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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: Oct 2017. | This topic last updated: Nov 21, 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.


Protective effect of breastfeeding against SIDS (November 2017)

Breastfeeding appears to have an independent protective effect against sudden infant death syndrome (SIDS). In a new meta-analysis of individual-level data from case-control studies, any breastfeeding for at least two months nearly halved the risk for SIDS, after controlling for potential confounders [1]. Protection against SIDS increased with longer duration of breastfeeding, but not with exclusive breastfeeding compared with partial breastfeeding. (See "Sudden infant death syndrome: Risk factors and risk reduction strategies", section on 'Protective factors'.)

E-cigarette use as a precursor to conventional cigarette smoking (November 2017)

Whether use of e-cigarettes by youth is associated with future initiation of conventional cigarette smoking has important implications for health. A large systematic review and meta-analysis of longitudinal studies among individuals aged 14 to 30 years showed that, compared with e-cigarette never-users, ever-users had a higher probability of initiating cigarette smoking (31 versus 8 percent) [2]. These studies do not distinguish if e-cigarette use increases the desire to smoke conventional cigarettes or whether e-cigarette users have a predisposition to smoke. Nonetheless, the finding of a greater likelihood of future conventional smoking among younger e-cigarette users is useful information for clinicians when educating patients about risks of tobacco use. (See "E-cigarettes", section on 'Effect on smoking initiation among youth'.)

Syphilis incidence in the United States (October 2017)

Syphilis causes a wide range of clinical syndromes and is associated with HIV transmission. The United States Centers for Disease Control and Prevention reported an approximately 18 percent increase in the rate of primary and secondary syphilis (the most infectious stages of the disease) in 2016, with 8.7 cases per 100,000 population, the highest rate since 1993 [3]. More than 600 cases of congenital syphilis were also reported. Although syphilis rates increased among men and women, the rise was primarily attributable to men who have sex with men (MSM). These findings stress the importance of screening and treatment for sexually transmitted infection, especially in MSM and pregnant women. (See "Syphilis: Epidemiology, pathophysiology, and clinical manifestations in HIV-uninfected patients", section on 'Epidemiology'.)

Prevalence of concussion in United States adolescents (October 2017)

A cross-sectional survey of over 13,000 United States middle and high school students found the prevalence of concussion to be approximately 20 percent [4]. Children participating in contact sports are more likely to report having had a concussion (32 percent) compared with those reporting noncontact sports participation (18 percent) or no sports participation (11 percent). Participation in contact sports was also associated with reporting more than one concussion. These findings, consistent with other evidence, indicate that concussion is a common injury that occurs most frequently in adolescent athletes who participate in contact sports such as American football, ice hockey, rugby, or soccer. (See "Concussion in children and adolescents: Clinical manifestations and diagnosis", section on 'Epidemiology'.)

Long-term cognitive outcomes in American high school football players (October 2017)

Based on increasing concerns about risk of chronic traumatic encephalopathy (CTE) in professional American football players and other athletes, there is a need for studies to determine whether less intensive exposure to high-risk sports poses risk. In a case-control study of nearly 3000 men whose cognitive function was assessed at age 65 years, past participation in high school American football was not associated with worse cognition, mood, or other emotional symptoms compared with non-participation [5]. Although somewhat reassuring, these data have significant limitations, and more longitudinal studies are needed to determine modifiable risk factors for CTE and other forms of dementia. (See "Risk factors for cognitive decline and dementia", section on 'Head trauma'.)

Single-dose secnidazole for bacterial vaginosis (September 2017)

Metronidazole is a preferred treatment for bacterial vaginosis (BV) and is given topically or orally as a multi-day course. In September 2017, the US Food and Drug Administration approved secnidazole, a related oral antibiotic with a longer half-life, for the treatment of BV [6]. In an earlier study, a single dose of secnidazole was as effective as, but not superior to, metronidazole for seven days. Secnidazole is an option for BV when a single dose is desired (eg, to enhance adherence), but it is more expensive than other regimens. (See "Bacterial vaginosis: Treatment", section on 'Secnidazole'.)

Family-based behavioral therapy for obesity in young children (September 2017)

For management of obesity in children, family-based approaches are often recommended, but the evidence base has been limited. In a new randomized trial in overweight or obese preschool-aged children, family-based behavioral therapy resulted in substantial improvement in weight status for both children and their parents, compared with a control intervention that counseled on healthy habits but not parenting or behavioral techniques [7]. The intervention consisted of monthly group sessions and phone calls for one year, and improvements were sustained during an additional year of low-intensity follow-up. These findings confirm the durable benefits of family-based counseling for childhood obesity. (See "Management of childhood obesity in the primary care setting", section on 'Family involvement'.)

Chemical constituents released by heat-not-burn (HNB) tobacco cigarettes (August 2017)

Heat-not-burn (HNB) tobacco cigarettes use an electric blade to heat a tobacco stick to a temperature much below that at which traditional tobacco cigarettes burn. In a laboratory study, HNB tobacco cigarettes released lower amounts of harmful constituents (nicotine, polycyclic aromatic hydrocarbons, and carbon monoxide) than conventional tobacco cigarette smoke [8]. Whether this translates to lower health risks is uncertain. HNB products are not currently available in many countries, including the United States. (See "Patterns of tobacco use", section on 'Heat-not-burn tobacco cigarettes'.)

Sugar-sweetened beverage consumption in pregnancy (August 2017)

A growing body of data suggests that prenatal exposures influence susceptibility to obesity. In a prospective cohort study, higher maternal consumption of sugar-sweetened beverages during pregnancy was associated with increasing adiposity among in utero-exposed school-aged offspring [9]. The association persisted after adjustment for multiple confounding variables and was independent of the offspring's beverage intake. We advise pregnant women to avoid or limit intake of sugar-sweetened beverages because they tend to be high in calories, low in nutritive value, and may impact offspring adiposity. (See "Nutrition in pregnancy", section on 'Sugar-sweetened beverages'.)

Interpretation of blood lead levels <5 mcg/dL (0.24 micromol/L) (August 2017)

Interpretation of blood lead levels <5 mcg/dL (0.24 micromol/L) is complicated by an increased risk of specimen contamination arising from blood collection equipment (eg, needles, blood collection tubes, or cryovials) causing false positives and the inability for many laboratories to quantify low levels of blood lead resulting in false negatives [10]. However, any detectable lead <5 mcg/dL (0.24 micromol/L) warrants careful evaluation and an attempt at determining the source of lead exposure. (See "Childhood lead poisoning: Management", section on 'Detectable BLL <5 mcg/dL (current reference level)'.)

