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What's new in pediatrics
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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: Apr 2017. | This topic last updated: May 25, 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

Medical use of prescription opioid medications and misuse in adolescents (May 2017)

Surveys of high school seniors in the United States over 40 years show that the use of prescription opioids is strongly correlated with misuse in adolescents and that misuse typically follows medical use by the patient [1]. Thus, health care providers should follow safe prescribing guidance for prescription opioids, including use of alternatives (eg, acetaminophen or ibuprofen) to control pain whenever possible, using the lowest effective dose and minimum quantity of prescription opioid medications when they are needed, and utilizing prescription drug monitoring programs, where available, to identify patients or caregivers who might be misusing (ie, abusing or diverting) prescription opioid medications. (See "Opioid intoxication in children and adolescents", section on 'Safe prescribing'.)

Safe storage of prescription opioids (May 2017)

Although safe storage of prescription opioid medications (eg, locked cabinet) is recommended, it infrequently occurs. In a United States nationally representative survey of over 1000 adults with prescription opioid use in the past 12 months, only 9 percent reported safe storage of their medications [2]. In further analysis of those adults with children younger than 18 years of age in the household, safe storage was reported in less than one-third of households with young children and 12 percent of households with children older than six years of age [3]. These results support the need for anticipatory guidance by health care providers, emphasizing opioid safe storage and how it may limit opioid misuse and overdose, especially in households with children and adolescents. Further research should focus on developing and implementing effective means of secure storage in households. (See "Opioid intoxication in children and adolescents", section on 'Safe storage'.)

Persistence of neurotoxicity of childhood lead poisoning into adulthood (May 2017)

Detectable blood lead levels (BLLs) are associated with irreversible neurocognitive deficits in children and a BLL lower limit for this toxicity has not been established. Previous studies had shown that this effect persists into adolescence. In a longitudinal cohort study of over 1000 patients, lead exposure, based upon BLLs obtained at 11 years of age, was associated in a dose-dependent fashion with lower intelligence quotient (IQ) and lower socioeconomic status at age 38 years after adjustment for maternal IQ, child IQ, and childhood socioeconomic status [4]. Thus, childhood lead exposure causes neurotoxicity that persists into adulthood. Primary prevention of lead exposure, including in pregnant women, can prevent these effects. (See "Childhood lead poisoning: Clinical manifestations and diagnosis", section on 'Neurologic'.)

Safety warnings issued for codeine and tramadol in breastfeeding women and children under age 12 years (April 2017)

The US Food and Drug Administration (FDA) issued a strong warning to restrict use of codeine and tramadol in breastfeeding women and children <12 years old because of increasing reports of life-threatening respiratory depression in young children exposed to these drugs [5]. Children who are ultra-rapid metabolizers metabolize these drugs faster than normal, leading to dangerously high levels of active drug. We suggest avoiding codeine and tramadol in breastfeeding women and children <12 years old. (See "Evaluation and management of pain in children", section on 'Agents not recommended'.)

Prevention of concussion in children playing hockey (April 2017)

Evidence is limited regarding specific interventions to prevent sport-related concussion. In a prospective study of the effect of a Canadian rule change on age eligibility for body checking in youth hockey, the rate of concussions decreased by 64 percent among 11- and 12-year-old hockey players after the eligible age for checking was raised to 13 years [6]. Thus, limiting types of contact until an older age appears to be an effective strategy to reduce the risk of concussion in younger players, although prior studies suggest that the risk of injuries other than concussion may be increased when players are introduced to body checking in subsequent seasons. (See "Concussion in children and adolescents: Management", section on 'Prevention'.)

IUD use does not impact human papillomavirus infection (March 2017)

A reduction in cervical cancer rates among intrauterine device (IUD) users has been observed and attributed to favorable effects of the device on human papillomavirus (HPV) clearance. However, a prospective cohort study that controlled for sexual and behavioral confounders reported no difference in HPV acquisition or clearance among women and girls with or without an IUD [7]. Thus, IUD use does not appear to impact HPV infection. (See "Intrauterine contraception: Devices, candidates, and selection", section on 'IUDs cause infection'.)

Maternal obesity and risk of cerebral palsy (March 2017)

Maternal obesity has been associated with several adverse pregnancy outcomes. Now, a population-based cohort study from Sweden has reported an increasing risk of cerebral palsy in offspring delivered at term as maternal body mass index (BMI) increases [8]. Although this observation requires confirmation, we continue to advise overweight and obese women to try to achieve a normal BMI before becoming pregnant because of established pregnancy and general health benefits. (See "Obesity in pregnancy: Complications and maternal management", section on 'Neurodevelopment'.)

