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

Disclosures: Alison G Hoppin, MD Nothing to disclose. Melanie S Kim, MD Nothing to disclose. Elizabeth TePas, MD, MS Nothing to disclose. Mary M Torchia, MD Nothing to disclose. Carrie Armsby, MD, MPH Nothing to disclose.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.

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All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Nov 2015. | This topic last updated: Dec 04, 2015.

The following represent additions to UpToDate from the past six months that were considered by the 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

Cost analysis following implementation of the Low Risk Ankle Rule in children (December 2015)

Use of the Low Risk Ankle Rule (LRAR) (figure 1) in addition to routine physical examination for children 3 to 16 years of age with acute isolated ankle injuries may help determine when plain radiographs of the ankle are not required and has been associated with reduced ankle radiography. In a cost analysis of over 2100 children undergoing evaluation for ankle injuries at multiple facilities, use of the LRAR was associated with significant overall cost reductions when compared with routine clinical practice [1]. The greatest savings were due to lower radiography costs and fewer orthopedic or emergency department follow-up visits. (See "Ankle fractures in children", section on 'Low Risk Ankle Rule'.)

Prevention of positional skull flattening (deformational plagiocephaly) (October 2015)

The frequency of positional skull flattening (deformational plagiocephaly) has increased, in part because of supine sleep positioning to prevent sudden infant death syndrome. Additional risk factors include limited head rotation and decreased activity levels. In a recent trial that randomly assigned parents to receive guidance on infant positioning to prevent sudden infant death syndrome (control group) or this guidance plus detailed advice about infant environment, handling, and positioning (intervention group), infants in the intervention group had a lower rate of positional flattening and less severe asymmetry [2]. Thus, creating a nonrestrictive infant environment that encourages spontaneous physical movement and enhances symmetrical motor development can prevent or diminish the severity of positional skull flattening. (See "Overview of craniosynostosis", section on 'Positional flattening (positional plagiocephaly)'.)

Outdoor activity for prevention of myopia in children (October 2015)

The prevalence of myopia (nearsightedness) increases throughout childhood, particularly during and after puberty. Myopia often progresses as children grow older and high levels of myopia are associated with an increased risk of sight-threatening complications later in life (eg, myopic macular degeneration and retinal detachment). In a recent study, 1913 school children in China were randomized (by school) to an additional daily 40-minute outdoor class or usual activity [3]. The cumulative incidence rate of myopia over three years was lower in the intervention group compared with the control group (30 versus 40 percent). This is the first study to demonstrate an effective preventative strategy. Increasing the amount of time children spend outdoors is a simple intervention and can be discussed with patients and their families as a strategy to reduce the risk of developing myopia and/or slow its progression. (See "Refractive errors in children", section on 'Myopia'.)

Prevention of alcohol use in children and adolescents (October 2015)

Alcohol is frequently used by children and adolescents in the United States and its use is associated with death and serious injury. In August 2015, the American Academy of Pediatrics (AAP) released a clinical report encouraging pediatric clinicians to talk about the dangers of alcohol with children as young as nine years of age, when they may begin to form positive attitudes towards alcohol [4]. The AAP also recommends screening all youth for alcohol use with a structured screening instrument, either as part of more general substance use screening or, if time is limited, with an instrument that focuses on alcohol, such as the two-question screen developed in collaboration with the National Institute on Alcohol Abuse and Alcoholism (table 1). We agree with these recommendations. (See "Screening tests in children and adolescents", section on 'Alcohol and substance use'.)

E-cigarette use and use of combustible tobacco products (August 2015)

Studies have associated e-cigarette use with an increased risk of conventional cigarette smoking among youth. A new prospective study was conducted in 2530 ninth-grade students who had never used a combustible tobacco product and compared students who had ever used e-cigarettes with never users [5]. Compared with never users, ever users of e-cigarettes were more likely to report use of any combustible tobacco product at both 6-month (31 versus 8 percent) and 12-month (25 versus 9 percent) follow-up. Additionally, after adjusting for other risk factors for smoking, baseline e-cigarette use was associated with a greater likelihood of use of any combustible tobacco product (OR 2.7), including conventional cigarettes, cigars, and hookahs. (See "E-cigarettes", section on 'Effect on smoking initiation among youth'.)

Breastfeeding and childhood leukemia risk (July 2015)

Several studies have suggested that breastfeeding is associated with a modest reduction in childhood cancers. Now, a meta-analysis of case-control studies has found that breastfeeding for six months or more is associated with a 19 percent reduction in the risk of childhood leukemia [6]. A smaller protective effect also was detected for shorter durations of breastfeeding. Possible mechanisms for the observed association include enhancement of the immune system or modification of the infant's microbiome. (See "Infant benefits of breastfeeding", section on 'Cancer'.)

Improving uptake of long-acting reversible contraceptives (July 2015)

Long-acting reversible contraceptives (LARC), which include implants and intrauterine devices, are the most effective reversible methods to prevent pregnancy. Interventions that increase LARC use lower the rate of unintended pregnancy. In a trial of 1500 women who were randomly assigned to receive either standardized counseling for LARC or routine contraceptive counseling, standardized counseling resulted in increased LARC use and a reduction in unintended pregnancies (8 versus 15 percent) [7]. Introduction of affordable LARC methods in the state of Colorado from 2009 to 2013 was associated with an approximately 40 percent reduction in teen birth and abortion rates compared with previous years [8]. These data add further support to our suggestion to use LARC for women who desire reversible contraception. (See "Overview of contraception", section on 'Effectiveness'.)

NEONATOLOGY

Rapid correction of neonatal hypoglycemia and neurodevelopmental outcomes (November 2015)

When parenteral glucose administration is used to treat neonatal hypoglycemia in asymptomatic newborns, it is typically initiated with a bolus 2 mL/kg of 10 percent dextrose in water followed by a continuous infusion of 4 to 6 mg/kg/min. However, a study of asymptomatic newborns (gestational age ≥35 weeks) at risk for hypoglycemia found rapid correction of hypoglycemia was associated with poorer neurodevelopmental outcomes at two years of age [9]. These results support starting therapy with continuous glucose infusion and bypassing the initial bolus of 2 mL/kg. (See "Management and outcome of neonatal hypoglycemia", section on 'Parenteral glucose (dextrose) infusion'.)