Targeted text messages or emails to promote safe infant sleep practices (August 2017)

In the United States, safe infant sleep practices improved during the 1990s, but have plateaued during the past decade, never reaching target levels despite public education campaigns. Now, a large trial has demonstrated benefits of using targeted electronic messaging to deliver sudden infant death syndrome (SIDS)-related education [11]. The intervention consisted of a series of health messages and short educational videos that were delivered to parents of young infants by text message or email and increased adherence to supine sleep, room-sharing without bed-sharing, no soft bedding use, and pacifier use. (See "Sudden infant death syndrome: Risk factors and risk reduction strategies", section on 'Prevention'.)

Risk of tympanic membrane perforation with topical quinolones after tympanostomy (August 2017)

An observational study reported that treatment with quinolone ear drops, with or without added topical corticosteroids, after tympanostomy tube (TT) placement was associated with increased risk of tympanic membrane (TM) perforation compared with treatment with neomycin plus hydrocortisone drops [12]. While the study raises concerns regarding the safety of quinolone ear drops, the findings should be viewed as preliminary given the observational design and source of the data (Medicaid encounter and pharmacy billing data). In addition, this study evaluated only the risk of TM perforation and did not address other adverse effects, including ototoxicity, which is a well-established side effect of neomycin (and other aminoglycosides). Until additional data are available, we continue to suggest fluoroquinolone-containing drops as our preferred treatment for uncomplicated acute TT otorrhea. (See "Tympanostomy tube otorrhea in children: Causes, prevention, and management", section on 'Uncomplicated acute TTO'.)

Low-dose ferrous sulfate for iron deficiency anemia (June 2017)

For infants and children with iron deficiency anemia, standard oral iron dosing is 3 to 6 mg/kg elemental iron per day, but the optimal dose and preparation have not been established. Now, a study reports that ferrous sulfate 3 mg/kg once daily without food was effective in most patients and was more effective than an equivalent dose of an iron polysaccharide complex formulation [13]. These findings support administering ferrous sulfate at the low end of the standard dose range as first-line treatment for nutritional iron deficiency in children. (See "Iron deficiency in infants and children <12 years: Treatment", section on 'Dose and scheduling'.)

Air mattresses/beds and sudden infant death syndrome (June 2017)

To reduce the risk for sudden infant death syndrome (SIDS), infants should sleep supine and only on a firm sleep surface designed specifically for infants. A new report emphasizes that air mattresses or air beds are not appropriate for infant sleep, even if they are firm and fully inflated, but parents often use these devices because of their low cost and portability [14,15]. This report highlights the importance of counseling parents specifically to avoid using air mattresses or air beds for infant sleep. (See "Sudden infant death syndrome: Risk factors and risk reduction strategies", section on 'Sleep position and environment'.)

Updated American Academy of Pediatrics guidelines on fruit juice for infants (June 2017)

Updated guidelines from the American Academy of Pediatrics (AAP) recommend avoiding fruit juice for infants younger than 12 months; previous guidelines recommended avoiding fruit juice for infants younger than 6 months [16]. Fruit juice provides no nutritional benefit over mashed or puréed whole fruit and may have adverse consequences, such as undernutrition, overnutrition, diarrhea, flatulence, abdominal distension, and dental caries. We agree with the AAP recommendation and now suggest mashed or puréed whole fruit rather than fruit juice for infants age 6 to 12 months. (See "Introducing solid foods and vitamin and mineral supplementation during infancy", section on 'Beverages to avoid'.)

Breastfeeding and risk of endometrial cancer (June 2017)

Breastfeeding has many maternal and infant benefits. In a meta-analysis of epidemiologic studies of women with endometrial cancer, ever-breastfeeding was associated with an 11 percent reduction in risk compared with never breastfeeding, and the greatest reduction was among those who breastfed for at least three months per child [17]. A decreased risk of endometrial cancer appears to be an additional maternal benefit of breastfeeding. (See "Endometrial carcinoma: Epidemiology and risk factors", section on 'Breastfeeding'.)

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 [18]. 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 [19]. 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 [20]. 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'.)


Buccal dextrose gel for neonatal hypoglycemia (November 2017)

In a subsequent analysis of data from a randomized trial of neonates (gestational age 35 to 42 weeks) at risk for hypoglycemia in the first 48 hours after birth, administration of buccal dextrose gel was associated with a greater increase in blood glucose level than placebo gel in hypoglycemic infants who were breast-fed, formula-fed, or fed expressed breast milk [21]. Breast-fed infants were less likely to have recurrent episodes of hypoglycemia. For asymptomatic infants with hypoglycemia, buccal administration of dextrose gel 200 mg/kg followed by breast-feeding is a reasonable intervention. (See "Management and outcome of neonatal hypoglycemia", section on 'Dextrose gel'.)

Childhood executive and visual motor function after neonatal hypoglycemia (November 2017)

In a follow-up report of a prospective study of newborns at risk for hypoglycemia, assessment performed at 4.5 years of age demonstrated an increased risk of poor executive and visual motor function among children treated for neonatal hypoglycemia compared with those without neonatal hypoglycemia [22]. The highest risk was in children who had severe, recurrent, or clinically undetected hypoglycemia for >10 minutes. The risk of combined neurosensory impairment was similar in the two groups. This study underscores the challenges of determining when intervention for neonatal hypoglycemia should be initiated to avoid long-term morbidity. (See "Management and outcome of neonatal hypoglycemia", section on 'Asymptomatic hypoglycemia' and "Pathogenesis, screening, and diagnosis of neonatal hypoglycemia", section on 'Challenge of defining neonatal hypoglycemia'.)

Delayed cord clamping in preterm infants (November 2017)

Delayed cord clamping has been recommended for vigorous preterm infants to decrease infant morbidity and increase iron stores, based on meta-analyses of a few small randomized trials. Now, the largest randomized trial of delayed versus immediate cord clamping in over 1500 infants <30 weeks of gestation found no reduction in death or major morbidity from the intervention [23]. There was no clear reason for the discordancy from previous trials. We delay cord clamping for at least 30 seconds in vigorous preterm infants but believe clinicians should use their judgment about whether and how long to delay cord clamping in individual preterm infants until definitive data are available. (See "Management of normal labor and delivery", section on 'Cord clamping'.)

