Best Recent Clinical Articles

From Current Clinical Pediatrics, presented April 20-24, 2009, by Boston University School of Medicine

Howard Bauchner, MD, Professor of Pediatrics and Public Health, Vice-Chair, Academic Affairs, and Director, Division of General Pediatrics, Boston University School of Medicine, Boston Medical Center, Boston, MA

Educational Objectives

The goal of this program is to update the physician on recent pediatric findings, which range from ventilating prema­ture infants to detecting cardiac abnormalities in athletes. After hearing and assimilating this program, the clinician will be better able to:

1.   Associate sensorineural hearing loss in infants with congenital cytomegalovirus (CMV) infection.

2.   Assess risk for Lyme disease in children with peripheral facial palsy.

3.   Discuss risk factors and long-term outcomes in children with apparently life threatening events (ALTEs).

4.   Describe outcomes for treatment of bronchiolitis with hypertonic saline.

5.   Discuss the cost-effectiveness of using electrocardiography (ECG) to detect cardiac abnormalities.

Faculty Disclosure

In adherence with ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial relationship with the manufacturer or provider of any commercial product or service discussed. For this pro­gram, the faculty and planning committee reported nothing to disclose.

Acknowledgments

Dr. Howard Bauchner was recorded at Current Clinical Pediatrics, sponsored by Boston University School of Medicine, and held April 20-24, 2009, in Hilton Head, SC. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.

Study choices: randomized controlled trials (RCTs)  —  favored by some; observational studies  —  carry less weight due to bias; eg, hormone replacement therapy practice based on »25 observational cohort studies (1 RCT can change practice); meta-analyses  —  adequate to determine drug efficacy, but less useful for determining dose and frequency

Ventilating premature infants (New England Journal of Medicine [NEJM] 2008): continuous positive airway pressure (CPAP) vs endotracheal intubation in premature infants; multisite international RCT; 610 infants (25-28 wk gestation) randomized to CPAP or intubation £5 min after birth; primary outcomes  —  authors conclude no dif­ference between CPAP (34%) and intubation (39%) in broncho-pulmonary dysplasia (BPD; usually defined by need for oxygen at time of discharge) or death by 36 wk gestational age; secondary outcomes  —  death or need for oxygen at 28 days; significant difference (CPAP 53.7% vs intubation 64.7%); number needed to treat  —  9; side effects  —pneumothorax more common in CPAP group (9.1%) than in intubation (3%); speaker’s conclusion  —  need longer follow-up to assess potential superiority of CPAP; BPD rates vary by nursery (due to ventilation tech­niques)

Obesity-related cancer (Lancet 2008): meta-analysis of >221 data sets, including >280,000 cancer cases and >130 million person-year follow-up; result  —  in both sexes, eg, increased body mass index (BMI) strongly associated with increased risk for esophageal adenocarcinoma; obesity associated with elevated risk for nearly all cancers (eg, endometrial, gallbladder, esophageal, leukemia, thyroid); slightly less clear in men than in women

Hearing loss and congenital cytomegalovirus (CMV) infection (Pediatrics 2008): CMV infection testing for new­borns who did not pass hearing screening tests; congenital CMV infection associated with sensorineural hearing loss (SNHL); study  —  single institutional trial;  »80,000 newborn screens; congenital SNHL confirmed in 256 (0.33%) infants (failed initial screen and had subsequent testing); all infants with SNHL had urine cultured for CMV; result  —congenital CMV infection in 16 of 256; clinical signs suggestive of CMV infection in 4 of 16 (other 12 identified by failed hearing screen); conclusions  —  CMV in urine usually detectable only in first 2 to 3 wk; if newborn fails first and second hearing screens during this period, obtain urine culture); avoid treating asymptom­atic children with CMV in urine; regimen for treatment complicated, and efficacy uncertain; many states starting to recommend CMV testing for children who fail SNHL screening in first month

