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What's new in pediatrics
Official reprint from UpToDate® ©2016 UpToDate®
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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: Sep 2016. | This topic last updated: Oct 20, 2016.

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.


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

A bag urine specimen for a screening urine dipstick and/or urinalysis may prevent the need for a catheterized urine culture in selected patients older than 6 months of age at low risk for a urinary tract infection (UTI). In an observational study of over 800 previously healthy, well-appearing children 6 to 24 months of age presenting to a pediatric emergency department for evaluation of fever, screening of urine obtained by a bag specimen reduced the number of subsequent urine cultures obtained by bladder catheterization from 63 to 30 percent without prolonging the length of stay or increasing rates of revisits or missed UTI [1]. Although potentially helpful for urine screening tests, bag urine samples should not be routinely used to obtain urine samples for culture, especially in situations where contamination of the specimen will complicate further management (eg, young infants or ill-appearing patients who warrant empiric parenteral antibiotics). (See "Urine collection techniques in infants and children with suspected urinary tract infection", section on 'Specimen for urine dipstick or urinalysis'.)

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

For patients with prolonged post-concussion symptoms, a multidisciplinary approach that includes mental health care by a psychologist or psychiatrist is associated with better outcomes. In a randomized trial of 49 children and adolescents (11 to 17 years of age) with persistent symptoms for one month or longer after a sports-related concussion, collaborative treatment consisting of care management, cognitive-behavioral therapy, and, when needed, psychopharmacologic consultation was associated with significant reductions in postconcussive and depression symptoms at six months when compared to usual treatment [2]. (See "Concussion in children and adolescents: Management", section on 'Persistent symptoms'.)

Strategies for preventing obesity and eating disorders (September 2016)

Clinicians and parents may be reluctant to address obesity in children because of concerns for promoting eating disorders. A new clinical report from the American Academy of Pediatrics outlines strategies that can be used to address obesity without promoting disordered eating [3]. These include counseling parents to avoid "weight talk" (comments that focus on weight or weight-related appearance, even if they are not directed at the child) and focusing goals on healthy food choices and healthy eating behaviors rather than dieting (which is distinguished by caloric restriction with a goal of weight loss). (See "Management of childhood obesity in the primary care setting", section on 'Raising the sensitive issue of weight'.)

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

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

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

Increasing evidence supports an association between shortened sleep duration and obesity in children. In a recent large longitudinal study, the risk of adolescent obesity in preschool children with early bedtimes (8:00 PM or earlier) was about half that of preschool children with late bedtimes (9:00 PM or later), after adjustment for several confounding variables, including maternal obesity, education, and income level [5]. (See "Definition; epidemiology; and etiology of obesity in children and adolescents", section on 'Sleep'.)

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

Antidepressant medications are often used to treat moderately to severely ill children with unipolar major depression. For children and adolescents with acute depressive disorders, first-line pharmacotherapy is typically fluoxetine. There are several randomized trials comparing antidepressant medications with placebo, but there are few head-to-head comparison trials. In a recent meta-analysis of 34 trials comparing one antidepressant with placebo or another active drug for the acute treatment of major depressive disorder in children and adolescents, fluoxetine, sertraline, and escitalopram were statistically more efficacious than placebo [6]. In addition, paroxetine was superior to clomipramine and fluoxetine was superior to nortriptyline. In a network meta-analysis subsequently performed to compare and rank antidepressants for the acute treatment of major depressive disorder, only fluoxetine was better than placebo. In comparison with other antidepressants, fluoxetine was significantly more effective than nortriptyline. Important limitations of the network meta-analysis include risk of bias within individual studies, lack of power and generalizability, and potential selective reporting. (See "Pediatric unipolar depression and pharmacotherapy: Choosing a medication", section on 'All antidepressants'.)

Lipid screening in children and adolescents (August 2016)

Increasing evidence suggests that atherosclerosis begins in childhood and adolescence, yet the optimal strategies for early screening and treatment of the disease remain uncertain. A recent statement of the US Preventive Services Task Force (USPSTF) concluded that the available evidence on screening for lipid disorders in children and adolescents is insufficient to assess the balance of benefits and harms of screening [7]. This position is unchanged from the 2007 USPSTF statement; however, it contradicts the 2011 National Heart, Lung, and Blood Institute (NHLBI) guidelines for cardiovascular health and risk reduction, which recommend screening in all children and adolescents and have been endorsed by the American Academy of Pediatrics (AAP) and the American Heart Association (AHA) [8]. We continue to suggest both age-based universal and selective screening for pediatric dyslipidemia. (See "Dyslipidemia in children: Definition, screening, and diagnosis", section on 'Recommendations of others'.)

Clinical manifestations of severe synthetic cannabinoid toxicity (July 2016)

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

USPSTF recommendations on syphilis screening in nonpregnant adults and adolescents (June 2016)

In June 2016, the United States Preventive Services Task Force updated its statement on syphilis screening in asymptomatic nonpregnant adolescents and adults to recommend screening for those who are at high risk for infection [10]. These include sexually active men who have sex with men (MSM), HIV-infected patients, and individuals with a history of incarceration or commercial sex work. The optimal frequency of routine screening in high-risk patients without a clear exposure is yet to be determined. Consistent with other expert guidelines, we suggest annual screening for sexually active MSM and HIV-infected individuals, with more frequent screening for those with high-risk behaviors, such as multiple or anonymous sexual partners. (See "Syphilis: Screening and diagnostic testing", section on 'Asymptomatic patients' and "Screening for sexually transmitted infections".)

Recommendations for sleep duration in children (June 2016)

Insufficient sleep is the leading cause of daytime sleepiness in children and teenagers. The American Academy of Sleep Medicine has made new consensus recommendations for sleep duration to promote optimal health, daytime functioning, and development [11]:

Infants 4 to 12 months – 12 to 16 hours (including naps)

Toddlers 1 to 2 years – 11 to 14 hours (including naps)

Children 3 to 5 years – 10 to 13 hours (including naps)

Children 6 to 12 years – 9 to 12 hours

Teens 13 to 18 years – 8 to 10 hours

These recommendations were endorsed by the American Academy of Pediatrics and are similar to those of the National Sleep Foundation. (See "Assessment of sleep disorders in children", section on 'Insufficient sleep'.)