Voiding cystourethrogram (VCUG) in neonates with first-time febrile UTI (September 2017)

For neonates with first-time urinary tract infection (UTI), the optimal approach to evaluating for vesicoureteral reflux (VUR) is uncertain, and expert opinion differs as to whether a voiding cystourethrogram (VCUG) is necessary in all cases. A recent study of 122 young infants with first-time febrile UTI found that high-grade VUR was far less likely among infants with normal renal ultrasound and Escherichia coli infection compared with those with abnormal renal ultrasound, non-E. coli pathogen, or both abnormal ultrasound and non-E. coli pathogen (1 versus 31, 26, and 55 percent, respectively) [24]. These data suggest that a VCUG may not be necessary for all neonates with first-time UTI, and they support a strategy of "watchful waiting" for low-risk infants. However, VCUG should be performed in neonates with abnormal renal ultrasound, non-E. coli pathogen, or recurrent UTI. (See "Urinary tract infections in neonates", section on 'Voiding cystourethrogram'.)

Procalcitonin monitoring to reduce antibiotic exposure in neonatal sepsis (August 2017)

In a multicenter randomized controlled trial in neonates with suspected early-onset sepsis, a risk assessment protocol that included serial procalcitonin (PCT) measurements reduced the duration of antibiotic therapy [25]. Rates of reinfection were low in both groups, and there was only one death (in the control group). Important limitations of the study include its fairly liberal suggested antibiotic duration for infants with negative cultures and high rates of noncompliance with the treatment protocols by the treating clinicians. Despite these limitations, the results suggest that PCT may have some utility in guiding the duration of antibiotic therapy in neonates with suspected sepsis. If PCT levels are obtained, they should be used in conjunction with other clinical indicators of sepsis and should not be the sole basis of decision-making. (See "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm infants", section on 'Other inflammatory markers'.)

Neonatal nCPAP and long-term adverse outcome (July 2017)

Nasal continuous positive airway pressure (nCPAP) is the preferred initial intervention to manage neonatal respiratory distress syndrome (RDS) versus a more invasive regimen (eg, endotracheal intubation and surfactant administration). However, an observational study of extremely preterm survivors (gestational age <28 weeks) has shown that the use of nCPAP is associated with long-term morbidity [26]. Data comparing use of respiratory support over three historical time periods showed that patients managed in the most recent period (2005) had the longest median duration of nCPAP use, the highest degree of airflow obstruction at eight years of age, and the greatest risk of bronchopulmonary dysplasia. Interpretation of these results must account for factors other than duration of nCPAP that also changed over time (decreasing use of postnatal steroids, decreasing neonatal mortality, and increasing use of nCPAP for other conditions). While these findings emphasize that clinicians need to follow the criteria for initiation and discontinuation of CPAP to avoid overuse and minimize long-term sequelae, CPAP remains the preferred intervention for the management of neonatal RDS based on evidence from clinical trials. (See "Prevention and treatment of respiratory distress syndrome in preterm infants", section on 'Long-term outcome'.)

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 [27]. 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'.)


Evidence-based guidelines for pediatric antiphospholipid syndrome (October 2017)

The first evidence-based guidelines for pediatric antiphospholipid syndrome (APS) and catastrophic APS have been published by the Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) initiative [28]. The panel concluded that the existing adult criteria for APS, while specific, may lack sensitivity for pediatric APS. Thus, the guideline calls for new pediatric classification criteria to be developed, which would incorporate both non-thrombotic and thrombotic manifestations in children. The recommendations also provide guidance on risks of perinatal thrombosis and neurodevelopmental abnormalities in children born to mothers with APS. (See "Diagnosis of antiphospholipid syndrome", section on 'Diagnosis'.)

Identification of children with low-risk past penicillin reactions (August 2017)

Many children who have mild adverse reactions to penicillins, such as maculopapular rash, hives, or gastrointestinal symptoms, are not allergic and can safely receive this class of antibiotics in the future. In a study of children presenting to an urban emergency department with histories of past penicillin reactions, nearly 600 parents/caregivers completed a questionnaire about the child’s past reaction [29]. The questionnaire included hives as a low-risk feature (for true allergy), but considered facial angioedema as a high-risk feature. One hundred of 434 patients with low-risk reactions were referred to an allergist for evaluation. Ninety-seven had negative skin tests, while three initially had positive skin tests that were negative upon later repeat testing. Ultimately, all 100 children passed oral challenge to amoxicillin. Despite these results, we consider both hives and angioedema as high-risk features and would advocate that children with past reactions involving either of these symptoms be referred to an allergy specialist to determine if penicillins can be safely used again. (See "Penicillin allergy: Delayed hypersensitivity reactions", section on 'Studies in children'.)

Data limited for probiotic plus oral immunotherapy for peanut allergy (August 2017)

Oral immunotherapy (OIT) for foods is an investigational treatment for food allergies that can lead to temporary desensitization to a food, but the ability of OIT to induce permanent tolerance to the food is less clear. Adding an immunostimulatory adjuvant, such as a probiotic, to OIT may improve sustained unresponsiveness (SU) to the food allergen. In a follow-up study four years after completion of a randomized trial and cessation of treatment, patients treated with peanut OIT plus probiotic were more likely to still be eating peanut and to have SU after eight weeks of avoidance compared with patients treated with placebo only [30]. However, there were significant flaws in the study design, and we await further data before recommending routine use of OIT (with or without an adjuvant). (See "Investigational therapies for food allergy: Oral immunotherapy", section on 'OIT plus adjuvant'.)

National Academies consensus report on food allergies (August 2017)

The National Academies of Sciences, Engineering, and Medicine consensus report on food allergies highlights a number of critical issues related to food allergy [31].

These include:

Judicious use of food allergy testing, performed and interpreted in the context of the patient's clinical history

Prompt treatment of anaphylaxis with epinephrine

Primary prevention of peanut allergy through early dietary introduction

Our approach to the diagnosis and management of food allergies is consistent with the recommendations in this report. (See "Diagnostic evaluation of food allergy", section on 'Role of allergy tests in diagnosis' and "Food-induced anaphylaxis", section on 'Epinephrine' and "Introducing highly allergenic foods to infants and children", section on 'Suggested approach'.)

