Showing papers in "JAMA Pediatrics in 2021"

Global Prevalence of Depressive and Anxiety Symptoms in Children and Adolescents During COVID-19: A Meta-analysis.

Abstract: Importance Emerging research suggests that the global prevalence of child and adolescent mental illness has increased considerably during COVID-19. However, substantial variability in prevalence rates have been reported across the literature. Objective To ascertain more precise estimates of the global prevalence of child and adolescent clinically elevated depression and anxiety symptoms during COVID-19; to compare these rates with prepandemic estimates; and to examine whether demographic (eg, age, sex), geographical (ie, global region), or methodological (eg, pandemic data collection time point, informant of mental illness, study quality) factors explained variation in prevalence rates across studies. Data Sources Four databases were searched (PsycInfo, Embase, MEDLINE, and Cochrane Central Register of Controlled Trials) from January 1, 2020, to February 16, 2021, and unpublished studies were searched inPsycArXivon March 8, 2021, for studies reporting on child/adolescent depression and anxiety symptoms. The search strategy combined search terms from 3 themes: (1) mental illness (including depression and anxiety), (2) COVID-19, and (3) children and adolescents (age ≤18 years). ForPsycArXiv, the key termsCOVID-19,mental health, andchild/adolescentwere used. Study Selection Studies were included if they were published in English, had quantitative data, and reported prevalence of clinically elevated depression or anxiety in youth (age ≤18 years). Data Extraction and Synthesis A total of 3094 nonduplicate titles/abstracts were retrieved, and 136 full-text articles were reviewed. Data were analyzed from March 8 to 22, 2021. Main Outcomes and Measures Prevalence rates of clinically elevated depression and anxiety symptoms in youth. Results Random-effect meta-analyses were conducted. Twenty-nine studies including 80 879 participants met full inclusion criteria. Pooled prevalence estimates of clinically elevated depression and anxiety symptoms were 25.2% (95% CI, 21.2%-29.7%) and 20.5% (95% CI, 17.2%-24.4%), respectively. Moderator analyses revealed that the prevalence of clinically elevated depression and anxiety symptoms were higher in studies collected later in the pandemic and in girls. Depression symptoms were higher in older children. Conclusions and Relevance Pooled estimates obtained in the first year of the COVID-19 pandemic suggest that 1 in 4 youth globally are experiencing clinically elevated depression symptoms, while 1 in 5 youth are experiencing clinically elevated anxiety symptoms. These pooled estimates, which increased over time, are double of prepandemic estimates. An influx of mental health care utilization is expected, and allocation of resources to address child and adolescent mental health concerns are essential.

Maternal and Neonatal Morbidity and Mortality Among Pregnant Women With and Without COVID-19 Infection: The INTERCOVID Multinational Cohort Study.

Abstract: Importance Detailed information about the association of COVID-19 with outcomes in pregnant individuals compared with not-infected pregnant individuals is much needed. Objective To evaluate the risks associated with COVID-19 in pregnancy on maternal and neonatal outcomes compared with not-infected, concomitant pregnant individuals. Design, Setting, and Participants In this cohort study that took place from March to October 2020, involving 43 institutions in 18 countries, 2 unmatched, consecutive, not-infected women were concomitantly enrolled immediately after each infected woman was identified, at any stage of pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed up until hospital discharge. Exposures COVID-19 in pregnancy determined by laboratory confirmation of COVID-19 and/or radiological pulmonary findings or 2 or more predefined COVID-19 symptoms. Main Outcomes and Measures The primary outcome measures were indices of (maternal and severe neonatal/perinatal) morbidity and mortality; the individual components of these indices were secondary outcomes. Models for these outcomes were adjusted for country, month entering study, maternal age, and history of morbidity. Results A total of 706 pregnant women with COVID-19 diagnosis and 1424 pregnant women without COVID-19 diagnosis were enrolled, all with broadly similar demographic characteristics (mean [SD] age, 30.2 [6.1] years). Overweight early in pregnancy occurred in 323 women (48.6%) with COVID-19 diagnosis and 554 women (40.2%) without. Women with COVID-19 diagnosis were at higher risk for preeclampsia/eclampsia (relative risk [RR], 1.76; 95% CI, 1.27-2.43), severe infections (RR, 3.38; 95% CI, 1.63-7.01), intensive care unit admission (RR, 5.04; 95% CI, 3.13-8.10), maternal mortality (RR, 22.3; 95% CI, 2.88-172), preterm birth (RR, 1.59; 95% CI, 1.30-1.94), medically indicated preterm birth (RR, 1.97; 95% CI, 1.56-2.51), severe neonatal morbidity index (RR, 2.66; 95% CI, 1.69-4.18), and severe perinatal morbidity and mortality index (RR, 2.14; 95% CI, 1.66-2.75). Fever and shortness of breath for any duration was associated with increased risk of severe maternal complications (RR, 2.56; 95% CI, 1.92-3.40) and neonatal complications (RR, 4.97; 95% CI, 2.11-11.69). Asymptomatic women with COVID-19 diagnosis remained at higher risk only for maternal morbidity (RR, 1.24; 95% CI, 1.00-1.54) and preeclampsia (RR, 1.63; 95% CI, 1.01-2.63). Among women who tested positive (98.1% by real-time polymerase chain reaction), 54 (13%) of their neonates tested positive. Cesarean delivery (RR, 2.15; 95% CI, 1.18-3.91) but not breastfeeding (RR, 1.10; 95% CI, 0.66-1.85) was associated with increased risk for neonatal test positivity. Conclusions and Relevance In this multinational cohort study, COVID-19 in pregnancy was associated with consistent and substantial increases in severe maternal morbidity and mortality and neonatal complications when pregnant women with and without COVID-19 diagnosis were compared. The findings should alert pregnant individuals and clinicians to implement strictly all the recommended COVID-19 preventive measures.

Susceptibility to SARS-CoV-2 Infection Among Children and Adolescents Compared With Adults: A Systematic Review and Meta-analysis.

