced cognitive delay (33.8% vs 38.3%), and
mental developmental index (MDI) <70 (12.9% vs 16.8%); need to treat 5 to 7 patients to benefit 1 patient; results inconsistent
with teaching that CP fixed prenatal or perinatal phenomenon; no side effects of caffeine reported
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| Natural history of egg allergy (Savage, 2007): case series from referral center; 795 children; median age at initial
visit, 14 mo; median follow-up time, 5 yr; diagnosis—clinical history of IgE mediated allergic reaction to egg or
IgE >2 kU/L (57%); 3 definitions of clinical tolerance—1) no reaction to egg concentrate; 2) IgE <2 or <6 kU/L and
no history of clinical reactivity in past 12 mo; clinical tolerance highly variable—by 6 yr of age, 12% to 38% of children
clinically tolerant (depending on definition); caveat—many children who develop tolerance probably lost to follow-up;
by 12 yr of age, 48% to 76% of children tolerant; at 8 yr of age, 32% with peak IgE 2 to 4.9 kU/L resolved vs
14% with peak IgE 20 to 49.9 kU/L; if asthma present at time of diagnosis of egg allergy, median time to tolerance
13.5 yr (vs 8.5 yr if asthma absent); comment—sample unique; follow-up highly variable; study offers some guidance
for talking with families; clearly, higher IgE levels and more disease (eg, asthma, other food allergies) at time of diagnosis
suggest longer persistence of disease
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| Changing recommendations for UTIs
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| Prophylactic antibiotics for UTIs (Conway, 2007): 611 children diagnosed with UTI (90% girls); 83 of 611 children
(14%) had recurrent infection; risk factors for recurrent infection included white ethnicity, age 3 to 5 yr at initial
UTI, and grade 4 to 5 vesicoureteral reflux (VUR); administration of prophylactic antibiotic not associated with
lower risk for UTI; patients who received prophylactic antibiotics more likely to have antibiotic-resistant organisms
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| Miron, 2007: normal prenatal renal ultrasonography (US) obviates need for post-UTI US
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| National Institute for Health and Clinical Excellence (NICE) guideline (Mori, 2007): imaging to detect VUR no
longer necessary because no evidence that detection of VUR prevents recurring UTI or VUR nephropathy; statement
controversial; US indicated in children who fail to respond to treatment or who have non–Escherichia coli infection
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| Recommendations for preventive pediatric health care (American Academy of Pediatrics, 2007): all
infants should be seen within 2 to 3 days after discharge from hospital; office visits added at ages 30 mo, and 7 and 9
yr; start measuring body mass index (BMI) at 2 yr of age; developmental screening (especially for speech and language
problems) indicated at ages 9, 18, and 30 mo; screening for autism recommended at 18 and 24 mo; urinalysis no
longer required; referral to dental “home” should be made after 12 mo of age; screen at-risk patients (based on family
history and physical examination) for dyslipidemia at 2, 4, 6, 8, and 10 yr of age, then annually through age 21 yr (biochemical
measure mandated between 18 and 21 yr of age); all sexually active patients should be screened for STIs;
summary—office visit added at 30 mo, and 7 and 9 yr of age; perform developmental screening and screening for autism
(although United States Preventive Services Task Force [USPSTF] uncertain about this)
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| Screening for celiac disease (CD)
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| Epidemiology: CD most common chronic disease (other than asthma) in children; “celiac iceberg” (90% of children
undiagnosed)
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| Study from Europe: 2676 children 6 yr of age underwent rapid screening test that detects IgA antibodies to tissue
transglutaminase antigen (if positive, confirmatory tests performed); rapid testing positive in 28 patients (1.05%; all
positive to IgA γ-glutamyltransferase [GGT]) and all 25 children who consented to biopsy had evidence of CD; 14
other children had positive IgA GGT, and 6 of 13 who consented to biopsy had evidence of CD; in total, 32 children
(1.2%; 24 girls and 8 boys) newly diagnosed with CD; height—boys with CD 6 cm shorter than controls (girls 3 cm
shorter); weight—boys weighed ≈4 kg less (girls ≈ 2 kg less); after 6 mo on gluten-free diet, serum antibody values
fell in all but 2 patients; growth improved; low hemoglobin values resolved
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| Should all children be screened for CD? non-gastrointestinal (GI) indications for screening (study)—every child with
type 1 diabetes should be screened for CD every 3 yr; thyroiditis shares common pathway with CD; short stature;
Down syndrome; family history of CD; iron deficiency anemia (IDA), particularly adolescents; associated GI
conditions—diarrhea, failure to thrive (FTT; link not seen in speaker’s practice), abdominal pain, bloating, and constipation;