Diluted apple juice for hydration in young children with mild gastroenteritis (May 2016)

Commercial oral rehydration solutions (ORS) are recommended for rehydration of children with gastroenteritis. More readily available household beverages, such as fruit juice, tea, sports drinks, and soft drinks, have not been recommended due to concerns that their lower sodium concentration and higher osmolarity (table 1) could induce osmotic diarrhea, leading to hyponatremia. However, a randomized trial in children 6 to 60 months of age with mild gastroenteritis and no clinical signs of dehydration demonstrated that hydration with half-strength apple juice resulted in fewer episodes of treatment failure than ORS (17 versus 25 percent) [12]. Treatment failure was defined as any of the following events occurring within seven days of enrollment: intravenous rehydration, hospitalization, subsequent unscheduled physician encounter, protracted symptoms, crossover to the other fluid, ≥3 percent weight loss, or signs of significant dehydration on a follow-up visit. Based on these findings, diluted apple juice followed by a permissive approach to fluid consumption is a reasonable alternative to ORS for hydration in young children with mild gastroenteritis and no clinical signs of dehydration. (See "Oral rehydration therapy", section on 'Common household beverages and fluids'.)

Nicotine poisoning from e-cigarette exposures in children (May 2016)

Since 2010, e-cigarette exposures (ingestion, dermal, inhalational, and ocular) have been rapidly increasing in the United States, from approximately 20 regional poison center calls per month in April 2012 to over 200 calls per month in April 2015 [13]. Children younger than six years of age account for a majority of exposures, and ingestion is the most common route. Typical clinical features of poisoning are related to nicotine toxicity and include eye irritation, nausea and vomiting, tachycardia, and lethargy. Life-threatening effects consist of seizures, coma, apnea, and cardiac arrest. When compared with ingestions of cigarettes or other tobacco products, e-cigarette exposure is associated with a significantly increased risk of hospitalization or severe effects. Although the regulation of e-cigarettes varies by country, many of these devices do not yet have child safety features to prevent exposure. (See "Toxic plant ingestions and nicotine poisoning in children: Management", section on 'Electronic cigarettes' and "E-cigarettes", section on 'Regulatory status'.)

BMI during adolescence and cardiovascular mortality during adulthood (April 2016)

A variety of studies have shown associations between obesity during adolescence and multiple cardiovascular risk factors (eg, hypertension, dyslipidemia, diabetes). Now, a large population-based study from Israel found that higher body mass index (BMI) during late adolescence is associated with cardiovascular mortality in mid-adulthood [14]. Of note, this association was seen even within the range of BMIs considered to be normal in adolescents, with a graded increase in risk of death as adolescent BMI rose above the 50th percentile (figure 1). This study supports and expands the body of evidence suggesting that the processes causing coronary heart disease begin during adolescence. (See "Comorbidities and complications of obesity in children and adolescents", section on 'Adult coronary heart disease'.)

Increasing vegetable consumption in children (April 2016)

Vegetables are an important component of a healthy diet, but national surveys indicate that vegetable consumption by young children falls short of the recommended 2.5 cup-equivalents per day. In a longitudinal study, six-year old children who had been offered a variety of vegetables at the initiation of complementary feedings were more willing to try new vegetables, ate more new vegetables, and liked new vegetables more than children who were offered little or no variety of vegetables [15]. Offering a vegetable that was initially disliked at eight subsequent meals was associated with increased acceptance of that vegetable and continuing to like and eat that vegetable at three and six years of age. These findings support recommendations to offer vegetables at least once per day, to offer a variety of vegetables, and to offer vegetables that are initially refused at subsequent meals. (See "Introducing solid foods and vitamin and mineral supplementation during infancy", section on 'Puréed foods'.)


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

For primary respiratory support of preterm infants, high-flow nasal cannulae (HFNC) has been proposed as an alternative delivery system to nasal continuous positive airway pressure (nCPAP), as HFNC is associated with less nasal trauma. However, a large multicenter trial of preterm infants (gestational age >28 weeks) was terminated early (564 patients recruited for a predetermined sample size of 750) when a predesignated interim analysis at 500 patient enrollment demonstrated a higher treatment failure rate among those randomly assigned to HFNC versus nCPAP for primary respiratory support (25.5 versus 13.3 percent) [16]. Treatment failure was defined as an infant receiving maximal support for either HFNC or nCPAP and with one or more of the following criteria: intubation and mechanical ventilation, receiving fraction of inspired oxygen (FiO2) ≥0.4, venous or arterial blood gas sample with a pH ≤7.2, partial pressure of carbon dioxide (PaCO2) >60 mmHg, and apnea episodes requiring positive pressure ventilation. As a result, we continue to use nCPAP as the initial respiratory support for preterm infants. (See "Oxygen monitoring and therapy in the newborn", section on 'High flow nasal cannula'.)

Neonatal phototherapy and potential increased risk of cancer (June 2016)

Phototherapy is used widely to treat neonatal hyperbilirubinemia and thought to be a relatively safe intervention, although concerns of an association with childhood cancer have been raised. Two recent studies have reinforced this uncertainty:

In a retrospective cohort study including almost 500,000 infants ≥35 weeks gestational age, the overall prevalence of childhood cancer was greater in children exposed to phototherapy compared with unexposed controls (25 versus 18 per 100,000 person-years) [17]. However, after controlling for confounding variables, the risks for overall cancer, nonlymphocytic leukemia, and liver cancer were similar for both groups.

In a study that linked birth and death certificate and hospital discharge data for infants born in California, infants with diagnosis codes for phototherapy were more likely to have a cancer diagnosis by one year of age than those without such codes (32.6 versus 21 per 100,000 patients) [18]. The risks for overall cancer, myeloid leukemia, and kidney cancer persisted after adjusting for confounders.

