Importance: Universal early screening for autism spectrum disorder (ASD) in primary care is becoming increasingly common and is believed to be a pivotal step toward early treatment. However, the diagnostic stability of ASD in large cohorts from the general population, particularly in those younger than 18 months, is unknown. Changes in the phenotypic expression of ASD across early development compared with toddlers with other delays are also unknown. Objectives: To examine the diagnostic stability of ASD in a large cohort of toddlers starting at 12 months of age and to compare this stability with that of toddlers with other disorders, such as developmental delay. Design, Setting, and Participants: In this prospective cohort study performed from January 1, 2006, to December 31, 2018, a total of 2241 toddlers were referred from the general population through a universal screening program in primary care or community referral. Eligible toddlers received their first diagnostic evaluation between 12 and 36 months of age and had at least 1 subsequent evaluation. Exposures: Diagnosis was denoted after each evaluation visit as ASD, ASD features, language delay, developmental delay, other developmental issue, typical sibling of an ASD proband, or typical development. Main Outcomes and Measures: Diagnostic stability coefficients were calculated within 2-month age bands, and logistic regression models were used to explore the associations of sex, age, diagnosis at first visit, and interval between first and last diagnosis with stability. Toddlers with a non-ASD diagnosis at their first visit diagnosed with ASD at their last were designated as having late-identified ASD. Results: Among the 1269 toddlers included in the study (918 [72.3%] male; median age at first evaluation, 17.6 months [interquartile range, 14.0-24.4 months]; median age at final evaluation, 36.2 months [interquartile range, 33.4-40.9 months]), the overall diagnostic stability for ASD was 0.84 (95% CI, 0.80-0.87), which was higher than any other diagnostic group. Only 7 toddlers (1.8%) initially considered to have ASD transitioned into a final diagnosis of typical development. Diagnostic stability of ASD within the youngest age band (12-13 months) was lowest at 0.50 (95% CI, 0.32-0.69) but increased to 0.79 by 14 months and 0.83 by 16 months (age bands of 12 vs 14 and 16 months; odds ratio, 4.25; 95% CI, 1.59-11.74). A total of 105 toddlers (23.8%) were not designated as having ASD at their first visit but were identified at a later visit. Conclusions and Relevance: The findings suggest that an ASD diagnosis becomes stable starting at 14 months of age and overall is more stable than other diagnostic categories, including language or developmental delay. After a toddler is identified as having ASD, there may be a low chance that he or she will test within typical levels at 3 years of age. This finding opens the opportunity to test the impact of very early-age treatment of ASD.
Karen Pierce, Vahid Gazestani, Elizabeth C. Bacon et al.
This study compares age-specific rates of suicide between black and white youths using data from the Web-based Injury Statistics Query and Reporting System (WISQARS) of the Centers for Disease Control and Prevention.
Jeffrey A. Bridge, Lisa M. Horowitz, Cynthia A. Fontanella et al.
