Find Print
0 Find synonyms

Find synonyms Find exact match

What's new in pediatrics
UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate®
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
What's new in pediatrics
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Dec 2016. | This topic last updated: Jan 14, 2017.

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

No role for routine serologic screening for genital herpes infection (December 2016)

Genital herpes, which can be caused by herpes simplex virus type 1 or 2 (HSV-1 or HSV-2), is one of the most common sexually transmitted infections, and sexual transmission can occur even in the absence of symptoms. Despite this, routine serologic screening for herpes simplex is not recommended in asymptomatic adolescents and adults due to significant limitations of available tests, as highlighted in a recent US Preventive Services Task Force statement [1]. Limitations include the low specificity and high false positive rate of serologic tests for HSV-2 and the inability of serologic tests for HSV-1 to differentiate oral from genital infection. Furthermore, there are no specific treatment interventions for asymptomatic patients, so the anxiety and disruption of personal relationships associated with a positive test outweigh any potential benefits. (See "Epidemiology, clinical manifestations, and diagnosis of genital herpes simplex virus infection", section on 'Screening'.)

FDA issues warning about anesthesia for pregnant patients and children under three years of age (December 2016)

The US Food and Drug Administration has warned about potential negative effects on the developing brain from administration of anesthetics and sedatives to pregnant women and children under age three, especially for repeated exposures or procedures lasting more than three hours [2]. However, the degree of risk remains unclear. A single, brief exposure to anesthesia probably does not cause neurotoxicity in healthy young children. Further study is required to determine the effects of prolonged or repeated anesthetics, variability among anesthetic agents and combinations of drugs, and patient factors that may confer vulnerability to anesthetic neurotoxicity. At present, there is no compelling evidence that any specific anesthetic agent should be avoided during pregnancy or in young children, or that necessary surgery should be delayed because of concerns about neurotoxicity. (See "Management of the pregnant patient undergoing nonobstetric surgery", section on 'Fetal brain development'.)

Benefits of weight loss surgery on renal function in adolescents (December 2016)

Severely obese adolescents are at risk for developing impaired renal function. In a longitudinal study of adolescents undergoing weight loss surgery, 25 percent had impaired renal function and 17 percent had albuminuria at baseline [3]. Both measures improved during the three years after surgery. Thus, kidney injury joins the list of comorbidities that improve or resolve after weight loss surgery in adolescents. (See "Surgical management of severe obesity in adolescents", section on 'Comorbidity improvement'.)

Positional plagiocephaly guidelines (November 2016)

New guidelines for diagnosis and treatment of positional plagiocephaly (positional skull flattening) have been issued by the Congress of Neurological Surgeons [4] and endorsed by the American Academy of Pediatrics. These guidelines are largely consistent with our approach:

The diagnosis is made by clinical examination, with imaging in equivocal cases.

Most cases can be treated by a change in positioning, alone or with physical therapy. Use of custom-fitted helmets should be restricted to severe or recalcitrant cases.

(See "Overview of craniosynostosis", section on 'Positional flattening (positional plagiocephaly)'.)

2016 European Society of Hypertension Guidelines for blood pressure management in children (November 2016)

The European Society of Hypertension (ESH) recently updated their guidelines for the management of blood pressure (BP) in children [5]. Key points include:

Continue to use normative data from the 2004 US National High Blood Pressure Education Program Working Group to define high BP and hypertension for children <16 years of age and use adult thresholds for individuals ≥16 years and older. (See "Definition and diagnosis of hypertension in children and adolescents", section on 'International'.)

Screen BP starting at three years of age. (See "Definition and diagnosis of hypertension in children and adolescents", section on 'Screening and monitoring BP'.)

Lower target BP goals for children with chronic kidney disease while maintaining previous target goals for all other pediatric conditions with cardiovascular risks. (See "Nonemergent treatment of hypertension in children and adolescents", section on 'Target blood pressure goals'.)

E-cigarette use and respiratory symptoms in adolescents (November 2016)

Use of e-cigarettes has been rising among adolescents in the United States, and the long-term health consequences of e-cigarette use are unknown. A survey of 11th and 12th grade students in California found an association between self-reported chronic bronchitic symptoms (chronic cough, phlegm, bronchitis in the past year) and current or past e-cigarette use that remained after adjustment for confounders such as cigarette smoking or secondhand smoke exposure; risk of respiratory symptoms increased with frequency of current use of e-cigarettes [6]. (See "E-cigarettes", section on 'Adverse health effects'.)

American Academy of Pediatrics guidelines for media use in children (November 2016)

The American Academy of Pediatrics has released updated guidelines on television and digital media use in children and adolescents [7,8]. Key recommendations include discouraging television and digital media use except for video chatting in children <18 months; helping parents choose high-quality programming when introducing media to children 18 to 24 months of age; limiting media use in children 2 to 5 years to ≤1 hour per day of high-quality programming; recommending that parents watch/use digital media with their children; and helping families to develop a "family media plan," which designates specific times and locations as media-free (eg, meal time, bedrooms). (See "Television and media violence", section on 'Family and individual'.)

Long-acting reversible contraception and teenage pregnancy rates (November 2016)

In a systematic review of nine studies including nearly 27,000 adolescent and young adult women (≤25 years), the 12-month continuation rate was nearly twice as high with the intrauterine device or contraceptive implant as with other contraceptive methods (approximately 85 percent versus 40 to 50 percent) [9]. Increased contraceptive use, particularly increased use of these highly effective long-acting reversible contraceptive (LARC) methods, contributed to the historically low teenage pregnancy rate in 2015 [10]. These observations support our recommendations to highlight LARC methods when discussing contraception with adolescents and young adults. (See "Pregnancy in adolescents", section on 'Epidemiology' and "Contraception: Overview of issues specific to adolescents", section on 'Long-acting reversible methods'.)

Adherence to safe infant sleeping practices (October 2016)

Although nonsupine infant sleep position and environmental hazards are well publicized risk factors for sudden infant death syndrome (SIDS), many families continue to use unsafe practices. In a study that videoed parents caring for their infants in their homes, nonsupine sleeping positions were used for 14 percent of one-month-old infants, rising to 18 percent at three months, and 33 percent at six months [11]. Moreover, potentially hazardous items (eg, pillows, stuffed animals, bumper pads, sleep positioners) were observed on the sleep surface in about 90 percent of infants in each age group. (See "Sudden infant death syndrome: Risk factors and risk reduction strategies", section on 'Prevention'.)

Updated recommendations for safe infant sleeping practices (October 2016)

Updated recommendations to reduce the risk of sleep-related infant deaths have been released by the American Academy of Pediatrics (AAP) [12]. Changes include increased emphasis on avoiding soft bedding accessories (particularly for older infants), further evidence supporting firm sleeping surfaces, and safe approaches to skin-to-skin contact immediately after birth. (See "Sudden infant death syndrome: Risk factors and risk reduction strategies", section on 'Sleep environment'.)

Bag urine specimen testing to determine the need for urine culture in children (October 2016)

A bag urine specimen for a screening urine dipstick and/or urinalysis may prevent the need for a catheterized urine culture in selected patients older than 6 months of age at low risk for a urinary tract infection (UTI). In an observational study of over 800 previously healthy, well-appearing children 6 to 24 months of age presenting to a pediatric emergency department for evaluation of fever, screening of urine obtained by a bag specimen reduced the number of subsequent urine cultures obtained by bladder catheterization from 63 to 30 percent without prolonging the length of stay or increasing rates of revisits or missed UTI [13]. Although potentially helpful for urine screening tests, bag urine samples should not be routinely used to obtain urine samples for culture, especially in situations where contamination of the specimen will complicate further management (eg, young infants or ill-appearing patients who warrant empiric parenteral antibiotics). (See "Urine collection techniques in infants and children with suspected urinary tract infection", section on 'Specimen for urine dipstick or urinalysis'.)

Multidisciplinary approach to children and adolescents with persistent concussion symptoms (September 2016)

For patients with prolonged post-concussion symptoms, a multidisciplinary approach that includes mental health care by a psychologist or psychiatrist is associated with better outcomes. In a randomized trial of 49 children and adolescents (11 to 17 years of age) with persistent symptoms for one month or longer after a sports-related concussion, collaborative treatment consisting of care management, cognitive-behavioral therapy, and, when needed, psychopharmacologic consultation was associated with significant reductions in postconcussive and depression symptoms at six months when compared to usual treatment [14]. (See "Concussion in children and adolescents: Management", section on 'Persistent symptoms'.)