If phototherapy is a risk factor for childhood cancer, the effect appears to be no more than modest. Given this possibility, phototherapy should be prescribed judiciously. (See "Treatment of unconjugated hyperbilirubinemia in term and late preterm infants", section on 'Childhood cancer'.)

Erythropoietin not associated with improved neurodevelopmental outcome in very preterm infants (June 2016)

Long-term neurodevelopmental delay is a significant complication of prematurity, especially for very preterm neonates (gestational age <32 weeks). Although erythropoietin (EPO) has been suggested as a neuroprotective agent, a randomized trial showed no difference in neurodevelopmental outcome at two years of age between very preterm patients assigned high-dose recombinant human EPO versus placebo [19]. Follow-up assessment for later cognitive and physical problems is ongoing. As this trial is not definitive, the use of neuroprotective agents, including EPO, remains an active area of clinical research. (See "Long-term neurodevelopmental outcome of preterm infants: Epidemiology and risk factors", section on 'Changes in clinical practice'.)

Early hydrocortisone therapy and bronchopulmonary dysplasia (May 2016)

In high-risk preterm infants (gestational age <28 weeks), postnatal systemic dexamethasone administration reduces the risk for bronchopulmonary dysplasia (BPD), but is not administered routinely because it appears to increase the risk for cerebral palsy. Hydrocortisone has been proposed as an alternative; however, it may increase the risk for intestinal perforation and evidence of efficacy is limited. These issues were addressed by a recent French multicenter trial that randomly assigned high-risk preterm infants to prophylactic treatment with hydrocortisone or placebo and found that hydrocortisone improved the rate of survival without BPD at 36 weeks postmenstrual age (60 versus 51 percent), without an increase in the rate of adverse events, including gastrointestinal perforation [20]. Data on neurodevelopmental outcome are not yet available and the trial was terminated early because of lack of funding. We continue to recommend not routinely administering prophylactic glucocorticoid therapy (hydrocortisone or dexamethasone) to prevent BPD as many infants would be exposed to these drugs unnecessarily and the balance between reduction of BPD and potential adverse effects remains unclear. In our practice, we limit hydrocortisone therapy to infants who develop severe BPD requiring sustained ventilator support. (See "Postnatal use of glucocorticoids in bronchopulmonary dysplasia", section on 'Hydrocortisone'.)

Platelet counts in neonatal alloimmune thrombocytopenia (April 2016)

In pregnancies with human platelet antigen (HPA)-1a incompatibility, data from retrospective studies suggest that fetal/neonatal platelet counts are lower in the second affected pregnancy. However, the only prospective study of neonatal platelet counts in 29 subsequent untreated pregnancies did not confirm this finding [21]. When the index pregnancy was complicated by neonatal alloimmune thrombocytopenia (NAIT), neonatal platelet counts in the subsequent pregnancy were the same or higher in two-thirds of cases. When the index pregnancy was complicated by NAIT with severe thrombocytopenia, neonatal platelet counts in the subsequent pregnancy were the same or higher in 29 percent of cases. These findings, if confirmed in larger studies, suggest that the severity of NAIT does not consistently worsen in subsequent pregnancies. (See "Neonatal alloimmune thrombocytopenia: Parental evaluation and pregnancy management", section on 'Background'.)


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

Exposure to farm animals, particularly early in life, is negatively associated with the development of allergic disease. A recent study compared 60 children from Amish and Hutterite communities, two genetically similar, reproductively isolated farming populations in the United States [22]. The Amish have traditional, single-family farms with exposure to horses and dairy cows, whereas the Hutterites live and work on large farms that are highly industrialized. Amish children have significantly lower rates of asthma and allergic sensitization than their Hutterite counterparts. Endotoxin levels were significantly higher in the Amish homes, and dust extracts from the Amish homes, but not the Hutterite homes, significantly blocked airway hyperresponsiveness and eosinophilia in a mouse model. In addition, in vitro studies showed an enhanced innate immune response in Amish, but not Hutterite, children. These findings suggest that the closer contact with farm animals in the Amish lifestyle may help prevent the development of asthma by altering the innate immune response. (See "Increasing prevalence of asthma and allergic rhinitis and the role of environmental factors", section on 'Farms, villages, worms, and other parasites'.)

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

More frequent use of acetaminophen was associated with increased asthma-related complications in children in observational studies, leading to the recommendation by some for children with asthma to avoid acetaminophen. However, these findings were not replicated in a prospective, randomized trial comparing acetaminophen and ibuprofen use [23]. In this trial, 300 children with mild persistent asthma were randomly assigned to as-needed treatment with acetaminophen or ibuprofen for fever or pain over a 48-week period. All children received standard controller therapy for asthma. There was no significant difference between the two groups in the number of asthma exacerbations requiring treatment with systemic glucocorticoids or in the number of asthma exacerbations. Thus, we do not advise restricting the use of acetaminophen in children with asthma. (See "Virus-induced wheezing and asthma: An overview", section on 'Acetaminophen use for febrile illnesses'.)

Screening and prevention of hydroxychloroquine retinopathy (August 2016)

Antimalarial agents hydroxychloroquine (HCQ) and chloroquine are widely used for the treatment of systemic lupus erythematosus, rheumatoid arthritis, and other inflammatory and dermatologic conditions, and are generally thought to be safe. Retinal toxicity is a known risk, however, and measures to minimize this potential toxicity are necessary. Recently, the American Academy of Ophthalmology issued revised recommendations for screening and prevention of retinopathy [24]. Key changes include the following:

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

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

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

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

Omalizumab, a monoclonal antibody to immunoglobulin E (IgE), is an option for patients with moderate to severe persistent asthma and sensitization to perennial aeroallergens who are inadequately controlled on inhaled glucocorticoids. The US Food and Drug Administration (FDA) has now lowered the approved age range from 12 to 6 years of age, expanding the therapeutic options in step 5 asthma management in children [25]. (See "Asthma in children younger than 12 years: Treatment of persistent asthma with controller medications", section on 'Step-up therapy' and "Asthma in children younger than 12 years: Treatment of persistent asthma with controller medications", section on 'Anti-IgE therapy' and "Anti-IgE therapy", section on 'Omalizumab therapy in asthma'.)