Four-food elimination diet for eosinophilic esophagitis (July 2017)

The traditional six-food (cow's milk, hen's egg, soy, wheat, peanut/tree nuts, and fish/shellfish) elimination diet for eosinophilic esophagitis (EoE) results in resolution of EoE in approximately three-quarters of children but is challenging and can have negative nutritional consequences. In a prospective study of four-food elimination (milk, soy, egg, wheat) in 78 children with EoE, histologic remission was achieved in 64 percent, with decreased symptoms in 91 percent [32]. Thus, we now suggest either the four-food or six-food empiric elimination diet for most patients who opt for dietary management of EoE. (See "Dietary management of eosinophilic esophagitis", section on 'Elimination diets'.)

Outcomes in children with ANCA-associated vasculitides (July 2017)

The combination of glucocorticoids and cyclophosphamide or other remittive agents (eg, methotrexate, rituximab) has greatly improved patient outcomes for systemic vasculitis. One study of early outcomes in 105 children with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) reported a remission rate of 42 percent, an improvement rate of 92 percent, and no fatalities at 12 months [33]. This compares with the nearly universal mortality due to one form of AAV, granulomatosis with polyangiitis, prior to the regimens now in use. However, more than half of the cohort had evidence of organ damage at 12 months despite high improvement rates and aggressive treatment. (See "Vasculitis in children: Management overview", section on 'Outcomes'.)

Countering the high cost of epinephrine autoinjectors (June 2017)

Physicians and patients in the United States have been struggling with the high cost of epinephrine autoinjectors, and alternatives, as well as ways to maximize the utility of expensive devices, have begun to appear:

A prefilled syringe (Symjepi) containing 0.3 mg epinephrine per dose was approved by the US Food and Drug Administration (FDA) in June 2017 and should offer a more affordable alternative to autoinjectors [34]. It will be available in upcoming months in just one dose, labeled for use in patients weighing ≥30 kg (66 lbs). (See "Prescribing epinephrine for anaphylaxis self-treatment", section on 'Prefilled syringes'.)

A study of 31 expired autoinjectors (EpiPens) found that devices as much as four years past the expiration date still contained 84 to 88 percent of the intended epinephrine dose [35]. Thus, patients should understand that expired devices retain most of their potency and that if anaphylaxis develops, using an outdated device is preferable to not injecting epinephrine at all. (See "Prescribing epinephrine for anaphylaxis self-treatment", section on 'Use of expired autoinjectors'.)

Introducing solids in infants with milk or soy FPIES (June 2017)

Food protein-induced enterocolitis syndrome (FPIES) is a nonimmunoglobulin E (IgE)-mediated gastrointestinal food hypersensitivity most commonly caused by cow's milk (CM) or soy protein. Recent international consensus guidelines from the American Academy of Allergy, Asthma & Immunology and the International FPIES Association advocacy group provide guidance on the introduction of solid foods in infants with CM or soy FPIES (table 1) [36]. In accordance with these guidelines, for infants with CM or soy FPIES, we suggest introduction of vegetables and then fruits, rather than cereals, at four to six months of age, to reduce the risk of reactions to rice and other grains that may occur among infants with CM or soy FPIES. (See "Food protein-induced enterocolitis syndrome (FPIES)", section on 'Introduction of new foods'.)

New guidelines for management of peanut and tree nut allergies (June 2017)

The most straightforward approach in managing any food allergy is complete avoidance of the culprit food and all similar foods, particularly for peanut and tree nuts. However, some patients may find this approach too burdensome. Reflecting a shift in clinical practice, the recent British Society of Allergy and Clinical Immunology guidelines permit, with certain restrictions, consumption of similar foods after confirming that they are safe, if the patient and family prefer this approach [37]. This guideline for the management of peanut and tree nut allergy is consistent with our approach. (See "Peanut, tree nut, and seed allergy: Management", section on 'Clinical scenarios'.)

Adalimumab for uveitis in juvenile idiopathic arthritis (May 2017)

Adalimumab, a human anti-tumor necrosis factor (TNF) alpha monoclonal antibody that is effective in adults with uveitis, has now been shown to be effective for treatment-resistant, juvenile idiopathic arthritis (JIA)-associated uveitis. In the randomized SYCAMORE trial involving 90 children, the addition of adalimumab to ongoing therapy with methotrexate and topical glucocorticoids with our without systemic glucocorticoids reduced intraocular inflammation and lowered the rate of treatment failure compared with placebo [38]. Serious adverse events were infrequent in both groups but occurred more commonly with adalimumab. Although more data are needed on long-term outcomes and safety, these results add support to the use of adalimumab in children with JIA-associated uveitis that fails to respond to glucocorticoids and methotrexate. (See "Oligoarticular juvenile idiopathic arthritis", section on 'Treatment'.)


Updated guidelines for management of coronary artery abnormalities in Kawasaki disease (September 2017)

The American Heart Association (AHA) updated its guidelines for management of Kawasaki disease (KD) [39]. New recommendations for evaluating and managing coronary artery abnormalities (CAAs) include an updated risk stratification schema based on CAA size (table 2), which is used to guide antithrombotic therapy (algorithm 1) and long-term follow-up. The guidelines panel concluded that patients with KD and no history of CAAs are probably not at increased risk for cardiovascular disease compared with the general pediatric population and can be managed with routine preventive counseling alone. Our recommendations for management of cardiovascular sequelae of KD are generally consistent with the 2017 AHA guidelines. (See "Cardiovascular sequelae of Kawasaki disease: Management and prognosis", section on 'Management'.)


Probiotics ineffective for the prevention of early childhood eczema (October 2017)

Two meta-analyses in 2012 and 2014 suggested that there was a modest protective effect of probiotics used in late pregnancy/early infancy on the development of eczema within the first two years of life, although subsequent trials did not confirm these findings. A recent randomized trial provides further evidence of the lack of effectiveness of probiotics for eczema prevention [40]. In this trial, 184 high-risk infants received either Lactobacillus rhamnosus GG plus inulin or inulin alone for the first six months of life. Eczema was diagnosed by age two in approximately 30 percent of the children in both groups. We suggest not giving probiotics during pregnancy and infancy for the prevention of eczema. (See "Prebiotics and probiotics for prevention of allergic disease", section on 'Efficacy'.)