B-type natriuretic peptide (BNP) for distinguishing heart disease (HD) from other problems (Pediatrics 2008): BNP marker for HD currently used in adults; asks whether BNP test can distinguish HD (congenital and acquired) problems; respiratory or cardiac symptoms usually arise within 1 to 2 mo of age; study  —  33 patients with newly di­agnosed, serious (requiring intensive care unit management) congenital (19 children, age 2 days to 25 mo) or ac­quired (14 children, age 3 days to 17.5 yr) HD with 70 matched controls; coarctation  —  most common congenital HD; cardiomyopathy  —  in all 14 children with acquired HD; all cardiac patients  —  BNP levels 521 to >5000 pg/mL (vs 5-174 pg/mL in controls); conclusion  —  BNP test useful; third study indicating 100% accuracy

Retesting adopted children for tuberculosis (TB; Pediatrics 2008): 527 internationally adopted children (mean 23 mo of age); most from Russia, China, and Guatemala; initial test  —79% negative and 21% positive (if high risk, ³10 mm induration); all who tested positive (»100 children)  —  diagnosed with latent TB, ie, positive purified pro­tein derivative (PPD; interpreted independent of bacillus Calmette-Guérin [BCG] vaccine) and negative chest x-ray; of all children  —   »50% (203) retested; 94% (191) read within 48 to 72 hr; results of retesting (191 children)  —  38 initially negative tested positive on retest; negative chest x-rays for all; positive result associated with improved nutritional status; at initial testing, some children may test negative due to inadequate nutritional status (ie, poor nu­trition hindered response to PPD); conservative estimate »10% positivity rate; take-home message  —recommend retesting for all internationally adopted children; note  —  study not based on blood interferon levels; efficacy of BCG strains varies based on manufacturer; do not retest too quickly (initial test can serve as primer for second)

Inhaled steroids for children with obstructive sleep apnea syndrome (OSAS) (Pediatrics 2008): challenging to distinguish between primary snoring and OSAS (sleep studies usually necessary); study  —  double-blind RCT; 62 children (mean age 8 yr) with mild OSAS (based on sleep study) assigned to intranasal budesonide (INB; 32 µg/nostril at bedtime for 6 wk) or placebo (wash-out period 2 wk after crossover); 43 children completed both arms of study; 19 completed first arm only (14 in placebo, and 5 INB); reasons for not completing  —  7 did not like spray; 6 parents opted for surgical adenotonsillectomy; 5 of 6 in INB group improved (did not start second arm); result  —  INB improved 2 primary outcomes of oxygenation (eg, 54% INB normalized obstructive apnea/hypopnea index vs 6% in placebo); no changes in children initially assigned to placebo who completed study, suggesting effect lasts ³8 wk; conclusion  —  INB reasonable first-line therapy for children with suspected OSAS; may be useful in place of sleep diagnostic study for primary snoring; effects may last 1-2 mo after discontinuation

Apparent life threatening events (ALTEs)

Study 1 (Pediatrics 2008): 596 infants (mean 2.6 mo of age) with ALTEs (normal range 1-5 mo of age); 274 chil­dren underwent toxicology screens; 23 of 50 tested positive, most commonly for over-the-counter drugs (eg, ephedrine, dextromethorphan); take-home message  —consider performing toxicology screens on all infants pre­senting with ALTEs

Study 2 (Pediatrics 2008): “concerning” outcome of children with ALTEs; 471 infants (mean 2.2 mo of age) with ALTEs; followed from 2.5 yr to 8 yr; diagnoses at discharge  —  gastroesophageal reflux (40%); apnea (17%); ALTE (9%); bronchiolitis (6%); convulsion (6%); cyanosis (4%); results  —  2 patients died, 54 (10%) victims of child abuse and 23 diagnosed with epilepsy or developmental delay; take-home messages  —  closer follow-up warranted; more attention to social situation