Importance: In young febrile infants, serious bacterial infections (SBIs), including urinary tract infections, bacteremia, and meningitis, may lead to dangerous complications. However, lumbar punctures and hospitalizations involve risks and costs. Clinical prediction rules using biomarkers beyond the white blood cell count (WBC) may accurately identify febrile infants at low risk for SBIs. Objective: To derive and validate a prediction rule to identify febrile infants 60 days and younger at low risk for SBIs. Design, Setting, and Participants: Prospective, observational study between March 2011 and May 2013 at 26 emergency departments. Convenience sample of previously healthy febrile infants 60 days and younger who were evaluated for SBIs. Data were analyzed between April 2014 and April 2018. Exposures: Clinical and laboratory data (blood and urine) including patient demographics, fever height and duration, clinical appearance, WBC, absolute neutrophil count (ANC), serum procalcitonin, and urinalysis. We derived and validated a prediction rule based on these variables using binary recursive partitioning analysis. Main Outcomes and Measures: Serious bacterial infection, defined as urinary tract infection, bacteremia, or bacterial meningitis. Results: We derived the prediction rule on a random sample of 908 infants and validated it on 913 infants (mean age was 36 days, 765 were girls [42%], 781 were white and non-Hispanic [43%], 366 were black [20%], and 535 were Hispanic [29%]). Serious bacterial infections were present in 170 of 1821 infants (9.3%), including 26 (1.4%) with bacteremia, 151 (8.3%) with urinary tract infections, and 10 (0.5%) with bacterial meningitis; 16 (0.9%) had concurrent SBIs. The prediction rule identified infants at low risk of SBI using a negative urinalysis result, an ANC of 4090/µL or less (to convert to ×109 per liter, multiply by 0.001), and serum procalcitonin of 1.71 ng/mL or less. In the validation cohort, the rule sensitivity was 97.7% (95% CI, 91.3-99.6), specificity was 60.0% (95% CI, 56.6-63.3), negative predictive value was 99.6% (95% CI, 98.4-99.9), and negative likelihood ratio was 0.04 (95% CI, 0.01-0.15). One infant with bacteremia and 2 infants with urinary tract infections were misclassified. No patients with bacterial meningitis were missed by the rule. The rule performance was nearly identical when the outcome was restricted to bacteremia and/or bacterial meningitis, missing the same infant with bacteremia. Conclusions and Relevance: We derived and validated an accurate prediction rule to identify febrile infants 60 days and younger at low risk for SBIs using the urinalysis, ANC, and procalcitonin levels. Once further validated on an independent cohort, clinical application of the rule has the potential to decrease unnecessary lumbar punctures, antibiotic administration, and hospitalizations.
Nathan Kuppermann, Peter S. Dayan, Deborah A. Levine et al.
Importance: Ensuring the well-being of the 73 million children in the United States is critical for improving the nation's health and influencing children's long-term outcomes as they grow into adults. Objective: To examine recent trends in children's health-related measures, including significant changes between 2019 and 2020 that might be attributed to the COVID-19 pandemic. Design, Setting, and Participants: Annual data were examined from the National Survey of Children's Health (2016-2020), a population-based, nationally representative survey of randomly selected children. Participants were children from birth to age 17 years living in noninstitution settings in all 50 states and the District of Columbia whose parent or caregiver responded to an address-based survey by mail or web. Weighted prevalence estimates account for probability of selection and nonresponse. Adjusted logistic regression models tested for significant trends over time. Main Outcomes and Measures: Diverse measures pertaining to children's current health conditions, positive health behaviors, health care access and utilization, and family well-being and stressors. Results: A total of 174 551 children were included (annual range = 21 599 to 50 212). Between 2016 and 2020, there were increases in anxiety (7.1% [95% CI, 6.6-7.6] to 9.2% [95% CI, 8.6-9.8]; +29%; trend P < .001) and depression (3.1% [95% CI, 2.9-3.5] to 4.0% [95% CI, 3.6-4.5]; +27%; trend P < .001). There were also decreases in daily physical activity (24.2% [95% CI, 23.1-25.3] to 19.8% [95% CI, 18.9-20.8]; -18%; trend P < .001), parent or caregiver mental health (69.8% [95% CI, 68.9-70.8] to 66.3% [95% CI, 65.3-67.3]; -5%; trend P < .001), and coping with parenting demands (67.2% [95% CI, 66.3-68.1] to 59.9% [95% CI, 58.8-60.9]; -11%; trend P < .001). In addition, from 2019 to 2020, there were increases in behavior or conduct problems (6.7% [95% CI, 6.1-7.4] to 8.1% [95% CI, 7.5-8.8]; +21%; P = .001) and child care disruptions affecting parental employment (9.4% [95% CI, 8.0-10.9] to 12.6% [95% CI, 11.2-14.1]; +34%; trend P = .001) as well as decreases in preventive medical visits (81.0% [95% CI, 79.7-82.3] to 74.1% [95% CI, 72.9-75.3]; -9%; trend P < .001). Conclusions and Relevance: Recent trends point to several areas of concern that can inform future research, clinical care, policy decision making, and programmatic investments to improve the health and well-being of children and their families. More analyses are needed to elucidate varying patterns within subpopulations of interest.
Lydie A. Lebrun‐Harris, Reem M. Ghandour, Michael D. Kogan et al.