Screening for thyroid disease in children with alopecia areata (September 2017)

Alopecia areata is associated with several other autoimmune diseases, and screening affected patients for thyroid disease is commonly performed. A single-center retrospective study of children with alopecia areata found the risk of thyroid abnormalities was increased among children with Down syndrome, atopy, or a family history of thyroid disease, and suggested that limiting screening to certain populations may be reasonable [41]. While this study provides a basis for additional research, we continue to screen all children with alopecia areata for thyroid disease, pending additional data to support other screening strategies. (See "Clinical manifestations and diagnosis of alopecia areata", section on 'Laboratory studies'.)

Guidelines for comorbidity screening in children with psoriasis (May 2017)

The best approach for screening children with psoriasis for comorbidities has been unclear. An expert consensus document by members of the Pediatric Dermatology Research Alliance and National Psoriasis Foundation provides the first set of guidelines, including recommendations for assessment for overweight or obese status, diabetes, hyperlipidemia, hypertension, nonalcoholic fatty liver disease, psoriatic arthritis, depression, anxiety, and substance abuse [42]. Our approach to screening children with psoriasis is consistent with these guidelines. (See "Psoriasis in children: Epidemiology, clinical manifestations, and diagnosis", section on 'Additional evaluation'.)


Music therapy for children with autism spectrum disorder (September 2017)

In small clinical trials in children with autism spectrum disorder (ASD), music therapy was associated with improved social skills, quality of life, and parent-child interaction. Now a multicenter randomized trial in over 360 young children with ASD reported the addition of music therapy to usual care plus parent ASD counseling did not improve social skills [43], but the duration of the intervention and follow-up may have been insufficient as the trial was stopped after five months due to limited funding. Given the limitations of existing evidence, we do not specifically encourage music therapy for children with ASD but consider it an acceptable component of a comprehensive behavior program. (See "Autism spectrum disorder in children and adolescents: Complementary and alternative therapies", section on 'Music therapy'.)


ACCM practice parameters for management of pediatric and neonatal septic shock (August 2017)

The American College of Critical Care Medicine (ACCM) has published new practice parameters for hemodynamic support of pediatric and neonatal septic shock that continue to emphasize timely fluid administration, early initiation of broad-spectrum antibiotics, and, in patients with fluid refractory shock, prompt administration of vasoactive drug infusions (algorithm 2) [44]. After resuscitation, management is targeted to improving physiologic indicators of perfusion and vital organ function within the first six hours of care (table 3). The guidelines also recommend that each pediatric institution develop multidisciplinary approaches or "bundles" designed to increase adherence to these guidelines, decrease time to therapy, and improve outcomes in pediatric septic shock. (See "Septic shock in children: Rapid recognition and initial resuscitation (first hour)" and "Septic shock in children: Ongoing management after resuscitation".)

Home use of topical anesthesia to control pain from corneal abrasions (August 2017)

In a retrospective study of 444 patients with corneal abrasions given a 24-hour supply of topical tetracaine at the initial emergency department visit, there were no documented serious complications or uncommon adverse events [45]. However, definitive outcomes were only known for 120 patients who returned for rechecks. Patients receiving topical tetracaine were more likely to return for emergency department reevaluation compared with patients who did not receive tetracaine. Topical analgesia was prescribed inappropriately in one-third of patients, for lesions other than simple corneal abrasion (eg, large corneal abrasions, retained rust rings, herpes keratitis, anterior uveitis, and corneal erosions). Because of the possibility of overuse (ie, use beyond 24 hours) and the risk of inappropriate administration, we favor other means of pain control and discourage the prescribing of topical anesthetic agents. More evidence is needed to establish the safety of this practice in patients with simple corneal abrasions. (See "Corneal abrasions and corneal foreign bodies: Management", section on 'Pain control'.)

The Pediatric Sedation State Scale to assess pediatric procedural sedation (July 2017)

The Pediatric Sedation State Scale (PSSS) identifies six levels of sedation based on patient behavior (including patient interference with the procedure and need for restraint) and physiologic parameters (table 4). The PSSS is derived from expert opinion and has been validated, using a small sample of patients and observers, with high inter- and intra-observer agreement [46]. Scales that simply measure the depth of sedation track only one aspect of this practice and do not assess key findings that identify whether the goals of procedural sedation are met. We suggest the use of the PSSS to provide a simple and rapid means of effectively documenting and communicating the quality of pediatric sedation. (See "Procedural sedation in children outside of the operating room", section on 'Sedation state'.)

Delay of appendectomy up to 24 hours not related to appendiceal perforation in children with appendicitis (June 2017)

In the past, appendicitis has been considered a surgical emergency that requires prompt appendectomy to avoid perforation and other complications. In a multicenter, prospective observational study of 955 children 3 to 18 years of age, all of whom were treated with appendectomy for appendicitis within 24 hours of arrival to the emergency department, duration of time between initial evaluation and operation was not associated with an increase in appendiceal perforation [47]. This study adds to a growing body of evidence that suggests that adverse outcomes are not increased for children who receive timely administration of antibiotics and undergo appendectomy less than 24 hours after diagnosis. (See "Acute appendicitis in children: Management", section on 'Timing of operation'.)


Insulin pump versus multiple daily insulin injections for children and young adults with type 1 diabetes (November 2017)

Small randomized trials and meta-analyses of controlled studies in children have generally suggested that insulin pump therapy is better than multiple daily injections (MDI) for managing type 1 diabetes. Now, a large observational study in children and young adults confirms that use of an insulin pump resulted in lower rates of severe hypoglycemia and ketoacidosis and lower mean hemoglobin A1C compared with MDI [48]. We recommend an intensive insulin regimen for children with type 1 diabetes, whenever possible, but the choice of insulin pump or MDI should be based on patient, family, and cost considerations and clinician preferences. (See "Management of type 1 diabetes mellitus in children and adolescents", section on 'Insulin pump'.)

Increasing incidence of type 2 diabetes among youth (June 2017)

The incidence of type 2 diabetes mellitus (T2DM) among youth in the United States continues to rise, in parallel with the increasing rate of severe obesity. In a report from a large US dataset of youth ages 10 to 19 years, the incidence of T2DM rose by almost 5 percent annually, with the greatest annual increases among Asian/Pacific Islanders and Native Americans [49]. These findings call for ongoing efforts to mitigate the modifiable risk factors for T2DM, including obesity and access to health care, particularly among high-risk groups. (See "Epidemiology, presentation, and diagnosis of type 2 diabetes mellitus in children and adolescents", section on 'Epidemiology'.)