Strategies for preventing obesity and eating disorders (September 2016)

Clinicians and parents may be reluctant to address obesity in children because of concerns for promoting eating disorders. A new clinical report from the American Academy of Pediatrics outlines strategies that can be used to address obesity without promoting disordered eating [15]. These include counseling parents to avoid "weight talk" (comments that focus on weight or weight-related appearance, even if they are not directed at the child) and focusing goals on healthy food choices and healthy eating behaviors rather than dieting (which is distinguished by caloric restriction with a goal of weight loss). (See "Management of childhood obesity in the primary care setting", section on 'Raising the sensitive issue of weight'.)

Infant simulator programs do not prevent teenage pregnancy (September 2016)

Infant simulator programs combine educational sessions with "care" for a doll that is programmed to replicate infant behaviors. They have become popular despite evidence from observational studies that they do not affect teenagers' attitudes toward teenage parenthood. A recent randomized trial provides additional evidence that infant simulator programs are ineffective [16]. In this trial, 57 schools were randomly assigned to provide an infant simulator intervention or standard health education curriculum to 13- to 15-year-old girls who volunteered to participate. By 20 years of age, participants from the simulation schools had higher rates of birth (8 versus 4 percent) and abortion (9 versus 6 percent) than those who received the standard curriculum. We suggest a multifaceted approach to teenage pregnancy prevention, focusing on comprehensive sexuality education, delaying onset of sexual activity, and promotion of consistent and correct use of effective contraception for teenagers who decide to become sexually active. (See "Pregnancy in adolescents", section on 'Prevention'.)

Sleep duration in preschool children and progression to obesity (August 2016)

Increasing evidence supports an association between shortened sleep duration and obesity in children. In a recent large longitudinal study, the risk of adolescent obesity in preschool children with early bedtimes (8:00 PM or earlier) was about half that of preschool children with late bedtimes (9:00 PM or later), after adjustment for several confounding variables, including maternal obesity, education, and income level [17]. (See "Definition; epidemiology; and etiology of obesity in children and adolescents", section on 'Sleep'.)

Effectiveness of antidepressants for pediatric unipolar major depression (August 2016)

Antidepressant medications are often used to treat moderately to severely ill children with unipolar major depression. For children and adolescents with acute depressive disorders, first-line pharmacotherapy is typically fluoxetine. There are several randomized trials comparing antidepressant medications with placebo, but there are few head-to-head comparison trials. In a recent meta-analysis of 34 trials comparing one antidepressant with placebo or another active drug for the acute treatment of major depressive disorder in children and adolescents, fluoxetine, sertraline, and escitalopram were statistically more efficacious than placebo [18]. In addition, paroxetine was superior to clomipramine and fluoxetine was superior to nortriptyline. In a network meta-analysis subsequently performed to compare and rank antidepressants for the acute treatment of major depressive disorder, only fluoxetine was better than placebo. In comparison with other antidepressants, fluoxetine was significantly more effective than nortriptyline. Important limitations of the network meta-analysis include risk of bias within individual studies, lack of power and generalizability, and potential selective reporting. (See "Pediatric unipolar depression and pharmacotherapy: Choosing a medication", section on 'All antidepressants'.)

Lipid screening in children and adolescents (August 2016)

Increasing evidence suggests that atherosclerosis begins in childhood and adolescence, yet the optimal strategies for early screening and treatment of the disease remain uncertain. A recent statement of the US Preventive Services Task Force (USPSTF) concluded that the available evidence on screening for lipid disorders in children and adolescents is insufficient to assess the balance of benefits and harms of screening [19]. This position is unchanged from the 2007 USPSTF statement; however, it contradicts the 2011 National Heart, Lung, and Blood Institute (NHLBI) guidelines for cardiovascular health and risk reduction, which recommend screening in all children and adolescents and have been endorsed by the American Academy of Pediatrics (AAP) and the American Heart Association (AHA) [20]. We continue to suggest both age-based universal and selective screening for pediatric dyslipidemia. (See "Dyslipidemia in children: Definition, screening, and diagnosis", section on 'Recommendations of others'.)

Clinical manifestations of severe synthetic cannabinoid toxicity (July 2016)

Synthetic cannabinoids consist of a heterogeneous group of chemical compounds that act as agonists at cannabinoid receptors with 2 to 800 times the potency of delta-9 tetrahydrocannabinol (THC), the active component of cannabis (marijuana). They have emerged as a popular recreational drug in the United States and Europe. In an observational study of a multicenter, hospital-based registry of medical toxicology consultations, over two-thirds of 277 patients with single-agent exposure to synthetic cannabinoids had altered mental status including severe agitation, toxic psychosis, hallucinations, seizures, and coma [21]. Rhabdomyolysis and acute kidney injury were present in approximately 5 percent of these patients. There were three deaths, including a 17-year-old adolescent with sudden death after first-time inhalational use. Thus, unlike cannabis, synthetic cannabinoids have significant potential to cause serious and life-threatening toxicity among recreational users. (See "Synthetic cannabinoids: Acute intoxication", section on 'Clinical manifestations'.)

NEONATOLOGY

Delayed cord clamping (January 2017)

Delaying umbilical cord clamping for at least 30 to 60 seconds after birth in both term and preterm vigorous infants is the recommendation of an updated committee opinion by the American College of Obstetricians and Gynecologists (ACOG) [22]. Previously, ACOG had recommended individualizing the timing of cord clamping in term infants. Although the optimal amount of time before cord clamping has not been studied extensively, we believe data support a minimum duration of delay of at least one minute in term births and 30 seconds in preterm births. (See "Management of normal labor and delivery", section on 'Cord clamping'.)

Risk of birth defects with Zika virus infection during pregnancy (January 2017)

The risk of birth defects resulting from in utero exposure to Zika virus was 6 and 42 percent in two recent reports [23,24]. The wide range likely reflects differences in study design, populations studied, maternal Zika case definition, and the range of clinical abnormalities included. The most common fetal/newborn findings in these reports were abnormal brain imaging, microcephaly, small size for gestational age, and abnormal neurologic examination. The greatest risk of serious sequelae in offspring appeared to be with first or second trimester infection, but serious sequelae also occurred with third trimester infection. (See "Zika virus infection: Evaluation and management of pregnant women", section on 'Risk of vertical transmission and anomalies' and "Congenital Zika virus infection: Clinical features, evaluation, and management of the neonate", section on 'Clinical findings'.)

Neonatal hypoglycemia in preterm infants and neurodevelopment impairment (December 2016)

For preterm and term infants, a low blood glucose threshold that accurately predicts long-term outcome has not been identified. An analysis of data from the Infant Health and Development Program study of infants born at a gestational age <32 weeks reported no difference in intellectual and cognitive skills or academic achievement at 3, 8, and 18 years of age between patients with and without neonatal hypoglycemia (defined as blood glucose level ≤45 mg/dL [2.5 mmol/L]) [25]. However, these findings do not provide a definitive threshold for treating neonatal hypoglycemia. We continue to use a threshold of 50 mg/dL (2.8 mmol/L) for intervention in preterm infants as this provides a margin of safety until conclusive evidence establishes a level that accurately predicts long-term outcome. (See "Management and outcome of neonatal hypoglycemia", section on 'Preterm infants'.)

Support for lower oxygen concentration for neonatal resuscitation for very preterm infants (December 2016)

Increasing evidence supports the use of a lower initial fraction of inspired oxygen (Fio2) when beginning resuscitation of preterm infants. In a follow-up report of two trials that compared initial resuscitation of preterm infants <32 weeks of gestation using an Fio2 of 30 percent versus 60 or 65 percent, no difference in survival or neurodevelopmental outcome was observed at 24 months corrected age between the groups [26]. These data support our practice of beginning resuscitation of preterm infants using an Fio2 of 30 percent, with subsequent adjustment based on our predetermined target ranges for peripheral capillary oxygen saturation (SpO2). (See "Neonatal resuscitation in the delivery room", section on 'Supplemental oxygen'.)

Pattern of anomalies in congenital Zika syndrome (November 2016)

The clinical spectrum of congenital Zika syndrome (CZS) is evolving as more cases are described. A comprehensive review of the available published data identified five unique features of CZS that are rarely seen with other congenital infections: (1) severe microcephaly with partially collapsed skull, (2) thin cerebral cortices with subcortical calcifications, (3) macular scarring and focal pigmentary retinal mottling, (4) congenital contractures (arthrogryposis), and (5) marked early hypertonia [27]. Recognition of this distinctive phenotype can help clinicians identify infants with CZS and ensure appropriate etiologic evaluation and comprehensive clinical investigation. (See "Congenital Zika virus infection: Clinical features, evaluation, and management of the neonate", section on 'Clinical findings'.)