Abstract: Importance The degree to which children and adolescents are infected by and transmit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. The role of children and adolescents in transmission of SARS-CoV-2 is dependent on susceptibility, symptoms, viral load, social contact patterns, and behavior. Objective To systematically review the susceptibility to and transmission of SARS-CoV-2 among children and adolescents compared with adults. Data Sources PubMed and medRxiv were searched from database inception to July 28, 2020, and a total of 13 926 studies were identified, with additional studies identified through hand searching of cited references and professional contacts. Study Selection Studies that provided data on the prevalence of SARS-CoV-2 in children and adolescents (younger than 20 years) compared with adults (20 years and older) derived from contact tracing or population screening were included. Single-household studies were excluded. Data Extraction and Synthesis PRISMA guidelines for abstracting data were followed, which was performed independently by 2 reviewers. Quality was assessed using a critical appraisal checklist for prevalence studies. Random-effects meta-analysis was undertaken. Main Outcomes and Measures Secondary infection rate (contact-tracing studies) or prevalence or seroprevalence (population screening studies) among children and adolescents compared with adults. Results A total of 32 studies comprising 41 640 children and adolescents and 268 945 adults met inclusion criteria, including 18 contact-tracing studies and 14 population screening studies. The pooled odds ratio of being an infected contact in children compared with adults was 0.56 (95% CI, 0.37-0.85), with substantial heterogeneity (I2 = 94.6%). Three school-based contact-tracing studies found minimal transmission from child or teacher index cases. Findings from population screening studies were heterogenous and were not suitable for meta-analysis. Most studies were consistent with lower seroprevalence in children compared with adults, although seroprevalence in adolescents appeared similar to adults. Conclusions and Relevance In this meta-analysis, there is preliminary evidence that children and adolescents have lower susceptibility to SARS-CoV-2, with an odds ratio of 0.56 for being an infected contact compared with adults. There is weak evidence that children and adolescents play a lesser role than adults in transmission of SARS-CoV-2 at a population level. This study provides no information on the infectivity of children.

Screening and Severity of Coronavirus Disease 2019 (COVID-19) in Children in Madrid, Spain.

Abstract: This case series describes the testing for and treatment of children with coronavirus disease 2019 (COVID-19) in Madrid, Spain.

Clinical Characteristics and Viral RNA Detection in Children With Coronavirus Disease 2019 in the Republic of Korea.

Abstract: Importance There is limited information describing the full spectrum of coronavirus disease 2019 (COVID-19) and the duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA detection in children. Objective To analyze the full clinical course and the duration of SARS-CoV-2 RNA detectability in children confirmed with COVID-19 in the Republic of Korea, where rigorous public health interventions have been implemented. Design, Setting, and Participants This case series of children with COVID-19 was conducted in 20 hospitals and 2 nonhospital isolation facilities across the country from February 18, 2020, to March 31, 2020. Children younger than 19 years who had COVID-19 were included. Exposures Confirmed COVID-19, detected via SARS-CoV-2 RNA in a combined nasopharyngeal and oropharyngeal swab or sputum by real-time reverse transcription–polymerase chain reaction. Main Outcomes and Measures Clinical manifestations during the observation period, including the time and duration of symptom occurrence. The duration of SARS-CoV-2 RNA detection was also analyzed. Results A total of 91 children with COVID-19 were included (median [range] age, 11 [0-18] years; 53 boys [58%]). Twenty children (22%) were asymptomatic during the entire observation period. Among 71 symptomatic cases, 47 children (66%) had unrecognized symptoms before diagnosis, 18 (25%) developed symptoms after diagnosis, and only 6 (9%) were diagnosed at the time of symptom onset. Twenty-two children (24%) had lower respiratory tract infections. The mean (SD) duration of the presence of SARS-CoV-2 RNA in upper respiratory samples was 17.6 (6.7) days. Virus RNA was detected for a mean (SD) of 14.1 (7.7) days in asymptomatic individuals. There was no difference in the duration of virus RNA detection between children with upper respiratory tract infections and lower respiratory tract infections (mean [SD], 18.7 [5.8] days vs 19.9 [5.6] days;P = .54). Fourteen children (15%) were treated with lopinavir-ritonavir and/or hydroxychloroquine. All recovered, without any fatal cases. Conclusions and Relevance In this case series study, inapparent infections in children may have been associated with silent COVID-19 transmission in the community. Heightened surveillance using laboratory screening will allow detection in children with unrecognized SARS-CoV-2 infection.

Assessment of Maternal and Neonatal Cord Blood SARS-CoV-2 Antibodies and Placental Transfer Ratios.

Abstract: Importance Maternally derived antibodies are a key element of neonatal immunity. Understanding the dynamics of maternal antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy and subsequent transplacental antibody transfer can inform neonatal management as well as maternal vaccination strategies. Objective To assess the association between maternal and neonatal SARS-CoV-2–specific antibody concentrations. Design, Setting, and Participants This cohort study took place at Pennsylvania Hospital in Philadelphia, Pennsylvania. A total of 1714 women delivered at the study site between April 9 and August 8, 2020. Maternal and cord blood sera were available for antibody measurement for 1471 mother/newborn dyads. Exposures SARS-CoV-2. Main Outcomes and Measures IgG and IgM antibodies to the receptor-binding domain of the SARS-CoV-2 spike protein were measured by enzyme-linked immunosorbent assay. Antibody concentrations and transplacental transfer ratios were analyzed in combination with demographic and clinical data. Results The study cohort consisted of 1714 parturient women, with median (interquartile range) age of 32 (28-35) years, of whom 450 (26.3%) identified as Black/non-Hispanic, 879 (51.3%) as White/non-Hispanic, 203 (11.8%) as Hispanic, 126 (7.3%) as Asian, and 56 (3.3%) as other race/ethnicity. Among 1471 mother/newborn dyads for which matched sera were available, SARS-CoV-2 IgG and/or IgM antibodies were detected in 83 of 1471 women (6%; 95% CI, 5%-7%) at the time of delivery, and IgG was detected in cord blood from 72 of 83 newborns (87%; 95% CI, 78%-93%). IgM was not detected in any cord blood specimen, and antibodies were not detected in any infant born to a seronegative mother. Eleven infants born to seropositive mothers were seronegative: 5 of 11 (45%) were born to mothers with IgM antibody only, and 6 of 11 (55%) were born to mothers with significantly lower IgG concentrations compared with those found among mothers of seropositive infants. Cord blood IgG concentrations were positively correlated with maternal IgG concentrations (r = 0.886;P Conclusions and Relevance In this cohort study, maternal IgG antibodies to SARS-CoV-2 were transferred across the placenta after asymptomatic as well as symptomatic infection during pregnancy. Cord blood antibody concentrations correlated with maternal antibody concentrations and with duration between onset of infection and delivery. Our findings demonstrate the potential for maternally derived SARS-CoV-2 specific antibodies to provide neonatal protection from coronavirus disease 2019.

Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic.

Abstract: Importance Multiple inflammatory syndrome in children (MIS-C) occurs in association with the COVID-19 pandemic. Objective To describe the clinical characteristics and geographic and temporal distribution of the largest cohort of patients with MIS-C in the United States to date. Design, Setting, and Participants Cross-sectional analysis was conducted on clinical and laboratory data collected from patients with MIS-C. The analysis included patients with illness onset from March 2020 to January 2021 and met MIS-C case definition. Main Outcomes and Measures Geographic and temporal distribution of MIS-C was compared with that of COVID-19 nationally, by region, and level of urbanicity by county. Clinical and laboratory findings and changes over time were described by age group and by presence or absence of preceding COVID-19. Results A total of 1733 patients with MIS-C were identified; 994 (57.6%) were male and 1117 (71.3%) were Hispanic or non-Hispanic Black. Gastrointestinal symptoms, rash, and conjunctival hyperemia were reported by 53% (n = 931) to 67% (n = 1153) of patients. A total of 937 patients (54%) had hypotension or shock, and 1009 (58.2%) were admitted for intensive care. Cardiac dysfunction was reported in 484 patients (31.0%), pericardial effusion in 365 (23.4%), myocarditis in 300 (17.3%), and coronary artery dilatation or aneurysms in 258 (16.5%). Patients aged 0 to 4 years had the lowest proportion of severe manifestations, although 171 patients (38.4%) had hypotension or shock and 197 (44.3%) were admitted for intensive care. Patients aged 18 to 20 years had the highest proportions with myocarditis (17 [30.9%]), pneumonia (20 [36.4%]), acute respiratory distress syndrome (10 [18.2%]), and polymerase chain reaction positivity (39 [70.9%]). These older adolescents also had the highest proportion reporting preceding COVID-19–like illness (63%). Nationally, the first 2 MIS-C peaks followed the COVID-19 peaks by 2 to 5 weeks. The cumulative MIS-C incidence per 100 000 persons younger than 21 years was 2.1 and varied from 0.2 to 6.3 by state. Twenty-four patients (1.4%) died. Conclusions and Relevance In this cross-sectional study of a large cohort of patients with MIS-C, 2 peaks that followed COVID-19 peaks by 2 to 5 weeks were identified. The geographic and temporal association of MIS-C with the COVID-19 pandemic suggested that MIS-C resulted from delayed immunologic responses to SARS-CoV-2 infection. The clinical manifestations varied by age and by presence or absence of preceding COVID-19.

Assessment of 135 794 Pediatric Patients Tested for Severe Acute Respiratory Syndrome Coronavirus 2 Across the United States.

Abstract: Importance There is limited information on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing and infection among pediatric patients across the United States. Objective To describe testing for SARS-CoV-2 and the epidemiology of infected patients. Design, Setting, and Participants A retrospective cohort study was conducted using electronic health record data from 135 794 patients younger than 25 years who were tested for SARS-CoV-2 from January 1 through September 8, 2020. Data were from PEDSnet, a network of 7 US pediatric health systems, comprising 6.5 million patients primarily from 11 states. Data analysis was performed from September 8 to 24, 2020. Exposure Testing for SARS-CoV-2. Main Outcomes and Measures SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19) illness. Results A total of 135 794 pediatric patients (53% male; mean [SD] age, 8.8 [6.7] years; 3% Asian patients, 15% Black patients, 11% Hispanic patients, and 59% White patients; 290 per 10 000 population [range, 155-395 per 10 000 population across health systems]) were tested for SARS-CoV-2, and 5374 (4%) were infected with the virus (12 per 10 000 population [range, 7-16 per 10 000 population]). Compared with White patients, those of Black, Hispanic, and Asian race/ethnicity had lower rates of testing (Black: odds ratio [OR], 0.70 [95% CI, 0.68-0.72]; Hispanic: OR, 0.65 [95% CI, 0.63-0.67]; Asian: OR, 0.60 [95% CI, 0.57-0.63]); however, they were significantly more likely to have positive test results (Black: OR, 2.66 [95% CI, 2.43-2.90]; Hispanic: OR, 3.75 [95% CI, 3.39-4.15]; Asian: OR, 2.04 [95% CI, 1.69-2.48]). Older age (5-11 years: OR, 1.25 [95% CI, 1.13-1.38]; 12-17 years: OR, 1.92 [95% CI, 1.73-2.12]; 18-24 years: OR, 3.51 [95% CI, 3.11-3.97]), public payer (OR, 1.43 [95% CI, 1.31-1.57]), outpatient testing (OR, 2.13 [1.86-2.44]), and emergency department testing (OR, 3.16 [95% CI, 2.72-3.67]) were also associated with increased risk of infection. In univariate analyses, nonmalignant chronic disease was associated with lower likelihood of testing, and preexisting respiratory conditions were associated with lower risk of positive test results (standardized ratio [SR], 0.78 [95% CI, 0.73-0.84]). However, several other diagnosis groups were associated with a higher risk of positive test results: malignant disorders (SR, 1.54 [95% CI, 1.19-1.93]), cardiac disorders (SR, 1.18 [95% CI, 1.05-1.32]), endocrinologic disorders (SR, 1.52 [95% CI, 1.31-1.75]), gastrointestinal disorders (SR, 2.00 [95% CI, 1.04-1.38]), genetic disorders (SR, 1.19 [95% CI, 1.00-1.40]), hematologic disorders (SR, 1.26 [95% CI, 1.06-1.47]), musculoskeletal disorders (SR, 1.18 [95% CI, 1.07-1.30]), mental health disorders (SR, 1.20 [95% CI, 1.10-1.30]), and metabolic disorders (SR, 1.42 [95% CI, 1.24-1.61]). Among the 5374 patients with positive test results, 359 (7%) were hospitalized for respiratory, hypotensive, or COVID-19–specific illness. Of these, 99 (28%) required intensive care unit services, and 33 (9%) required mechanical ventilation. The case fatality rate was 0.2% (8 of 5374). The number of patients with a diagnosis of Kawasaki disease in early 2020 was 40% lower (259 vs 433 and 430) than in 2018 or 2019. Conclusions and Relevance In this large cohort study of US pediatric patients, SARS-CoV-2 infection rates were low, and clinical manifestations were typically mild. Black, Hispanic, and Asian race/ethnicity; adolescence and young adulthood; and nonrespiratory chronic medical conditions were associated with identified infection. Kawasaki disease diagnosis is not an effective proxy for multisystem inflammatory syndrome of childhood.