Smartphone-integrated infant physiologic monitors not beneficial (March 2017)

A new class of smartphone-integrated infant physiologic monitors with sensors built into socks, clothing, or diaper clips is being marketed directly to consumers. There is no evidence that these devices have any benefit for prevention of sudden infant death syndrome (SIDS) or any other adverse outcome. Moreover, concerns have been raised that parents might feel falsely reassured by the use of such devices and fail to use established SIDS preventive practices [9]. (See "Sudden infant death syndrome: Risk factors and risk reduction strategies", section on 'No benefit from home monitors'.)

Tonsillectomy or watchful waiting for children with recurrent throat infections (February 2017)

A systematic review of studies comparing tonsillectomy with watchful waiting for children with mild to moderate recur­rent throat infections concluded that tonsillectomy provided a modest reduction in number of throat infections and health care utilization in the first postsurgical year, but little to no long-term difference in these outcomes or quality of life [10]. Hence, we suggest not performing tonsillectomy in children who are only mildly or moderately affected. Tonsillectomy is an option for children who are severely affected (ie, ≥7 episodes in one year, ≥5 episodes in each of two years, or ≥3 episodes in each of three years), although watchful waiting is a reasonable alternative. The decision should be made on a case-by-case basis after weighing the risks and benefits in the individual child, and the values and preferences of the family and child. (See "Tonsillectomy and/or adenoidectomy in children: Indications and contraindications", section on 'Mildly or moderately affected children'.)

Expanding demographics of e-cigarette users (February 2017)

The rapid increase in e-cigarette smoking by youth in the United States has not affected the downward trend in cigarette use [11]. Moreover, analysis of psychosocial risk factors suggest that many youth who use e-cigarettes are unlikely to have initiated tobacco smoking with cigarettes. These findings suggest that e-cigarettes are expanding the demographics and overall use of tobacco products among youth, rather than replacing other nicotine sources. (See "Prevention of smoking initiation in children and adolescents", section on 'E-cigarettes' and "Prevention of smoking initiation in children and adolescents", section on 'Prevalence and trends'.)

United States guidelines for fish consumption during pregnancy and lactation (February 2017)

Fish may be contaminated by environmental pollutants, such as methylmercury, which can cause fetal neurologic problems. The US Food and Drug Administration and Environmental Protection Agency released updated recommendations about fish consumption for women who are pregnant or nursing, or who might become pregnant [12]. Revisions include guidance on many more types of fish and recommendations for best choices versus good choices (table 1). (See "Nutrition in pregnancy", section on 'Fish consumption'.)

Updated American Academy of Pediatrics guidelines for developmental dysplasia of the hip (January 2017)

The American Academy of Pediatrics has released updated guidelines for evaluation and referral of infants with developmental dysplasia of the hip (DDH) [13]. Changes from the previous guidelines include the option for infants with a reduced femoral head that is dislocatable or subluxatable (ie, a positive Barlow test) to be followed with serial physical examinations by the primary care clinician rather than an orthopedic surgeon. The update also included breech presentation as a risk factor for male as well as female infants and clarified that breech presentation refers to breech position during the third trimester, whether or not the infant was delivered by cesarean section. (See "Developmental dysplasia of the hip: Clinical features and diagnosis", section on 'Approach to diagnosis and referral'.)

Obesity trends in low-income preschool-aged children (January 2017)

After peaking in 2004, the overall prevalence of obesity in preschool-aged children in the United States has declined, although rates among low-income children remained high. A new study reports a modest decrease in obesity rates from 2010 to 2014 among these low-income children, and this trend was reflected in a majority of states [14]. Nevertheless, obesity rates among low-income children continue to exceed those in the general population, highlighting the continued need for preventive efforts among this high-risk group. (See "Definition; epidemiology; and etiology of obesity in children and adolescents", section on 'Trends'.)

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 [15]. 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 [16]. 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 [17]. 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'.)

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 [18]. 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'.)

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 [19] 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)'.)

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 [20]. (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 [21,22]. 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) [23]. 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 [24]. 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'.)

NEONATOLOGY

Buprenorphine treatment of neonatal abstinence syndrome (May 2017)

Morphine and methadone are the preferred drugs for initial pharmacologic management of neonatal abstinence syndrome (NAS). However, in a single-center trial that randomly assigned 63 infants with NAS to sublingual buprenorphine or oral morphine, sublingual buprenorphine resulted in a shorter median duration of treatment and median length of hospital stay, with no difference in the use of adjunctive phenobarbital or in adverse events [25]. Until these findings are confirmed in trials with larger numbers of patients and from other centers, we continue to use either morphine or methadone for initial pharmacologic treatment of NAS. (See "Neonatal abstinence syndrome", section on 'Opioid therapy'.)

