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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: Jun 2017. | This topic last updated: Jul 26, 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

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 [1]. 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 young children: 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 [2,3]. 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 [4]. 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 [5]. 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 [6]. 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 [7]. 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 [8]. 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 [9]. 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 [10]. 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 [11]. 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 [12]. 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 [13]. 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 [14]. (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 [15]. 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 [16]. 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 [17]. 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) [18]. 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 [19]. 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'.)

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 [20]. 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 [21]. 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) [22]. 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) [23]. 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) [24]. 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 [25]. 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 [26]. 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 [27]. 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) [28]. 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'.)

ALLERGY, IMMUNOLOGY, AND RHEUMATOLOGY

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 [29]. 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 [30]. 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 [31]. 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 2) [32]. 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 [33]. 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 [34]. 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'.)

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) [35]. 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 [36]. 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 [37]. 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'.)

EMERGENCY MEDICINE

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 [38]. 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'.)

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

In a systematic review of 10 studies that provided outcomes for over 400 children undergoing nonoperative treatment (NOT, antibiotics without immediate surgery) of early, uncomplicated appendicitis, initial treatment was effective in 88 to 99 percent of patients and was associated with no appendectomy at reported follow-up in 62 to 92 percent of patients [39]. Complications and total length of hospital stay appeared similar during follow-up for NOT and appendectomy. Pooled estimates were performed by the investigators but, given the underlying variation in methodology of the included studies, may be misleading, particularly given subsequent evidence suggesting that patient selection strongly influences outcomes of NOT for appendicitis [40-42]. Although appendectomy remains the treatment of choice for most children with early, uncomplicated appendicitis, NOT is an alternative for selected patients based upon caregiver preference. Additional research is 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 [43]. 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'.)

ENDOCRINOLOGY

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 [44]. 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'.)

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 [45]. 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]) [46]. 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

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 [47]. 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 [48]. (See "Acute liver failure in children: Etiology and evaluation", section on 'Young infants'.)

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 [49]. 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 [50]. 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 [51]. (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 [52]. 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 [53]. 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'.)

HEMATOLOGY AND ONCOLOGY

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 [54]. 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'.)

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 [55]. 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 [56]. 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 [57]. 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 [58]. (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 [59]. 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 [60]. 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 [61]. 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 [62,63]. 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) [64]. 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 [15]. 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 [27]. 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'.)

NEPHROLOGY AND UROLOGY

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 [65,66]. 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'.)

NEUROLOGY

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 a normal 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 pediatric emergency departments with a complex febrile seizure, rates of bacterial meningitis and herpes simplex encephalitis were 0.7 and 0 percent, respectively [67]. 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 [68]. 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'.)

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 [69]. 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".)

PULMONOLOGY

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 [70,71]. 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 4). (See "Cystic fibrosis: Overview of the treatment of lung disease", section on 'Ivacaftor for G551D, other gating mutations, and residual function mutations'.)

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 [72]. 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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