Outcomes of Neonates Born to Mothers With Severe Acute Respiratory Syndrome Coronavirus 2 Infection at a Large Medical Center in New York City.

Abstract: Importance Limited data on vertical and perinatal transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and health outcomes of neonates born to mothers with symptomatic or asymptomatic coronavirus disease 2019 (COVID-19) are available. Studies are needed to inform evidence-based infection prevention and control (IPC interquartile range [IQR], DOL-1 to DOL-3). Two newborns had indeterminate test results, indicative of low viral load (2.0%; 95% CI, 0.2%-7.0%); 1 newborn never underwent retesting but remained well on follow-up, and the other had negative results on retesting. Maternal severe/critical COVID-19 was associated with newborns born approximately 1 week earlier (median gestational age, 37.9 [IQR, 37.1-38.4] vs 39.1 [IQR, 38.3-40.2] weeks;P = .02) and at increased risk of requiring phototherapy (3 of 10 [30.0%] vs 6 of 91 [7.0%];P = .04) compared with newborns of mothers with asymptomatic/mild COVID-19. Fifty-five newborns were followed up in a new COVID-19 Newborn Follow-up Clinic at DOL-3 to DOL-10 and remained well. Twenty of these newborns plus 3 newborns followed up elsewhere had 32 nonroutine encounters documented at DOL-3 to DOL-25, and none had evidence of SARS-CoV-2 infection, including 6 with negative retesting results. Conclusions and Relevance No clinical evidence of vertical transmission was identified in 101 newborns of mothers positive for or with suspected SARS-CoV-2 infection, despite most newborns rooming-in and direct breastfeeding practices.

Prevalence of SARS-CoV-2 Infection in Children and Their Parents in Southwest Germany.

Abstract: Importance School and daycare closures were enforced as measures to confine the novel coronavirus disease 2019 (COVID-19) pandemic, based on the assumption that young children may play a key role in severe acute respiratory coronavirus 2 (SARS-CoV-2) spread. Given the grave consequences of contact restrictions for children, a better understanding of their contribution to the COVID-19 pandemic is of great importance. Objective To describe the rate of SARS-CoV-2 infections and the seroprevalence of SARS-CoV-2 antibodies in children aged 1 to 10 years, compared with a corresponding parent of each child, in a population-based sample. Design, Setting, and Participants This large-scale, multicenter, cross-sectional investigation (the COVID-19 BaWu study) enrolled children aged 1 to 10 years and a corresponding parent between April 22 and May 15, 2020, in southwest Germany. Exposures Potential exposure to SARS-CoV-2. Main Outcomes and Measures The main outcomes were infection and seroprevalence of SARS-CoV-2. Participants were tested for SARS-CoV-2 RNA from nasopharyngeal swabs by reverse transcription–polymerase chain reaction and SARS-CoV-2 specific IgG antibodies in serum by enzyme-linked immunosorbent assays and immunofluorescence tests. Discordant results were clarified by electrochemiluminescence immunoassays, a second enzyme-linked immunosorbent assay, or an in-house Luminex-based assay. Results This study included 4964 participants: 2482 children (median age, 6 [range, 1-10] years; 1265 boys [51.0%]) and 2482 parents (median age, 40 [range, 23-66] years; 615 men [24.8%]). Two participants (0.04%) tested positive for SARS-CoV-2 RNA. The estimated SARS-CoV-2 seroprevalence was low in parents (1.8% [95% CI, 1.2–2.4%]) and 3-fold lower in children (0.6% [95% CI, 0.3-1.0%]). Among 56 families with at least 1 child or parent with seropositivity, the combination of a parent with seropositivity and a corresponding child with seronegativity was 4.3 (95% CI, 1.19-15.52) times higher than the combination of a parent who was seronegative and a corresponding child with seropositivity. We observed virus-neutralizing activity for 66 of 70 IgG-positive serum samples (94.3%). Conclusions and Relevance In this cross-sectional study, the spread of SARS-CoV-2 infection during a period of lockdown in southwest Germany was particularly low in children aged 1 to 10 years. Accordingly, it is unlikely that children have boosted the pandemic. This SARS-CoV-2 prevalence study, which appears to be the largest focusing on children, is instructive for how ad hoc mass testing provides the basis for rational political decision-making in a pandemic.

Trends in Use and Perceptions of Nicotine Vaping Among US Youth From 2017 to 2020.