Hydrocortisone and prophylaxis for bronchopulmonary dysplasia in preterm infants (April 2017)

Although prophylactic postnatal dexamethasone therapy reduces the risk of bronchopulmonary dysplasia (BPD), its use has been restricted because of an increased risk for cerebral palsy. Hydrocortisone treatment has been studied as an alternative to dexamethasone, but data regarding efficacy and potential harms are discordant and limited by early termination of the trials. One previous trial demonstrated a reduced risk of BPD in high-risk preterm infants (gestational age <28 weeks) treated with hydrocortisone, compared with placebo, and no increase in the rate of short-term adverse events. Now, a follow-up study of these infants at a median corrected age of 22 months found no difference in neurodevelopmental outcome, including cerebral palsy, between the two groups [26]. However, before exposing a significant number of preterm infants to hydrocortisone prophylaxis, further data are needed regarding the balance between reduction of BPD and potential adverse effects of this approach. (See "Postnatal use of corticosteroids in bronchopulmonary dysplasia", section on 'Hydrocortisone'.)

Docosahexaenoic acid supplementation and bronchopulmonary dysplasia in preterm infants (April 2017)

Although previous data suggested that docosahexaenoic acid (DHA) supplementation lowered the risk of bronchopulmonary dysplasia (BPD) in preterm infants, a multicenter randomized trial in infants (gestational age <29 weeks) showed that daily DHA supplementation 60 mg/kg of body weight increased the risk of BPD compared with placebo (49 versus 44 percent) [27]. These results confirm our recommendation to not provide supplemental DHA to prevent BPD in preterm infants. (See "Prevention of bronchopulmonary dysplasia", section on 'Docosahexaenoic acid'.)

Potential predictive tool for successful discontinuation of phototherapy for neonatal hyperbilirubinemia (March 2017)

For clinicians managing neonatal jaundice, the optimal time to discontinue phototherapy to minimize need for reinitiation of therapy is unclear. A clinical tool to estimate the probability of rebound hyperbilirubinemia after inpatient phototherapy was developed using retrospective data from a large birth cohort of infants ≥35 weeks gestational age (GA) [28]. The prediction tool, which calculated a score based on three indices: GA <38 weeks, younger age at phototherapy initiation, and total bilirubin level relative to the treatment phototherapy threshold at termination, performed well in the validation data set. However, external validation is needed prior to recommending clinical use of this tool. (See "Treatment of unconjugated hyperbilirubinemia in term and late preterm infants", section on 'Rebound hyperbilirubinemia'.)

Increase in survival without impairment for periviable infants (March 2017)

For periviable infants, both overall survival and survival without neurodevelopmental impairment have increased over time. In a multicenter National Institute of Child Health and Human Development (NICHD) study of infants born at 22 to 24 weeks of gestation, survival and survival without neurodevelopmental impairment assessed at 18 to 22 months of corrected age increased across three consecutive birth-year epochs (2000 to 2003, 2004 to 2007, and 2008 to 2011) [29]. However, prognosis still remains guarded as only 36 percent of these infants survived and only 20 percent survived without neurodevelopmental impairment in the most recent epoch. (See "Periviable birth (Limit of viability)", section on 'Changes in survival rate without impairment'.)

Patterns of tobacco use in the United States (February 2017)

A nationally representative longitudinal study of tobacco product usage in 2013 and 2014 in the United States found that 28 percent of adults used tobacco regularly and 9 percent of youths 12 to 17 years of age had used a tobacco product within the previous 30 days [30]. Two-thirds of adult and one-half of youth tobacco users smoke tobacco cigarettes. Other forms of tobacco (or other nicotine products), including cigar, e-cigarettes, hookah/waterpipe, smokeless tobacco, snus pouch, and dissolvable tobacco, constitute a considerable portion of tobacco use, and 40 percent who reported tobacco use were using more than one form. This study will be repeated over time to establish trends of use. These results illustrate the importance of asking patients not only if they smoke cigarettes, but also if they use one or more other forms of tobacco or nicotine. (See "Patterns of tobacco use", section on 'Tobacco usage: overview'.)