High-flow nasal cannula versus nCPAP for primary respiratory support of preterm infants (September 2016)

For primary respiratory support of preterm infants, high-flow nasal cannulae (HFNC) has been proposed as an alternative delivery system to nasal continuous positive airway pressure (nCPAP), as HFNC is associated with less nasal trauma. However, a large multicenter trial of preterm infants (gestational age >28 weeks) was terminated early (564 patients recruited for a predetermined sample size of 750) when a predesignated interim analysis at 500 patient enrollment demonstrated a higher treatment failure rate among those randomly assigned to HFNC versus nCPAP for primary respiratory support (25.5 versus 13.3 percent) [28]. Treatment failure was defined as an infant receiving maximal support for either HFNC or nCPAP and with one or more of the following criteria: intubation and mechanical ventilation, receiving fraction of inspired oxygen (FiO2) ≥0.4, venous or arterial blood gas sample with a pH ≤7.2, partial pressure of carbon dioxide (PaCO2) >60 mmHg, and apnea episodes requiring positive pressure ventilation. As a result, we continue to use nCPAP as the initial respiratory support for preterm infants. (See "Oxygen monitoring and therapy in the newborn", section on 'High flow nasal cannula'.)

ALLERGY, IMMUNOLOGY, AND RHEUMATOLOGY

Guidelines on introduction of peanut to children (January 2017)

Formal guidelines from the National Institute of Allergy and Infectious Diseases for the introduction of peanut to children have been revised [29]. The revised guidelines advise peanut introduction as early as four to six months of age, particularly in high-risk infants (eg, severe eczema, egg allergy), based upon the Learning Early about Peanut Allergy (LEAP) trial and other studies showing decreased rates of peanut allergy with early introduction. Testing for peanut allergy prior to introduction is indicated in high-risk populations. Our approach is consistent with these guidelines (algorithm 1). (See "Introducing highly allergenic foods to infants and children", section on 'Suggested approach'.)

Early introduction of egg for the prevention of egg allergy (December 2016)

Four recent randomized trials have examined introduction of egg for the prevention of egg allergy, with variable success. These studies are the Prevention of Egg Allergy with Tiny Amount Intake (PETIT) trial [30], the Starting Time of Egg Protein (STEP) trial [31], the Beating Egg Allergy Trial (BEAT) [32], and the Hen’s Egg Allergy Prevention (HEAP) trial [33]. Each trial enrolled a slightly different population and introduced different doses and forms of egg at ages ranging from 4 to 6 months. The most successful trial (PETIT) involved infants with eczema given a low dose of heated egg starting at 6 months of age, which resulted in egg allergy at 12 months in 8 and 38 percent in the treatment and placebo groups, respectively. The other trials that used pasteurized raw egg and started dosing as early as 4 months were negative. Further studies are needed to determine the optimal timing, patient population, and form of egg to introduce. (See "Introducing highly allergenic foods to infants and children", section on 'Introduction in a high-risk population'.)

Farm animals, asthma, and the innate immune response (September 2016)

Exposure to farm animals, particularly early in life, is negatively associated with the development of allergic disease. A recent study compared 60 children from Amish and Hutterite communities, two genetically similar, reproductively isolated farming populations in the United States [34]. The Amish have traditional, single-family farms with exposure to horses and dairy cows, whereas the Hutterites live and work on large farms that are highly industrialized. Amish children have significantly lower rates of asthma and allergic sensitization than their Hutterite counterparts. Endotoxin levels were significantly higher in the Amish homes, and dust extracts from the Amish homes, but not the Hutterite homes, significantly blocked airway hyperresponsiveness and eosinophilia in a mouse model. In addition, in vitro studies showed an enhanced innate immune response in Amish, but not Hutterite, children. These findings suggest that the closer contact with farm animals in the Amish lifestyle may help prevent the development of asthma by altering the innate immune response. (See "Increasing prevalence of asthma and allergic rhinitis and the role of environmental factors", section on 'Farms, villages, worms, and other parasites'.)

Lack of association between acetaminophen and asthma in children (September 2016)

More frequent use of acetaminophen was associated with increased asthma-related complications in children in observational studies, leading to the recommendation by some for children with asthma to avoid acetaminophen. However, these findings were not replicated in a prospective, randomized trial comparing acetaminophen and ibuprofen use [35]. In this trial, 300 children with mild persistent asthma were randomly assigned to as-needed treatment with acetaminophen or ibuprofen for fever or pain over a 48-week period. All children received standard controller therapy for asthma. There was no significant difference between the two groups in the number of asthma exacerbations requiring treatment with systemic glucocorticoids or in the number of asthma exacerbations. Thus, we do not advise restricting the use of acetaminophen in children with asthma. (See "Virus-induced wheezing and asthma: An overview", section on 'Acetaminophen use for febrile illnesses'.)

Screening and prevention of hydroxychloroquine retinopathy (August 2016)

Antimalarial agents hydroxychloroquine (HCQ) and chloroquine are widely used for the treatment of systemic lupus erythematosus, rheumatoid arthritis, and other inflammatory and dermatologic conditions, and are generally thought to be safe. Retinal toxicity is a known risk, however, and measures to minimize this potential toxicity are necessary. Recently, the American Academy of Ophthalmology issued revised recommendations for screening and prevention of retinopathy [36]. Key changes include the following:

The maximum daily dose of HCQ should not exceed 5 mg/kg (previously 6.5 mg/kg), and the maximum daily dose of chloroquine should not exceed 2.3 mg/kg (previously 3 mg/kg).

Real body weight should be used to calculate dose limits instead of ideal body weight.

In addition to exceeding the recommended daily dose, major risk factors for retinal toxicity include antimalarial use for greater than five years, renal disease, concomitant tamoxifen use, and the presence of macular disease. All patients should undergo a baseline eye examination before or within a year of beginning treatment with an antimalarial drug and, if normal, at least annually after five years of exposure for patients without major risk factors. For the treatment of rheumatic diseases, we typically use standard daily doses of HCQ (non-weight-based, eg, up to 400 mg) in individuals weighing 80 kg or more. In patients weighing less than 80 kg, we use a lower daily dose of HCQ up to the maximum of 5 mg/kg of real body weight. (See "Antimalarial drugs in the treatment of rheumatic disease", section on 'Ocular health'.)

Omalizumab for allergic asthma in children 6 to 11 years of age (July 2016)

Omalizumab, a monoclonal antibody to immunoglobulin E (IgE), is an option for patients with moderate to severe persistent asthma and sensitization to perennial aeroallergens who are inadequately controlled on inhaled glucocorticoids. The US Food and Drug Administration (FDA) has now lowered the approved age range from 12 to 6 years of age, expanding the therapeutic options in step 5 asthma management in children [37]. (See "Asthma in children younger than 12 years: Treatment of persistent asthma with controller medications", section on 'Step-up therapy' and "Asthma in children younger than 12 years: Treatment of persistent asthma with controller medications", section on 'Anti-IgE therapy' and "Anti-IgE therapy", section on 'Omalizumab therapy in asthma'.)

Extensively heated egg in children with egg allergy (July 2016)

The majority of children with egg allergy can tolerate extensively heated egg, and introduction of cooked egg can both improve quality of life and hasten resolution of egg allergy. A recent study examined whether various cooking methods affected tolerance and whether skin testing with the different cooked forms of the food was predictive of the oral food challenge (OFC) results [38]. Fifty-four children with a history of egg allergy and positive skin testing to raw egg were tested with baked egg in a wheat matrix (cake), egg frittata (fried then baked, no wheat), and boiled egg. They were then challenged to the same forms of egg and pass rates were 88, 74, and 56 percent for baked in wheat matrix, fried/baked, and boiled egg, respectively. The OFC pass rates and higher internal temperatures for the cake and frittata compared with the boiled egg suggest that degree of cooking of the food is more important than the presence of a wheat matrix. Negative skin testing (ie, mean wheal diameters were <3 mm) with a given form of heated egg had a 100 percent negative predictive value for reacting to ingestion of that same form of egg. Although these results suggest that patients could introduce extensively heated egg without first undergoing an oral food challenge (OFC) if skin testing to the cooked form was negative, supervised OFCs are still recommended until these results have been confirmed in more patients, because of the lack of standardization with this type of testing and the risk of anaphylaxis with a failed challenge. (See "Egg allergy: Management", section on 'Extensively heated egg'.)