Self-administered hypnotherapy for functional abdominal pain in children and adolescents (June 2017)

Increasing evidence suggests that gut-directed hypnotherapy reduces pain frequency and intensity in children and adolescents with functional abdominal pain disorders (FAPDs). In a trial of this therapy that randomly assigned children (age 8 to 18 years) with FAPDs to a self-administered home-based approach using a compact disc or to individual therapy with a qualified therapist for three months, over 60 percent of each group had ≥50 percent reduction in pain frequency and intensity at one-year follow-up [50]. These findings suggest that self-directed hypnotherapy is a reasonable option for children and adolescents with FAPDs, particularly if trained therapists are not available. (See "Functional abdominal pain in children and adolescents: Management in primary care", section on 'Improved coping'.)

Lactate and pyruvate in pediatric acute liver failure (May 2017)

Mitochondrial disorders are increasingly recognized as an important cause of pediatric acute liver failure (PALF), especially in young infants. Data from a large registry study shows that lactic acidosis and an elevated molar ratio of lactate to pyruvate occur across all diagnostic categories in PALF, and thus are not reliable measures to identify patients with a mitochondrial disorder [51]. (See "Acute liver failure in children: Etiology and evaluation", section on 'Young infants'.)


Perioperative management of patients with skeletal dysplasia (November 2017)

Individuals with skeletal dysplasia, such as achondroplasia, are at increased risk for perioperative morbidity and mortality due to abnormalities of their upper airway, chest wall, and upper cervical spine. A new best practices report from a multidisciplinary, international expert panel has outlined recommendations for the perioperative management of these patients, with the goal of reducing complications and improving clinical outcomes [52]. Recommendations include preoperative pulmonary, cardiac, and neurologic evaluations and imaging of the cervical spine. (See "Achondroplasia", section on 'Management'.)

Newborn screening for lysosomal storage disorders (November 2017)

Newborn screening (NBS) for lysosomal storage disorders (LSDs) is under investigation because enzyme replacement therapy is available. A pilot study screening for five LSDs identified all affected infants; however, the false positive rate was high, mostly due to low enzyme levels in preterm infants or pseudodeficiency [53]. Early diagnosis led to early treatment in only a small fraction of newborns. Asymptomatic infants with a positive test for later onset disease or indeterminate tests will require ongoing monitoring for symptom development. Long-term follow-up is needed to determine the true value of NBS for these diseases. (See "Gaucher disease: Pathogenesis, clinical manifestations, and diagnosis", section on 'Newborn screening' and "Lysosomal acid alpha-glucosidase deficiency (Pompe disease, glycogen storage disease II, acid maltase deficiency)", section on 'Newborn screening'.)

Increased nuchal translucency and Noonan syndrome (August 2017)

Increased nuchal translucency on first trimester ultrasound screening has been associated with over 100 developmental and genetic syndromes. In a retrospective study in which a Noonan syndrome gene sequencing panel was obtained in 39 euploid fetuses with nuchal translucency ≥3.0 mm (median thickness 4.0 mm), 10 percent had variants consistent with Noonan syndrome [54]. It may be reasonable to offer screening for genetic mutations associated with Noonan syndrome in euploid fetuses with nuchal translucency ≥3.0 mm, but prospective studies are still needed to validate this result. (See "Cystic hygroma and increased nuchal translucency", section on 'Targeted genetic studies'.)

Genomic sequencing to identify inherited pathogenic genes in families of individuals with multiple congenital malformations (August 2017)

Next-generation sequencing, such as whole exome or whole genome sequencing, is used to aid in diagnosis of complex diseases such as severe intellectual disability or developmental delay. A study that used these techniques to evaluate patients with multiple congenital malformations and their family members identified four families with loss-of-function variants in two genes leading to nicotinamide adenine dinucleotide (NAD) deficiency (HAAO, encoding 3-hydroxyanthranilic acid 3,4-dioxygenase, and KYNU, encoding kynureninase) [55]. In a mouse model of these defects, niacin supplementation during gestation corrected the NAD deficiency and prevented abnormal embryogenesis and fetal death. (See "Birth defects: Causes", section on 'Disorders due to single gene defects' and "Principles and clinical applications of next-generation DNA sequencing", section on 'Diagnosis of complex diseases'.)


Updated guidelines for empiric antifungal therapy for children with fever and neutropenia (June 2017)

Updated guidelines from the International Pediatric Fever and Neutropenia Guideline Panel consider children with cancer or hematopoietic cell transplant as high risk for invasive fungal infection if they have acute myelogenous leukemia, high-risk acute lymphoblastic leukemia, relapsed acute leukemia, neutropenia for >10 days, or are receiving high-dose corticosteroids [56]. In contrast to the previous guideline, they weakly recommend against initiating empiric antifungal therapy for low-risk patients, using serial galactomannan to guide antifungal therapy, and obtaining computed tomography images of the sinuses before initiating antifungal therapy unless the patient has localizing signs or symptoms. They also now suggest abdominal imaging before initiation of antifungal therapy in high-risk patients. (See "Fever in children with chemotherapy-induced neutropenia", section on 'Antifungal therapy'.)


Comparison of influenza diagnostic tests (October 2017)

Conventional reverse-transcriptase polymerase chain reaction (RT-PCR) is currently the preferred test for influenza due to its high sensitivity and specificity. Newer tests include rapid molecular assays using nucleic acid amplification and digital immunoassays (DIAs) using automated antigen detection. Both provide results more quickly than conventional RT-PCR and have higher sensitivity than traditional antigen detection tests. In a meta-analysis that compared various influenza assays with conventional RT-PCR for influenza A, the pooled sensitivities of rapid molecular assays and DIAs were 92 and 80 percent, respectively [57]. Both had higher sensitivity than traditional rapid antigen tests (sensitivity 54 percent). If available, a rapid molecular assay can be used as an alternative to conventional RT-PCR. (See "Diagnosis of seasonal influenza in adults", section on 'Molecular assays' and "Diagnosis of seasonal influenza in adults", section on 'Choice of diagnostic test' and "Seasonal influenza in children: Clinical features and diagnosis", section on 'Approach to testing'.)

