ALLERGY AND IMMUNOLOGY

PFAPA syndrome — Two randomized trials [1,2] have confirmed observational findings [3] that support the effectiveness of tonsillectomy with or without adenoidectomy in inducing remission or decreasing symptoms in some, but not all, patients with periodic fever with aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome. Nonetheless, we suggest that tonsillectomy be reserved for patients with PFAPA who fail to respond to medical therapy because tonsillectomy has attendant significant risks. (See "Periodic fever with aphthous stomatitis, pharyngitis and adenitis (PFAPA syndrome)", section on 'Tonsillectomy'.)

CARDIOLOGY

Congenital heart disease/pulse oximetry — A statement from the American Academy of Pediatrics and the American Heart Association concluded that it remains uncertain whether neonatal pulse oximetry screening for congenital heart disease (CHD) should become standard of care [4]. Although published data have shown that most cases of CHD are detected by neonatal pulse oximetry, the overall cost effectiveness of screening is unknown. (See "Suspected heart disease in the newborn: Criteria for referral", section on 'Pulse oximetry screening'.)

Sudden death and ADHD treatment — Although a retrospective study funded by the Food and Drug Administration (FDA) reported an association between stimulant ADHD medication and sudden unexpected death (SUD) [5], the FDA concluded that this study was not able to verify a relationship between the use of stimulant therapy and SUD because of methodologic limitations [6]. (See "Cardiac evaluation of children receiving pharmacotherapy for attention deficit hyperactivity disorder", section on 'FDA ongoing safety review'.)

DERMATOLOGY

Infantile hemangiomas — Recent reports have suggested that propranolol is an effective therapy for severe infantile hemangiomas. In an observational study of 32 children with hemangiomas, all patients exhibited clinical improvement with propranolol therapy [7]. Hypotension, bradycardia, bronchospasm, and hypoglycemia may occur with treatment; children treated with this drug should be closely monitored. (See "Management of infantile hemangiomas", section on 'Propranolol'.)

DRUGS

Atomoxetine — An observational study suggests that evening administration of once-daily atomoxetine is associated with fewer adverse effects and may be better tolerated than morning administration when initiating atomoxetine therapy for attention deficit hyperactivity disorder [8]. (See "Attention deficit hyperactivity disorder in children and adolescents: Pharmacotherapy", section on 'Atomoxetine'.)

Erythromycin ophthalmic ointment — As of October 2009, there is a shortage of 0.5 percent erythromycin ophthalmic ointment in the United States. The Food and Drug Administration (FDA) recommends that this ointment be used only for neonatal prophylactic eye care [9].

If 0.5 percent erythromycin ophthalmic ointment is unavailable, the Center of Disease Control (CDC) recommends 1 percent azithromycin ophthalmic solution (dose 1 to 2 drops placed in the conjunctival sac of each eye) for neonatal prophylactic eye care [10]. If neither of these medications is available, alternatives include 0.3 percent gentamicin ophthalmic ointment (Gentak) and 0.3 percent tobramycin ophthalmic ointment (Tobrex). (See "Overview of the routine management of the newborn infant", section on 'Eye care'.)

Heparin — Unfractionated heparin (UFH) manufactured in the United States and shipped after October 8, 2009 will be less potent than previous products, with a 10 percent lower activated partial thromboplastin time (aPTT) per USP unit of heparin [11]. Because of the simultaneous availability of heparin products with different potency, clinicians should determine which heparin preparation is being used and make the appropriate changes in initial dosing. All children who receive UFH should be monitored by both aPTT and heparin levels. (See "Diagnosis and treatment of venous thromboembolism in infants and children", section on 'Unfractionated heparin'.)

Oseltamivir for infants — The United States Food and Drug Administration (FDA) has issued an Emergency Use Authorization to permit the use of oseltamivir for the treatment of influenza in infants younger than one year of age [12]. To avoid dosing errors, providers and pharmacists should counsel the caregiver(s) regarding proper administration and provide a dosing device with units of measure (mg or mL) that match the units of measure on the prescription [13-15]. (See "Antiviral drugs for the prevention and treatment of influenza in children", section on 'Treatment dosing'.)