AAP guidance on use of biologic response modifiers (July 2016)

Biologic response modifiers (BRMs) are immunosuppressive agents that are used to treat autoimmune disorders such as juvenile idiopathic arthritis and inflammatory bowel disease. Patients receiving BRMs have an increased risk of infection, particularly mycobacterial, viral, and fungal infections. Thus, the American Academy of Pediatrics has published guidance for clinicians using these agents [39]. A thorough history is recommended to help determine infectious risk, with performance of screening tests as indicated depending upon the history and biologic agent chosen. Administration of routine immunizations at least two weeks prior to starting a BRM is advised for inactivated or subunit vaccines and at least four weeks prior for live vaccines, if treatment can be safely delayed. Administration of live vaccines is not recommended during treatment with BRMs. An infectious disease specialist should be consulted if a live vaccine is deemed necessary while a patient is on biologic therapy. Inactivated and subunit vaccines can be given while on therapy, and an annual inactivated influenza vaccine is recommended. (See "Systemic juvenile idiopathic arthritis: Treatment", section on 'Biologic therapy'.)

CARDIOLOGY

Restrictive postoperative transfusion strategy in infants and children with congenital heart disease (October 2016)

In a randomized trial of restrictive versus liberal postoperative transfusion strategies in 162 infants with congenital heart disease undergoing surgical repair or palliation, a restrictive transfusion strategy reduced the red cell transfusion rate, without increasing in-hospital mortality, need for extracorporeal membrane oxygenation (ECMO) support, or hospital length of stay [40]. The restrictive group was transfused for hemoglobin <7.0 g/dL for biventricular repairs or <9.0 g/dL for palliative procedures plus a clinical indication; the liberal group was transfused for hemoglobin <9.5 g/dL for biventricular repairs or <12 g/dL for palliative procedures. Larger more definitive trials are needed before clear transfusion guidelines in this population can be made. (See "Red blood cell transfusion in infants and children: Indications", section on 'Surgery'.)

DERMATOLOGY

Topical crisaborole for atopic dermatitis (December 2016)

A topical preparation containing 2% crisaborole, an investigational boron-based, small-molecule, phosphodiesterase-4 inhibitor, was approved by the US Food and Drug Administration in December 2016 for the treatment of mild to moderate atopic dermatitis in patients two years of age and older [41]. In four-week clinical trials, topical crisaborole was more effective than placebo in reducing pruritus, skin inflammation, excoriation, and lichenification. However, trials comparing topical crisaborole with other topical treatments for atopic dermatitis are lacking. (See "Treatment of atopic dermatitis (eczema)", section on 'Crisaborole'.)

Persistence of pediatric atopic dermatitis (November 2016)

Atopic dermatitis (AD) is a chronic disease with a highly variable course. Although most children are thought to “outgrow” it before adolescence, little is known about the factors associated with its persistence into adulthood. A meta-analysis including over 110,000 subjects found that 20 percent of children with AD had persistent disease eight years after the diagnosis, and less than 5 percent had persistent disease 20 years later [42]. Children who developed AD before two years of age had a much lower risk of persistent disease than those who developed AD later in childhood or during adolescence. Other predictors of persistent AD were severity and duration of AD and female sex, whereas hypersensitivity to one or more allergens at disease onset did not seem to influence the persistence of disease. (See "Pathogenesis, clinical manifestations, and diagnosis of atopic dermatitis (eczema)", section on 'Clinical course and complications'.)

New guidelines for the management of Stevens-Johnson/toxic epidermal necrolysis syndrome (August 2016)

The British Association of Dermatologists released new guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), a severe and potentially fatal mucocutaneous drug reaction [43]. The guidelines provide evidence-based recommendations for the diagnosis, severity assessment, and management of SJS/TEN. Specific areas covered include initial management, supportive care, and therapies intended to reduce mortality, such as intravenous immune globulins, systemic corticosteroids, and cyclosporine. The treatment of eye involvement, including systemic therapies and amniotic membrane transplantation to prevent permanent ocular sequelae, as well as the management of oral, urogenital, and airway mucosal involvement are also addressed. (See "Stevens-Johnson syndrome and toxic epidermal necrolysis: Management, prognosis, and long-term sequelae", section on 'General principles'.)

DEVELOPMENTAL AND BEHAVIORAL PROBLEMS

Age of symptom onset and diagnosis of adult ADHD (September 2016)

Attention deficit hyperactivity disorder (ADHD) is conceptualized as a disorder with childhood onset that persists in adulthood. DSM-5 diagnostic criteria for adult ADHD require the presence of several symptoms prior to age 12 years. Multiple recent studies, however, have challenged this understanding of the disorder. One of them, a longitudinal cohort study, followed all children born in Pelotas, Brazil in 1993 up to the ages of 18 or 19 years [44]. Three hundred ninety-three of the 5249 children were diagnosed with ADHD at age 11 and 492 were diagnosed with ADHD at age 18 or 19 years. Only 60 children with ADHD continued to have ADHD as young adults (17.2 percent) and only 60 young adults with ADHD had the disorder in childhood (12.6 percent). The requirement of childhood onset for the diagnosis of adult ADHD is controversial and may be reexamined as further data become available. (See "Attention deficit hyperactivity disorder in adults: Epidemiology, pathogenesis, clinical features, course, assessment, and diagnosis", section on 'Course'.)

Oxytocin induction not associated with autism (August 2016)

A possible association between oxytocin induction of labor and development of autism in offspring has been widely publicized in the lay press, based on findings from a single epidemiological study. Recently, a nationwide epidemiologic study in Sweden found no association between labor induction and autism in offspring when adjustments were made for environmental and genetic factors shared by siblings [45]. A strength of this study was that comparison of exposure-discordant births to the same woman allowed control for all unmeasured factors shared by siblings. We believe an association between oxytocin induction and autism is unlikely. (See "Induction of labor", section on 'Other'.)

Discontinuation of desmopressin treatment of nocturnal enuresis in children (July 2016)

Desmopressin is an effective short-term treatment for nocturnal enuresis in children, but relapse rates are high after discontinuation. A recent meta-analysis of four randomized trials including 500 patients demonstrated the benefit of tapering desmopressin rather than abrupt discontinuation (sustained response rate: 57 versus 42 percent) [46]. In subgroup analyses, gradually decreasing the effective dose prevented relapse, but increasing the interval between doses did not. When discontinuing daily desmopressin, we suggest decreasing the daily dose rather than extending the interval between doses or abrupt discontinuation. (See "Nocturnal enuresis in children: Management", section on 'Discontinuation'.)

EMERGENCY MEDICINE

Early physical activity following acute concussion in children and adolescents (January 2017)

Although physical rest is routinely recommended after concussion, there are few data to determine whether avoidance of physical activity hastens recovery. In a prospective, multicenter cohort study of over 2400 children who were diagnosed with an acute concussion during an emergency department visit, early physical activity (within seven days of injury) compared with physical rest was associated with a significantly reduced risk of persistent postconcussive symptoms (PPCS) at 28 days [47]. However, the difference in PPCS may be the result of confounding, and clinical trials are needed to confirm this result. We suggest that children and adolescents with concussions adhere to full physical rest until they have no symptoms of concussion (table 1) and normal balance or return to baseline on standardized testing. In the minority of patients with prolonged symptoms beyond seven days after injury, we introduce light, subsymptom threshold aerobic exercise (eg, light stationary bicycling), which can often be tolerated and may improve symptoms. (See "Concussion in children and adolescents: Management", section on 'Physical rest'.)

Clinical prediction rule for abusive head trauma in well-appearing infants (August 2016)

Detection of abusive head trauma (AHT) is challenging in well-appearing infants who typically present with an unrelated complaint and no history of trauma. High-risk complaints include apnea or acute life-threatening event, seizure, vomiting without diarrhea, soft-tissue scalp swelling, bruising, lethargy, fussiness, or poor feeding. In a prospective multicenter validation of a clinical prediction rule in over 1000 well-appearing infants younger than one year of age (109 with abuse) who presented with high-risk complaints for possible abuse, a score of two or more had high sensitivity for an abnormality on computed tomography (CT) of the head [48]. This rule, which assigns points based upon age, head circumference, skin examination, and serum hemoglobin, has significant potential for assisting the clinician with decisions about neuroimaging in well-appearing infants with equivocal findings for abuse. Magnetic resonance imaging is preferred to CT in such patients if there is timely availability of the study and interpretation by a pediatric neuroradiologist. (See "Child abuse: Evaluation and diagnosis of abusive head trauma in infants and children", section on 'Well-appearing infants'.)

GASTROENTEROLOGY, HEPATOLOGY, AND NUTRITION

Direct or conjugated bilirubin as a screening test for biliary atresia in neonates (September 2016)

Retrospective studies suggest that infants who develop biliary atresia often have a mildly elevated conjugated bilirubin level (>0.3 mg/dL) in the first few days of life, weeks to months before they develop symptoms. A pilot study recently investigated whether this observation could be used as a screening test in neonates [49]. The authors screened more than 11,000 neonates using a two-stage approach to identify those with persistent elevations of direct or conjugated bilirubin, resulting in early identification of two infants with biliary atresia and one with alpha-1 antitrypsin deficiency. Further studies are needed to determine the sensitivity and cost-effectiveness of this approach and its potential effect on patient outcome. (See "Biliary atresia", section on 'Laboratory studies'.)