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

The majority of children with egg allergy can tolerate extensively heated egg, and introduction of cooked egg can both improve quality of life and hasten resolution of egg allergy. A recent study examined whether various cooking methods affected tolerance and whether skin testing with the different cooked forms of the food was predictive of the oral food challenge (OFC) results [26]. Fifty-four children with a history of egg allergy and positive skin testing to raw egg were tested with baked egg in a wheat matrix (cake), egg frittata (fried then baked, no wheat), and boiled egg. They were then challenged to the same forms of egg and pass rates were 88, 74, and 56 percent for baked in wheat matrix, fried/baked, and boiled egg, respectively. The OFC pass rates and higher internal temperatures for the cake and frittata compared with the boiled egg suggest that degree of cooking of the food is more important than the presence of a wheat matrix. Negative skin testing (ie, mean wheal diameters were <3 mm) with a given form of heated egg had a 100 percent negative predictive value for reacting to ingestion of that same form of egg. Although these results suggest that patients could introduce extensively heated egg without first undergoing an oral food challenge (OFC) if skin testing to the cooked form was negative, supervised OFCs are still recommended until these results have been confirmed in more patients, because of the lack of standardization with this type of testing and the risk of anaphylaxis with a failed challenge. (See "Egg allergy: Management", section on 'Extensively heated egg'.)

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

Biologic response modifiers (BRMs) are immunosuppressive agents that are used to treat autoimmune disorders such as juvenile idiopathic arthritis and inflammatory bowel disease. Patients receiving BRMs have an increased risk of infection, particularly mycobacterial, viral, and fungal infections. Thus, the American Academy of Pediatrics has published guidance for clinicians using these agents [27]. A thorough history is recommended to help determine infectious risk, with performance of screening tests as indicated depending upon the history and biologic agent chosen. Administration of routine immunizations at least two weeks prior to starting a BRM is advised for inactivated or subunit vaccines and at least four weeks prior for live vaccines, if treatment can be safely delayed. Administration of live vaccines is not recommended during treatment with BRMs. An infectious disease specialist should be consulted if a live vaccine is deemed necessary while a patient is on biologic therapy. Inactivated and subunit vaccines can be given while on therapy, and an annual inactivated influenza vaccine is recommended. (See "Systemic juvenile idiopathic arthritis: Treatment", section on 'Biologic therapy'.)

Mild skin-limited allergic reactions to antibiotics in children (June 2016)

It is not uncommon for young children to develop mild skin-limited reactions (eg, rash, hives) to antibiotics, particularly amoxicillin, during treatment for routine infections. Most of these reactions do not represent serious drug allergy, but IgE-mediated anaphylaxis can first present in this manner, so caution is necessary. In a new study of over 800 young children referred to an allergy clinic with past mild cutaneous reactions to amoxicillin, all children underwent a two-step challenge [28]. Ninety-four percent had no reaction, 2 percent had mild immediate reactions (isolated hives), and 4 percent had mild delayed reactions. Skin testing was later performed on the subset with immediate initial reactions, and only 1 of 17 children had a positive result, indicating that skin testing would not have been useful in identifying these children before challenge. At present, we do not advocate this approach unless there is no alternative antibiotic and allergy referral is not available. However, this study provides valuable information about the pathophysiology of this common type of reaction and may allow for safe rechallenge protocols to be developed in the future for use in the primary care setting. (See "Penicillin allergy: Delayed hypersensitivity reactions", section on 'Children'.)

Failed food challenges and resolution of food allergy (May 2016)

Parents often express concern that a failed oral food challenge (OFC) will prolong their child's food allergy. An observational study examining this question demonstrated that neither food-specific immunoglobulin E (IgE) levels nor skin prick tests changed with either accidental or intentional exposures [29]. The absence of increased sensitization after OFCs that result in an allergic reaction suggests that these exposures will not alter the natural course or resolution of food allergy. (See "Food allergy in children: Prevalence, natural history, and monitoring for resolution", section on 'Role of avoidance'.)


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

In a randomized trial of restrictive versus liberal postoperative transfusion strategies in 162 infants with congenital heart disease undergoing surgical repair or palliation, a restrictive transfusion strategy reduced the red cell transfusion rate, without increasing in-hospital mortality, need for extracorporeal membrane oxygenation (ECMO) support, or hospital length of stay [30]. The restrictive group was transfused for hemoglobin <7.0 g/dL for biventricular repairs or <9.0 g/dL for palliative procedures plus a clinical indication; the liberal group was transfused for hemoglobin <9.5 g/dL for biventricular repairs or <12 g/dL for palliative procedures. Larger more definitive trials are needed before clear transfusion guidelines in this population can be made. (See "Red blood cell transfusion in infants and children: Indications", section on 'Surgery'.)


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

The British Association of Dermatologists released new guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), a severe and potentially fatal mucocutaneous drug reaction [31]. The guidelines provide evidence-based recommendations for the diagnosis, severity assessment, and management of SJS/TEN. Specific areas covered include initial management, supportive care, and therapies intended to reduce mortality, such as intravenous immune globulins, systemic corticosteroids, and cyclosporine. The treatment of eye involvement, including systemic therapies and amniotic membrane transplantation to prevent permanent ocular sequelae, as well as the management of oral, urogenital, and airway mucosal involvement are also addressed. (See "Stevens-Johnson syndrome and toxic epidermal necrolysis: Management, prognosis, and long-term sequelae", section on 'General principles'.)

New guidelines for the management of acne vulgaris (May 2016)

The American Academy of Dermatology released new guidelines of care for the management of acne vulgaris in adolescents and adults [32]. The guidelines reviewed efficacy, regimens, and side effects of acne therapies and included an updated treatment algorithm for acne vulgaris (table 2). Specific areas covered by the guidelines include indications for evaluating patients for androgen excess, the role of topical antimicrobial and topical retinoid preparations, effective combination therapies, and optimal use of systemic antibiotics, hormonal therapies, and oral isotretinoin. (See "Treatment of acne vulgaris", section on 'General approach'.)