Propylthiouracil hepatotoxicity — The antithyroid drugs methimazole and propylthiouracil (PTU) are commonly used for treatment of Graves' disease in children and adolescents. Recent reports suggest that side effects are more frequent and more severe with propylthiouracil and include a small risk of severe hepatotoxicity [16,17]. Because of these safety concerns, the Endocrine Society now recommends AGAINST the use of propylthiouracil as first-line treatment for Graves' disease in children [18]. The American Thyroid Association and the US Food and Drug Administration also recommend that PTU not be prescribed as the first-line drug in children or adults [19]. (See "Treatment and prognosis of Graves' disease in children and adolescents" and "Pharmacology and toxicity of thionamides".)

TNF inhibitors — Based upon a safety review of tumor necrosis factor (TNF) inhibitors, the FDA concluded that that there is an increased risk of lymphoma and other cancers associated with their use in children and adolescents [20]. This information has been included in a boxed warning for TNF inhibitors. Healthcare providers should review the risks and the potential benefits of these drugs, as well as the risks and benefits of alternative treatment. (See "Tumor necrosis factor-alpha inhibitors: Risk of malignancy", section on TNF inhibitor FDA warning.)

ENDOCRINOLOGY

Type 1 diabetes — The incidence of childhood type 1 disease is rising rapidly worldwide, particularly in younger children. A report using data from 17 European countries revealed an annual rate increase of 3.9 percent [21]. If these trends continue, the number of new cases of type 1 diabetes mellitus in children younger than five years of age may double by 2020. The reasons for the increasing incidence are unknown. (See "Epidemiology, presentation, and diagnosis of type 1 diabetes mellitus in children and adolescents", section on 'Epidemiology'.)

Type 2 diabetes — Until recently, glycated hemoglobin (A1C) was not recommended as a screening test for diabetes mellitus, in part because of widely divergent methodologies used for the assay. However, an international expert committee has recommended that an A1C level ≥6.5 percent (on two occasions) be used to diagnose diabetes in adults [22]. The applicability of this recommendation to children has not been assessed. (See "Diagnosis of diabetes mellitus", section on Hemoglobin A1C (A1C).)

GASTROENTEROLOGY

Celiac disease — There is emerging evidence that the timing and manner of gluten exposure may affect the risk for or clinical expression of celiac disease. Observational studies suggest that the risk for celiac disease might be reduced by continuing breastfeeding while introducing gluten into an infant's diet, and by introducing gluten gradually [23,24]. (See "Clinical manifestations and diagnosis of celiac disease in children", section on 'Infant feeding practices'.)

GENERAL PEDIATRICS

Obesity — Activity-enhancing video games seek to encourage physical activity in children. Two studies examined some of the most commonly used games and found that the activity levels of the games were comparable to moderate-intensity walking [25,26]. This level of activity is greater than that when playing sedentary video games but not of sufficiently high intensity to contribute to the recommended daily amount of exercise for children. (See "Definition; epidemiology; and etiology of obesity in children and adolescents", section on 'Video games'.)

GENETIC DISEASES

Glycogen storage disease type Ib — Patients with glycogen storage disease type Ib (GSD Ib, glucose-6-phosphatase deficiency, von Gierke disease) have chronic or intermittent neutropenia and neutrophil dysfunction, which are thought to be related to reactive oxygen species [27]. In a small observational study, vitamin E supplementation in patients with GSD Ib was associated with increased mean neutrophil count and decreased frequency and severity of infections, mouth ulcers, and perianal lesions compared with the year before supplementation [27]. These findings must be replicated in placebo-controlled trials before vitamin E therapy can be routinely suggested. (See "Glucose-6-phosphatase deficiency (glycogen storage disease I, von Gierke disease)", section on 'Neutropenia'.)

IMMUNIZATIONS

Haemophilus influenzae type b — The United States Food and Drug Administration has licensed Hiberix, a Haemophilus influenzae type b (Hib) conjugate vaccine, for use as the booster dose in children aged 15 months through 4 years who have completed their primary series of Hib conjugate vaccines [28]. (See "Prevention of Haemophilus influenzae infection", section on Conjugate vaccines".)