GENETICS AND PEDIATRIC METABOLISM

Selumetinib for plexiform neurofibromas in NF1 (January 2017)

Medical management of plexiform neurofibromas in patients with neurofibromatosis 1 is challenging, with no standard therapies. In a phase I trial of selumetinib, an inhibitor of mitogen-activated protein kinases, 17 of 24 children with inoperable plexiform neurofibromas experienced a ≥20 percent reduction in neurofibroma volume and none had disease progression [50]. Additional studies are in progress. (See "Neurofibromatosis type 1 (NF1): Management and prognosis", section on 'Plexiform neurofibromas'.)

HEMATOLOGY AND ONCOLOGY

Restrictive postoperative transfusion strategy in infants and children with congenital heart disease (October 2016)

In a randomized trial of restrictive versus liberal postoperative transfusion strategies in 162 infants with congenital heart disease undergoing surgical repair or palliation, a restrictive transfusion strategy reduced the red cell transfusion rate, without increasing in-hospital mortality, need for extracorporeal membrane oxygenation (ECMO) support, or hospital length of stay [40]. The restrictive group was transfused for hemoglobin <7.0 g/dL for biventricular repairs or <9.0 g/dL for palliative procedures plus a clinical indication; the liberal group was transfused for hemoglobin <9.5 g/dL for biventricular repairs or <12 g/dL for palliative procedures. Larger more definitive trials are needed before clear transfusion guidelines in this population can be made. (See "Red blood cell transfusion in infants and children: Indications", section on 'Surgery'.)

Risk of inherited thrombophilia and central venous catheter-associated venous thromboembolism in children (September 2016)

The majority of venous thromboembolism (VTE) in children is associated with central venous catheter (CVC) use. The association between inherited thrombophilia (IT) and CVC-related VTE is unclear. A recent systematic review and meta-analysis found that IT is associated with an increased likelihood of CVC-associated VTE (odds ratio 3.2 [95% CI 1.6-6.5]) [51]. However, the meta-analysis was limited by significant heterogeneity among studies and a relatively high prevalence of elevated factor VIII, which may represent an inherited disorder or may be acquired. The prevalence of most other IT traits in the meta-analysis was low and their associations with CVC-related VTE were relatively weak. The available evidence is insufficient to support routinely performing IT testing to inform management decisions in children with CVC-related VTE. (See "Screening for inherited thrombophilia in children", section on 'First episode of CVC-related VTE'.)

INFECTIOUS DISEASES AND IMMUNIZATIONS

Guidelines on diagnosis of tuberculosis (January 2017)

Guidelines from the American Thoracic Society, Infectious Diseases Society of America, and the Centers for Disease Control and Prevention on the diagnosis of tuberculosis in adults and children were published in December 2016 [52]. They state that an interferon-gamma release assay (IGRA) is generally preferred for diagnosis of latent tuberculosis infection (LTBI) in individuals five years or older who have low-to-intermediate risk of progression to active disease (table 2), although the tuberculin skin test (TST) is an acceptable alternative if IGRA is not available or too costly. For those who have high risk of progression to active disease, either IGRA or TST is acceptable, but many guideline panel members noted using the alternative test if the initial one was negative and considering a positive result from either test to indicate LTBI. The evaluation of suspected tuberculosis disease should include three sputum specimens for acid-fast bacilli (AFB) smear and culture and one or more specimens for nucleic acid amplification (NAA) testing. (See "Diagnosis of latent tuberculosis infection (tuberculosis screening) in HIV-uninfected adults" and "Diagnosis of pulmonary tuberculosis in HIV-uninfected patients" and "Latent tuberculosis infection in children" and "Tuberculosis disease in children".)

Risk of birth defects with Zika virus infection during pregnancy (January 2017)

The risk of birth defects resulting from in utero exposure to Zika virus was 6 and 42 percent in two recent reports [23,24]. The wide range likely reflects differences in study design, populations studied, maternal Zika case definition, and the range of clinical abnormalities included. The most common fetal/newborn findings in these reports were abnormal brain imaging, microcephaly, small size for gestational age, and abnormal neurologic examination. The greatest risk of serious sequelae in offspring appeared to be with first or second trimester infection, but serious sequelae also occurred with third trimester infection. (See "Zika virus infection: Evaluation and management of pregnant women", section on 'Risk of vertical transmission and anomalies' and "Congenital Zika virus infection: Clinical features, evaluation, and management of the neonate", section on 'Clinical findings'.)

Pattern of anomalies in congenital Zika syndrome (November 2016)

The clinical spectrum of congenital Zika syndrome (CZS) is evolving as more cases are described. A comprehensive review of the available published data identified five unique features of CZS that are rarely seen with other congenital infections: (1) severe microcephaly with partially collapsed skull, (2) thin cerebral cortices with subcortical calcifications, (3) macular scarring and focal pigmentary retinal mottling, (4) congenital contractures (arthrogryposis), and (5) marked early hypertonia [27]. Recognition of this distinctive phenotype can help clinicians identify infants with CZS and ensure appropriate etiologic evaluation and comprehensive clinical investigation. (See "Congenital Zika virus infection: Clinical features, evaluation, and management of the neonate", section on 'Clinical findings'.)

Meningococcal conjugate vaccination for HIV-infected patients (November 2016)

Growing evidence has suggested that HIV-infected individuals have a disproportionate incidence of invasive meningococcal disease, with an estimated risk 5 to 13 times that of the general population. Because of this, the Centers for Disease Control and Prevention in the United States now recommends meningococcal conjugate vaccination (with MenACWY-CRM [Menveo] or MenACWY-D [Menactra]) for all HIV-infected individuals older than two months [53]. This includes a primary vaccine series for those who have not previously received it and interval booster doses every several years; the precise schedule depends on the age of the patient (table 3). Individuals may also have separate indications for serogroup B meningococcal vaccination. Evidence of vaccine efficacy in HIV-infected patients is limited to immunologic outcomes. (See "Immunizations in HIV-infected patients", section on 'Meningococcal vaccine' and "Meningococcal vaccines".)

Incidence of sexually transmitted infections in the United States (November 2016)

The total number of cases of chlamydia (over 1.5 million), gonorrhea (nearly 400,000), and syphilis (nearly 24,000) reported to the Centers for Disease Control and Prevention in the United States in 2015 was the highest ever recorded in a given year [54]. Chlamydia and gonorrhea continued to occur most commonly among 15 to 24 year olds, and men who have sex with men accounted for the majority of gonorrhea and primary/secondary syphilis cases. These surveillance data highlight the importance of sexually transmitted infection prevention efforts, screening, and treatment among at-risk individuals. (See "Epidemiology of Chlamydia trachomatis infections", section on 'Incidence' and "Epidemiology and pathogenesis of Neisseria gonorrhoeae infection", section on 'Incidence' and "Syphilis: Epidemiology, pathophysiology, and clinical manifestations in HIV-uninfected patients", section on 'Epidemiology' and "Screening for sexually transmitted infections".)

HPV vaccine dosing for individuals younger than 15 years (November 2016)

For individuals younger than 15 years receiving human papillomavirus (HPV) vaccination, two vaccine doses administered at least six months apart are now recommended by the Centers for Disease Control and Prevention in the United States [55]. This new vaccine schedule is similar to schedules used in other countries and is supported by data demonstrating that two vaccine doses in young females have similar immunogenicity to three doses. However, the efficacy of fewer than three doses for prevention of cervical neoplastic disease has not been directly established. Three doses are still recommended for individuals older than 15 years because they have lower immunologic responses to HPV vaccination. (See "Recommendations for the use of human papillomavirus vaccines", section on 'Immunization schedule'.)

Duration of passive protection of the infant from maternal influenza vaccination (September 2016, Modified September 2016)

A randomized trial of trivalent inactivated influenza vaccination of pregnant women reported 86 percent efficacy against laboratory confirmed influenza among infants ≤8 weeks of age and 25 to 30 percent efficacy among infants 8 to 24 weeks of age, compared with placebo vaccination [56]. These data suggest that the passive protection afforded by maternal influenza vaccination declines significantly before the infant is eligible for influenza vaccination at six months of age. (See "Influenza and pregnancy", section on 'Infant protection'.)