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

Attention deficit hyperactivity disorder (ADHD) is conceptualized as a disorder with childhood onset that persists in adulthood. DSM-5 diagnostic criteria for adult ADHD require the presence of several symptoms prior to age 12 years. Multiple recent studies, however, have challenged this understanding of the disorder. One of them, a longitudinal cohort study, followed all children born in Pelotas, Brazil in 1993 up to the ages of 18 or 19 years [33]. Three hundred ninety-three of the 5249 children were diagnosed with ADHD at age 11 and 492 were diagnosed with ADHD at age 18 or 19 years. Only 60 children with ADHD continued to have ADHD as young adults (17.2 percent) and only 60 young adults with ADHD had the disorder in childhood (12.6 percent). The requirement of childhood onset for the diagnosis of adult ADHD is controversial and may be reexamined as further data become available. (See "Attention deficit hyperactivity disorder in adults: Epidemiology, pathogenesis, clinical features, course, assessment, and diagnosis", section on 'Course'.)

Oxytocin induction not associated with autism (August 2016)

A possible association between oxytocin induction of labor and development of autism in offspring has been widely publicized in the lay press, based on findings from a single epidemiological study. Recently, a nationwide epidemiologic study in Sweden found no association between labor induction and autism in offspring when adjustments were made for environmental and genetic factors shared by siblings [34]. A strength of this study was that comparison of exposure-discordant births to the same woman allowed control for all unmeasured factors shared by siblings. We believe an association between oxytocin induction and autism is unlikely. (See "Induction of labor", section on 'Other'.)

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

Desmopressin is an effective short-term treatment for nocturnal enuresis in children, but relapse rates are high after discontinuation. A recent meta-analysis of four randomized trials including 500 patients demonstrated the benefit of tapering desmopressin rather than abrupt discontinuation (sustained response rate: 57 versus 42 percent) [35]. In subgroup analyses, gradually decreasing the effective dose prevented relapse, but increasing the interval between doses did not. When discontinuing daily desmopressin, we suggest decreasing the daily dose rather than extending the interval between doses or abrupt discontinuation. (See "Nocturnal enuresis in children: Management", section on 'Discontinuation'.)


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

Detection of abusive head trauma (AHT) is challenging in well-appearing infants who typically present with an unrelated complaint and no history of trauma. High-risk complaints include apnea or acute life-threatening event, seizure, vomiting without diarrhea, soft-tissue scalp swelling, bruising, lethargy, fussiness, or poor feeding. In a prospective multicenter validation of a clinical prediction rule in over 1000 well-appearing infants younger than one year of age (109 with abuse) who presented with high-risk complaints for possible abuse, a score of two or more had high sensitivity for an abnormality on computed tomography (CT) of the head [36]. This rule, which assigns points based upon age, head circumference, skin examination, and serum hemoglobin, has significant potential for assisting the clinician with decisions about neuroimaging in well-appearing infants with equivocal findings for abuse. Magnetic resonance imaging is preferred to CT in such patients if there is timely availability of the study and interpretation by a pediatric neuroradiologist. (See "Child abuse: Evaluation and diagnosis of abusive head trauma in infants and children", section on 'Well-appearing infants'.)

Ultrasound for the detection of distal forearm fractures in children (July 2016)

Distal forearm fractures are among the most common fractures in children. Plain radiographs of the forearm are considered the gold standard for definitive diagnosis. However, there is a growing interest in ultrasound diagnosis of distal forearm fracture due, in part, to the absence of exposure to radiation. In a metaanalysis of 12 studies (951 children 18 years of age and younger) comparing ultrasound with the reference standard of conventional radiography, ultrasound detected distal forearm fractures with a pooled sensitivity of 98 percent and a specificity of 96 percent [37]. These findings correspond to an estimated 3 out of 100 distal forearm fractures missed by ultrasound. Detection of distal forearm fractures is a developing use of bedside ultrasound, especially when plain radiographs are not readily available. However, most centers still use plain radiographs for diagnosis of forearm fractures. (See "Distal forearm fractures in children: Diagnosis and assessment", section on 'Ultrasound'.)

Fluid management in resource-limited countries for children with impaired circulation (May 2016)

The World Health Organization (WHO) has updated its emergency triage and treatment (ETAT) guidelines for fluid management in children with signs of circulatory impairment who are receiving treatment in resource-limited settings (table 3) [38]. Compared with the previous WHO ETAT guidelines, this guidance promotes less aggressive fluid resuscitation for children with shock, especially those with severe anemia or malnutrition. This update is based, in part, on a trial in a resource-limited setting showing higher mortality in children with severe febrile illness and impaired perfusion who received fluid boluses compared with those who did not [39]. (See "Initial management of shock in children", section on 'Resource-limited settings'.)

Nicotine poisoning from e-cigarette exposures in children (May 2016)

Since 2010, e-cigarette exposures (ingestion, dermal, inhalational, and ocular) have been rapidly increasing in the United States, from approximately 20 regional poison center calls per month in April 2012 to over 200 calls per month in April 2015 [13]. Children younger than six years of age account for a majority of exposures, and ingestion is the most common route. Typical clinical features of poisoning are related to nicotine toxicity and include eye irritation, nausea and vomiting, tachycardia, and lethargy. Life-threatening effects consist of seizures, coma, apnea, and cardiac arrest. When compared with ingestions of cigarettes or other tobacco products, e-cigarette exposure is associated with a significantly increased risk of hospitalization or severe effects. Although the regulation of e-cigarettes varies by country, many of these devices do not yet have child safety features to prevent exposure. (See "Toxic plant ingestions and nicotine poisoning in children: Management", section on 'Electronic cigarettes' and "E-cigarettes", section on 'Regulatory status'.)