Given the anticipated improvement in Hib conjugate vaccine supply, the Centers for Disease Control and Prevention (CDC) recommend Hib immunization (with any available Hib-containing vaccine) at the earliest opportunity for children aged 12 months through 4 years whose Hib booster was deferred because of the Hib vaccine shortage. The CDC also recommends provider-initiated recall of such children when office supply of Hib conjugate vaccine permits [28]. (See "Prevention of Haemophilus influenzae infection", section on 'Improvement in Hib conjugate vaccine supply'.)

Meningococcal vaccine — The US Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) has published updated recommendations regarding revaccination of individuals at prolonged increased risk for meningococcal disease [29]. Individuals who were previously vaccinated with either the quadrivalent meningococcal conjugate vaccine (Menactra, MCV4) or the quadrivalent meningococcal polysaccharide vaccine (Menomune, MPSV4) who remain at increased risk for meningococcal disease should be revaccinated with MCV4 according to the following schedule:

• Individuals who were vaccinated at two to six years of age should be revaccinated three years after receiving their previous meningococcal vaccine.
• Individuals who were vaccinated at ≥7 years of age should be revaccinated five years after receiving their previous meningococcal vaccine.
• Individuals who remain at increased risk for meningococcal disease should continue to be revaccinated at five-year intervals.

The ACIP states that college freshmen living in dormitories who were previously vaccinated with MCV4 do not need to be revaccinated and that those who were vaccinated with MPSV4 ≥5 years earlier should be vaccinated with MCV4. We would suggest that it is also reasonable to revaccinate college freshmen who received MCV4 ≥5 years earlier. (See "Meningococcal vaccines", section on 'Revaccination'.)

Pandemic H1N1 influenza — Vaccines against pandemic H1N1 influenza are being produced. Preliminary results from clinical trials have shown that a single dose of pandemic H1N1 vaccine is likely to be immunogenic in a substantial percentage of healthy adults and in children ≥10 years of age [30-32].

The US Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) has recommended the following order for administration of the pandemic H1N1 influenza vaccine, starting with the highest-priority groups [33]:

• Pregnant women
• Household contacts and caregivers of children younger than six months of age (eg, parents, siblings, and daycare providers)
• Healthcare and emergency medical services personnel
• Individuals from 6 months through 24 years of age
• Individuals from 25 through 64 years of age with health conditions associated with increased risk of influenza complications

(See "Prevention of pandemic H1N1 influenza ('swine influenza')", section on 'Pandemic H1N1 influenza vaccination'.)

The recommended target groups for pandemic H1N1 influenza vaccination differ from those for seasonal influenza. (See "Seasonal influenza vaccination in children", section on 'Target groups'.)

Rabies prophylaxis — The Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) has revised the guidelines for postexposure prophylaxis with rabies vaccine [34]. A four-dose series is now recommended (on days 0, 3, 7, and 14); the previously recommended fifth dose on day 28 has been eliminated. (See "Rabies immune globulin and vaccine", section on 'Postexposure prophylaxis for previously vaccinated persons'.)

INFECTIOUS DISEASES

Acute sinusitis — A randomized controlled trial supports the use of antimicrobial therapy to hasten resolution of symptoms in children with acute bacterial sinusitis (ABS) when ABS is defined by strict clinical criteria (symptoms for >10 days without improvement; acutely worsening symptoms; or temperature of ≥102ºF (38.9ºC) and purulent nasal discharge for ≥3 consecutive days) [35]. Previous trials have had conflicting results [36,37], perhaps related to methodologic differences including less stringent entry criteria and insufficient dosing [37]. (See "Acute bacterial sinusitis in children: Microbiology and treatment", section on 'Efficacy'.)

Treatment of influenza — The United States Centers for Disease Control and Prevention (CDC) has issued interim recommendations for the use of antiviral medications during the 2009-2010 influenza season [38]. The recommendations will be updated as necessary (www.cdc.gov/flu/professionals).