EEG unproven predictor for neurodevelopment outcome in preterm infants (February 2017)

Although small observational studies have suggested that amplitude-integrated electroencephalography (aEEG) and conventional EEG predict neurodevelopmental outcome for preterm infants, a systematic review concluded that these studies varied widely in study design and had a high risk of bias [31]. As a result, UpToDate advises restricting aEEG and EEG to the research setting and not using these tests clinically pending further study. (See "Long-term neurodevelopmental outcome of preterm infants: Management", section on 'Electroencephalography: Unproven tool'.)

Newborn screening for congenital CMV infection (February 2017)

The value of screening newborns for congenital cytomegalovirus (CMV) infection is controversial. A study including nearly 100,000 neonates performed both CMV and hearing screening in all newborns, with additional testing and follow-up for those with abnormal screening results [32]. CMV infection was identified in 0.4 percent of newborns, of whom 8 percent were diagnosed with CMV-related sensorineural hearing loss (SNHL). Newborn hearing screening alone failed to detect 43 percent of newborns with CMV-related SNHL because the onset of hearing loss was delayed. Although this study adds to mounting evidence supporting newborn CMV screening, CMV is not included on the national routine universal screening panel in the United States since the most reliable and cost effective method for CMV screening in newborns has not been established. (See "Congenital cytomegalovirus infection: Clinical features and diagnosis", section on 'Targeted newborn screening'.)

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) [33]. 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'.)

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]) [34]. 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 [35]. 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 [36]. 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'.)

ALLERGY, IMMUNOLOGY, AND RHEUMATOLOGY

Methotrexate for moderate oligoarticular juvenile idiopathic arthritis (February 2017)

Methotrexate is used as part of initial therapy in oligoarticular juvenile idiopathic arthritis (JIA) for those with severe disease activity and poor prognostic risk factors, but it is not clear if it should be used in patients with moderate disease. In a randomized, open-label trial of over 200 children with moderate oligoarticular JIA, the addition of oral methotrexate to glucocorticoid injections did not improve the proportion of children who achieved inactive disease or clinical remission at 12 months, although it did increase the time to flare (by approximately four months) [37]. Further study is needed to determine if methotrexate should be used for the initial therapy of children with moderate-risk JIA, including whether oral methotrexate is as effective as subcutaneous administration in this setting. (See "Oligoarticular juvenile idiopathic arthritis", section on 'Initial therapy'.)

Risk of recurrence in anaphylaxis in children (January 2017)

Individuals who experience an initial episode of anaphylaxis are at risk for subsequent episodes. In the first prospective study to assess the risk of recurrent anaphylaxis, nearly 300 children treated for anaphylaxis (mostly food-induced) in the emergency department were followed for one year, during which 18 percent suffered another episode [38]. Concomitant asthma and treatment of the initial episode with epinephrine were associated with an increased risk of recurrence. These results highlight the importance of prompt intervention (equipping patients/caregivers with epinephrine autoinjectors and referring to an allergist) after the initial episode. (See "Anaphylaxis: Emergency treatment", section on 'Risk of recurrence'.)

Adjuvant glucocorticoids for initial treatment of Kawasaki disease (January 2017)

The use of glucocorticoids to treat children with Kawasaki disease has been a subject of debate. In a meta-analysis of comparative studies examining initial treatment with glucocorticoids plus intravenous immune globulin (IVIG) compared with IVIG alone, combination therapy was associated with a lower rate of coronary artery abnormalities, with the greatest benefit in patients predicted to be at high risk for IVIG resistance at baseline [39]. The Kobayashi criteria can be used to determine this risk status in Japanese children but are not reliable in other populations. When increased risk for IVIG resistance cannot be determined, we do not recommend routine use of glucocorticoids for initial therapy. (See "Kawasaki disease: Initial treatment and prognosis", section on 'Glucocorticoids'.)

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 [40]. 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 [41], the Starting Time of Egg Protein (STEP) trial [42], the Beating Egg Allergy Trial (BEAT) [43], and the Hen’s Egg Allergy Prevention (HEAP) trial [44]. 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'.)

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 [45]. 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 [46]. 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'.)

EMERGENCY MEDICINE

Safety and efficacy of nonoperative treatment of pediatric appendicitis (March 2017)

In a meta-analysis of 10 studies that provided outcomes for over 400 children undergoing nonoperative treatment (antibiotics without immediate surgery) of early, uncomplicated appendicitis, initial treatment was effective in 97 percent of patients and was associated with no appendectomy at reported follow-up in 82 percent of patients [47]. Complications and total length of hospital stay appeared similar during follow-up for nonoperative treatment and appendectomy. Although appendectomy remains the treatment of choice for most children with early, uncomplicated appendicitis, nonoperative management is an alternative option in selected patients based upon caregiver preference. Additional studies are needed to determine which patients are least likely to fail nonoperative treatment. (See "Acute appendicitis in children: Management", section on 'Nonoperative management'.)