Inactivated influenza vaccine for 2016-2017 season in the northern hemisphere (August 2016)

The effectiveness of seasonal influenza vaccines varies from season to season and is determined by a number of factors, including the match between circulating influenza strains and influenza strains in the vaccine. During the 2015-2016 influenza season, data from the United States Influenza Vaccine Effectiveness Network indicated that inactivated influenza vaccine (IIV) was 63 percent effective in preventing influenza in children, but live attenuated influenza vaccine (LAIV) was not effective [57]. Findings of poor or lower than expected LAIV effectiveness were also noted during the 2013-2014 and 2014-2015 seasons in the United States. These findings are inconsistent with studies sponsored by the manufacturer and studies from other countries that found LAIV was effective (ranging from 46 to 58 percent) during the 2015-2016 season [58-61]; however, LAIV was less effective than IIV in all of these studies [62]. In August 2016, the United States Centers for Disease Control and Prevention recommended that LAIV not be used during the 2016-2017 influenza season [63]. While some countries have elected to continue using LAIV [58], we suggest IIV rather than LAIV for the 2016-2017 influenza season in the northern hemisphere. (See "Seasonal influenza in children: Prevention with vaccines", section on 'IIV versus LAIV' and "Seasonal influenza vaccination in adults", section on 'Choice of vaccine formulation'.)

Absence of pyuria in children with UTI (July 2016)

The diagnosis of urinary tract infection (UTI) in children is usually based on the finding of significant bacteriuria plus pyuria. However, in a retrospective review of 1181 children <18 years of age with symptomatic UTI and significant growth of a single uropathogen, microscopic urinalysis did not show pyuria in 13 percent [64]. The frequency of pyuria was lower in children with Enterococcus (54 percent), Pseudomonas aeruginosa (62 percent), and Klebsiella (74 percent) than in children with E. coli (89 percent). Therefore, if the urine culture of a child with UTI symptoms demonstrates significant growth (≥50,000 colony-forming units [CFU]/mL from a catheterized specimen or ≥100,000 CFU/mL from a clean voided specimen) of Enterococcus, Klebsiella, or P. aeruginosa, UTI may be diagnosed in the absence of pyuria. (See "Urinary tract infections in infants and children older than one month: Clinical features and diagnosis", section on 'Pyuria'.)

Treatment failure of pharyngeal gonorrhea following combination antimicrobial therapy (July 2016)

Because of concerns about the decreasing susceptibility of Neisseria gonorrhoeae to several classes of antibiotics, combination antimicrobial therapy with ceftriaxone plus a second agent, preferably azithromycin, is the recommended treatment for uncomplicated gonorrhea. However, treatment failure following combination therapy has now been reported, in a heterosexual man from the United Kingdom who presented with both urogenital and pharyngeal infection [65]. Although the urogenital infection was successfully treated with ceftriaxone plus azithromycin, the pharyngeal infection persisted, and decreased susceptibility to both agents was detected in the post-treatment isolate. This report, in addition to surveillance reports suggesting increasing rates of decreased susceptibility to azithromycin in N. gonorrhoeae isolates in the United States [66], highlights the need for novel treatment strategies for gonorrhea in the face of rising antimicrobial resistance. (See "Treatment of uncomplicated gonococcal infections", section on 'Monitoring for and managing treatment failure' and "Treatment of uncomplicated gonococcal infections", section on 'Rationale for dual therapy'.)

NEPHROLOGY AND UROLOGY

Acute kidney injury in critically ill children (November 2016)

Children cared for in intensive care units (ICUs) are at increased risk of acute kidney injury (AKI). In a large prospective multicenter study of patients 3 months to 25 years of age cared for in over 30 pediatric ICUs worldwide, approximately 27 percent developed AKI and 12 percent developed severe AKI (stage 2 or 3 AKI) (table 4) [67]. Severe AKI was independently associated with an increased risk of death, and increasing severity was associated with increasing risk of death. These data reinforce the need to identify patients at risk for AKI or with mild AKI so that interventions to prevent further injury can be implemented. (See "Acute kidney injury in children: Clinical features, etiology, evaluation, and diagnosis", section on 'Critically ill children'.)

Complement-mediated HUS, eculizumab, meningococcal group B vaccine, and risk for hemolytic anemia (September 2016)

The introduction of eculizumab (a monoclonal antibody that blocks activation of the terminal complement cascade) has significantly improved the outcome of patients with complement-mediated hemolytic uremic syndrome (HUS), a rare, potentially life-threatening disease. Eculizumab therapy increases the risk of meningococcal infection, and vaccination against Neisseria meningitidis (with a quadrivalent vaccine and, for patients older than 10 years, a serogroup B vaccine) has been recommended in treated patients. However, a review from Health Canada reported an increased risk of hemolytic anemia following receipt of the multicomponent meningococcal serogroup B vaccine (Bexsero, MenB-4C) among patients who were already being treated with eculizumab [68]. To minimize the risk of hemolysis, serogroup B meningococcal vaccination should be performed prior to the initiation of eculizumab therapy, if possible. In cases where prior vaccination is not possible, the manufacturer of eculizumab recommends that serogroup B meningococcal vaccination should be administered when patients are stable and their disease is well controlled and it is assumed that the blood level of eculizumab is high. (See "Complement-mediated hemolytic uremic syndrome", section on 'Adverse effects'.)

NEUROLOGY

Nusinersen for spinal muscular atrophy (January 2017)

Nusinersen, an antisense oligonucleotide, is the first drug approved to treat spinal muscular atrophy (SMA) by the US Food and Drug Administration (FDA). In an interim analysis of the double-blind ENDEAR trial, which enrolled 82 infants with SMA, improvement in motor milestones was observed in 40 percent of patients treated with nusinersen, versus none for those who received the sham procedure [69]. The FDA based its approval upon data from this trial and open-label studies in older patients with SMA [70,71]. We recommend nusinersen for pediatric and adult patients with SMA. (See "Spinal muscular atrophy", section on 'Nusinersen'.)

Amitriptyline and topiramate for prevention of pediatric migraine (November 2016)

Amitriptyline and topiramate are commonly used as prophylactic agents for pediatric migraine, and two previous randomized trials found that topiramate was effective for this indication. However, neither amitriptyline nor topiramate was better than placebo for headache prevention in the 24-week CHAMP trial of children and adolescents (8 to 17 years of age) with episodic or chronic migraine [72]. Adverse events were more common in the amitriptyline and topiramate groups. There is no single best preventive treatment for migraine in children, and choice of therapy should be individualized based on comorbidities and patient preferences. (See "Preventive treatment of migraine in children", section on 'Amitriptyline'.)

Pattern of anomalies in congenital Zika syndrome (November 2016)

The clinical spectrum of congenital Zika syndrome (CZS) is evolving as more cases are described. A comprehensive review of the available published data identified five unique features of CZS that are rarely seen with other congenital infections: (1) severe microcephaly with partially collapsed skull, (2) thin cerebral cortices with subcortical calcifications, (3) macular scarring and focal pigmentary retinal mottling, (4) congenital contractures (arthrogryposis), and (5) marked early hypertonia [27]. Recognition of this distinctive phenotype can help clinicians identify infants with CZS and ensure appropriate etiologic evaluation and comprehensive clinical investigation. (See "Congenital Zika virus infection: Clinical features, evaluation, and management of the neonate", section on 'Clinical findings'.)

Eteplirsen for Duchenne muscular dystrophy (September 2016)

Small studies of eteplirsen, an exon 51 skipping drug, suggest that it can increase dystrophin production in skeletal muscle without drug-related adverse effects in patients with Duchenne muscular dystrophy (DMD) with an amenable dystrophin gene mutation. Based upon this finding, the US Food and Drug Administration granted accelerated approval of eteplirsen in September 2016 for the treatment patients with DMD who have a confirmed mutation of the dystrophin gene amenable to exon 51 skipping [73]. The mutation is present in approximately 13 percent of patients with DMD. (See "Treatment of Duchenne and Becker muscular dystrophy", section on 'Eteplirsen'.)

Everolimus for refractory epilepsy associated with tuberous sclerosis (September 2016)

Tuberous sclerosis complex (TSC) is characterized by the development of benign tumors in multiple organs, including the brain, and medically intractable epilepsy is a major cause of morbidity. The mammalian target of rapamycin (mTOR) pathway is over-activated in TSC, and mTOR inhibitors such as everolimus are known to have antitumor efficacy. Data on antiseizure effects have been limited, however. In the recent 18-week EXIST-3 trial, which enrolled over 360 subjects with TSC and treatment-resistant epilepsy, the proportion of subjects achieving a ≥50 percent reduction in seizure frequency was significantly greater for the low- and high-exposure everolimus groups compared with placebo (28, 40, and 15 percent, respectively) [74]. The most common adverse events associated with everolimus were stomatitis, diarrhea, and pyrexia. While longer-term data are needed, these results suggest that everolimus is an effective and safe treatment option for patients with TSC and treatment-resistant epilepsy. (See "Tuberous sclerosis complex: Management", section on 'Refractory epilepsy'.)