Antiviral medications are prioritized for:

• Individuals hospitalized with suspected or confirmed influenza
• Individuals at high risk of influenza-related complications (including children younger than two years, pregnant women, children receiving long-term aspirin therapy, and individuals with chronic disease)
• Individuals with suspected or confirmed influenza who are severely ill (eg, evidence of lower-respiratory-tract infection or rapid clinical deterioration), regardless of age or previous health

Laboratory confirmation with culture or polymerase chain reaction tests should not delay the initiation of antiviral therapy for individuals in whom therapy is indicated [38]. Negative rapid diagnostic tests do not exclude influenza. (See "Antiviral drugs for the prevention and treatment of influenza in children", section on 'Antiviral therapy'.)

NEONATOLOGY

Breastfeeding and pacifier use — The use of a pacifier is associated with a reduced risk of sudden infant death syndrome. However, there have been concerns that pacifier use would interfere with exclusive breastfeeding. In a trial of 15-day old infants in whom breastfeeding was well-established, the rate of exclusive breastfeeding at three months of age did not differ between infants who were offered pacifiers compared to those who were not offered pacifiers (85.8 versus 86.4 percent) [39]. (See "Breastfeeding: Parental education and support", section on 'Maintaining breastfeeding'.)

Hyperbilirubinemia — The United States Preventive Services Task Force (USPSTF) concluded that published data were insufficient to recommend universal bilirubin newborn screening to prevent kernicterus [40]. In a commentary, several neonatal experts in the field although agreeing that the evidence recommending universal screening was limited, continue to recommend universal bilirubin newborn screening despite the USPSTF position [41]. Opinions differ on the acceptance of severe hyperbilirubinemia as an appropriate clinical surrogate for kernicterus. The expert neonatal group supports universal bilirubin screening, which they view as easily implementable, because they believe severe hyperbilirubinemia is an acceptable clinical surrogate for kernicterus. (See "Evaluation of unconjugated hyperbilirubinemia in term and late preterm infants", section on 'Universal screening'.)

Newborn screening — The effectiveness of newborn screening was demonstrated by an Australian cohort study that compared outcomes of neonatal screened and unscreened children at six years of age [42]. Neonatal screening compared to no screening was associated with a higher diagnostic rate of inborn errors of metabolism, and a lower incidence of death or significant intellectual and physical impairment. (See "Newborn screening", section on 'Screening outcome'.)

Single umbilical artery — A prospective English cohort study found no difference in the risk of significant clinical renal abnormalities in infants with an isolated single umbilical artery compared to match controls [43]. (See "Care of the umbilicus and management of umbilical disorders", section on 'Single umbilical artery'.)

NEPHROLOGY

Antenatal hydronephrosis — In a study of two-month-old infants with moderate unilateral hydronephrosis, 94 percent of infants had resolution of their hydronephrosis by 12 to 14 months of age [44]. Resolution was defined as two consecutive ultrasounds that demonstrated a renal pelvic diameter less than or equal to 5 mm. (See "Postnatal management of antenatal hydronephrosis", section on 'Moderate and mild unilateral hydronephrosis'.)

ONCOLOGY

CNS preventive therapy in ALL — The five-year remission rate was higher in children with ALL who were treated with prophylactic triple intrathecal therapy compared to historical controls who received cranial irradiation (91 versus 73 percent) [45]. Although these results support the use of intrathecal therapy versus cranial irradiation to prevent recurrence of ALL in the central nervous system (CNS), decisions regarding CNS preventive therapies need to be made in concert with the associated systemic therapy regimens. (See "Overview of the treatment of acute lymphoblastic leukemia in children", section on CNS preventive therapy.)

UROLOGY

Voiding dysfunction — In children, the most commonly used anticholinergic agent for overactive bladder (OAB) is oxybutynin. In a study based on data from the United States Food and Drug Administration Adverse Event Reporting System, central nervous system (CNS) side effects associated with oxybutynin appeared to occur more frequently in children than adults and included hallucination, agitation, sedation, confusion, amnesia, and nightmares. [46]. (See "Management of voiding dysfunction in children", section on 'Oxybutynin'.)