Abstract: Importance US adolescent nicotine vaping increased at a record pace from 2017 to 2019, prompting new national policies to reduce access to flavors of vaping products preferred by youth. Objective To estimate prevalence, perceived harm, and accessibility of nicotine vaping products among US adolescents from 2017 to 2020. Design, Setting, and Participants This survey study includes data from Monitoring the Future, which conducted annual, cross-sectional, school-based, nationally representative surveys from 2017 to 2020 of 10th- and 12th-grade students (results pooled grades, n = 94 320) about vaping and other topics. Main Outcomes and Measures Prevalence of self-reported nicotine vaping; vaping brand and flavor used most often; perceived risk of nicotine vaping; and perceived ease of getting vaping devices, nicotine solutions for vaping, and flavored solutions. Results In 2020, Monitoring the Future surveyed 8660 students in 10th and 12th grade, of whom 50.6% (95% CI, 47%-54%) were female, 13% (95% CI, 8%-21%) were non-Hispanic Black, 29% (95% CI, 21%-40%) were Hispanic, and 53% (95% CI, 42%-63%) were non-Hispanic White. Nicotine vaping prevalence in 2020 was 22% (95% CI, 19%-25%) for past 30-day use, 32% (95% CI, 28%-37%) for past 12-month use, and 41% (95% CI, 37%-46%) for lifetime use; these levels did not significantly change from 2019. Daily nicotine vaping (use on ≥20 days of the last 30 days) significantly declined from 9% (95% CI, 8%-10%) to 7% (95% CI, 6%-9%) over 2019 to 2020. JUUL brand prevalence in the past 30 days decreased from 20% (95% CI, 18%-22%) in 2019 to 13% (95% CI, 11%-15%) in 2020, while use of other brands increased. Among youth who vaped in the past 30 days in 2020, the most often used flavor was fruit at 59% (95% CI, 55%-63%), followed by mint at 27% (95% CI, 24%-30%) and menthol at 7% (95% CI, 5%-9%); significantly fewer reported easy access to vaping devices and nicotine solutions compared with 2019; and 80% (95% CI, 75%-84%) reported they could easily get a vaping flavor other than tobacco or menthol. Among all youth, perceived risk of both occasional and regular nicotine vaping increased from 2019 to 2020. Conclusions and Relevance Increasing US adolescent nicotine vaping trends from 2017 to 2019 halted in 2020, including a decline in daily vaping. Decreases in perceived accessibility of some vaping products, as well as increases in perceived risk of nicotine vaping, occurred from 2019 to 2020. Yet, adolescent nicotine vaping remains highly prevalent, flavors remain highly accessible, and declines in JUUL use were countered by increased use of other brands.

Association of Age and Pediatric Household Transmission of SARS-CoV-2 Infection.

Abstract: Importance As a result of low numbers of pediatric cases early in the COVID-19 pandemic, pediatric household transmission of SARS-CoV-2 remains an understudied topic. Objective To determine whether there are differences in the odds of household transmission by younger children compared with older children. Design, Setting, and Participants This population-based cohort study took place between June 1 and December 31, 2020, in Ontario, Canada. Private households in which the index case individual of laboratory-confirmed SARS-CoV-2 infection was younger than 18 years were included. Individuals were excluded if they resided in apartments missing suite information, in households with multiple index cases, or in households where the age of the index case individual was missing. Exposures Age group of pediatric index cases categorized as 0 to 3, 4 to 8, 9 to 13, and 14 to 17 years. Main Outcomes and Measures Household transmission, defined as households where at least 1 secondary case occurred 1 to 14 days after the pediatric index case. Results A total of 6280 households had pediatric index cases, and 1717 households (27.3%) experienced secondary transmission. The mean (SD) age of pediatric index case individuals was 10.7 (5.1) years and 2863 (45.6%) were female individuals. Children aged 0 to 3 years had the highest odds of transmitting SARS-CoV-2 to household contacts compared with children aged 14 to 17 years (odds ratio, 1.43; 95% CI, 1.17-1.75). This association was similarly observed in sensitivity analyses defining secondary cases as 2 to 14 days or 4 to 14 days after the index case and stratified analyses by presence of symptoms, association with a school/childcare outbreak, or school/childcare reopening. Children aged 4 to 8 years and 9 to 13 years also had increased odds of transmission (aged 4-8 years: odds ratio, 1.40; 95% CI, 1.18-1.67; aged 9-13 years: odds ratio, 1.13; 95% CI, 0.97-1.32). Conclusions and Relevance This study suggests that younger children may be more likely to transmit SARS-CoV-2 infection compared with older children, and the highest odds of transmission was observed for children aged 0 to 3 years. Differential infectivity of pediatric age groups has implications for infection prevention within households, as well as schools/childcare, to minimize risk of household secondary transmission. Additional population-based studies are required to establish the risk of transmission by younger pediatric index cases.

Early Intervention for Children Aged 0 to 2 Years With or at High Risk of Cerebral Palsy: International Clinical Practice Guideline Based on Systematic Reviews.

Abstract: Importance: Cerebral palsy (CP) is the most common childhood physical disability. Early intervention for children younger than 2 years with or at risk of CP is critical. Now that an evidence-based guideline for early accurate diagnosis of CP exists, there is a need to summarize effective, CP-specific early intervention and conduct new trials that harness plasticity to improve function and increase participation. Our recommendations apply primarily to children at high risk of CP or with a diagnosis of CP, aged 0 to 2 years. Objective: To systematically review the best available evidence about CP-specific early interventions across 9 domains promoting motor function, cognitive skills, communication, eating and drinking, vision, sleep, managing muscle tone, musculoskeletal health, and parental support. Evidence Review: The literature was systematically searched for the best available evidence for intervention for children aged 0 to 2 years at high risk of or with CP. Databases included CINAHL, Cochrane, Embase, MEDLINE, PsycInfo, and Scopus. Systematic reviews and randomized clinical trials (RCTs) were appraised by A Measurement Tool to Assess Systematic Reviews (AMSTAR) or Cochrane Risk of Bias tools. Recommendations were formed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework and reported according to the Appraisal of Guidelines, Research, and Evaluation (AGREE) II instrument. Findings: Sixteen systematic reviews and 27 RCTs met inclusion criteria. Quality varied. Three best-practice principles were supported for the 9 domains: (1) immediate referral for intervention after a diagnosis of high risk of CP, (2) building parental capacity for attachment, and (3) parental goal-setting at the commencement of intervention. Twenty-eight recommendations (24 for and 4 against) specific to the 9 domains are supported with key evidence: motor function (4 recommendations), cognitive skills (2), communication (7), eating and drinking (2), vision (4), sleep (7), tone (1), musculoskeletal health (2), and parent support (5). Conclusions and Relevance: When a child meets the criteria of high risk of CP, intervention should start as soon as possible. Parents want an early diagnosis and treatment and support implementation as soon as possible. Early intervention builds on a critical developmental time for plasticity of developing systems. Referrals for intervention across the 9 domains should be specific as per recommendations in this guideline.