Pre-exposure prophylaxis for HIV in adolescent men who have sex with men (September 2017)

For adults at high risk for acquiring HIV, consistent use of daily tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) can reduce the risk of acquiring HIV by greater than 90 percent. In the United States, TDF-FTC for pre-exposure prophylaxis (PrEP) is approved only for patients over 18 years of age; however, young men who have sex with men (MSM) are at particularly high risk of acquiring HIV. The Adolescent Trials Network studied daily TDF-FTC for PrEP in MSM aged 15 to 17 years; it was well tolerated among those who took their medications, but adherence was suboptimal [58]. Thus, clinicians using PrEP for this vulnerable population should closely assess adherence and promptly address potential barriers (eg, depression, active substance use, stigma). (See "Patient evaluation and selection for HIV pre-exposure prophylaxis", section on 'Adolescents'.)

Third dose of MMR for prevention of mumps in an outbreak setting (September 2017)

In the setting of a mumps outbreak, in addition to ensuring that incompletely immunized individuals receive the standard two-dose measles, mumps, and rubella (MMR) vaccine series, public health authorities may recommend a third dose of the MMR vaccine under certain circumstances (eg, two-dose vaccination coverage >90 percent, intense exposure setting, high attack rate). During a mumps outbreak at a university with over 20,000 enrolled students, almost all of whom had previously received two vaccine doses, nearly 5000 students received a third MMR dose [59]. The mumps attack rate (259 cases overall) was lower among students who had received three rather than two vaccine doses (6.7 versus 14.5 cases per 1000 persons); in an adjusted analysis, the third MMR dose was associated with a 78 percent lower risk of mumps. (See "Mumps", section on 'Prevention'.)

2017-2018 influenza immunization recommendations for the United States (September 2017)

The Advisory Committee on Immunization Practices (ACIP) and the American Academy of Pediatrics (AAP) have released recommendations for influenza immunization for the 2017-2018 season in the United States [60,61]. Routine influenza immunization with a licensed, age-appropriate vaccine (table 5) is recommended for all persons ≥6 months of age. Live attenuated influenza vaccine is not recommended for the 2017-2018 season. Pregnant women and persons with egg allergy of any severity can receive any licensed, age-appropriate inactivated influenza vaccine with standard immunization precautions. Although neither the ACIP nor the AAP provide a preference for a particular formulation, we favor a quadrivalent vaccine when available for adults <65 years and we recommend the high-dose vaccine for those ≥65 years. (See "Seasonal influenza in children: Prevention with vaccines", section on 'Types of vaccine' and "Seasonal influenza vaccination in adults", section on 'Choice of vaccine formulation' and "Influenza and pregnancy", section on 'Vaccination' and "Influenza vaccination in individuals with egg allergy", section on 'Safety of vaccines in patients with egg allergy'.)

Risk of congenital Zika virus syndrome (June 2017)

The magnitude of risk of birth defects resulting from in utero exposure to Zika virus is uncertain. The Centers for Disease Control and Prevention identified over 2500 pregnant women in US territories with Zika virus infection in early 2017 [62]. Maternal Zika virus infection in the first trimester was associated with an 8 percent incidence of offspring with birth defects, but fell to 4 to 5 percent with infection in the second and third trimesters. Because of study limitations, these figures likely understate the true risk of any congenital adverse outcome. Importantly, structural birth defects were seen with similar frequency in infants born to women with and without clinical signs and symptoms of Zika virus infection during pregnancy. (See "Zika virus infection: Evaluation and management of pregnant women", section on 'Risk of vertical transmission and anomalies'.)

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 [63]. 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 [64]. 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 [65]. (See "Immunizations during pregnancy", section on 'Rationale, efficacy, and safety'.)


2017 AAP guidelines for screening and managing pediatric high BP (August 2017)

The American Academy of Pediatrics recently published revised guidelines for screening and managing high blood pressure (BP) for children and adolescents [66]. Clinically significant changes include:

Definitions for BP categories were revised into two age groups (table 6) with revised normative tables for boys (table 7) and girls (table 8), which excluded overweight and obese children and thus list BP values several mm Hg lower than prior publications.

Annual BP screening is recommended for children ≥3 years of age without risk factors for hypertension (HTN), with more frequent screening for children of any age with risk factors (table 9 and table 10); BP thresholds that warrant further evaluation were also defined (table 11).

Renal ultrasound is recommended during the initial evaluation of HTN in children <6 years of age and in those with abnormal urinalysis or renal function, and echocardiography is recommended only when pharmacologic therapy is being considered. Additional recommended laboratory testing for obese children with HTN includes hemoglobin A1C, aspartate and alanine transaminases, and fasting lipid profile.

The target BP goal with nonpharmacologic or pharmacologic therapy is a reduction in the systolic and diastolic BP <90th percentile or <130/80 in adolescents. Beta blocker therapy is no longer recommended as initial therapy for pediatric HTN due to adverse effects and the availability of other effective agents with fewer side effects.

(See "Definition and diagnosis of hypertension in children and adolescents", section on 'United States' and "Evaluation of hypertension in children and adolescents" and "Nonemergent treatment of hypertension in children and adolescents" and "Screening tests in children and adolescents", section on 'Hypertension'.)

Prevention of meningococcal infection in patients receiving eculizumab (August 2017)

Eculizumab is a monoclonal antibody used for treatment of complement-mediated hemolytic uremic syndrome and paroxysmal nocturnal hemoglobinuria. It has been associated with a 1000 to 2000-fold increased incidence of meningococcal disease, including life-threatening and fatal infection. Therefore, patients should be immunized with meningococcal vaccines (both ACYW135 and serogroup B), if possible, at least two weeks prior to receiving a first dose of eculizumab. However, invasive meningococcal disease has occurred among patients receiving eculizumab despite receipt of meningococcal vaccine, including infections caused by non-typeable strains not included in the vaccines [67]. Accordingly, in addition to vaccination, we suggest daily antimicrobial prophylaxis (penicillin or, for penicillin-allergic patients, a macrolide) for prevention of meningococcal infection in all patients treated with eculizumab. In addition, patients should be monitored for signs of meningococcal infection and evaluated immediately if infection is suspected. (See "Treatment and prevention of meningococcal infection", section on 'Patients receiving eculizumab'.)

