Association of Broad- vs Narrow-Spectrum Antibiotics With Treatment Failure, Adverse Events, and Quality of Life in Children With Acute Respiratory Tract Infections

Question  Does treatment with broad-spectrum antibiotics result in better clinical or patient-centered outcomes than narrow-spectrum antibiotics for children with acute respiratory tract infections?

Findings  In a retrospective cohort of 30 159 children with acute otitis media, group A streptococcal pharyngitis, and acute sinusitis, treatment with broad-spectrum vs narrow-spectrum antibiotics was not associated with treatment failure but was associated with higher rates of adverse events (3.7% vs 2.7%, respectively). In a prospective cohort of 2472 children, receipt of broad-spectrum vs narrow-spectrum antibiotics was associated with a slightly worse child quality of life and higher rates of adverse events (35.6% vs 25.1%, respectively).

Meaning  Use of broad-spectrum vs narrow-spectrum antibiotics was not associated with better clinical or patient-centered outcomes in children with acute respiratory tract infections.

Reference: JAMA. 2017;318(23):2325-2336.


Simulation of Growth Trajectories of Childhood Obesity into Adulthood


Although the current obesity epidemic has been well documented in children and adults, less is known about long-term risks of adult obesity for a given child at his or her present age and weight. We developed a simulation model to estimate the risk of adult obesity at the age of 35 years for the current population of children in the United States.


We pooled height and weight data from five nationally representative longitudinal studies totaling 176,720 observations from 41,567 children and adults. We simulated growth trajectories across the life course and adjusted for secular trends. We created 1000 virtual populations of 1 million children through the age of 19 years that were representative of the 2016 population of the United States and projected their trajectories in height and weight up to the age of 35 years. Severe obesity was defined as a body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) of 35 or higher in adults and 120% or more of the 95th percentile in children.


Given the current level of childhood obesity, the models predicted that a majority of today’s children (57.3%; 95% uncertainly interval [UI], 55.2 to 60.0) will be obese at the age of 35 years, and roughly half of the projected prevalence will occur during childhood. Our simulations indicated that the relative risk of adult obesity increased with age and BMI, from 1.17 (95% UI, 1.09 to 1.29) for overweight 2-year-olds to 3.10 (95% UI, 2.43 to 3.65) for 19-year-olds with severe obesity. For children with severe obesity, the chance they will no longer be obese at the age of 35 years fell from 21.0% (95% UI, 7.3 to 47.3) at the age of 2 years to 6.1% (95% UI, 2.1 to 9.9) at the age of 19 years.


On the basis of our simulation models, childhood obesity and overweight will continue to be a major health problem in the United States. Early development of obesity predicted obesity in adulthood, especially for children who were severely obese. (Funded by the JPB Foundation and others.)

A growth reference for mid upper arm circumference for age among school age children and adolescents, and validation for mortality: growth curve construction and longitudinal cohort study

Objectives To construct growth curves for mid-upper-arm circumference (MUAC)-for-age z score for 5-19 year olds that accord with the World Health Organization growth standards, and to evaluate their discriminatory performance for subsequent mortality.

Design Growth curve construction and longitudinal cohort study.

Setting United States and international growth data, and cohorts in Kenya, Uganda, and Zimbabwe.

Participants The Health Examination Survey (HES)/National Health and Nutrition Examination Survey (NHANES) US population datasets (age 5-25 years), which were used to construct the 2007 WHO growth reference for body mass index in this age group, were merged with an imputed dataset matching the distribution of the WHO 2006 growth standards age 2-6 years. Validation data were from 685 HIV infected children aged 5-17 years participating in the Antiretroviral Research for Watoto (ARROW) trial in Uganda and Zimbabwe; and 1741 children aged 5-13 years discharged from a rural Kenyan hospital (3.8% HIV infected). Both cohorts were followed-up for survival during one year.

Main outcome measures Concordance with WHO 2006 growth standards at age 60 months and survival during one year according to MUAC-for-age and body mass index-for-age z scores.