Importance: Individuals with prediabetes are at increased risk of developing type 2 diabetes, chronic kidney disease, and cardiovascular disease. The incidence and prevalence of type 2 diabetes in the US adolescent population have increased in the last decade. Therefore, it is important to monitor the prevalence of prediabetes and varying levels of glucose tolerance to assess the future risk of type 2 diabetes in the youngest segment of the population. Objective: To examine the prevalence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and increased glycated hemoglobin A1c (HbA1c) levels in US adolescents (aged 12-18 years) and young adults (aged 19-34 years) without diabetes. Design, Setting, and Participants: This cross-sectional analyses of the 2005-2016 National Health and Nutrition Examination Survey assessed a population-based sample of adolescents and young adults who were not pregnant, did not have diabetes, and had measured fasting plasma glucose, 2-hour plasma glucose after a 75-g oral glucose tolerance test, and HbA1c levels. Analysis began in April 2017. Main Outcomes and Measures: Impaired fasting glucose was defined as fasting plasma glucose of 100 mg/dL to less than 126 mg/dL, IGT as 2-hour plasma glucose of 140 mg/dL to less than 200 mg/dL, and increased HbA1c level as HbA1c level between 5.7% and 6.4%. The prevalence of IFG, isolated IFG, IGT, isolated IGT, increased HbA1c level, isolated increased HbA1c level, and prediabetes (defined as having IFG, IGT, or increased HbA1c level) were estimated. Fasting insulin levels and cardiometabolic risk factors across glycemic abnormality phenotypes were also compared. Obesity was defined as having age- and sex-specific body mass index (calculated as weight in kilograms divided by height in meters squared) in the 95th percentile or higher in adolescents or 30 or higher in young adults. Results: Of 5786 individuals, 2606 (45%) were adolescents and 3180 (55%) were young adults. Of adolescents, 50.6% (95% CI, 47.6%-53.6%) were boys, and 50.6% (95% CI, 48.8%-52.4%) of young adults were men. Among adolescents, the prevalence of prediabetes was 18.0% (95% CI, 16.0%-20.1%) and among young adults was 24.0% (95% CI, 22.0%-26.1%). Impaired fasting glucose constituted the largest proportion of prediabetes, with prevalence of 11.1% (95% CI, 9.5%-13.0%) in adolescents and 15.8% (95% CI, 14.0%-17.9%) in young adults. In multivariable logistic models including age, sex, race/ethnicity, and body mass index, the predictive marginal prevalence of prediabetes was significantly higher in male than in female individuals (22.5% [95% CI, 19.5%-25.4%] vs 13.4% [95% CI, 10.8%-16.5%] in adolescents and 29.1% [95% CI, 26.4%-32.1%] vs 18.8% [95% CI, 16.5%-21.3%] in young adults). Prediabetes prevalence was significantly higher in individuals with obesity than in those with normal weight (25.7% [95% CI, 20.0%-32.4%] vs 16.4% [95% CI, 14.3%-18.7%] in adolescents and 36.9% [95% CI, 32.9%-41.1%] vs 16.6% [95% CI, 14.2%-19.4%] in young adults). Compared with persons with normal glucose tolerance, adolescents and young adults with prediabetes had significantly higher non-high-density lipoprotein cholesterol levels, systolic blood pressure, central adiposity, and lower insulin sensitivity (P < .05 for all). Conclusions and Relevance: In the United States, about 1 of 5 adolescents and 1 of 4 young adults have prediabetes. The adjusted prevalence of prediabetes is higher in male individuals and in people with obesity. Adolescents and young adults with prediabetes also present an unfavorable cardiometabolic risk profile, putting them both at increased risk of type 2 diabetes and cardiovascular diseases.
Linda J. Andes, Yiling J. Cheng, Deborah B. Rolka et al.