PULMONOLOGY

Safety of inhaled glucocorticoid-LABA combination therapy in asthma (September 2016)

In early studies, a small increase in asthma-related deaths associated with salmeterol led the US Food and Drug Administration to place a boxed warning on the use of long-acting beta agonists (LABAs) in asthma. While concerning, the number of events was small, and it could not be determined if the potential risk of salmeterol could be mitigated by combining LABAs with inhaled glucocorticoids. Three large randomized trials including 30,000 children and adults found no increase in asthma-related adverse events or deaths among patients who used combination inhalers with salmeterol or formoterol plus an inhaled glucocorticoid versus glucocorticoid monotherapy [75-77]. These studies support the safety of these fixed-dose combination inhalers in patients with moderate-to-severe asthma. (See "Beta agonists in asthma: Controversy regarding chronic use", section on 'Potential risk mitigation'.)

Evaluation of recurrent wheezing in children <2 years of age (August 2016)

The American Thoracic Society has developed guidelines for evaluation of children <2 years of age who have recurrent wheezing that is unresponsive to bronchodilators or inhaled or systemic glucocorticoids [78]. Suggested evaluation includes one or more of the following: videofluoroscopic swallowing study (modified barium swallow) for possible swallowing dysfunction; 24-hour esophageal pH monitoring for assessment of gastroesophageal reflux; and/or flexible fiberoptic bronchoscopy bronchoalveolar lavage (BAL) to assess for lower airway bacterial infection. Our approach is consistent with these guidelines. (See "Approach to wheezing in infants and children", section on 'Radiography' and "Approach to wheezing in infants and children", section on 'Endoscopy' and "Approach to wheezing in infants and children", section on 'Evaluation for gastroesophageal reflux'.)

Use of UpToDate is subject to the Subscription and License Agreement.