Metformin use and reduced kidney function (April 2016)

The use of metformin is contraindicated in patients with factors predisposing to lactic acidosis, including impaired renal function. The precise renal thresholds for the safe use of metformin remain uncertain. Improved clinical outcomes with metformin have been reported in observational studies of patients with diabetes and renal impairment (estimated glomerular filtration rate [eGFR] 45 to 60 mL/min). On the basis of these studies, the US Food and Drug Administration (FDA) revised its labeling of metformin, which previously had identified metformin as contraindicated in women and men with serum creatinine levels ≥1.4 mg/dL (124 micromol/L) and ≥1.5 mg/dL (133 micromol/L), respectively [40]. The use of metformin is contraindicated in patients with an eGFR <30 mL/min, and the initiation of metformin is not recommended in patients with an eGFR between 30 and 45 mL/min. For patients taking metformin whose eGFR falls below 45 mL/min, the benefits and risks of continuing treatment should be assessed, whereas metformin should be discontinued if the eGFR falls below 30 mL/min. For patients with eGFR between 30 and 60 mL/min, we typically reduce the metformin dose by half (no more than 1000 mg per day), although there are no data to support this approach. (See "Metformin in the treatment of adults with type 2 diabetes mellitus", section on 'Contraindications'.)


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

Retrospective studies suggest that infants who develop biliary atresia often have a mildly elevated conjugated bilirubin level (>0.3 mg/dL) in the first few days of life, weeks to months before they develop symptoms. A pilot study recently investigated whether this observation could be used as a screening test in neonates [41]. The authors screened more than 11,000 neonates using a two-stage approach to identify those with persistent elevations of direct or conjugated bilirubin, resulting in early identification of two infants with biliary atresia and one with alpha-1 antitrypsin deficiency. Further studies are needed to determine the sensitivity and cost-effectiveness of this approach and its potential effect on patient outcome. (See "Biliary atresia", section on 'Laboratory studies'.)


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

In a randomized trial of restrictive versus liberal postoperative transfusion strategies in 162 infants with congenital heart disease undergoing surgical repair or palliation, a restrictive transfusion strategy reduced the red cell transfusion rate, without increasing in-hospital mortality, need for extracorporeal membrane oxygenation (ECMO) support, or hospital length of stay [30]. The restrictive group was transfused for hemoglobin <7.0 g/dL for biventricular repairs or <9.0 g/dL for palliative procedures plus a clinical indication; the liberal group was transfused for hemoglobin <9.5 g/dL for biventricular repairs or <12 g/dL for palliative procedures. Larger more definitive trials are needed before clear transfusion guidelines in this population can be made. (See "Red blood cell transfusion in infants and children: Indications", section on 'Surgery'.)

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

The majority of venous thromboembolism (VTE) in children is associated with central venous catheter (CVC) use. The association between inherited thrombophilia (IT) and CVC-related VTE is unclear. A recent systematic review and meta-analysis found that IT is associated with an increased likelihood of CVC-associated VTE (odds ratio 3.2 [95% CI 1.6-6.5]) [42]. However, the meta-analysis was limited by significant heterogeneity among studies and a relatively high prevalence of elevated factor VIII, which may represent an inherited disorder or may be acquired. The prevalence of most other IT traits in the meta-analysis was low and their associations with CVC-related VTE were relatively weak. The available evidence is insufficient to support routinely performing IT testing to inform management decisions in children with CVC-related VTE. (See "Screening for inherited thrombophilia in children", section on 'First episode of CVC-related VTE'.)

Risk of inhibitors in hemophilia A (June 2016)

Individuals with hemophilia who receive coagulation factor infusions are at risk of developing an autoantibody to the factor (a factor inhibitor); this occurs in approximately 25 to 30 percent of individuals with severe hemophilia A. The SIPPET trial (Survey of Inhibitors in Plasma-Product Exposed Toddlers) is the first randomized trial to evaluate the risk of inhibitors with recombinant versus plasma-derived factor VIII products [43]. In SIPPET, 264 children who required factor VIII infusions were randomly assigned to receive a recombinant or a plasma-derived product. Inhibitors were seen more frequently with the recombinant products (37 versus 23 percent). The mechanism of this difference is unknown; the presence of von Willebrand factor in the plasma-derived products or the use of non-human cell lines to produce the recombinant products has been suggested. These results may not apply to recombinant products made in human cell lines or those engineered to have extended half-lives. (See "Factor VIII and factor IX inhibitors in patients with hemophilia", section on 'Recombinant versus plasma-derived products'.)


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

A randomized trial of trivalent inactivated influenza vaccination of pregnant women reported 86 percent efficacy against laboratory confirmed influenza among infants ≤8 weeks of age and 25 to 30 percent efficacy among infants 8 to 24 weeks of age, compared with placebo vaccination [44]. These data suggest that the passive protection afforded by maternal influenza vaccination declines significantly before the infant is eligible for influenza vaccination at six months of age. (See "Influenza and pregnancy", section on 'Infant protection'.)

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

The effectiveness of seasonal influenza vaccines varies from season to season and is determined by a number of factors, including the match between circulating influenza strains and influenza strains in the vaccine. During the 2015-2016 influenza season, data from the United States Influenza Vaccine Effectiveness Network indicated that inactivated influenza vaccine (IIV) was 63 percent effective in preventing influenza in children, but live attenuated influenza vaccine (LAIV) was not effective [45]. Findings of poor or lower than expected LAIV effectiveness were also noted during the 2013-2014 and 2014-2015 seasons in the United States. These findings are inconsistent with studies sponsored by the manufacturer and studies from other countries that found LAIV was effective (ranging from 46 to 58 percent) during the 2015-2016 season [46-49]; however, LAIV was less effective than IIV in all of these studies [50]. In August 2016, the United States Centers for Disease Control and Prevention recommended that LAIV not be used during the 2016-2017 influenza season [51]. While some countries have elected to continue using LAIV [46], we suggest IIV rather than LAIV for the 2016-2017 influenza season in the northern hemisphere. (See "Seasonal influenza in children: Prevention with vaccines", section on 'IIV versus LAIV' and "Seasonal influenza vaccination in adults", section on 'Choice of vaccine formulation'.)