Importance: After initial resuscitation, critically ill children may accumulate fluid and develop fluid overload. Accruing evidence suggests that fluid overload contributes to greater complexity of care and worse outcomes. Objective: To describe the methods to measure fluid balance, define fluid overload, and evaluate the association between fluid balance and outcomes in critically ill children. Data Sources: Systematic search of MEDLINE, EMBASE, Cochrane Library, trial registries, and selected gray literature from inception to March 2017. Study Selection: Studies of children admitted to pediatric intensive care units that described fluid balance or fluid overload and reported outcomes of interest were included. No language restrictions were applied. Data Extraction and Synthesis: All stages were conducted independently by 2 reviewers. Data extracted included study characteristics, population, fluid metrics, and outcomes. Risk of bias was assessed using the Newcastle-Ottawa Scale. Narrative description of fluid assessment methods and fluid overload definitions was done. When feasible, pooled analyses were performed using random-effects models. Main Outcomes and Measures: Mortality was the primary outcome. Secondary outcomes included treatment intensity, organ failure, and resource use. Results: A total of 44 studies (7507 children) were included in this systematic review and meta-analysis. Of those, 27 (61%) were retrospective cohort studies, 13 (30%) were prospective cohort studies, 3 (7%) were case-control studies, and 1 study (2%) was a secondary analysis of a randomized trial. The proportion of children with fluid overload varied by case mix and fluid overload definition (median, 33%; range, 10%-83%). Fluid overload, however defined, was associated with increased in-hospital mortality (17 studies [n = 2853]; odds ratio [OR], 4.34 [95% CI, 3.01-6.26]; I2 = 61%). Survivors had lower percentage fluid overload than nonsurvivors (22 studies [n = 2848]; mean difference, -5.62 [95% CI, -7.28 to -3.97]; I2 = 76%). After adjustment for illness severity, there was a 6% increase in odds of mortality for every 1% increase in percentage fluid overload (11 studies [n = 3200]; adjusted OR, 1.06 [95% CI, 1.03-1.10]; I2 = 66%). Fluid overload was associated with increased risk for prolonged mechanical ventilation (>48 hours) (3 studies [n = 631]; OR, 2.14 [95% CI, 1.25-3.66]; I2 = 0%) and acute kidney injury (7 studies [n = 1833]; OR, 2.36 [95% CI, 1.27-4.38]; I2 = 78%). Conclusions and Relevance: Fluid overload is common and is associated with substantial morbidity and mortality in critically ill children. Additional research should now ideally focus on interventions aimed to mitigate the potential for harm associated with fluid overload.
Rashid Alobaidi, Catherine Morgan, Rajit K. Basu et al.
Importance: Invasive disease owing to group B Streptococcus (GBS) remains an important cause of illness and death among infants younger than 90 days in the United States, despite declines in early-onset disease (EOD; with onset at 0-6 days of life) that are attributed to intrapartum antibiotic prophylaxis (IAP). Maternal vaccines to prevent infant GBS disease are currently under development. Objective: To describe incidence rates, case characteristics, antimicrobial resistance, and serotype distribution of EOD and late-onset disease (LOD; with onset at 7-89 days of life) in the United States from 2006 to 2015 to inform IAP guidelines and vaccine development. Design, Setting, and Participants: This study used active population-based and laboratory-based surveillance for invasive GBS disease conducted through Active Bacterial Core surveillance in selected counties of 10 states across the United States. Residents of Active Bacterial Core surveillance areas who were younger than 90 days and had invasive GBS disease in 2006 to 2015 were included. Data were analyzed from December 2017 to April 2018. Exposures: Group B Streptococcus isolated from a normally sterile site. Main Outcomes and Measures: Early-onset disease and LOD incidence rates and associated GBS serotypes and antimicrobial resistance. Results: The Active Bacterial Core surveillance program identified 1277 cases of EOD and 1387 cases of LOD. From 2006 to 2015, EOD incidence declined significantly from 0.37 to 0.23 per 1000 live births (P < .001), and LOD rates remained stable (mean, 0.31 per 1000 live births). Among the mothers of 1277 infants with EOD, 617 (48.3%) had no indications for IAP and did not receive it, and 278 (21.8%) failed to receive IAP despite having indications. Serotype data were available for 1743 of 1897 patients (91.3%) from 7 sites that collect GBS isolates. Among patients with EOD, serotypes Ia (242 [27.3%]) and III (242 [27.3%]) were most common. Among patients with LOD, serotype III was most common (481 [56.2%]), and this increased from 2006 to 2015 from 0.12 to 0.20 cases per 1000 live births (P < .001). Serotype IV caused 53 cases (6.2%) of EOD and LOD combined. The 6 most common serotypes (Ia, Ib, II, III, IV, and V) caused 881 EOD cases (99.3%) and 853 LOD cases (99.7%). No β-lactam resistance was identified; 359 isolates (20.8%) tested showed constitutive clindamycin resistance. In 2015, an estimated 840 EOD cases and 1265 LOD cases occurred nationally. Conclusions and Relevance: The rates of LOD among US infants are now higher than EOD rates. Combined with addressing IAP implementation gaps, an effective vaccine covering the most common serotypes might further reduce EOD rates and help prevent LOD, for which there is no current public health intervention.