Endotracheal suctioning does not benefit nonvigorous neonates with meconium-stained amniotic fluid (May 2015, Modified November 2015)

New American Heart Association, American Academy of Pediatrics, and International Liaison Committee on Resuscitation guidelines no longer recommend routine endotracheal suction for nonvigorous (depressed) newborns with meconium-stained amniotic fluid in the delivery room (ie, newborns with absent or depressed respirations, decreased muscle tone, or heart rate less than 100 beats/minute) [10,11]. This change was prompted by findings from a recent randomized clinical trial of endotracheal suctioning versus no suctioning in 122 nonvigorous term newborns with meconium-stained amniotic fluid [12]. No differences were observed between groups in meconium aspiration syndrome, need for mechanical ventilation, survival at nine months of age, and mental and motor developmental status at nine months of age. Our criteria for intervention for newborns with meconium-stained amniotic fluid are the same as those used for intervention in all neonates (algorithm 1). (See "Prevention and management of meconium aspiration syndrome", section on 'Neonatal care' and "Neonatal resuscitation in the delivery room", section on 'Next steps'.)

Defining neonatal hypoglycemia (October 2015)

Defining significant neonatal hypoglycemia requiring intervention based on blood glucose level remains challenging, as illustrated by a recent large prospective study of newborns delivered at ≥35 weeks and at risk for hypoglycemia (eg, maternal diabetes, large for gestational age, fetal growth restriction, prematurity) [9]. Hypoglycemic infants who were treated to maintain blood glucose above 47 mg/dL (2.61 mmol/L) had similar neurodevelopmental outcomes at two years of age as infants who did not develop hypoglycemia within 48 hours of birth. However, these findings did not provide a definitive threshold for treating neonatal hypoglycemia. We continue to use threshold goals that provide a margin of safety for infants at risk for hypoglycemia that are consistent with guidelines developed by the American Academy of Pediatrics and the Pediatric Endocrine Society. (See "Pathogenesis, screening, and diagnosis of neonatal hypoglycemia", section on 'Challenge of defining neonatal hypoglycemia' and "Management and outcome of neonatal hypoglycemia", section on 'Target blood glucose levels'.)

Inhaled steroids and bronchopulmonary dysplasia (October 2015)

Systematic reviews have reported that postnatal administration of inhaled glucocorticoids (eg, budesonide) does not prevent bronchopulmonary dysplasia (BPD) in high-risk extremely preterm infants (gestational age less than 28 weeks). In contrast, a recent large randomized trial in these infants found that early administration of inhaled budesonide (within 24 hours after birth) decreased the incidence of BPD compared with placebo (28 versus 38 percent) [13]. However, a nonstatistical increase in mortality was also observed (16.9 versus 13.6 percent). The authors expressed concerns that the beneficial effect of early inhaled budesonide on BPD prevention was at the expense of increased mortality. We continue to not recommend routine use of inhaled glucocorticoids to prevent BPD until further data clearly demonstrate that this intervention is both efficacious and safe. (See "Postnatal use of glucocorticoids in bronchopulmonary dysplasia", section on 'Prevention of BPD'.)

Conjunctival icterus and bilirubin levels in newborn infants (September 2015)

Based on currently available data, the presence and extent of jaundice has not been a consistently reliable method to predict total serum or plasma bilirubin (TB) concentration for neonatal hyperbilirubinemia. However, a recent observational study of 240 term or late preterm neonates reported that conjunctival icterus may be a useful clinical marker. In this study, all infants with conjunctival icterus had TB levels that were either in the high intermediate or high risk category for severe hyperbilirubinemia (defined as TB >25 mg/dL [428 micromol/L]) using the hour-specific Bhutani nomogram (figure 2) [14]. In addition, most infants with conjunctival icterus had TB >15 mg/dL (257 micromol/L). These results suggest that TB or transcutaneous bilirubin levels should be measured in an infant with conjunctival icterus as these infants are at risk for developing severe hyperbilirubinemia. (See "Clinical manifestations of unconjugated hyperbilirubinemia in term and late preterm infants", section on 'Jaundice'.)

Filtered sunlight phototherapy for neonatal hyperbilirubinemia (September 2015)

A recent Nigerian trial confirmed results from a previous observational study that filtered sunlight using commercial window tinting films (which selectively allow the transmission of blue light and removal of significant amounts of harmful ultraviolet and infrared light rays) is a safe and efficacious method for treating neonatal hyperbilirubinemia [15]. In this trial of 447 term and late preterm infants with an elevated total serum bilirubin (TSB), filtered sunlight therapy for at least five hours a day was as effective as conventional daytime phototherapy in treating neonatal hyperbilirubinemia without adverse effects. Of note, afternoon TSB were measured in all infants, and conventional nighttime phototherapy was provided to all infants from both groups if their afternoon TSB reached a targeted level for phototherapy. These data suggest filtered sunlight phototherapy for neonatal hyperbilirubinemia may be a reasonable option in resource-limited tropical regions with limited availability of conventional phototherapy. (See "Treatment of unconjugated hyperbilirubinemia in term and late preterm infants", section on 'Sunlight exposure'.)

Prolonged hypoxia and increased late mortality and morbidity for extremely premature infants (August 2015)

A meta-analysis of several large clinical trials of extremely premature (EP) infants (gestational age <28 weeks) demonstrated low target pulse oximetry levels of hemoglobin saturation (SpO₂) compared with high target SpO₂levels (85 to 89 versus 91 to 95 percent) were associated with increased mortality at hospital discharge but not mortality or morbidity at 24 months corrected age (CA). However, in a subsequent post hoc analysis of one of the included trials (Canadian Oxygen Trial), prolonged hypoxemic episodes during the first two to three months after birth were associated with late mortality or neurodevelopment impairment at 18 months CA [16]. Of note, this association was stronger for infants randomly assigned to the high SpO₂ group than for those in the low SpO₂ group. Nevertheless, based on currently available data, we continue to recommend an SpO₂ target range between 90 to 95 percent for EP infants. (See "Oxygen monitoring and therapy in the newborn", section on 'Clinical trials'.)