Results The new growth curves transitioned smoothly with WHO growth standards at age 5 years. MUAC-for-age z scores of −2 to −3 and less than−3, compared with −2 or more, was associated with hazard ratios for death within one year of 3.63 (95% confidence interval 0.90 to 14.7; P=0.07) and 11.1 (3.40 to 36.0; P<0.001), respectively, among ARROW trial participants; and 2.22 (1.01 to 4.9; P=0.04) and 5.15 (2.49 to 10.7; P<0.001), respectively, among Kenyan children after discharge from hospital. The AUCs for MUAC-for-age and body mass index-for-age z scores for discriminating subsequent mortality were 0.81 (95% confidence interval 0.70 to 0.92) and 0.75 (0.63 to 0.86) in the ARROW trial (absolute difference 0.06, 95% confidence interval −0.032 to 0.16; P=0.2) and 0.73 (0.65 to 0.80) and 0.58 (0.49 to 0.67), respectively, in Kenya (absolute difference in AUC 0.15, 0.07 to 0.23; P=0.0002).

Conclusions The MUAC-for-age z score is at least as effective as the body mass index-for-age z score for assessing mortality risks associated with undernutrition among African school aged children and adolescents. MUAC can provide simplified screening and diagnosis within nutrition and HIV programmes, and in research.

Reference: BMJ 2017;358:j3423

Effect of High-Dose vs Standard-Dose Wintertime Vitamin D Supplementation on Viral Upper Respiratory Tract Infections in Young Healthy Children

Question  Does high-dose vitamin D supplementation (2000 IU/d) help to prevent wintertime viral upper respiratory tract infections compared with standard-dose vitamin D supplementation (400 IU/d) among preschool children?

Findings  In this multisite randomized clinical trial that included 703 children, the number of wintertime laboratory-confirmed viral upper respiratory tract infections was higher in the high-dose group than the standard-dose group, not a statistically significant difference.

Meaning  Vitamin D dosing higher than 400 IU/d may not be indicated for preventing wintertime viral upper respiratory tract infections in children.

Reference: JAMA. 2017;318(3):245-254.

Screening for Obesity and Intervention for Weight Management in Children and Adolescents

Importance  Obesity is common in children and adolescents in the United States, is associated with negative health effects, and increases the likelihood of obesity in adulthood.

Objective  To systematically review the benefits and harms of screening and treatment for obesity and overweight in children and adolescents to inform the US Preventive Services Task Force.

Data Sources  MEDLINE, PubMed, PsycINFO, Cochrane Collaboration Registry of Controlled Trials, and the Education Resources Information Center through January 22, 2016; references of relevant publications; government websites. Surveillance continued through December 5, 2016.

Study Selection  English-language trials of benefits or harms of screening or treatment (behavior-based, orlistat, metformin) for overweight or obesity in children aged 2 through 18 years, conducted in or recruited from health care settings.

Data Extraction and Synthesis  Two investigators independently reviewed abstracts and full-text articles, then extracted data from fair- and good-quality trials. Random-effects meta-analysis was used to estimate the benefits of lifestyle-based programs and metformin.

Main Outcomes and Measures  Weight or excess weight (eg, body mass index [BMI]; BMI zscore, measuring the number of standard deviations from the median BMI for age and sex), cardiometabolic outcomes, quality of life, other health outcomes, harms.

Results  There was no direct evidence on the benefits or harms of screening children and adolescents for excess weight. Among 42 trials of lifestyle-based interventions to reduce excess weight (N = 6956), those with an estimated 26 hours or more of contact consistently demonstrated mean reductions in excess weight compared with usual care or other control groups after 6 to 12 months, with no evidence of causing harm. Generally, intervention groups showed absolute reductions in BMI z score of 0.20 or more and maintained their baseline weight within a mean of approximately 5 lb, while control groups showed small increases or no change in BMI z score, typically gaining a mean of 5 to 17 lb. Only 3 of 26 interventions with fewer contact hours showed a benefit in weight reduction. Use of metformin (8 studies, n = 616) and orlistat (3 studies, n = 779) were associated with greater BMI reductions compared with placebo: −0.86 (95% CI, −1.44 to −0.29; 6 studies; I2 = 0%) for metformin and −0.50 to −0.94 for orlistat. Groups receiving lifestyle-based interventions offering 52 or more hours of contact showed greater improvements in blood pressure than control groups: −6.4 mm Hg (95% CI, −8.6 to −4.2; 6 studies; I2 = 51%) for systolic blood pressure and −4.0 mm Hg (95% CI, −5.6 to −2.5; 6 studies; I2 = 17%) for diastolic blood pressure. There were mixed findings for insulin or glucose measures and no benefit for lipids. Medications showed small or no benefit for cardiometabolic outcomes, including fasting glucose level. Nonserious harms were common with medication use, although discontinuation due to adverse effects was usually less than 5%.

Conclusions and Relevance  Lifestyle-based weight loss interventions with 26 or more hours of intervention contact are likely to help reduce excess weight in children and adolescents. The clinical significance of the small benefit of medication use is unclear.