Srinivas Acharya Nanduri, Susan Petit, Chad B. Smelser et al.
Importance: Early-onset sepsis (EOS) remains a potentially fatal newborn condition. Ongoing surveillance is critical to optimize prevention and treatment strategies. Objective: To describe the current incidence, microbiology, morbidity, and mortality of EOS among a cohort of term and preterm infants. Design, Setting, and Participants: This prospective surveillance study included a cohort of infants born at a gestational age (GA) of at least 22 weeks and birth weight of greater than 400 g from 18 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network from April 1, 2015, to March 31, 2017. Data were analyzed from June 14, 2019, to January 28, 2020. Main Outcomes and Measures: Early-onset sepsis defined by isolation of pathogenic species from blood or cerebrospinal fluid culture within 72 hours of birth and antibiotic treatment for at least 5 days or until death. Results: A total of 235 EOS cases (127 male [54.0%]) were identified among 217 480 newborns (1.08 [95% CI, 0.95-1.23] cases per 1000 live births). Incidence varied significantly by GA and was highest among infants with a GA of 22 to 28 weeks (18.47 [95% CI, 14.57-23.38] cases per 1000). No significant differences in EOS incidence were observed by sex, race, or ethnicity. The most frequent pathogens were Escherichia coli (86 [36.6%]) and group B streptococcus (GBS; 71 [30.2%]). E coli disease primarily occurred among preterm infants (68 of 131 [51.9%]); GBS disease primarily occurred among term infants (54 of 104 [51.9%]), with 24 of 45 GBS cases (53.3%) seen in infants born to mothers with negative GBS screening test results. Intrapartum antibiotics were administered to 162 mothers (68.9%; 110 of 131 [84.0%] preterm and 52 of 104 [50.0%] term), most commonly for suspected chorioamnionitis. Neonatal empirical antibiotic treatment most frequently included ampicillin and gentamicin. All GBS isolates were tested, but only 18 of 81 (22.2%) E coli isolates tested were susceptible to ampicillin; 6 of 77 E coli isolates (7.8%) were resistant to both ampicillin and gentamicin. Nearly all newborns with EOS (220 of 235 [93.6%]) displayed signs of illness within 72 hours of birth. Death occurred in 38 of 131 infected infants with GA of less than 37 weeks (29.0%); no term infants died. Compared with earlier surveillance (2006-2009), the rate of E coli infection increased among very low-birth-weight (401-1500 g) infants (8.68 [95% CI, 6.50-11.60] vs 5.07 [95% CI, 3.93-6.53] per 1000 live births; P = .008). Conclusions and Relevance: In this study, EOS incidence and associated mortality disproportionately occurred in preterm infants. Contemporary cases have demonstrated the limitations of current GBS prevention strategies. The increase in E coli infections among very low-birth-weight infants warrants continued study. Ampicillin and gentamicin remained effective antibiotics in most cases, but ongoing surveillance should monitor antibiotic susceptibilities of EOS pathogens.
Barbara J. Stoll, Karen Marie Puopolo, Nellie I. Hansen et al.