Absence of pyuria in children with UTI (July 2016)

The diagnosis of urinary tract infection (UTI) in children is usually based on the finding of significant bacteriuria plus pyuria. However, in a retrospective review of 1181 children <18 years of age with symptomatic UTI and significant growth of a single uropathogen, microscopic urinalysis did not show pyuria in 13 percent [52]. The frequency of pyuria was lower in children with Enterococcus (54 percent), Pseudomonas aeruginosa (62 percent), and Klebsiella (74 percent) than in children with E. coli (89 percent). Therefore, if the urine culture of a child with UTI symptoms demonstrates significant growth (≥50,000 colony-forming units [CFU]/mL from a catheterized specimen or ≥100,000 CFU/mL from a clean voided specimen) of Enterococcus, Klebsiella, or P. aeruginosa, UTI may be diagnosed in the absence of pyuria. (See "Urinary tract infections in infants and children older than one month: Clinical features and diagnosis", section on 'Pyuria'.)

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

Because of concerns about the decreasing susceptibility of Neisseria gonorrhoeae to several classes of antibiotics, combination antimicrobial therapy with ceftriaxone plus a second agent, preferably azithromycin, is the recommended treatment for uncomplicated gonorrhea. However, treatment failure following combination therapy has now been reported, in a heterosexual man from the United Kingdom who presented with both urogenital and pharyngeal infection [53]. Although the urogenital infection was successfully treated with ceftriaxone plus azithromycin, the pharyngeal infection persisted, and decreased susceptibility to both agents was detected in the post-treatment isolate. This report, in addition to surveillance reports suggesting increasing rates of decreased susceptibility to azithromycin in N. gonorrhoeae isolates in the United States [54], highlights the need for novel treatment strategies for gonorrhea in the face of rising antimicrobial resistance. (See "Treatment of uncomplicated gonococcal infections", section on 'Monitoring for and managing treatment failure' and "Treatment of uncomplicated gonococcal infections", section on 'Rationale for dual therapy'.)

WHO recommendations for infant prophylaxis to prevent mother-to-child HIV transmission (July 2016)

The World Health Organization (WHO) has updated its guidelines on the use of antiretroviral agents to manage and prevent HIV infection [55]. One major change from previous WHO statements involves post-exposure prophylaxis of infants born to HIV-infected mothers. The recommended regimen for infant prophylaxis now takes into account the infant's risk of infection, as determined by the timing of maternal infection and maternal antiretroviral treatment, in addition to the type of infant feeding; a two-drug regimen is recommended for high-risk infants (algorithm 1). This recommendation was based, in part, on earlier data that demonstrated a lower HIV transmission rate with dual-agent rather than single-agent prophylaxis among infants born to mothers who had not received antiretroviral agents during pregnancy. (See "Prevention of mother-to-child HIV transmission in resource-limited settings", section on 'Infant antiretroviral use'.)

Outbreak of Burkholderia cepacia infection associated with contaminated oral liquid docusate (June 2016)

In June 2016, a multistate outbreak of Burkholderia cepacia infection was reported in the United States [56]. B. cepacia typically causes lung colonization and infection in patients with cystic fibrosis (CF), but most cases in this outbreak have involved mechanically ventilated intensive care unit patients without CF. The types of infections involved have not yet been reported. Because cases in one state have been associated with contaminated oral liquid docusate, the United States Centers for Disease Control and Prevention (CDC) recommends that facilities not use liquid docusate products for any patient. PharmaTech LLC, the manufacturer of the contaminated product, Diocto Liquid, has voluntarily recalled all non-expired lots [57]. Updated information about the outbreak and public health reporting can be found on the CDC’s website. (See "Epidemiology, pathogenesis, microbiology, and diagnosis of hospital-acquired and ventilator-associated pneumonia in adults", section on 'Outbreak of Burkholderia cepacia infection'.)

Nebulized hypertonic saline does not reduce length of stay in children with bronchiolitis (June 2016)

In previous meta-analyses, compared with a placebo (nebulized normal saline), nebulized hypertonic saline appeared to reduce the length of stay in children hospitalized with bronchiolitis, but the findings were limited by heterogeneity. A new meta-analysis reanalyzed the data controlling for the major sources of heterogeneity (imbalance in duration of illness between treatment groups and a widely divergent outcome definition in one study population) [58]. In the reanalysis, nebulized hypertonic saline had no effect on length of stay. This finding supports our suggestion against the routine use of nebulized hypertonic saline in hospitalized children with bronchiolitis. Maintenance of adequate hydration, provision of oxygen and respiratory support as necessary, monitoring disease progression, and anticipatory guidance are the mainstays of management of severe bronchiolitis. (See "Bronchiolitis in infants and children: Treatment; outcome; and prevention", section on 'Nebulized hypertonic saline'.)

Influenza postexposure prophylaxis with inhaled laninamivir (May 2016)

Laninamivir, a long-acting inhaled neuraminidase inhibitor, has been reported to be effective for preventing influenza infection in the household contacts of patients with influenza. In a randomized trial, family members living with a patient with influenza infection within 48 hours of symptom onset were randomly assigned to receive a single dose of laninamivir, two doses of laninamivir given daily for two days, or placebo [59]. The proportion of participants who developed clinical influenza that was confirmed by laboratory testing was significantly lower in the laninamivir groups than in the placebo group. Laninamivir is approved for use in Japan, but remains investigational elsewhere. (See "Prevention of seasonal influenza with antiviral drugs in adults", section on 'General' and "Seasonal influenza in children: Prevention and treatment with antiviral drugs", section on 'Choice of drug'.)

Nonoccupational postexposure prophylaxis to prevent HIV infection (April 2016)

A discrete course of antiretroviral therapy (ART) administered after a possible exposure to HIV may reduce the risk of HIV acquisition. The US Centers for Disease Control and Prevention (CDC) has issued updated guidelines on HIV prophylaxis following a nonoccupational exposure [60]. A 28-day course of a three-drug regimen (eg, tenofovir disoproxil fumarate-emtricitabine plus either raltegravir or dolutegravir) should be offered to patients who present within 72 hours of a high-risk exposure (eg, condomless receptive or insertive vaginal or anal intercourse or a percutaneous exposure to blood or bloody body fluids) from a source who is HIV-infected or is at high risk for HIV infection. Exposed patients should be educated about the signs and symptoms of acute HIV infection, and have follow up HIV testing. (See "Nonoccupational exposure to HIV in adults".)