Autoantigens and type 1 diabetes (NEJM 2008): autoantigens  —  induce immunologic tolerance; shown to prevent type 1 diabetes in mice; Scandinavian investigation motivated by doubling of incidence in last decade; 70 patients; onset of diabetes within past 18 mo; fasting C-peptide >0.1 nmol/L; 2 injections (days 1 and 30) of autoantigen (re­combinant human autoantigen glutamic acid decarboxylase [GAD]) or placebo; primary outcome  —  no difference in fasting C-peptide between baseline and 15 mo; secondary outcome  —  at 30 mo, C-peptide levels declined less in GAD group; hemoglobin A_1c similar in both groups; other outcomes  —  stimulated C-peptide level increase in GAD group; conclusion  —  larger clinical trials needed to assess potential of autoantigen to prevent type 1 diabetes

Facial palsy and Lyme disease (LD) (Pediatrics 2008): case series of 313 children (mean 11 yr of age) with periph­eral facial palsy (sparing of forehead musculature excluded) children entering emergency department over 12 yr; LD confirmed by presence of erythema migrans (pathognomonic clinical sign in endemic area) or serologic evi­dence of pathogen; result  —  of 313, 34% LD, 10% had otitis; LD associated with 4 factors  —  June to October pre­sentation (odds ratio [OR] 5.3); absence of previous herpetic lesion (OR 6.3); presence of fever (OR 3.9); history of headache (OR 3.8); children with ³3 factors  —  diagnosis of LD varied (50%-90%); children with 2 factors  —   »33% diagnosed with LD; take-home messages  —  evaluate children for LD who present with facial paralysis from June to October; necessity for LD screening depends on geographic area

Autism and precipitation levels (Archives of Pediatric and Adolescent Medicine [Arch Pediatr Adolesc Med] 2008): prevalence of autism varies widely (eg, lowest in Mississippi, New Mexico, Colorado, and Oklahoma and highest in Indiana, Maine, and Massachusetts); result  —  significant relationship found between prevalence of au­tism (2005) and mean annual county-level precipitation (1987-2001) in Washington, Oregon, and California; au­thors’ conclusion  —  in genetically vulnerable children, 35% to 40% fewer autism cases would occur with elimination of exposure to this environmental trigger; note — study did not control for physician density (ie, greater density of physicians in area of higher precipitation levels influenced diagnosis rates)

Pediatric malpractice (Pediatrics 2008): common conditions for lawsuits against pediatricians; data from trade as­sociation malpractice insurance companies over 10 yr; most common  —  meningitis in children <1 yr of age; young febrile child  —  remains of concern; appendicitis  —  split between young adolescents and infants; proportion of ap­pendicitis with perforation higher for certain ages (<3 yr and >10 yr of age); developmental dysplasia of hip  —dra­matic decline in claims; congenital anomalies  —  include spine and foot deformities, metatarsus varus and valgus, bowing and genu recurvatum; listen to newborn heartbeat, pick up baby, check orifices, and examine bones, limbs, and hips; drug allergies  —  14% of medication-related claims; involve failure to ask about allergies or read medical chart; remaining question  —  whether every young febrile child should receive acyclovir; 11 suggestions by authors  —  include documenting all findings and flagging charts of children with risk factors for specific conditions; other suggestions  —  after visits for acute illness, tell parent to contact physician if anything unexpected occurs; pay attention to family history; schedule follow-up for children with uncertain diagnoses or diagnoses that can lead to substantial morbidity; beware of hyperbilirubinemia

Treatment for bronchiolitis (2009 study): meta-analysis of 4 RCTs assessing 3% saline for bronchiolitis; 189 inpa­tients and 65 outpatients; saline volume inhalation  —  4 mL in 3 trials and 2 mL in 1 trial; bronchodilators  —  added to 3% saline in 3 trials (2 trials with epinephrine and 1 with terbutyline); in other trial, physicians discouraged from using bronchodilator (37% gave albuterol, 23% gave racemic epinephrine, as needed); in 3 trials, 3% saline with bronchodilators given every 8 hr; primary outcome  —length of stay reduced by 0.94 days (1 in 4 days); clinical correlation  —  in 2 inpatient and 1 outpatient RCTs, lower postinhalation clinical scores for bronchiolitis in patients who received 3% saline; take-home messages  —  3% saline likely safe, but tested in only »170 patients; insufficient data on side effects; speaker will encourage staff to try every 8 hr with bronchodilator; not tested  —  3% saline alone vs placebo