Acetaminophen alone not effective in reducing neonatal pain (August 2015)

Acetaminophen (paracetamol) has been used in the management of mild to moderate procedural and postoperative neonatal pain. However, a recent systematic review of randomized trials found that acetaminophen alone was not more effective than placebo in preventing or reducing pain associated with heel lance or eye examination in newborns [17]. As a result, we do not recommend using acetaminophen as the sole agent in newborns to reduce pain from painful procedures. (See "Prevention and treatment of neonatal pain", section on 'Lack of efficacy'.)

Universal versus selective screening for patent ductus arteriosus in preterm infants (July 2015)

It remains uncertain whether the outcome of preterm infants is improved by universal echocardiographic screening for patent ductus arteriosus (PDA) versus echocardiographic evaluation based on the presence of clinical signs of PDA. Support for universal screening was provided by a report from EPIPAGE 2, a French national prospective population-based cohort study of extremely premature infants (born at 24 to 28 weeks of gestation), that found screening for a PDA before day three of life versus no screening was associated with lower in-hospital mortality and a lower risk of pulmonary hemorrhage [18]. However, this study may be limited due to a potential bias that the non-screening group may have included a greater proportion of more severely affected infants. As a result, our clinical practice remains selective echocardiography based on the presence of clinical signs of PDA. (See "Management of patent ductus arteriosus in premature infants", section on 'Screening'.)

Effect of active resuscitation on survival at borderline viability (June 2015)

A major issue regarding the ability to predict neonatal outcome at borderline viability is the impact of initial management. Interpretation of outcome data should always take into account whether neonatal resuscitation was offered at delivery, because neonatal outcome varies depending on the degree of assistance offered to the infant, particularly for those born at or below 23 weeks of gestation. This was illustrated in a recent National Institute of Child Health and Human Development (NICHHD) study that included data from 24 hospitals and nearly 5000 infants [19]. In a multivariable analysis, differences in practice regarding the initiation of active treatment for infants born below 24 weeks of gestation accounted for three-quarters of the between-hospital variation in neonatal survival and survival without impairment. These findings emphasize the difficulty in determining the optimal management for infants at the limit of viability. (See "Limit of viability", section on 'Impact of initial management'.)

ALLERGY, IMMUNOLOGY, AND RHEUMATOLOGY

Early use of azithromycin to prevent lower respiratory tract illness in preschool children (December 2015)

The potential utility of macrolides in the treatment of recurrent wheezing/asthma has been considered, given their anti-inflammatory properties and antimicrobial effects against Mycoplasma pneumonia and Chlamydia pneumonia, although there is a paucity of literature supporting their use in this setting. One multicenter trial examined whether the early use of azithromycin prevented lower respiratory tract illness (LRTI) in preschool children with a history of severe recurrent wheezing [20]. Treatment was initiated at the onset of respiratory illness in conjunction with signs/symptoms that usually preceded the development of a severe LRTI specific to each child. In this trial, 607 children were randomly assigned to oral azithromycin or placebo for five days in addition to albuterol. The risk of progressing to severe LRTI was significantly lower in the treatment group compared with the control, although there was no difference in urgent care utilization, emergency department visits, or hospitalizations. Although this study provides some evidence for the early use of azithromycin in specific patient populations, further study is needed. (See "Treatment of recurrent virus-induced wheezing in young children", section on 'Antibiotics'.)

Updated guidelines for the diagnosis and management of primary immunodeficiency (November 2015)

A revised “Practice parameter for the diagnosis and management of primary immunodeficiency,” developed by the three national allergy and immunology societies in the United States, has been published to aid allergy/immunology specialists and other practitioners in the recognition, diagnosis, and general management of these disorders [21]. Highlights include screening and advanced laboratory tests for the different components of immune function, characteristic clinical manifestations and laboratory findings for a number of disorders, internet resources, antibiotic prophylaxis, and indications for hematopoietic cell transplantation or gene therapy. There are now more than 200 genetically distinct disorders of immune function that are classified using the system devised by the World Health Organization (WHO) and International Union of Immunological Societies (IUIS). Consultation with an immunology specialist with experience in diagnosing and managing primary immunodeficiencies is recommended. Our approach is consistent with that outlined in this practice parameter. (See "Approach to the child with recurrent infections" and "Laboratory evaluation of the immune system" and "Medical management of immunodeficiency".)

n-3 LCPUFA supplementation in pregnancy and allergies in offspring (November 2015)

It has been hypothesized that maternal intake of long chain polyunsaturated fatty acids (n-3 LCPUFA) during pregnancy may prevent development of allergies in offspring. However, a recent systematic review of randomized trials assessing the effect of n-3 LCPUFA supplementation during pregnancy and/or breastfeeding on allergy outcomes in offspring found supplementation did not significantly reduce childhood allergic disease (food allergy, atopic dermatitis, allergic rhinitis, asthma) at 36 months of age compared with no treatment/placebo [22]. (See "Fish consumption during pregnancy", section on 'Other outcomes'.)

Auvi-Q and Allerject epinephrine autoinjectors recalled by manufacturer (October 2015)

A manufacturer's recall was issued in October 2015 of all Auvi-Q epinephrine autoinjectors in the United States, as well as all Allerject devices in Canada, including both the 0.15 and 0.3 mg strengths, due to potentially inaccurate dose delivery [23,24]. Patients should be provided with a prescription for an alternate epinephrine device and return Auvi-Q and Allerject autoinjectors to their pharmacy for replacement and instruction on how to use the new device. Patients should only use Auvi-Q or Allerject if no other device is available in a severe allergic reaction and then immediately contact 9-1-1 or emergency medical services. (See "Prescribing epinephrine for anaphylaxis self-treatment", section on 'Types of autoinjectors'.)

Antibiotic use and development of juvenile idiopathic arthritis (August 2015)

A few studies have found a link between antibiotic use and the development of juvenile idiopathic arthritis (JIA). In one of these case-control studies, previous antibiotic prescriptions were compared in 152 children newly diagnosed with JIA and 1520 controls in the United Kingdom [25]. As with a previous study, this study found that any use of antibiotics was associated with a twofold increased risk of JIA. The risk was dose dependent and was greatest for antibiotic exposures that occurred within one year of diagnosis. The potential underlying mechanism is unknown, but alteration of the intestinal microbiome with subsequent immune dysregulation is postulated. Alternative explanations include the possibility that these patients develop more frequent infections due to some intrinsic abnormalities in the immune system that also predispose them to JIA. (See "Juvenile idiopathic arthritis: Epidemiology and immunopathogenesis", section on 'Antibiotics'.)