Ultrasound to improve the success rate of lumbar puncture in young infants (February 2017)

Ultrasound has been proposed as a means to increase the success rate of lumbar puncture (LP) in infants. In a small, unblinded trial of 43 young infants undergoing LP in the emergency department, ultrasound-assisted LP was associated with a significantly higher rate of success compared with the landmark technique [48]. We suggest that when equipment and properly trained providers are available, ultrasound guidance be used to identify the best site and safest depth for LP in young infants. (See "Lumbar puncture: Indications, contraindications, technique, and complications in children", section on 'Ultrasound guidance'.)

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 [49]. 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 2) 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'.)

ENDOCRINOLOGY

High risk for vascular complications in youth with type 2 diabetes (April 2017)

In a large prospective study following outcomes in youth who had been diagnosed with diabetes before age 20, those with type 2 diabetes mellitus (T2DM) had high rates of diabetic kidney disease, retinopathy, and neuropathy (20, 9, and 18 percent, respectively) after a mean diabetes duration of eight years [50]. Moreover, the risk of these complications was more than twofold higher than in those diagnosed with type 1 diabetes mellitus (T1DM), after adjustment for age, disease duration, glycemia, and obesity. These findings emphasize the need to monitor youth with either T2DM or T1DM for development of complications. (See "Comorbidities and complications of type 2 diabetes mellitus in children and adolescents", section on 'Introduction'.)

Target blood glucose levels in critically ill children (March 2017)

Optimal target blood glucose levels in critically ill children are unknown. In the HALF-Pint randomized trial of intensive insulin therapy (IIT), a lower target blood glucose level (80 to 110 mg/dL [4.4 to 6.1 mmol/L] did not reduce the number of intensive care unit-free days in critically ill children when compared with a higher target level (150 to 180 mg/dL [8.3 to 10 mmol/L]) [51]. Rates of hypoglycemia and health care-associated infections were increased for the lower target group, but there was no difference in mortality. These results are consistent with trials in adults and, as in adults, we recommend against treatment with IIT regimens that target blood glucose levels between 80 to 110 mg/dL [4.4 to 6.1 mmol/L] in critically ill children. (See "Glycemic control and intensive insulin therapy in critical illness", section on 'Children'.)

GASTROENTEROLOGY, HEPATOLOGY, AND NUTRITION

Psychological and behavioral symptoms in young children with celiac disease (May 2017)

Untreated celiac disease in children has been associated with subtle neurologic or behavioral symptoms, but previous studies may have been confounded by the parents' knowledge of the child's celiac disease diagnosis. A new study has found that three-year-old children with persistently positive tissue transglutaminase (tTG) antibodies and not on a gluten-free diet were more likely to manifest subtle behavioral symptoms (anxiety, depression, aggressive behavior, or sleep problems) compared with those with negative tTG antibodies [52]. The parents were unaware of the child's tTG status when they reported the behavioral symptoms. These findings lend further support to an association between celiac disease and behavioral symptoms in young children. (See "Epidemiology, pathogenesis, and clinical manifestations of celiac disease in children", section on 'Neurologic disease and behavioral symptoms'.)

USPSTF statement on screening for celiac disease (April 2017)

Testing for celiac disease in the absence of suggestive signs or symptoms is controversial. A US Preventive Services Task Force report has concluded that there are insufficient data to support screening for celiac disease [53]. However, we continue to test for celiac disease in asymptomatic first-degree relatives of patients with a confirmed diagnosis of celiac disease because of their increased risk for disease. We also recommend screening asymptomatic children with several conditions associated with celiac disease, including type 1 diabetes and Down syndrome. Our recommendations are consistent with guidelines from the American College of Gastroenterology and from Pediatric Gastroenterology societies [54]. (See "Diagnosis of celiac disease in adults", section on 'Who should be tested'.)

GENETICS AND PEDIATRIC METABOLISM

Predictive tool for sleep apnea in children with Down syndrome (March 2017)

Polysomnography or pulse oximetry monitoring during sleep is recommended in all children with Down syndrome by four years of age because of their increased risk of obstructive sleep apnea (OSA). A predictive model using a validated sleep questionnaire, medication history, patient age, anthropometric measurements, vital signs, and physical exam findings had a high negative predictive value for moderate to severe OSA [55]. If confirmed in validation studies, this tool could decrease the number of diagnostic sleep studies needed in children with Down syndrome. (See "Down syndrome: Management", section on 'Sleep apnea'.)