Screening Children for Cardiac Abnormalities

Background: controversy about need for electrocardiography (ECG) for student athletes before participation; physi­cal examinations (PE) common for athletes, but few schools in US require ECGs; ECGs required in European schools and for participation in Olympics

Findings commonly missed on PE: noncritical coarctation  —  average age at detection 15 yr; difference in outcome if detected at 5 yr of age vs 15 yr of age, but murmur of coarctation difficult to detect; atrial septal defect (ASD)  —  not much difference in outcome if detected at 15 yr of age vs 5 yr of age (when listening to heart, know important lesions); prolonged QT interval  —  data indicate risk varies by country (higher in southern Europe than in United States); when screening, know underlying risk for rare disease

Study (Arch Pediatr Adolesc Med, 2009): »25,000 Taiwanese children given medical history questionnaire, phono­cardiography, and ECG (Step 1); if positive finding, pediatric cardiologist reviewed results, performed more de­tailed PE, and referred child for full evaluation

Step 1 results: 5,000 of 25,000 positive; 762 of 5,000 children needed full evaluation; 12 of 762 diagnosed with sig­nificant new structural abnormalities (4 with ASDs, 2 dextrocardia, 2 pulmonary stenosis, and 4 with miscella­neous lesions [1 coarctation]); 148 children with “significant” ECG abnormalities (more information needed); ECG abnormalities  —14 with complete atrioventricular block (serious finding); 10 with atrial premature com­plex and 29 with right bundle branch block (more data needed to assess urgency); 15 with prolonged QT interval (serious); 60 with premature ventricular complex (more information needed); 18 with preexcitation syndrome (serious)

Step 2 results:  »1000 children who screened negative on Step 1 served as controls; 18 positive and 2 with con­firmed structural abnormalities; positive predictive value of screen, 29%; negative predictive value, 99.8%

Conclusion: pediatrician colleagues skeptical about recommending ECGs for all children; detecting structural lesions  —  12 of 5,000 in Step 1 positive group and 2 of 1100 in control group; not significantly different (ie, screening protocol did not increase rate of detection of structural abnormalities); electrophysiologic screening  —  effective even with conservative estimate of significant ECGs (allows detection of ³1 in 250 children with sub­stantial electrophysiologic abnormality); pediatricians screen routinely for considerably less common conditions

Take-home messages: analysis of cost-effectiveness of screening complicated; eg, for PKU and thyroid testing in newborns, screening clearly cost-effective (interventions well-known and test highly precise); for other conditions, much debate; ECG abnormalities  —  require consultation with pediatric cardiologist (significantly increases costs); decision about ECG screening requires attention to family history, (particularly of sudden death) and any symptoms that suggest cardiac abnormalities (particularly in athletes); investigation continues

Suggested Reading

Bonkowsky JL et al: Death, child abuse, and adverse neurological outcome of infants after an apparent life-threaten­ing event. Pediatrics 122:125, 2008; Kheirandish-Gozal L et al: Intranasal budesonide treatment for children with mild obstructive sleep apnea syndrome. Pediatrics 122:e149, 2008; Ludvigsson J et al: GAD treatment and insulin secretion in recent-onset type 1 diabetes. N Engl J Med 359:1909, 2008; Maher KO et al: B-type natriuretic peptide in the emergency diagnosis of critical heart disease in children. Pediatrics 121:e1484, 2008; McAbee GN et al: Med­ical diagnoses commonly associated with pediatric malpractice lawsuits in the United States. Pediatrics 122:e1282, 2008; Morley CJ et al: Nasal CPAP or intubation at birth for very preterm infants. N Engl J Med 358:700, 2008; Ni­grovic LE et al: Clinical predictors of Lyme disease among children with a peripheral facial palsy at an emergency department in a Ly