Predictors of the need for repeat epinephrine doses in anaphylaxis (August 2015)

Epinephrine is the first-line therapy for anaphylaxis, and retrospective studies suggest that up to one-third of patients may require a second dose. However, predictive factors for requiring more than one dose are not well defined. In a prospective cohort study of over 500 patients (all ages) treated for anaphylaxis in a tertiary care emergency department, 14 percent of those requiring any epinephrine required more than one dose [26]. Patients with a history of previous anaphylaxis, and those presenting with flushing, diaphoresis, or dyspnea, were more likely to require multiple doses of epinephrine to control symptoms. Anaphylaxis is an inherently unpredictable disorder, but this study provides some insight into predictors of a more complicated treatment course and may help clinicians managing such patients. (See "Anaphylaxis: Rapid recognition and treatment", section on 'Dosing and administration'.)

Ease of use of different epinephrine autoinjectors for anaphylaxis (July 2015)

Epinephrine autoinjectors can be life saving for patients with serious allergies, but even with specific training, many people have trouble using the various devices properly. A randomized trial of mothers of food-allergic children, tested in simulated anaphylaxis scenarios, suggested that the Auvi-Q device, a rectangular cassette that has audible instructions to guide the user through the injection process, was easier to use than non-audible pen devices [27]. When prescribing an epinephrine autoinjector, ease of use, cost, the need for multiple injectors, and patient facility with self-injection should all be considered. (See "Prescribing epinephrine for anaphylaxis self-treatment", section on 'Ease of use'.)

Dedicator of cytokinesis 2 deficiency (June 2015)

Dedicator of cytokinesis 2 (DOCK2) deficiency is a newly recognized combined immunodeficiency (CID). Biallelic (homozygous or compound heterozygous) mutations in the DOCK2 gene were identified through whole-exome sequencing in a group of unrelated patients with early-onset invasive bacterial and viral infections, lymphopenia, and defective T, B, and NK cell responses [28]. DOCK2 deficiency results in impaired activation of RAC1 that leads to defects in actin polymerization, lymphocyte proliferation and migration, natural killer cell degranulation, and response to viral infections in fibroblasts and peripheral blood mononuclear cells. Other CIDs that are the result of defects in actin regulation include Wiskott-Aldrich syndrome and DOCK8 deficiency. (See "Combined immunodeficiencies", section on 'Dedicator of cytokinesis 2 deficiency'.)

Low allergic cross-reactivity between penicillins and carbapenems (May 2015)

Carbapenems (eg, imipenem, meropenem) share a common beta-lactam ring with penicillins and hence the potential for allergic cross-reactivity, and some drug information systems list penicillin allergy as a contraindication to the use of carbapenems (figure 3). In the largest study to date, 212 patients with allergy to penicillins, confirmed by skin testing, were then tested with carbapenems [29]. All subjects were negative to carbapenem skin testing and tolerated graded challenges to three different carbapenems. Based on this and other series, the rate of reactivity to carbapenems in patients with confirmed penicillin allergy is estimated at <1 percent. This supports our current recommendations on administration of carbapenems to patients reporting immediate-type penicillin allergy: Perform penicillin skin testing when available. If negative, patients may safely receive penicillins and carbapenems. If penicillin skin testing is positive or not available, carbapenems may be administered via a graded challenge. (See "Penicillin-allergic patients: Use of cephalosporins, carbapenems, and monobactams", section on 'Carbapenems'.)

CARDIOLOGY

Maternal hypertension and risk of congenital heart disease in offspring (November 2015)

Women with chronic hypertension, either treated or untreated, may be at increased risk of having offspring with congenital heart disease (CHD) compared with normotensive women. In a recent systematic review including 16 studies and five million subjects, the frequency of CHD in offspring of hypertensive pregnant women who received or did not receive treatment increased by 100 percent and 40 percent, respectively, compared with normotensive pregnant women [30]. The magnitude of effect was generally similar across subtypes of CHD and across the range of antihypertension therapies. These results should be interpreted with caution, as neither a dose-response relationship between maternal hypertension medication and CHDs nor some potentially important characteristics of the population (eg, severity of hypertension) could be ascertained. We suggest avoiding antihypertensive therapy for mild hypertension in pregnancy as there is no clear maternal or fetal benefit and it may be harmful. Severe hypertension should be treated to reduce the risk of maternal stroke. (See "Management of hypertension in pregnant and postpartum women", section on 'Antihypertensive therapy'.)

Early cardiovascular disease in youth with depressive and bipolar disorders (October 2015)

The American Heart Association recently proposed that major depression and bipolar disorder in adolescents be positioned alongside other pediatric diseases that are considered moderate risk conditions for early cardiovascular disease (CVD), which include chronic inflammatory diseases (eg, systemic lupus erythematosus), HIV infection, and nephrotic syndrome [31]. There is growing evidence that major depression and bipolar disorder are associated with accelerated atherosclerosis and early CVD. In addition, traditional risk factors for CVD (eg, obesity, diabetes mellitus, sedentary lifestyle, and smoking) are more prevalent in youth with major depression and bipolar disorder. Although psychotropic medication may contribute to the elevated risk of CVD, particularly in youths with bipolar disorder, it appears that the association between depression and CVD is independent of medication effects. Management of youth with major depression and bipolar disorder should thus include monitoring and management of other CVD risk factors, including body mass index, blood pressure, lipids, and fasting glucose. (See "Diseases associated with atherosclerosis in childhood", section on 'Depressive and bipolar disorders'.)