REFERENCES

  1. US Preventive Services Task Force, Bibbins-Domingo K, Grossman DC, et al. Serologic Screening for Genital Herpes Infection: US Preventive Services Task Force Recommendation Statement. JAMA 2016; 316:2525.
  2. http://www.fda.gov/Drugs/DrugSafety/ucm532356.htm.
  3. Nehus EJ, Khoury JC, Inge TH, et al. Kidney outcomes three years after bariatric surgery in severely obese adolescents. Kidney Int 2016.
  4. Guidelines for the Management of Patients With Positional Plagiocephaly. https://www.cns.org/guidelines/guidelines-management-patients-positional-plagiocephaly.
  5. Lurbe E, Agabiti-Rosei E, Cruickshank JK, et al. 2016 European Society of Hypertension guidelines for the management of high blood pressure in children and adolescents. J Hypertens 2016; 34:1887.
  6. McConnell R, Barrington-Trimis JL, Wang K, et al. Electronic-cigarette Use and Respiratory Symptoms in Adolescents. Am J Respir Crit Care Med 2016.
  7. Council on Communications and Media. Media use in school-aged children and adolescents. Pediatrics 2016.
  8. Council on Communications and Media. Media and young minds. Pediatrics 2016.
  9. Usinger KM, Gola SB, Weis M, Smaldone A. Intrauterine Contraception Continuation in Adolescents and Young Women: A Systematic Review. J Pediatr Adolesc Gynecol 2016; 29:659.
  10. Martin JA, Hamilton BE, Osterman MJ, et al. Births: Final data for 2015. Natl Vital Stat Rep 2017; 66:1.
  11. Batra EK, Teti DM, Schaefer EW, et al. Nocturnal Video Assessment of Infant Sleep Environments. Pediatrics 2016; 138.
  12. Moon RY, TASK FORCE ON SUDDEN INFANT DEATH SYNDROME. SIDS and Other Sleep-Related Infant Deaths: Evidence Base for 2016 Updated Recommendations for a Safe Infant Sleeping Environment. Pediatrics 2016; 138.
  13. Lavelle JM, Blackstone MM, Funari MK, et al. Two-Step Process for ED UTI Screening in Febrile Young Children: Reducing Catheterization Rates. Pediatrics 2016; 138.
  14. McCarty CA, Zatzick D, Stein E, et al. Collaborative Care for Adolescents With Persistent Postconcussive Symptoms: A Randomized Trial. Pediatrics 2016; 138.
  15. Golden NH, Schneider M, Wood C, et al. Preventing Obesity and Eating Disorders in Adolescents. Pediatrics 2016; 138.
  16. Brinkman SA, Johnson SE, Codde JP, et al. Efficacy of infant simulator programmes to prevent teenage pregnancy: a school-based cluster randomised controlled trial in Western Australia. Lancet 2016; 388:2264.
  17. Anderson SE, Andridge R, Whitaker RC. Bedtime in Preschool-Aged Children and Risk for Adolescent Obesity. J Pediatr 2016; 176:17.
  18. Cipriani A, Zhou X, Del Giovane C, et al. Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis. Lancet 2016; 388:881.
  19. US Preventive Services Task Force, Bibbins-Domingo K, Grossman DC, et al. Screening for Lipid Disorders in Children and Adolescents: US Preventive Services Task Force Recommendation Statement. JAMA 2016; 316:625.
  20. Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents, National Heart, Lung, and Blood Institute. Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. Pediatrics 2011; 128 Suppl 5:S213.
  21. Riederer AM, Campleman SL, Carlson RG, et al. Acute Poisonings from Synthetic Cannabinoids - 50 U.S. Toxicology Investigators Consortium Registry Sites, 2010-2015. MMWR Morb Mortal Wkly Rep 2016; 65:692.
  22. Committee Opinion No. 684: Delayed Umbilical Cord Clamping After Birth. Obstet Gynecol 2017; 129:e5.
  23. Brasil P, Pereira JP Jr, Moreira ME, et al. Zika Virus Infection in Pregnant Women in Rio de Janeiro. N Engl J Med 2016; 375:2321.
  24. Honein MA, Dawson AL, Petersen EE, et al. Birth Defects Among Fetuses and Infants of US Women With Evidence of Possible Zika Virus Infection During Pregnancy. JAMA 2016.
  25. Goode RH, RettigantiM, Li J, et al. Developmental Outcomes of Preterm Infants With Neonatal Hypoglycemia. Pediatrics 2016.
  26. Boronat N, Aguar M, Rook D, et al. Survival and Neurodevelopmental Outcomes of Preterms Resuscitated With Different Oxygen Fractions. Pediatrics 2016; 138.
  27. Moore CA, Staples JE, Dobyns WB, et al. Characterizing the Pattern of Anomalies in Congenital Zika Syndrome for Pediatric Clinicians. JAMA Pediatr 2016.
  28. Roberts CT, Owen LS, Manley BJ, et al. Nasal High-Flow Therapy for Primary Respiratory Support in Preterm Infants. N Engl J Med 2016; 375:1142.
  29. Togias A, Cooper SF, Acebal ML, et al. Addendum Guidelines for the Prevention of Peanut Allergy in the United States: Report of the National Institute of Allergy and Infectious Diseases-Sponsored Expert Panel. Pediatr Dermatol 2017; 34:e1.
  30. Natsume O, Kabashima S, Nakazato J, et al. Two-step egg introduction for prevention of egg allergy in high-risk infants with eczema (PETIT): a randomised, double-blind, placebo-controlled trial. Lancet 2016.
  31. Palmer DJ, Sullivan TR, Gold MS, et al. Randomized controlled trial of early regular egg intake to prevent egg allergy. J Allergy Clin Immunol 2016.
  32. Wei-Liang Tan J, Valerio C, Barnes EH, et al. A randomized trial of egg introduction from 4 months of age in infants at risk for egg allergy. J Allergy Clin Immunol 2016.
  33. Bellach J, Schwarz V, Ahrens B, et al. Randomized placebo-controlled trial of hen's egg consumption for primary prevention in infants. J Allergy Clin Immunol 2016.
  34. Stein MM, Hrusch CL, Gozdz J, et al. Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children. N Engl J Med 2016; 375:411.
  35. Sheehan WJ, Mauger DT, Paul IM, et al. Acetaminophen versus Ibuprofen in Young Children with Mild Persistent Asthma. N Engl J Med 2016; 375:619.
  36. Marmor MF, Kellner U, Lai TY, et al. Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision). Ophthalmology 2016; 123:1386.
  37. Omalizumab. http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/103976s5225lbl.pdf (Accessed on July 13, 2016).
  38. Miceli Sopo S, Greco M, Cuomo B, et al. Matrix effect on baked egg tolerance in children with IgE-mediated hen's egg allergy. Pediatr Allergy Immunol 2016; 27:465.
  39. American Acedemy of Pediatrics Clinical Report: Infectious complications with the use of biologic response modifiers in infants and children. http://pediatrics.aappublications.org/content/pediatrics/early/2016/07/14/peds.2016-1209.full.pdf (Accessed on July 19, 2016).
  40. Cholette JM, Swartz MF, Rubenstein J, et al. Outcomes Using a Conservative Versus Liberal Red Blood Cell Transfusion Strategy in Infants Requiring Cardiac Operation. Ann Thorac Surg 2016.
  41. www.accessdata.fda.gov/drugsatfda_docs/appletter/2016/207695Orig1s000ltr.pdf (Accessed on December 20, 2016).
  42. Kim JP, Chao LX, Simpson EL, Silverberg JI. Persistence of atopic dermatitis (AD): A systematic review and meta-analysis. J Am Acad Dermatol 2016; 75:681.
  43. Creamer D, Walsh SA, Dziewulski P, et al. U.K. guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults 2016. Br J Dermatol 2016; 174:1194.
  44. Caye A, Rocha TB, Anselmi L, et al. Attention-Deficit/Hyperactivity Disorder Trajectories From Childhood to Young Adulthood: Evidence From a Birth Cohort Supporting a Late-Onset Syndrome. JAMA Psychiatry 2016; 73:705.
  45. Oberg AS, D'Onofrio BM, Rickert ME, et al. Association of Labor Induction With Offspring Risk of Autism Spectrum Disorders. JAMA Pediatr 2016; 170:e160965.
  46. Chua ME, Silangcruz JM, Chang SJ, et al. Desmopressin Withdrawal Strategy for Pediatric Enuresis: A Meta-analysis. Pediatrics 2016; 138.
  47. Grool AM, Aglipay M, Momoli F, et al. Association Between Early Participation in Physical Activity Following Acute Concussion and Persistent Postconcussive Symptoms in Children and Adolescents. JAMA 2016; 316:2504.
  48. Berger RP, Fromkin J, Herman B, et al. Validation of the Pittsburgh Infant Brain Injury Score for Abusive Head Trauma. Pediatrics 2016; 138.
  49. Harpavat S, Garcia-Prats JA, Shneider BL. Newborn Bilirubin Screening for Biliary Atresia. N Engl J Med 2016; 375:605.
  50. Dombi E, Baldwin A, Marcus LJ, et al. Activity of Selumetinib in Neurofibromatosis Type 1-Related Plexiform Neurofibromas. N Engl J Med 2016; 375:2550.
  51. Neshat-Vahid S, Pierce R, Hersey D, et al. Association of thrombophilia and catheter-associated thrombosis in children: a systematic review and meta-analysis. J Thromb Haemost 2016; 14:1749.
  52. Lewinsohn DM, Leonard MK, LoBue PA, et al. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children. Clin Infect Dis 2016.
  53. MacNeil JR, Rubin LG, Patton M, et al. Recommendations for Use of Meningococcal Conjugate Vaccines in HIV-Infected Persons - Advisory Committee on Immunization Practices, 2016. MMWR Morb Mortal Wkly Rep 2016; 65:1189.
  54. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance, 2015. Atlanta, GA: US Department of Health and Human Services; October 2016.
  55. CDC recommends only two HPV shots for younger adolescents, October 19, 2016. https://www.cdc.gov/media/releases/2016/p1020-hpv-shots.html (Accessed on October 22, 2016).
  56. Nunes MC, Cutland CL, Jones S, et al. Duration of Infant Protection Against Influenza Illness Conferred by Maternal Immunization: Secondary Analysis of a Randomized Clinical Trial. JAMA Pediatr 2016; 170:840.
  57. Centers for Disease Control and Prevention. ACIP votes down use of LAIV for 2016-2017 flu season. http://www.cdc.gov/media/releases/2016/s0622-laiv-flu.html (Accessed on June 24, 2016).
  58. Hawkes N. UK stands by nasal flu vaccine for children as US doctors are told to stop using it. BMJ 2016; 353:i3546.
  59. AstraZeneca provides update on Flumist quadrivalent vaccine in the US for the 2016-2017 influenza season. https://www.astrazeneca.com/media-centre/press-releases/2016/astrazeneca-provides-update-on-flumist-quadrivalent-vaccine-in-the-us-for-the-2016-17-influenza-season-23062016.html (Accessed on June 27, 2016).
  60. Influenza vaccine effectiveness (VE) in adults and children in primary care in the UK: provisional end-of-season results 2015-2016. https://www.gov.uk/government/publications/influenza-vaccine-effectiveness-2015-to-2016-estimates (Accessed on June 27, 2016).
  61. Seasonal childhood influenza vaccinations. Experiences from Finland. http://www.nvm2016.is/sites/default/files/Nohynek_NorVac_influenzaLessonsNohynek_short.pdf (Accessed on June 27, 2016).
  62. New information regarding Flumist quadrivalent (Influenza Vaccine Live, Intranasal) https://www.besse.com/Documents/ACIP%202016%20HCP%20Letter-%20Final.pdf (Accessed on June 27, 2016).
  63. Grohskopf LA, Sokolow LZ, Broder KR, et al. Prevention and Control of Seasonal Influenza with Vaccines. MMWR Recomm Rep 2016; 65:1.
  64. Shaikh N, Shope TR, Hoberman A, et al. Association Between Uropathogen and Pyuria. Pediatrics 2016; 138.
  65. Fifer H, Natarajan U, Jones L, et al. Failure of Dual Antimicrobial Therapy in Treatment of Gonorrhea. N Engl J Med 2016; 374:2504.
  66. Kirkcaldy RD, Harvey A, Papp JR, et al. Neisseria gonorrhoeae Antimicrobial Susceptibility Surveillance — The Gonococcal Isolate Surveillance Project, 27 Sites, United States, 2014. MMWR Surveill Summ 2016;65(No. SS-7):1–19.
  67. Kaddourah A, Basu RK, Bagshaw SM, et al. Epidemiology of Acute Kidney Injury in Critically Ill Children and Young Adults. N Engl J Med 2017; 376:11.
  68. www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/soliris-bexsero-eng.php (Accessed on September 23, 2016).
  69. FDA approves first drug for spinal muscular atrophy. U.S. Food & Drug Administration. www.fda.gov/newsevents/newsroom/pressannouncements/ucm534611.htm (Accessed on January 03, 2017).
  70. Finkel RS, Chiriboga CA, Vajsar J, et al. Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study. Lancet 2016.
  71. Chiriboga CA, Swoboda KJ, Darras BT, et al. Results from a phase 1 study of nusinersen (ISIS-SMN(Rx)) in children with spinal muscular atrophy. Neurology 2016; 86:890.
  72. Powers SW, Coffey CS, Chamberlin LA, et al. Trial of Amitriptyline, Topiramate, and Placebo for Pediatric Migraine. N Engl J Med 2016.
  73. FDA grants accelerated approval to first drug for Duchenne muscular dystrophy. U.S. Food & Drug Administration. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm521263.htm (Accessed on September 22, 2016).
  74. French JA, Lawson JA, Yapici Z, et al. Adjunctive everolimus therapy for treatment-resistant focal-onset seizures associated with tuberous sclerosis (EXIST-3): a phase 3, randomised, double-blind, placebo-controlled study. Lancet 2016; 388:2153.
  75. Stempel DA, Raphiou IH, Kral KM, et al. Serious Asthma Events with Fluticasone plus Salmeterol versus Fluticasone Alone. N Engl J Med 2016; 374:1822.
  76. Stempel DA, Szefler SJ, Pedersen S, et al. Safety of Adding Salmeterol to Fluticasone Propionate in Children with Asthma. N Engl J Med 2016; 375:840.
  77. Peters SP, Bleecker ER, Canonica GW, et al. Serious Asthma Events with Budesonide plus Formoterol vs. Budesonide Alone. N Engl J Med 2016; 375:850.
  78. Official American Thoracic Society Clinical Practice Guidelines: Diagnostic Evaluation of Infants with Recurrent or Persistent Wheezing. http://www.thoracic.org/about/newsroom/press-releases/journal/wheezing-in-infants.pdf.
Topic 2841 Version 6957.0

Topic Outline

GRAPHICS

RELATED TOPICS

All topics are updated as new information becomes available. Our peer review process typically takes one to six weeks depending on the issue.