Importance: Sport-related concussion (SRC) is a significant public health problem without an effective treatment. Objective: To assess the effectiveness of subsymptom threshold aerobic exercise vs a placebo-like stretching program prescribed to adolescents in the acute phase of recovery from SRC. Design, Setting, and Participants: This multicenter prospective randomized clinical trial was conducted at university concussion centers. Male and female adolescent athletes (age 13-18 years) presenting within 10 days of SRC were randomly assigned to aerobic exercise or a placebo-like stretching regimen. Interventions: After systematic determination of treadmill exercise tolerance on the first visit, participants were randomly assigned to a progressive subsymptom threshold aerobic exercise or a progressive placebo-like stretching program (that would not substantially elevate heart rate). Both forms of exercise were performed approximately 20 minutes per day, and participants reported daily symptoms and compliance with exercise prescription via a website. Main Outcomes and Measures: Days from injury to recovery; recovery was defined as being asymptomatic, having recovery confirmed through an assessment by a physician blinded to treatment group, and returning to normal exercise tolerance on treadmill testing. Participants were also classified as having normal (<30 days) or delayed (≥30 days) recovery. Results: A total of 103 participants were included (aerobic exercise: n = 52; 24 female [46%]; stretching, n = 51; 24 female [47%]). Participants in the aerobic exercise group were seen a mean (SD) of 4.9 (2.2) days after the SRC, and those in the stretching group were seen a mean (SD) of 4.8 (2.4) days after the SRC. There were no differences in age, sex, previous concussions, time from injury, initial symptom severity score, or initial exercise treadmill test and physical examination results. Aerobic exercise participants recovered in a median of 13 (interquartile range [IQR], 10-18.5) days, whereas stretching participants recovered in 17 (IQR, 13-23) days (P = .009 by Mann-Whitney test). There was a nonsignificant lower incidence of delayed recovery in the aerobic exercise group (2 participants [4%] in the aerobic group vs 7 [14%] in the placebo group; P = .08). Conclusions and Relevance: This is, to our knowledge, the first RCT to show that individualized subsymptom threshold aerobic exercise treatment prescribed to adolescents with concussion symptoms during the first week after SRC speeds recovery and may reduce the incidence of delayed recovery. Trial Registration: ClinicalTrials.gov identifier: NCT02710123.
John J. Leddy, Mohammad Nadir Haider, Michael J. Ellis et al.
Importance: There is considerable public and scientific debate as to whether screen use helps or hinders early child development, particularly the development of language skills. Objective: To examine via meta-analyses the associations between quantity (duration of screen time and background television), quality (educational programming and co-viewing), and onset of screen use and children's language skills. Data Sources: Searches were conducted in MEDLINE, Embase, and PsycINFO in March 2019. The search strategy included a publication date limit from 1960 through March 2019. Study Selection: Inclusion criteria were a measure of screen use; a measure of language skills; and statistical data that could be transformed into an effect size. Exclusion criteria were qualitative studies; child age older than 12 years; and language assessment preverbal. Data Extraction and Synthesis: The following variables were extracted: effect size, child age and sex, screen measure type, study publication year, and study design. All studies were independently coded by 2 coders and conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Main Outcomes and Measures: Based on a priori study criteria, quantity of screen use included duration of screen time and background television, quality of screen use included co-viewing and exposure to educational programs, and onset of screen use was defined as the age children first began viewing screens. The child language outcome included assessments of receptive and/or expressive language. Results: Participants totaled 18 905 from 42 studies included. Effect sizes were measured as correlations (r). Greater quantity of screen use (hours per use) was associated with lower language skills (screen time [n = 38; r = -0.14; 95% CI, -0.18 to -0.10]; background television [n = 5; r = -0.19; 95% CI, -0.33 to -0.05]), while better-quality screen use (educational programs [n = 13; r = 0.13; 95% CI, 0.02-0.24]; co-viewing [n = 12; r = 0.16; 95% CI, 0.07-.24]) were associated with stronger child language skills. Later age at screen use onset was also associated with stronger child language skills [n = 4; r = 0.17; 95% CI, 0.07-0.27]. Conclusions and Relevance: The findings of this meta-analysis support pediatric recommendations to limit children's duration of screen exposure, to select high-quality programming, and to co-view when possible.
Sheri L. Madigan, Brae Anne McArthur, Ciana Anhorn et al.