DERMATOLOGY

Stevens-Johnson syndrome outbreak associated with M. pneumoniae (August 2015)

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a rare, severe blistering mucocutaneous reaction, most commonly triggered by medications, characterized by extensive necrosis and detachment of the epidermis and mucosa. Mycoplasma pneumoniae and cytomegalovirus infections are the next most common trigger of SJS/TEN, particularly in children. Between September and November 2013, an outbreak of eight pediatric cases of M. pneumoniae-associated SJS/TEN was reported in Colorado, likely related to high levels of M. pneumoniae infection in the region [32]. All children had severe oropharyngeal mucositis; the conjunctiva was involved in seven children and the genital mucosa in five. (See "Stevens-Johnson syndrome and toxic epidermal necrolysis: Pathogenesis, clinical manifestations, and diagnosis", section on 'Infection'.)

DEVELOPMENTAL AND BEHAVIORAL PROBLEMS

Stimulant medications for ADHD not associated with new onset or worsening tics in meta-analysis (October 2015)

New onset and worsening of tics have been reported in children receiving stimulants for attention deficit hyperactivity disorder (ADHD), and stimulants are often avoided in these children if they have a personal or family history of tics. However, in a meta-analysis of 22 randomized trials of the efficacy of stimulants in the treatment of children with ADHD, the risk of tics was similar in both the stimulant and placebo groups (5.7 and 6.5 percent, respectively) [33]. For children with ADHD in whom stimulants were discontinued because of new or worsening tics, another course of stimulant therapy may be warranted, particularly if ADHD symptoms are not as well controlled with nonstimulant medications. (See "Pharmacology of drugs used to treat attention deficit hyperactivity disorder in children and adolescents", section on 'Tics'.)

Genetic testing in autism spectrum disorder (September 2015)

Genetic testing is often performed in children with autism spectrum disorder (ASD) to provide information about prognosis and recurrence. The suggested evaluation has evolved with advances in molecular diagnostic techniques. In a population-based study, the yield of genetic diagnosis with whole-exome sequencing was similar to that with chromosomal microarray (CMA): 8.4 and 9.3 percent, respectively; and 15.8 percent when both tests were performed [34]. Genetic diagnosis was achieved more often in children with higher levels of dysmorphology, suggesting that severity of dysmorphology is predictive of genetic abnormalities [35]. Pending additional studies, we continue to suggest genetic testing by CMA and DNA analysis for fragile X syndrome for all children with ASD, whether or not they have dysmorphic features. (See "Autism spectrum disorder: Diagnosis", section on 'Genetic testing'.)

Course of ADHD during adulthood (June 2015)

While it is well established that 40 to 60 percent of children with attention deficit hyperactivity disorder (ADHD) go on to have significant ADHD-related problems as adults, little is known about the course of the disorder during adulthood. A recent, prospective follow-up study reported on the persistence of ADHD in a clinical sample of 344 Brazilian outpatients [36]. Participants met DSM-IV criteria for ADHD during childhood and as adults at the start of the study (mean age 34 years). Approximately one-third of participants did not meet diagnostic criteria for the disorder after an average of seven years, and 12 percent of the sample met criteria for full remission. The persistence of ADHD was associated with higher numbers of inattention and hyperactivity/impulsivity symptoms, and with co-occurring oppositional defiant disorder and social phobia. Despite expectations that adult ADHD might be nonremitting, these findings suggest that some adults with the disorder experience improvement over time. (See "Attention deficit hyperactivity disorder in adults: Epidemiology, pathogenesis, clinical features, course, assessment, and diagnosis", section on 'Course'.)

EMERGENCY MEDICINE

Metronome use during chest compressions in children (October 2015)

The 2010 American Heart Association and International Liaison Committee on Resuscitation Cardiopulmonary Resuscitation guidelines emphasize the importance of hard, fast chest compression at an optimal rate of 100 compressions per minute. Health care providers who use a metronome are more likely to achieve this rate. In a crossover trial of 155 medical personnel who performed compressions on a pediatric manikin with or without a metronome, the mean percentage of compressions delivered at an optimal rate was achieved more often when a metronome was used (72 versus 50 percent) [37]. The rescuers tended to perform compressions too fast when a metronome was not used. (See "Pediatric basic life support for healthcare providers", section on 'Chest compressions'.)

Lower mortality for children treated in pediatric trauma centers (October 2015)

In a retrospective analysis of a national database of almost 176,000 pediatric trauma patients, the unadjusted mortality rate was lowest among patients treated in pediatric trauma centers (0.6 percent) compared with adult trauma centers (2.3 percent) and mixed trauma centers (1.8 percent) [38]. After adjustment, children treated in adult or mixed trauma centers had an estimated 57 and 45 percent increased risk of dying, respectively, when compared with patients treated in pediatric trauma centers (PTC). Because optimal outcomes occur when the critically injured child is initially resuscitated and subsequently managed in a PTC, it is preferable to provide care in such facilities from the outset, whenever possible, or to arrange transfer to a PTC for ongoing management. (See "Trauma management: Approach to the unstable child", section on 'Definitive care'.)

Contrast regimens for children requiring abdominal and pelvic computed tomography after blunt trauma (September 2015)

In a multicenter, prospective observational study of over 5000 children with blunt trauma undergoing abdominal and pelvic computed tomography (CT) with intravenous (IV) contrast, of whom 1010 also received oral contrast, the sensitivity for identifying intraabdominal injury was not significantly different with or without oral contrast (99 versus 98 percent, respectively) [39]. Patients who received oral contrast had a significantly longer delay in undergoing CT (median 12 minutes) compared with children who received IV contrast alone. Thus, oral contrast does not improve detection of intraabdominal injury in children but delays time to imaging. We suggest that hemodynamically stable children undergoing CT of the abdomen and pelvis after blunt trauma receive IV contrast alone rather than IV and oral contrast. (See "Overview of blunt abdominal trauma in children", section on 'Use of contrast'.)

Timely administration of epinephrine improves survival following pediatric arrest (August 2015)

Epinephrine is recommended during cardiopulmonary resuscitation for children with asystole or pulseless electrical activity without ventricular fibrillation or tachycardia. In a retrospective review of registry data on 1558 children with inpatient arrest and a documented nonshockable initial rhythm, adjusted survival to discharge occurred in up to 37 percent of patients who received epinephrine one minute or less after arrest and decreased 5 percent for every additional minute delay in epinephrine administration [40]. Survival with favorable neurologic outcome at discharge occurred in approximately 16 percent of all patients and in adjusted analysis also decreased 5 percent for every additional minute of delay in epinephrine administration. Thus, timely administration of epinephrine is associated with improved outcomes after pediatric arrests with nonshockable cardiac rhythms. (See "Guidelines for pediatric advanced life support".)