other non-GI conditions—Turner syndrome, Addison’s disease, unexplained increase in liver function test
[LFT] values
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| Prevention of atopic disease (Greer, 2008): atopic disease defined as asthma, eczema, food allergy, allergic rhinitis
(affects 20% of children <5 yr of age in United States); infants at high risk if sibling or parent has atopic disease;
restriction of maternal consumption of milk, eggs, and peanuts during pregnancy does not prevent development of
atopic dermatitis; antigen avoidance in breast-feeding mother may protect against development of eczema, but not
asthma or food allergy; in high-risk infants, exclusive breast-feeding (compared to formula with cow’s milk protein)
significantly reduces development of eczema and cow’s milk allergy in first 2 yr of life; in infants not exclusively
breast-fed during first 4 to 6 mo of life, modest evidence that extensively hydrolyzed and partially hydrolyzed formulas
may delay or prevent development of eczema (but for asthma, food allergies, and rhinitis, recommendation uncertain);
no evidence that soy formulas convey benefit; solid foods should not be introduced before 4 to 6 mo of age;
delayed introduction of eggs, peanuts, tree nuts, and fish offers no benefit; Hays and Wood, 2005—incidence of atopic
disease reduced among high-risk infants 12 to 60 mo of age fed extensively hydrolyzed casein formulas or partially
hydrolyzed whey formulas instead of cow’s milk formulas
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| Breakfast and obesity (Timlin, 2008): is breakfast most important meal of day? investigators analyzed impact of
eating breakfast on self-reported BMI in 2216 adolescents; compared to daily eaters, BMI of those who never ate
breakfast or who ate it intermittently increased substantially more than those who ate breakfast regularly (difference in
BMI 2.2 vs 2.0 vs 1.6 over 5 yr)
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Suggested Reading
Clark E et al: A randomized, controlled trial of acetaminophen, ibuprofen, and codeine for acute pain relief in children
with musculoskeletal trauma. Pediatrics 119:460, 2007; Conway PH et al: Recurrent urinary tract infections in
children: risk factors and association with prophylactic antimicrobials. JAMA 298:179, 2007; Fergusson DM et al:
Circumcision status and risk of sexually transmitted infection in young adult males: an analysis of a longitudinal birth
cohort. Pediatrics 118:1971, 2006; Gray RH et al: Male circumcision for HIV prevention in men in Rakai, Uganda: a
randomized trial. Lancet 369:257, 2007; Greer et al: Effects of early nutritional interventions on the development of
atopic disease in infants and children: the role of maternal dietary restriction, breastfeeding, timing of introduction of
complementary foods, and hydrolyzed formulas. Pediatrics 121:183, 2008; Hack WW et al: Correction of cryptorchidism
and testicular cancer. N Engl J Med 357:825, 2007; Hack WW et al: Prevalence of acquired undescended
testis in 6-year, 9-year and 13-year-old Dutch schoolboys. Arch Dis Child 92:17, 2007; Hays T, Wood RA: A systematic
review of the role of hydrolyzed infant formulas in allergy prevention. Arch Pediatr Adolesc Med 159:810, 2005;
Korpnay-Szabo IR et al: Population screening for coeliac disease in primary care by district nurses using a rapid antibody
test: diagnostic accuracy and feasibility study. BMJ 335:1244, 2007; Kuzik BA et al: Nebulized hypertonic saline
in the treatment of viral bronchiolitis in infants. J Pediatr 151:266, 2007; McCann D et al: Food additives and
hyperactive behaviour in 3-year-old and 8/9-year-old children in the community: a randomized, double-blinded, placebo-controlled
trial. Lancet 370:1560, 2007; Miron D et al: Is omitting post urinary-tract-infection renal ultrasound
safe after normal antenatal ultrasonography? An observational study. Arch Dis Child 92:502, 2007; Mori R et al: Diagnosis
and management of urinary tract infection in children: summary of NICE guideline. BMJ 335:395, 2007; Newell
ML, Barnighusen T: Male circumcision to cut HIV risk in the general population. Lancet 369:617, 2007; Newman
TB et al: Outcomes among newborns with total serum bilirubin levels of 25 mg per deciliter or more. N Engl J Med
354:1889, 2006; Pettersson A et al: Age at surgery for undescended testes and risk of testicular cancer. N Engl J Med
356:1835, 2007; Savage JH et al: The natural history of egg allergy. J Allergy Clin Immunol 120:1413, 2007; Savino
F et al: Reduction of crying episodes owing to infantile colic: A randomized controlled study on the efficacy of a new
infant formula. Eur J Clin Nutr 60:1304, 2006; Schmidt B et al: Long-term effects of caffeine therapy for apnea of
prematurity. N Engl J Med 357:1893, 2007; Thompson WW et al: Early thimerosal exposure and neuropsychologic
outcomes at 7 to 10 years. N Engl J Med 357:1281, 2007; Timlin MT et al: Breakfast eating and weight change in a 5-
year prospective analysis of adolescents: Project EAT (Eating Among Teens). Pediatrics 121:e638, 2008.
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