Reference: JAMA. 2017;317(23):2427-2444.

Trial of Amitriptyline, Topiramate, and Placebo for Pediatric Migraine


Which, medication, if any, to use to prevent the headache of pediatric migraine has not been established.


We conducted a randomized, double-blind, placebo-controlled trial of amitriptyline (1 mg per kilogram of body weight per day), topiramate (2 mg per kilogram per day), and placebo in children and adolescents 8 to 17 years of age with migraine. Patients were randomly assigned in a 2:2:1 ratio to receive one of the medications or placebo. The primary outcome was a relative reduction of 50% or more in the number of headache days in the comparison of the 28-day baseline period with the last 28 days of a 24-week trial. Secondary outcomes were headache-related disability, headache days, number of trial completers, and serious adverse events that emerged during treatment.


A total of 361 patients underwent randomization, and 328 were included in the primary efficacy analysis (132 in the amitriptyline group, 130 in the topiramate group, and 66 in the placebo group). The trial was concluded early for futility after a planned interim analysis. There were no significant between-group differences in the primary outcome, which occurred in 52% of the patients in the amitriptyline group, 55% of those in the topiramate group, and 61% of those in the placebo group (amitriptyline vs. placebo, P=0.26; topiramate vs. placebo, P=0.48; amitriptyline vs. topiramate, P=0.49). There were also no significant between-group differences in headache-related disability, headache days, or the percentage of patients who completed the 24-week treatment period. Patients who received amitriptyline or topiramate had higher rates of several adverse events than those receiving placebo, including fatigue (30% vs. 14%) and dry mouth (25% vs. 12%) in the amitriptyline group and paresthesia (31% vs. 8%) and weight loss (8% vs. 0%) in the topiramate group. Three patients in the amitriptyline group had serious adverse events of altered mood, and one patient in the topiramate group had a suicide attempt.


There were no significant differences in reduction in headache frequency or headache-related disability in childhood and adolescent migraine with amitriptyline, topiramate, or placebo over a period of 24 weeks. The active drugs were associated with higher rates of adverse events. (Funded by the National Institutes of Health; CHAMP number, NCT01581281).

N Engl J Med 2017; 376:115-124January 12, 2017

Shortened Antimicrobial Treatment for Acute Otitis Media in Young Children


Limiting the duration of antimicrobial treatment constitutes a potential strategy to reduce the risk of antimicrobial resistance among children with acute otitis media.


We assigned 520 children, 6 to 23 months of age, with acute otitis media to receive amoxicillin–clavulanate either for a standard duration of 10 days or for a reduced duration of 5 days followed by placebo for 5 days. We measured rates of clinical response (in a systematic fashion, on the basis of signs and symptomatic response), recurrence, and nasopharyngeal colonization, and we analyzed episode outcomes using a noninferiority approach. Symptom scores ranged from 0 to 14, with higher numbers indicating more severe symptoms.


Children who were treated with amoxicillin–clavulanate for 5 days were more likely than those who were treated for 10 days to have clinical failure (77 of 229 children [34%] vs. 39 of 238 [16%]; difference, 17 percentage points [based on unrounded data]; 95% confidence interval, 9 to 25). The mean symptom scores over the period from day 6 to day 14 were 1.61 in the 5-day group and 1.34 in the 10-day group (P=0.07); the mean scores at the day-12-to-14 assessment were 1.89 versus 1.20 (P=0.001). The percentage of children whose symptom scores decreased more than 50% (indicating less severe symptoms) from baseline to the end of treatment was lower in the 5-day group than in the 10-day group (181 of 227 children [80%] vs. 211 of 233 [91%], P=0.003). We found no significant between-group differences in rates of recurrence, adverse events, or nasopharyngeal colonization with penicillin-nonsusceptible pathogens. Clinical-failure rates were greater among children who had been exposed to three or more children for 10 or more hours per week than among those with less exposure (P=0.02) and were also greater among children with infection in both ears than among those with infection in one ear (P<0.001).


Among children 6 to 23 months of age with acute otitis media, reduced-duration antimicrobial treatment resulted in less favorable outcomes than standard-duration treatment; in addition, neither the rate of adverse events nor the rate of emergence of antimicrobial resistance was lower with the shorter regimen. (Funded by the National Institute of Allergy and Infectious Diseases and the National Center for Research Resources; number, NCT01511107.)

N Engl J Med 2016; 375:2446-2456December 22, 2016