Oxyhemoglobin desaturation during rapid sequence intubation in children (June 2015)

Timing the laryngoscopy duration during a pediatric endotracheal intubation attempt and discontinuing it if intubation is unsuccessful within a specific time period (eg, 30 seconds) may prevent oxyhemoglobin desaturation. In an observational study that used video review of 114 children undergoing rapid sequence intubation in a pediatric emergency department, at least one episode of oxyhemoglobin desaturation (pulse oximetry <90 percent) occurred in 33 percent of patients [41]. Oxyhemoglobin desaturation was more common in children two years of age or younger compared with older children (59 versus 10 percent) and was strongly associated with the duration of laryngoscopy; 82 percent of patients experiencing desaturations had laryngoscopy durations of 30 seconds or longer. There was no association between the number of intubation attempts and episodes of desaturation. (See "Emergency endotracheal intubation in children", section on 'During laryngoscopy/intubation'.)

ENDOCRINOLOGY

Enzyme replacement therapy for hypophosphatasia (November 2015)

Hypophosphatasia is a rare, autosomal disease that is associated with low levels of alkaline phosphatase in serum and bone and the development of osteomalacia and severe periodontal disease. It may present in the perinatal period, when it is lethal; in infancy, where rachitic deformities develop by age six months; in childhood, with premature loss of deciduous teeth, delayed walking, and waddling gait; or in adulthood, where it is characterized by the presence of recurrent metatarsal stress fractures and bone pain, and an increased incidence of chondrocalcinosis. Historically, there have been few treatment options. However, enzyme replacement therapy (asfotase alfa) for perinatal, infantile, and juvenile-onset hypophosphatasia became available in October 2015, based upon the results of open-label prospective studies in 99 patients with perinatal, infantile, or juvenile-onset hypophosphatasia, in whom enzyme replacement therapy was associated with improved overall survival, ventilator-free survival, growth, and bone mineralization compared with a historic cohort [42]. (See "Clinical manifestations, diagnosis, and treatment of osteomalacia", section on 'Other causes'.)

GASTROENTEROLOGY, HEPATOLOGY, AND NUTRITION

Oral recombinant H. pylori vaccine (October 2015)

In a randomized phase 3 trial, 4464 H. pylori uninfected children (ages 6 to 15 years) were assigned to a three-dose oral recombinant H. pylori vaccine or placebo [43]. At one year, the incidence of H. pylori infection was significantly lower in the vaccine group. Among patients who completed extended follow-up, H. pylori acquisition continued to be lower in vaccinated as compared with unvaccinated children, but protection levels were lower in the second and third year. There were no serious adverse events related to the vaccine. Additional studies with long-term follow-up are needed to validate these results. (See "Pathophysiology of and immune response to Helicobacter pylori infection", section on 'Vaccination'.)

GENETICS AND PEDIATRIC METABOLISM

Down syndrome-specific growth charts (November 2015)

Down syndrome (DS)-specific growth charts derived from a population of patients in the United States (US) are now available and are consistent with the more contemporary charts based upon data from European populations [44]. These growth charts revealed that weight gain in children <3 years of age has improved and stature in males has increased, compared with growth chart data on DS from the 1960s. The DS-specific US growth charts will most likely supplant the US Centers for Disease Control (CDC) and World Health Organization (WHO) growth charts for assessing growth and nutritional status in children with DS. The new charts include weight-for-length and corresponding body mass index (BMI) charts that are needed to adequately assess nutritional status, although optimal weight-for-length and BMI levels for individuals with DS are not yet established. (See "Down syndrome: Management", section on 'Growth' and "Down syndrome: Clinical features and diagnosis", section on 'Growth'.)

Down syndrome disintegrative disorder (September 2015)

It is not clear if Down syndrome disintegrative disorder is one disorder or several different disorders with similar presentations [45]. The etiology is not known, but autoimmunity is suspected. There are no established diagnosis or treatment recommendations for this clinical association, although some patients respond to psychiatric care. Further research is needed in this area. (See "Down syndrome: Clinical features and diagnosis", section on 'Behavioral and psychiatric disorders'.)

Medical food supplements for organic acidemias (August 2015)

Patients with organic acidemias such as methylmalonic acidemia (MMA) are treated with a low-protein diet that is supplemented with an amino acid mixture that excludes the problematic amino acids. However, excessive consumption of this "medical food" in patients with MMA, while uncommon, can result in increased leucine intake that causes depletion of the essential amino acids valine and isoleucine [46]. These amino acid deficiencies are associated with poor growth outcomes. Patients with cobalamin C (cblC) defects, which cause combined MMA and homocystinuria, should be treated carefully with the medical food used for MMA, since this medical food is devoid of methionine and is relatively high in leucine content. Use of this medical food in patients with cblC deficiency could potentially adversely affect brain growth and development [47]. Patients with these disorders should have plasma amino acid analysis performed on a regular basis to prevent these and other complications. (See "Organic acidemias", section on 'Treatment'.)

HEMATOLOGY AND ONCOLOGY

Eltrombopag for chronic ITP in children (November 2015)

Approximately 10 to 20 percent of children who present with immune thrombocytopenia (ITP) go on to have chronic ITP with ongoing bleeding risk. In adults with refractory chronic ITP, thrombopoietin (TPO) receptor agonists increase platelet counts and reduce bleeding events, although the effect generally lasts only as long the drug is continued. A recent study found similar effects in pediatric patients. In a multicenter, randomized, double-blind trial of 92 children with chronic ITP, 40 percent of patients in the eltrombopag group achieved a sustained response in their platelet count compared with 3 percent in the placebo group [48]. Bleeding events occurred less frequently in the eltrombopag group (37 versus 55 percent). During the subsequent 24-week open-label treatment period, 81 percent of patients achieved a response. The drug was well tolerated and serious adverse events did not differ between the treatment and placebo groups. Due to cost considerations and limited pediatric experience with TPO receptor agonists in children, UpToDate reserves these agents for children with chronic ITP who fail or are ineligible for treatment with splenectomy and/or rituximab and for those requiring a high platelet count for surgery when this cannot be achieved with other therapies (eg, steroids, intravenous immune globulin). (See "Immune thrombocytopenia (ITP) in children: Management of chronic disease", section on 'Thrombopoietin receptor agonists'.)