Population vs Individual Prediction of Poor Health From Results of Adverse Childhood Experiences Screening.

Abstract: Importance Adverse childhood experiences (ACEs) are well-established risk factors for health problems in a population However, it is not known whether screening for ACEs can accurately identify individuals who develop later health problems Objective To test the predictive accuracy of ACE screening for later health problems Design, Setting, and Participants This study comprised 2 birth cohorts: the Environmental Risk (E-Risk) Longitudinal Twin Study observed 2232 participants born during the period from 1994 to 1995 until they were aged 18 years (2012-2014); the Dunedin Multidisciplinary Health and Development Study observed 1037 participants born during the period from 1972 to 1973 until they were aged 45 years (2017-2019) Statistical analysis was performed from May 28, 2018, to July 29, 2020 Exposures ACEs were measured prospectively in childhood through repeated interviews and observations in both cohorts ACEs were also measured retrospectively in the Dunedin cohort through interviews at 38 years Main Outcomes and Measures Health outcomes were assessed at 18 years in E-Risk and at 45 years in the Dunedin cohort Mental health problems were assessed through clinical interviews using the Diagnostic Interview Schedule Physical health problems were assessed through interviews, anthropometric measurements, and blood collection Results Of 2232 E-Risk participants, 2009 (1051 girls [52%]) were included in the analysis Of 1037 Dunedin cohort participants, 918 (460 boys [50%]) were included in the analysis In E-Risk, children with higher ACE scores had greater risk of later health problems (any mental health problem: relative risk, 114 [95% CI, 110-118] per each additional ACE; any physical health problem: relative risk, 109 [95% CI, 107-112] per each additional ACE) ACE scores were associated with health problems independent of other information typically available to clinicians (ie, sex, socioeconomic disadvantage, and history of health problems) However, ACE scores had poor accuracy in predicting an individual’s risk of later health problems (any mental health problem: area under the receiver operating characteristic curve, 058 [95% CI, 056-061]; any physical health problem: area under the receiver operating characteristic curve, 060 [95% CI, 058-063]; chance prediction: area under the receiver operating characteristic curve, 050) Findings were consistent in the Dunedin cohort using both prospective and retrospective ACE measures Conclusions and Relevance This study suggests that, although ACE scores can forecast mean group differences in health, they have poor accuracy in predicting an individual’s risk of later health problems Therefore, targeting interventions based on ACE screening is likely to be ineffective in preventing poor health outcomes

Should We Mandate a COVID-19 Vaccine for Children?

Abstract: The zeal to develop and implement a vaccine to prevent coronavirus disease 2019 (COVID-19) infection has been exceptional. Operation Warp Speed, the Trump administration's proposal, seeks to produce hundreds of millions of doses of a vaccine by January 2021. Recent polls show as many as 70% of adults in the United States plan to get vaccinated against COVID-19 once a vaccine is available.1 And thousands of adults have registered to participate as volunteers in human challenge trials to speed up the development of a new vaccine.2 We anticipate that this fervor will eventually lead to discussions about making a COVID-19 vaccine mandatory. An obvious group to target for mandatory vaccination is children. Not only do we already mandate several vaccines for them to attend school, but strategies to reopen schools or keep them open may be predicated on it. Some might suggest the current US approach to influenza vaccine should inform our approach to a COVID-19 vaccine: no states require influenza vaccination for children to attend school. The analogy is understandable because the virus that causes COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), is a respiratory virus transmitted by human contact, with the most common symptoms being cough and fever. In fact, President Trump compared COVID-19 to influenza, and many Americans believe that COVID-19 is like influenza. However, there are important differences between SARS-CoV-2 and influenza viruses, and these differences can lead to very different conclusions about whether and for whom the administration of a COVID-19 vaccine should be required. One important difference is the role of children in transmission of disease. Children play a central role in the spread of influenza, sometimes with life-threatening consequences for seniors and others. However, initial reports suggest children transmit SARS-CoV-2 less easily than the influenza virus.3 Although there is much more to understand regarding the role of children in the transmission of SARS-CoV-2, it would be more difficult to justify requiring a COVID-19 vaccine in children for a disease that appears to be mild in most children, particularly if children play a minimal role in spreading the infection to others. On the other hand, SARS-CoV-2 appears to spread more efficiently than influenza. The number of others to whom an infected person would spread the disease if he or she were placed in a totally susceptible population (ie, the reproduction number [R0]) is approximately 1 for the influenza virus. For SARS-CoV-2, the R0 is 2 to 2.5.4 It is easier to make the case for mandating a vaccine for an infectious agent with a higher R0 because the higher the R0, the more individuals with immunity will be needed to prevent spread of disease, and a vaccine mandate may be the only way to achieve the high herd immunity threshold needed to provide wide community protection. Consider the measles virus. It has an R0 of 12 to 18; as a result, approximately 92% to 94% of the population must be immune to prevent spread. This has been achieved by requiring 2 doses of measles vaccine for children in all states before enrollment in school, with only very limited ways to opt out. Rather than resort to analogies, we can use 9 standard criteria that can help guide whether a COVID-19 vaccine for children should be mandated (Box).5,6 These criteria can be divided into 3 categories: 4 criteria related to the vaccine, 2 related to the disease, and 3 related to implementation. Ordinarily, each of these criteria would be considered in determining whether a vaccine should be mandated for children, although the weight given to each criterion may differ. In times of great public health need, such as the present pandemic, however, we propose that each criterion continue to be evaluated in making vaccine policy, but 5 criteria should be prioritized. The criterion that should be prioritized over all others is the first: there must be evidence that a COVID-19 vaccine is safe for children with an acceptable level of risk. Fulfilling this criterion normally requires both prelicensure safety data and data from postlicensure studies to monitor for adverse effects after the vaccine has been administered to many people. Accumulation of the data needed to fulfill this criterion often requires years of research. It would be a mistake to consider making a COVID-19 vaccine mandatory without these data. Vaccine safety is fundamental to maintaining the public's trust in vaccines, and skirting this safety criterion could have far-reaching consequences. Although less stringent safety benchmarks may be used to justify emergency or voluntary uses of a COVID-19 vaccine, it is imperative that any policy mandating use of a COVID-19 vaccine follow the fullest assessment of its safety. As such, this first criterion should function moreasapreconditionratherthanaconsiderationthatcan be weighed against other criteria. There are 4 other criteria to prioritize in considering whether to make a COVID-19 vaccine mandatory for children. First, the burden of COVID-19 disease ought to be substantial in at least a subset of the population (fifth criterion). This criterion has already been met. Second, vaccinating children should reduce the risk of transmission of disease (sixth criterion). Fundamental to any mandatory vaccine policy involving children is that increasing the proportion who are immune prevents disease in others. This criterion, however, relies on the role of children in person-to-person transmission of SARS-CoV-2, which is still poorly understood. Third, the COVID-19 vaccine must also be effective in protecting a child from the disease (second criterion). It need not be 100% effective, but a COVID-19 vaccine should have effectiveness VIEWPOINT