Revised clinical criteria for neurofibromatosis type 2 (March 2017)

Clinical criteria for neurofibromatosis type 2 (NF2), caused by mutations in the NF2 gene, have been modified to include requirement for negative LZTR1 genetic testing in patients with a unilateral vestibular schwannoma and two or more non-intradermal schwannomas [56]. Previously, these patients would have met clinical criteria for NF2. The change was prompted by recognition that the phenotypic spectrum of both NF2 and LZTR1-related schwannomatosis includes unilateral vestibular schwannoma in selected patients. (See "Neurofibromatosis type 2", section on 'Clinical criteria'.)

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 [57]. Additional studies are in progress. (See "Neurofibromatosis type 1 (NF1): Management and prognosis", section on 'Plexiform neurofibromas'.)

HEMATOLOGY AND ONCOLOGY

Decline in secondary malignancies among childhood cancer survivors (March 2017)

In addition to recurrences of primary malignancies, cancer survivors are at a higher risk for secondary malignancies as a result of their cancer treatments. In a study of over 23,000 survivors of childhood cancer, 6.9 percent of survivors experienced neoplasms, most commonly breast or thyroid cancer, over a mean follow-up of 20.5 years [58]. The frequency of subsequent malignancies decreased by decade of diagnosis (2.1, 1.7 and 1.3 percent for the 1970s, 1980s and 1990s, respectively). This decline may be related to a decrease in the proportion of individuals receiving radiation and the median radiation dose administered over time. (See "Overview of cancer survivorship care for primary care and oncology providers".)

INFECTIOUS DISEASES AND IMMUNIZATIONS

Rising rates of HCV infection in young women in the United States (May 2017)

In parallel with the opioid and injection drug use epidemic in the United States, rates of hepatitis C virus (HCV) infection have been increasing over the past decade. In particular, the annual number of acute HCV cases among women aged 15 to 44 years rose 3.6-fold from 2006 to 2014 [59]. An estimated 29,000 women with HCV infection gave birth each year between 2011 and 2014; since the risk of vertical transmission is approximately 5.8 percent, this implies that an estimated 1700 infants were infected annually during this time. These numbers highlight the importance of screening at-risk individuals and arranging follow-up for those with HCV infection. (See "Vertical transmission of hepatitis C virus", section on 'Incidence' and "Hepatitis C virus infection in children", section on 'Epidemiology'.)

Investigational low-cost, heat-stable rotavirus vaccine for infants (May 2017)

Rotavirus gastroenteritis is an important cause of mortality in children younger than five years. Although effective vaccines are available, cost and need for refrigeration have limited vaccine uptake. Bovine rotavirus pentavalent vaccine (BRV-PV) is an investigational live, oral, heat-stable vaccine that is administered to infants at 6, 10, and 14 weeks of age. In a placebo-controlled randomized trial in more than 3500 Nigerien infants, BRV-PV was 67 percent efficacious in preventing laboratory-confirmed severe rotavirus gastroenteritis [60]. BRV-PV is less expensive than currently licensed vaccines and holds promise for vaccination programs in areas where cold-chain capacity is limited. (See "Rotavirus vaccines for infants", section on 'Other vaccines'.)

Maternal Tdap vaccination and prevention of infant pertussis (May 2017)

Immunization with the tetanus, diphtheria, and acellular pertussis (Tdap) vaccine is recommended for women during each pregnancy in order to provide passive protection against pertussis to their infants. Although passive transfer of maternal antibodies can blunt the infant's own immune response to infant doses of the diphtheria, tetanus toxoids, and acellular pertussis (DTaP) vaccine, it does not appear to interfere with clinical vaccine efficacy. In a retrospective study of nearly 150,000 infants at every level of DTaP vaccine exposure, infants exposed in utero to Tdap vaccine were better protected against pertussis during the first year of life than infants not exposed in utero [61]. (See "Immunizations during pregnancy", section on 'Rationale, efficacy, and safety'.)

Decreased susceptibility to fluoroquinolones in Shigella infection (April 2017)

When treatment for Shigella infection is indicated, susceptibility testing should be performed to guide antimicrobial selection. In the United States, an increasing proportion of Shigella isolates have minimum inhibitory concentrations (MIC) to ciprofloxacin of 0.12 to 1 mcg/mL [62]. Although these MIC values are considered susceptible and their impact on treatment outcomes in Shigella is unknown, they are associated with resistance genes that result in worse outcomes with fluoroquinolone treatment in other Enterobacteriaceae. Clinicians should request the MIC to ciprofloxacin if it is not provided with susceptibility results and avoid fluoroquinolones if the MIC is ≥0.12 mcg/mL. (See "Shigella infection: Clinical manifestations and diagnosis", section on 'Susceptibility testing' and "Shigella infection: Treatment and prevention in adults", section on 'Antibiotic selection'.)