Gardos channel mutations in hereditary stomatocytosis (October 2015)

Hereditary stomatocytosis (HSt) is a rare inherited disorder that presents with hemolytic anemia and mouth-shaped red blood cells (RBCs) known as stomatocytes. The causative genetic defect has been unclear in many affected families. Recently, three groups reported several HSt kindreds with mutations in the gene encoding the Gardos channel (KCNN4), a potassium channel in the RBC membrane [49-51]. This finding explains the anemia and suggests that one form of HSt is essentially the same as another rare condition, stomatocytic hereditary xerocytosis. Genetic testing is not yet widely available; at present diagnosis is based on clinical features and RBC testing. (See "Stomatocytosis and xerocytosis", section on 'Gardos channel'.)

INFECTIOUS DISEASES AND IMMUNIZATIONS

Shortened interval for postvaccination serology in infants born to HBsAg-positive mothers (October 2015)

To prevent transmission of hepatitis B infection, infants born to women who are hepatitis B surface antigen (HBsAg)-positive should receive hepatitis B immune globulin and the first dose of hepatitis B vaccine within 12 hours of birth and complete the hepatitis B vaccine series at age six months or soon thereafter. Postvaccination serology (HBsAg and antibody to HBsAg) is necessary to see if postexposure prophylaxis was successful (table 2). In agreement with updated recommendations from the Centers for Disease Control and Prevention [52], we now obtain postvaccination serology at age 9 to 12 months (or one to two months after the final dose) rather than at age 9 to 18 months as previously recommended. The shortened interval permits earlier revaccination of susceptible infants and may avoid unnecessary revaccination of infants who responded appropriately but whose antibody levels declined with time. (See "Hepatitis B virus immunization in infants, children, and adolescents", section on 'Postvaccination serology'.)

Influenza vaccination and influenza-associated pneumonia (October 2015)

Many studies have demonstrated that influenza vaccination decreases the incidence of laboratory-confirmed influenza infection, but few have evaluated the effect on the serious complications of influenza. Recent data suggest that vaccination is associated with a reduced risk of influenza pneumonia. In a case-control study of adult and pediatric patients hospitalized for community-acquired pneumonia (CAP), those with laboratory-confirmed influenza-associated pneumonia had lower odds of having received an influenza vaccine during the same influenza season compared with those with CAP not associated with influenza [53]. The estimated vaccine effectiveness for preventing influenza-associated pneumonia was 57 percent. (See "Seasonal influenza vaccination in adults", section on 'Trivalent inactivated vaccines'.)

WHO recommendations on HIV treatment and prevention (October 2015)

In 2015, the World Health Organization (WHO) updated its guidelines for the prevention and treatment of HIV infection to recommend initiation of lifelong antiretroviral (ART) for all HIV-infected patients, regardless of CD4 cell count or clinical stage [54]. This recommendation was based, in part, on mounting evidence that the clinical benefit of ART extends to those with very high CD4 cell counts and data demonstrating a dramatic reduction in sexual HIV transmission to uninfected partners with successful ART. The updated guidelines also recommend pre-exposure prophylaxis (PrEP) with a tenofovir-containing regimen as part of the HIV prevention strategy for individuals at substantial risk of HIV infection (ie, those for whom the predicted incidence of infection would be >3 per 100 person years). (See "The impact of antiretroviral therapy on morbidity and mortality of HIV infection in resource-limited settings", section on 'Initiation of antiretroviral therapy' and "Pre-exposure prophylaxis against HIV infection" and "Prevention of mother-to-child HIV transmission in resource-limited settings", section on 'Recommended antiretroviral management'.)

Influenza vaccine recommendations for 2015-2016 influenza season (August 2015)

In August 2015, the Advisory Committee on Immunization Practices released recommendations for the prevention and control of influenza during the 2015-2016 influenza season in the United States. As in previous seasons, seasonal influenza vaccination is recommended for everyone ≥6 months of age [55]. Changes for the 2015-2016 season include:

●Different influenza A H3N2 and influenza B (Yamagata lineage) antigens than were in the 2014-2015 vaccines

●A simplified dosing algorithm for children six months through eight years (algorithm 2)

●Availability of a quadrivalent intradermal vaccine for adults 18 through 64 years of age (table 3)

(See "Seasonal influenza in children: Prevention with vaccines", section on 'Schedule' and "Seasonal influenza vaccination in adults", section on 'Overview'.)

Repeat testing for women treated for trichomoniasis (July 2015)

The risk of repeat infection following treatment for a sexually transmitted infection (STI) is high. In the United States, reinfection with Trichomonas vaginalis has been reported to occur in up to 17 percent of women following treatment for an initial infection. The 2015 Centers for Disease Control and Prevention (CDC) guidelines on the management of STIs recommend that women treated for confirmed T. vaginalis infection undergo repeat testing within three months of treatment, regardless of partner treatment status [56]. Prior guidelines had only listed retesting as a consideration. The preferred diagnostic test for repeat testing is a nucleic acid amplification test (NAAT) on a vaginal swab, which can be performed as soon as two weeks after treatment. Data are insufficient to support retesting men. (See "Trichomoniasis", section on 'Follow-up'.)

Updated CDC guidelines on the management of sexually transmitted infections (June 2015)

The US Centers for Disease Control and Prevention (CDC) updated its guidelines on the management of sexually transmitted infections in June 2015 [57]. Major revisions include a lower threshold for the diagnosis of urethritis based on microscopy of a urethral specimen, a new emphasis on the role of Mycoplasma genitalium in persistent urethritis and cervicitis, preference for nucleic acid amplification-based testing for the diagnosis of Trichomonas vaginalis, and a recommendation to retest women after treatment for T. vaginalis to evaluate for reinfection. New screening recommendations include annual hepatitis C virus (HCV) testing for HIV-infected men who have sex with men and T. vaginalis testing for HIV-infected women annually and when pregnant. (See "Urethritis in adult men", section on 'Diagnostic criteria' and "Mycoplasma genitalium infection in men and women", section on 'Nongonococcal urethritis' and "Trichomoniasis", section on 'Follow-up' and "Primary care of the HIV-infected adult", section on 'Sexually transmitted infections'.)