Discontinuation of eculizumab in complement-mediated hemolytic uremic syndrome (June 2017)

Eculizumab is an effective treatment for complement-mediated hemolytic uremic syndrome (HUS). Monthly intravenous maintenance administration has been the standard of care for patients attaining complete remission. Now, two case series have reported successful discontinuation of eculizumab in most patients, with successful remission after early resumption of therapy in those who relapsed [68,69]. Although these results are promising, further studies are needed to determine the optimal time to discontinue eculizumab therapy and the patient population in whom therapy can be safely discontinued. Until these data are available, the decision to withdraw eculizumab therapy should be made in conjunction with a clinician with expertise in managing patients with complement-mediated HUS. Close monitoring after withdrawal is required so eculizumab can be reinitiated if relapse occurs. (See "Complement-mediated hemolytic uremic syndrome", section on 'Discontinuation'.)


Epilepsy surgery in children with drug-resistant epilepsy (October 2017)

In the only randomized trial of epilepsy surgery to date in children with drug-resistant epilepsy, surgery plus medical therapy was superior to medical therapy alone on multiple one-year outcomes, including rate of seizure freedom at one year (77 versus 7 percent), seizure severity, quality of life, social maturity, and child behavior [70]. Rates of seizure freedom ranged from 100 percent in 14 children who underwent temporal lobectomy to 0 percent in 10 children who underwent corpus callosotomy. Postoperative hemiparesis occurred exclusively among children who underwent hemispherectomy, all of whom had baseline deficits; all but two recovered to antigravity strength or better by one year. These results support the role of surgery as a treatment option for selected children with refractory epilepsy following a comprehensive and individualized epilepsy evaluation. (See "Seizures and epilepsy in children: Refractory seizures and prognosis", section on 'Specific procedures'.)

Hematopoietic stem cell gene therapy for adrenoleukodystrophy (October 2017)

Childhood cerebral adrenoleukodystrophy (ALD) is a severe neurologic disease that rapidly progresses to total disability and death unless treated with allogeneic hematopoietic cell transplantation (HCT), which has considerable morbidity and mortality. Gene therapy with autologous hematopoietic stem cells is emerging as a possible alternative treatment. A study of 17 boys with early-stage cerebral ALD enrolled to undergo transplantation with autologous CD34+ cells transfected with Lenti-D (a lentiviral vector containing manufactured ABCD1 complementary DNA) reported 88 percent were alive with no major functional disabilities at 24 months posttransplantation [71]. One boy died from disease progression that began during pretransplantation conditioning, and one was withdrawn from the study and died from complications of subsequent allogeneic HCT. None of the survivors had evidence of graft failure or graft-versus-host disease. These results suggest that autologous hematopoietic stem cell gene therapy may be as effective as, and safer than, HCT for treatment of early cerebral ALD. The treatment has not received regulatory approval. The clinical trial is ongoing and important uncertainties remain. (See "Adrenoleukodystrophy", section on 'Gene therapy'.)

Complex motor behaviors during REM sleep in children with narcolepsy type 1 (September 2017)

Complex motor behaviors during rapid eye movement (REM) sleep are well described in adults with narcolepsy, but their prevalence in children has not been well documented. In a series of 40 children with narcolepsy type 1 who underwent video polysomnography, nearly one-third of patients exhibited motor behaviors during REM sleep ranging from classic dream enactment (eg, vigorous reaching or throwing movements) to more calm, slow pantomime-like events [72]. Events were more common among children with impaired nighttime sleep, worse daytime sleepiness, and severe cataplexy. (See "Narcolepsy in children", section on 'Other sleep disturbances'.)

Genetic testing in neonates with epileptic encephalopathy (August 2017)

The role of genetic testing in the clinical care of neonates with epilepsy is evolving as the number of monogenetic causes of early epileptic encephalopathy increases and specific treatments become available for some syndromes. In a prospective cohort study of over 600 consecutive newborns with seizures, 13 percent had an epilepsy syndrome, including 35 infants (6 percent) with epileptic encephalopathy [73]. Among these, the large majority had a genetic etiology identified by genetic testing, most commonly KCNQ2 encephalopathy, for which sodium channel blocking antiseizure drugs are a preferred therapy. We pursue genetic testing in neonates with epilepsy who do not have an acute symptomatic cause identified on initial history, examination, and neuroimaging. (See "Clinical features, evaluation, and diagnosis of neonatal seizures", section on 'Genetic testing'.)

Low yield of lumbar puncture after complex febrile seizure (July 2017)

After a febrile seizure, lumbar puncture to assess for infection can be avoided in most well-appearing children who have returned to their baseline, even when the febrile seizure has complex features (ie, focal onset, >15 minutes in duration, or recurrent within 24 hours). In a multicenter cohort study of more than 800 children age six months to five years presenting to a pediatric emergency department with a complex febrile seizure, rates of bacterial meningitis and herpes simplex encephalitis were 0.7 and 0 percent, respectively [74]. All five cases of infection occurred in children with a clinical examination suggestive of meningitis. (See "Clinical features and evaluation of febrile seizures", section on 'Lumbar puncture'.)

Cannabidiol in patients with Dravet syndrome and refractory epilepsy (May 2017)

Although cannabidiol (CBD), a component of cannabis, has received interest in the epilepsy community, particularly in children with Dravet syndrome (DS), controlled trials have not been available. In the first multicenter trial comparing oral CBD solution with placebo (in addition to standard antiseizure treatment) in 120 children and young adults with DS, seizure frequency was decreased at 14 weeks in the CBD group [75]. Common side effects of CBD were diarrhea, sedation, and fatigue. Further study of CBD in patients with refractory epilepsy is indicated. In the absence of an available regulated preparation of CBD, we do not advocate use of cannabis or its derivatives outside of the context of a clinical trial. (See "Dravet syndrome: Management and prognosis", section on 'Cannabinoids'.)


Ivacaftor for treatment of cystic fibrosis (June 2017)

Ivacaftor is an effective therapy for patients with cystic fibrosis caused by certain types of cystic fibrosis transmembrane regulator (CFTR) mutations. It is used in patients with G551D and nine other mutations. Now, the US Food and Drug Administration (FDA) has expanded the indications for ivacaftor treatment to include 23 additional mutations, based primarily on in vitro testing of responsiveness to ivacaftor [76,77]. We recommend treatment with ivacaftor for patients two years and older who carry at least one copy of G551D or another mutation listed in the table (table 12). (See "Cystic fibrosis: Overview of the treatment of lung disease", section on 'Ivacaftor for G551D, other gating mutations, and residual function mutations'.)

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