Adolescents' Substance Use and Physical Activity Before and During the COVID-19 Pandemic.

Abstract: Importance: Stay-at-home policies related to the COVID-19 pandemic could disrupt adolescents' substance use and physical activity. Objective: To compare adolescents' substance use and physical activity behaviors before and after stay-at-home restrictions. Design, Setting, and Participants: Ongoing prospective cohort study of tobacco use behaviors among ninth- and tenth-grade students enrolled at 8 public high schools in Northern California from March 2019 to February 2020 and followed up from September 2019 to September 2020. Race/ethnicity was self-classified from investigator-provided categories and collected owing to racial/ethnic differences in tobacco and substance use. Exposures: In California, a COVID-19 statewide stay-at-home order was imposed March 19, 2020. In this study, 521 six-month follow-up responses were completed before the order and 485 were completed after the order. Main Outcomes and Measures: The prevalence of substance use (ie, past 30-day use of e-cigarettes, other tobacco, cannabis, and alcohol) and physical activity (active ≥5 days/week) was compared at baseline and follow-up. A difference-in-difference approach was used to assess whether changes from baseline to 6-month follow-up varied if follow-up occurred after the stay-at-home order, adjusting for baseline behaviors and characteristics. All models were weighted for losses to follow-up using the inverse probability method. Weights were derived from a logistic regression model for having a follow-up response (dependent variable), as predicted by baseline characteristics and behaviors. Results: Of 1423 adolescents enrolled at baseline, 1006 completed 6-month follow-up (623 [62%] were female, and 492 [49%] were non-Hispanic White). e-Cigarette use declined from baseline to 6-month follow-up completed before the stay-at-home order (17.3% [89 of 515] to 11.3% [58 of 515]; McNemar χ2 = 13.54; exact P < .001) and 6-month follow-up completed after the stay-at-home order (19.9% [96 of 482] to 10.8% [52 of 482]; McNemar χ2 = 26.16; exact P < .001), but the extent of decline did not differ statistically between groups responding before vs after the stay-at-home order (difference-in-difference adjusted odds ratio, 0.84; 95% CI, 0.47-1.52; P = .58). In contrast, being physically active was unchanged from baseline if follow-up was before the order (53.7% [279 of 520] to 52.9% [275 of 520]; McNemar χ2 = 0.09; exact P = .82) but declined sharply from baseline if follow-up was after the order (54.0% [261 of 483] to 38.1% [184 of 483]; McNemar χ2 = 30.72; exact P < .001), indicating a pronounced difference in change from baseline after the stay-at-home order (difference-in-difference adjusted odds ratio, 0.49; 95% CI, 0.35-0.69; P < .001). Overall in the cohort, reported use of other tobacco, cannabis, and alcohol did not differ meaningfully before and after the order. Conclusions and Relevance: In this cohort, a reduction in e-cigarette use occurred independently of COVID-19 stay-at-home restrictions, but persistent cannabis and alcohol use suggest continued need for youth substance use prevention and cessation support. Declining physical activity during the pandemic is a health concern.

Association of Race/Ethnicity and Social Disadvantage With Autism Prevalence in 7 Million School Children in England

Abstract: Importance The global prevalence of autism spectrum disorder (ASD) has been reported to be between 1% and 2% of the population, with little research in Black, Asian, and other racial/ethnic minority groups. Accurate estimates of ASD prevalence are vital to planning diagnostic, educational, health, and social care services and may detect possible access barriers to diagnostic pathways and services and inequalities based on social determinants of health. Objective To evaluate whether socioeconomic disadvantage is associated with ASD prevalence and the likelihood of accessing ASD services in racial/ethnic minority and disadvantaged groups in England. Design, Setting, and Participants This case-control prevalence cohort study used the Spring School Census 2017 from the Pupil Level Annual Schools Census of the National Pupil Database, which is a total population sample that includes all English children, adolescents, and young adults aged 2 to 21 years in state-funded education. Data were collected on January 17, 2017, and analyzed from August 2, 2018, to January 28, 2020. Exposures Age and sex were treated as a priori confounders while assessing correlates of ASD status according to (1) race/ethnicity, (2) social disadvantage, (3) first language spoken, (4) Education, Health and Care Plan or ASD Special Educational Needs and Disability support status, and (5) mediation analysis to assess how social disadvantage and language might affect ASD status. Main Outcomes and Measures Sex- and age-standardized ASD prevalence by race/ethnicity and 326 English local authority districts in pupils aged 5 to 19 years. Results The final population sample consisted of 7 047 238 pupils (50.99% male; mean [SD] age, 10.18 [3.47] years) and included 119 821 pupils with ASD, of whom 21 660 also had learning difficulties (18.08%). The standardized prevalence of ASD was 1.76% (95% CI, 1.75%-1.77%), with male pupils showing a prevalence of 2.81% (95% CI, 2.79%-2.83%) and female pupils a prevalence of 0.65% (95% CI, 0.64%-0.66%), for a male-to-female ratio (MFR) of 4.32:1. Standardized prevalence was highest in Black pupils (2.11% [95% CI, 2.06%-2.16%]; MFR, 4.68:1) and lowest in Roma/Irish Travelers (0.85% [95% CI, 0.67%-1.03%]; MFR, 2.84:1). Pupils with ASD were more likely to face social disadvantage (adjusted prevalence ratio, 1.61; 95% CI, 1.59-1.63) and to speak English as an additional language (adjusted prevalence ratio, 0.64; 95% CI, 0.63-0.65). The effect of race/ethnicity on ASD status was mediated mostly through social disadvantage, with Black pupils having the largest effect (standardized mediation coefficient, 0.018;P Conclusions and Relevance These findings suggest that significant differences in ASD prevalence exist across racial/ethnic groups and geographic areas and local authority districts, indicating possible differential phenotypic prevalence or differences in detection or referral for racial/ethnic minority groups.