Prevalence and clinical presentation of Borrelia miyamotoi infection (June 2015)

Borrelia miyamotoi is an emerging zoonotic pathogen that is transmitted by the same genus of ticks (eg, Ixodes scapularis, Ixodes pacificus) that transmits Borrelia burgdorferi (the agent of Lyme disease), Anaplasma phagocytophilum, and Babesia species. In one case series, B. miyamotoi was identified using polymerase chain reaction (PCR) in approximately 1 percent of specimens from 11,515 patients in the northeastern United States who presented with an acute febrile episode from April through November in 2013 and 2014 [58]. Clinical information was available for 51 patients with B. miyamotoi infection; the majority had marked headache, myalgia, arthralgia, malaise, and/or fatigue, and 24 percent were hospitalized. Diagnostic testing is not widely available, but doxycycline, which is used to treat many other tick-borne infections, is also effective against B. miyamotoi. (See "Borrelia miyamotoi infection", section on 'Clinical manifestations'.)

US ACIP recommendations for serogroup B meningococcal vaccination (June 2015)

In late 2014 and early 2015, the US Food and Drug Administration approved two serogroup B meningococcal vaccines (Trumenba, MenB-FHbp and Bexsero, MenB-4C). In June 2015, the Advisory Committee on Immunization Practices (ACIP) issued recommendations for serogroup B meningococcal vaccine for high-risk individuals aged 10 years or older; these include individuals with persistent complement component deficiencies, individuals with anatomic or functional asplenia, microbiologists routinely exposed to N. meningitidis isolates, and individuals at increased risk because of a serogroup B meningococcal disease outbreak [59]. These indications overlap with those for the quadrivalent meningococcal conjugate vaccine and are summarized in the table (table 4). Among patients with none of the above risk factors, the ACIP advises discussion between doctors and patients regarding vaccination against serogroup B meningococcus; routine vaccination has not been recommended [60]. (See "Meningococcal vaccines", section on 'Use in United States'.)

Antimicrobial-resistant Shigella infections in the United States (June 2015)

Antimicrobial resistance in Shigella is an increasing problem in the United States. Fluoroquinolones are typically the antibiotic class of choice in adults, and azithromycin is often used if fluoroquinolone resistance is suspected or documented. Clusters of ciprofloxacin-resistant cases, likely introduced by international travelers with subsequent domestic spread, have been reported throughout the country, and isolates with decreased susceptibility to azithromycin have caused outbreaks and sporadic cases, predominantly among men who have sex with men (MSM) [61,62]. Scattered infections with extremely drug-resistant isolates that are ciprofloxacin-resistant and have decreased susceptibility to azithromycin have also been reported [63]. These reports highlight the importance of obtaining susceptibility testing to ensure adequate efficacy of the chosen antimicrobial when managing shigellosis and emphasizing prevention measures, primarily hygiene practices around food preparation or consumption and oral or anal sex. (See "Shigella infection: Treatment and prevention in adults", section on 'Antimicrobial resistance' and "Shigella infection: Treatment and prevention in children", section on 'Antibiotic resistance'.)

NEUROLOGY

New ILAE definition of status epilepticus (November 2015)

The International League Against Epilepsy (ILAE) has published a revised definition of status epilepticus, which now incorporates two operational dimensions, t1 and t2 [64]. Specifically, status epilepticus is defined as:

●A condition resulting from either the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms which lead to abnormally prolonged seizures (after time point t1); and

●A condition that can have long-term consequences (after time point t2), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures.

For generalized convulsive status epilepticus (GCSE), the ILAE definition specifies a duration of five minutes for t1 and 30 minutes for t2. The five-minute window for GCSE is consistent with our previous recommendations for initiating urgent intervention to control seizures. (See "Convulsive status epilepticus in adults: Classification, clinical features, and diagnosis", section on 'Definition' and "Clinical features and complications of status epilepticus in children", section on 'Definition'.)

PULMONOLOGY

Lumacaftor-ivacaftor for patients with cystic fibrosis and homozygous for the F508del mutation (August 2015)

Lumacaftor-ivacaftor is a combination of two cystic fibrosis transmembrane conductance regulator (CFTR) modulators that was approved by the US Food and Drug Administration in July 2015. The approval was based on two randomized trials with 1100 homozygous F508del subjects ages 12 years and older [65]. Compared with placebo, the groups receiving lumacaftor-ivacaftor for 24 weeks had small but statistically significant improvements in percent predicted FEV1 and body mass index (BMI), and reduced frequency of pulmonary exacerbations. Adverse effects included chest discomfort and dyspnea and were more common in subjects with worse baseline lung function. The improvement in absolute FEV1 from baseline compared with placebo (2.6 to 4 percentage points) is similar in magnitude to that achieved by treatments with inhaled dornase alfa or tobramycin. We suggest use of lumacaftor-ivacaftor for F508del homozygotes because it has modest short-term benefits and is tolerated by most patients. However, the expense of the drug and drug-drug interactions should be considered when deciding on its use. (See "Cystic fibrosis: Overview of the treatment of lung disease", section on 'Efficacy'.)

Outcomes of infants with inconclusive newborn screening for cystic fibrosis (July 2015)

CFTR-related metabolic syndrome (CRMS) describes infants with an equivocal diagnosis following newborn screening for cystic fibrosis (CF). These infants usually have elevated levels of immunoreactive trypsinogen, but inconclusive results of subsequent sweat and DNA testing. The natural history of infants with CRMS is unclear. Now, a small study of infants with an initial diagnosis of CRMS reports that 48 percent were later diagnosed with CF, most within the first year of life [66]. Affected individuals had a somewhat milder CF phenotype compared with infants who were diagnosed with CF by newborn screening. These findings highlight the importance of longitudinal clinical and laboratory follow-up of infants with CRMS. (See "Cystic fibrosis: Clinical manifestations and diagnosis", section on 'CFTR-related metabolic syndrome'.)

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