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

The introduction of eculizumab (a monoclonal antibody that blocks activation of the terminal complement cascade) has significantly improved the outcome of patients with complement-mediated hemolytic uremic syndrome (HUS), a rare, potentially life-threatening disease. Eculizumab therapy increases the risk of meningococcal infection, and vaccination against Neisseria meningitidis (with a quadrivalent vaccine and, for patients older than 10 years, a serogroup B vaccine) has been recommended in treated patients. However, a review from Health Canada reported an increased risk of hemolytic anemia following receipt of the multicomponent meningococcal serogroup B vaccine (Bexsero, MenB-4C) among patients who were already being treated with eculizumab [61]. To minimize the risk of hemolysis, serogroup B meningococcal vaccination should be performed prior to the initiation of eculizumab therapy, if possible. In cases where prior vaccination is not possible, the manufacturer of eculizumab recommends that serogroup B meningococcal vaccination should be administered when patients are stable and their disease is well controlled and it is assumed that the blood level of eculizumab is high. (See "Complement-mediated hemolytic uremic syndrome", section on 'Adverse effects'.)

Polyhydramnios due to X-linked Bartter syndrome (May 2016)

The most common type of Bartter syndrome presenting in utero is an autosomal recessive disorder that results in fetal polyuria and subsequent polyhydramnios between 24 and 30 weeks of gestation. Persistent postnatal renal salt wasting requires life-long treatment. Recently, a severe but transient type of antenatal Bartter's syndrome was attributed to mutations in the MAGED2 gene, which maps to the X-chromosome and appears to be essential for fetal renal salt reabsorption and maintenance of normal amniotic fluid homeostasis [62]. This X-linked disorder has very early onset of severe polyhydramnios (median 19 to 20 weeks of gestation), often resulting in preterm birth (median gestational age 22 to 34 weeks), but symptoms disappear spontaneously in infants who survive. Prenatal or early postnatal genetic diagnosis can avoid potentially harmful therapeutic interventions. (See "Polyhydramnios", section on 'Etiology'.)


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

Tuberous sclerosis complex (TSC) is characterized by the development of benign tumors in multiple organs, including the brain, and medically intractable epilepsy is a major cause of morbidity. The mammalian target of rapamycin (mTOR) pathway is over-activated in TSC, and mTOR inhibitors such as everolimus are known to have antitumor efficacy. Data on antiseizure effects have been limited, however. In the recent 18-week EXIST-3 trial, which enrolled over 360 subjects with TSC and treatment-resistant epilepsy, the proportion of subjects achieving a ≥50 percent reduction in seizure frequency was significantly greater for the low- and high-exposure everolimus groups compared with placebo (28, 40, and 15 percent, respectively) [63]. The most common adverse events associated with everolimus were stomatitis, diarrhea, and pyrexia. While longer-term data are needed, these results suggest that everolimus is an effective and safe treatment option for patients with TSC and treatment-resistant epilepsy. (See "Tuberous sclerosis complex: Management", section on 'Refractory epilepsy'.)

Botulinum toxin type A for children with spastic cerebral palsy (April 2016)

Botulinum toxin type A (BTX A) is a common treatment for spasticity in children with cerebral palsy (CP); however, studies to date have been small and have not focused on functional outcomes. In a recent randomized placebo-controlled trial of 235 children with spastic CP with dynamic equinus foot deformity, BTX A treatment improved muscle tone and resulted in a modest overall improvement in clinical status [64]. The growing evidence of successful use of BTX A in children with spastic CP supports the use of this agent in patients who have increased muscle tone that interferes with function or is likely to lead to joint contracture with growth. (See "Management and prognosis of cerebral palsy", section on 'Botulinum toxin'.)


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

In early studies, a small increase in asthma-related deaths associated with salmeterol led the US Food and Drug Administration to place a boxed warning on the use of long-acting beta agonists (LABAs) in asthma. While concerning, the number of events was small, and it could not be determined if the potential risk of salmeterol could be mitigated by combining LABAs with inhaled glucocorticoids. Three large randomized trials including 30,000 children and adults found no increase in asthma-related adverse events or deaths among patients who used combination inhalers with salmeterol or formoterol plus an inhaled glucocorticoid versus glucocorticoid monotherapy [65-67]. These studies support the safety of these fixed-dose combination inhalers in patients with moderate-to-severe asthma. (See "Beta agonists in asthma: Controversy regarding chronic use", section on 'Potential risk mitigation'.)

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

The American Thoracic Society has developed guidelines for evaluation of children <2 years of age who have recurrent wheezing that is unresponsive to bronchodilators or inhaled or systemic glucocorticoids [68]. Suggested evaluation includes one or more of the following: videofluoroscopic swallowing study (modified barium swallow) for possible swallowing dysfunction; 24-hour esophageal pH monitoring for assessment of gastroesophageal reflux; and/or flexible fiberoptic bronchoscopy bronchoalveolar lavage (BAL) to assess for lower airway bacterial infection. Our approach is consistent with these guidelines. (See "Approach to wheezing in infants and children", section on 'Radiography' and "Approach to wheezing in infants and children", section on 'Endoscopy' and "Approach to wheezing in infants and children", section on 'Evaluation for gastroesophageal reflux'.)

Effects of CPAP on facial and dental development in children (June 2016)

In children, chronic use of a nasal mask to provide continuous positive airway pressure (CPAP) can alter growth of the facial skeleton, causing hypoplasia of the mid-face and flaring of the upper incisors [69]. Steps to minimize this complication include proper fitting of the patient-device interface, with minimal tension on the straps, and periodically changing the type of interface (eg, from mask to nasal pillows or different masks) to distribute the pressure on the face over time. (See "CPAP for pediatric obstructive sleep apnea", section on 'Patient-device interface'.)

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