IDSA guidelines on healthcare-associated ventriculitis and meningitis (April 2017)

The Infectious Diseases Society of America published new guidelines related to healthcare-associated ventriculitis and meningitis in March 2017 [63]. They provide guidance for clinicians on the clinical manifestations, diagnosis, treatment, and prevention of ventriculitis and meningitis in patients with central nervous system hardware, with a focus on cerebrospinal fluid shunts and drains, and in patients who have had neurosurgery or head trauma. Main concepts include the need for a low threshold of suspicion given the potentially subtle clinical findings of these infections and the importance of selecting an antimicrobial regimen that has bactericidal activity and achieves adequate concentrations in the cerebrospinal fluid. Our recommendations are generally consistent with these guidelines. (See "Infections of cerebrospinal fluid shunts and other devices", section on 'Treatment' and "Initial therapy and prognosis of bacterial meningitis in adults", section on 'Healthcare-associated meningitis' and "Gram-negative bacillary meningitis: Treatment".)

E. coli O157:H7 outbreak associated with soy nut butter (March 2017)

Escherichia coli O157:H7, which causes bloody diarrhea and is associated with the hemolytic-uremic syndrome, is typically transmitted through contaminated beef products and produce, but other foods have also been implicated in outbreaks. In the United States, a particular brand of soy nut butter (I.M. Healthy) has been linked to a multistate E. coli O157:H7 outbreak that has affected mainly children [64]. Although the soy nut butter products have been recalled, individuals should be advised to avoid and discard any remaining product, and the possibility of E. coli O157:H7 infection should be considered in exposed patients with diarrheal illnesses. Details on the outbreak can be found on the Centers for Disease Control and Prevention website. (See "Microbiology, pathogenesis, epidemiology, and prevention of enterohemorrhagic Escherichia coli (EHEC)", section on 'Other foods'.)

Recommended immunization schedule—United States, 2017 (March 2017)

The Advisory Committee on Immunization Practices has released the 2017 recommended immunization schedule for children and adolescents in the United States [65,66]. New recommendations include the following:

All infants should now receive monovalent hepatitis B vaccine within 24 hours of birth; earlier recommendations allowed some infants born to hepatitis B surface antigen-negative mothers to receive the vaccine after discharge. (See "Hepatitis B virus immunization in infants, children, and adolescents", section on 'Mother's HBsAg status unknown, birth weight ≥2 kg'.)

When administered during pregnancy, the tetanus and diphtheria toxoids and acellular pertussis (Tdap) vaccine should be given as early as possible between 27 and 36 weeks of gestation. (See "Immunizations during pregnancy", section on 'Tetanus, diphtheria, and pertussis vaccination'.)

For individuals receiving the meningococcal serogroup B vaccine MenBFHbp (Trumenba), two doses are recommended for healthy adolescents and young adults who are not at increased risk for meningococcal disease. Three doses are recommended for individuals ≥10 years of age at increased risk for meningococcal disease and for use during serogroup B meningococcal disease outbreaks (table 3). Previously, three doses were recommended for all recipients. The dosing frequency and interval for the other serogroup B vaccine, MenB-4C (Bexsero), have not changed. (See "Meningococcal vaccines", section on 'Serogroup B meningococcus vaccines'.)

Early initiation of heated humidified high-flow nasal cannula therapy in children with bronchiolitis (February 2017)

In an open randomized trial comparing heated humidified high-flow nasal cannula (HFNC) with standard low-flow oxygen therapy in 200 children with moderately severe bronchiolitis, early initiation of HFNC did not shorten the median duration of oxygen therapy (approximately 22 hours in both groups) [67]. However, HFNC was associated with avoidance of intensive care unit admission when it was used as a rescue therapy for clinical deterioration in children treated with standard therapy. No serious adverse effects occurred. These findings provide additional support for HFNC as a rescue therapy in children with bronchiolitis, although the efficacy of this approach remains unproven. (See "Bronchiolitis in infants and children: Treatment, outcome, and prevention", section on 'HFNC and CPAP'.)

Tonsillectomy or watchful waiting for children with recurrent throat infections (February 2017)

A systematic review of studies comparing tonsillectomy with watchful waiting for children with mild to moderate recur­rent throat infections concluded that tonsillectomy provided a modest reduction in number of throat infections and health care utilization in the first postsurgical year, but little to no long-term difference in these outcomes or quality of life [10]. Hence, we suggest not performing tonsillectomy in children who are only mildly or moderately affected. Tonsillectomy is an option for children who are severely affected (ie, ≥7 episodes in one year, ≥5 episodes in each of two years, or ≥3 episodes in each of three years), although watchful waiting is a reasonable alternative. The decision should be made on a case-by-case basis after weighing the risks and benefits in the individual child, and the values and preferences of the family and child. (See "Tonsillectomy and/or adenoidectomy in children: Indications and contraindications", section on 'Mildly or moderately affected children'.)

Newborn screening for congenital CMV infection (February 2017)

The value of screening newborns for congenital cytomegalovirus (CMV) infection is controversial. A study including nearly 100,000 neonates performed both CMV and hearing screening in all newborns, with additional testing and follow-up for those with abnormal screening results [32]. CMV infection was identified in 0.4 percent of newborns, of whom 8 percent were diagnosed with CMV-related sensorineural hearing loss (SNHL). Newborn hearing screening alone failed to detect 43 percent of newborns with CMV-related SNHL because the onset of hearing loss was delayed. Although this study adds to mounting evidence supporting newborn CMV screening, CMV is not included on the national routine universal screening panel in the United States since the most reliable and cost effective method for CMV screening in newborns has not been established. (See "Congenital cytomegalovirus infection: Clinical features and diagnosis", section on 'Targeted newborn screening'.)

Duration of treatment for acute otitis media in children younger than two years (January 2017)

Methodologic limitations in previous studies evaluating duration of treatment for acute otitis media (AOM) in young children were addressed in a trial that randomly assigned more than 500 infants and young children (age 6 through 23 months) with strictly defined AOM to treatment with amoxicillin-clavulanate for 10 days or 5 days; those assigned to 5 day treatment received an additional 5 days of placebo [68]. The 10-day group had lower rates of clinical failure (16 versus 34 percent) without more adverse events. These findings support a standard 10-day course of antimicrobial therapy for AOM in children <2 years. (See "Acute otitis media in children: Treatment", section on 'Duration of therapy'.)

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 [69]. 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 4), 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 adults" 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 10 and 42 percent in two recent reports [70,71]. 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 [36]. 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 [72]. 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".)

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 5) [73]. 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'.)

NEUROLOGY

Consensus panel guidelines on Dravet syndrome in children and adults (April 2017)

A North American consensus panel has published guidelines on the diagnosis and management of Dravet syndrome (DS), an early-onset epileptic encephalopathy most often due to de novo mutations in the voltage-gated sodium channel, alpha-1 subunit (SCN1A) gene [74]. The document includes a description of the typical clinical presentation of DS; guidance on genetic testing and family counseling; and recommendations for first-line treatment with clobazam and/or valproic acid, avoidance of sodium channel blocking drugs, and provision of home rescue medications and an emergency seizure protocol. DS should be suspected in previously healthy infants presenting with recurrent tonic-clonic seizures, often in the setting of fever, beginning before one year of age and associated with neurodevelopmental regression after the onset of seizures. (See "Dravet syndrome: Genetics, clinical features, and diagnosis" and "Dravet syndrome: Management and prognosis".)

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 intrathecal nusinersen, versus none for those who received the sham procedure [75]. The FDA based its approval upon data from this trial and open-label studies in older patients with SMA [76,77]. We recommend nusinersen for most infants with SMA and select children ages 2 to 12 years with SMA. (See "Spinal muscular atrophy", section on 'Nusinersen'.)

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 [36]. 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'.)

PULMONOLOGY

Guidelines for the diagnosis of primary ciliary dyskinesia (February 2017)

Primary ciliary dyskinesia (PCD, also called the immotile cilia syndrome) is an inherited disease that presents, often in childhood, with recurrent respiratory infections and chronic rhinosinusitis. The European Respiratory Society has published new guidelines for the diagnosis of PCD [78]. For patients with clinical features suggestive of PCD, a combination of tests is usually needed to confirm or exclude the diagnosis, given that there is no “gold standard.” The most commonly used tests are nasal nitric oxide, high-speed videomicroscopy analysis, and transmission electron microscopy. Genotyping may be useful in a small number of selected patients. (See "Primary ciliary dyskinesia (immotile-cilia syndrome)", section on 'Diagnostic evaluation'.)

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