Comparison of Symptoms and RNA Levels in Children and Adults With SARS-CoV-2 Infection in the Community Setting.

Abstract: Importance The association between COVID-19 symptoms and SARS-CoV-2 viral levels in children living in the community is not well understood. Objective To characterize symptoms of pediatric COVID-19 in the community and analyze the association between symptoms and SARS-CoV-2 RNA levels, as approximated by cycle threshold (Ct) values, in children and adults. Design, Setting, and Participants This cross-sectional study used a respiratory virus surveillance platform in persons of all ages to detect community COVID-19 cases from March 23 to November 9, 2020. A population-based convenience sample of children younger than 18 years and adults in King County, Washington, who enrolled online for home self-collection of upper respiratory samples for SARS-CoV-2 testing were included. Exposures Detection of SARS-CoV-2 RNA by reverse transcription–polymerase chain reaction (RT-PCR) from participant-collected samples. Main Outcomes and Measures RT-PCR–confirmed SARS-CoV-2 infection, with Ct values stratified by age and symptoms. Results Among 555 SARS-CoV-2–positive participants (mean [SD] age, 33.7 [20.1] years; 320 were female [57.7%]), 47 of 123 children (38.2%) were asymptomatic compared with 31 of 432 adults (7.2%). When symptomatic, fewer symptoms were reported in children compared with adults (mean [SD], 1.6 [2.0] vs 4.5 [3.1]). Symptomatic individuals had lower Ct values (which corresponded to higher viral RNA levels) than asymptomatic individuals (adjusted estimate for children, −3.0; 95% CI, −5.5 to −0.6;P = .02; adjusted estimate for adults, −2.9; 95% CI, −5.2 to −0.6;P = .01). The difference in mean Ct values was neither statistically significant between symptomatic children and symptomatic adults (adjusted estimate, −0.7; 95% CI, −2.2 to 0.9;P = .41) nor between asymptomatic children and asymptomatic adults (adjusted estimate, −0.6; 95% CI, −4.0 to 2.8;P = .74). Conclusions and Relevance In this community-based cross-sectional study, SARS-CoV-2 RNA levels, as determined by Ct values, were significantly higher in symptomatic individuals than in asymptomatic individuals and no significant age-related differences were found. Further research is needed to understand the role of SARS-CoV-2 RNA levels and viral transmission.

Incidence Rates, Household Infection Risk, and Clinical Characteristics of SARS-CoV-2 Infection Among Children and Adults in Utah and New York City, New York.

Abstract: Importance Data about the risk of SARS-CoV-2 infection among children compared with adults are needed to inform COVID-19 risk communication and prevention strategies, including COVID-19 vaccination policies for children. Objective To compare incidence rates and clinical characteristics of SARS-CoV-2 infection among adults and children and estimated household infection risks within a prospective household cohort. Design, Setting, and Participants Households with at least 1 child aged 0 to 17 years in selected counties in Utah and New York City, New York, were eligible for enrollment. From September 2020 through April 2021, participants self-collected midturbinate nasal swabs for reverse transcription–polymerase chain reaction testing for SARS-CoV-2 and responded to symptom questionnaires each week. Participants also self-collected additional respiratory specimens with onset of COVID-19–like illness. For children unable to self-collect respiratory specimens, an adult caregiver collected the specimens. Main Outcomes and Measures The primary outcome was incident cases of any SARS-CoV-2 infection, including asymptomatic and symptomatic infections. Additional measures were the asymptomatic fraction of infection calculated by dividing incidence rates of asymptomatic infection by rates of any infection, clinical characteristics of infection, and household infection risks. Primary outcomes were compared by participant age group. Results A total of 1236 participants in 310 households participated in surveillance, including 176 participants (14%) who were aged 0 to 4 years, 313 (25%) aged 5 to 11 years, 163 (13%) aged 12 to 17 years, and 584 (47%) 18 years or older. Overall incidence rates of SARS-CoV-2 infection were 3.8 (95% CI, 2.4-5.9) and 7.7 (95% CI, 4.1-14.5) per 1000 person-weeks among the Utah and New York City cohorts, respectively. Site-adjusted incidence rates per 1000 person-weeks were similar by age group: 6.3 (95% CI, 3.6-11.0) for children 0 to 4 years, 4.4 (95% CI, 2.5-7.5) for children 5 to 11 years, 6.0 (95% CI, 3.0-11.7) for children 12 to 17 years, and 5.1 (95% CI, 3.3-7.8) for adults (≥18 years). The asymptomatic fractions of infection by age group were 52%, 50%, 45%, and 12% among individuals aged 0 to 4 years, 5 to 11 years, 12 to 17 years, and 18 years or older, respectively. Among 40 households with 1 or more SARS-CoV-2 infections, the mean risk of SARS-CoV-2 infection among all enrolled household members was 52% (range, 11%-100%), with higher risks in New York City compared with Utah (80% [95% CI, 64%-91%] vs 44% [95% CI, 36%-53%];P Conclusions and Relevance In this study, children had similar incidence rates of SARS-CoV-2 infection compared with adults, but a larger proportion of infections among children were asymptomatic.

Effect of Preemptive Intervention on Developmental Outcomes Among Infants Showing Early Signs of Autism: A Randomized Clinical Trial of Outcomes to Diagnosis

Abstract: Importance Intervention for individuals with autism spectrum disorder (ASD) typically commences after diagnosis. No trial of an intervention administered to infants before diagnosis has shown an effect on diagnostic outcomes to date. Objective To determine the efficacy of a preemptive intervention for ASD beginning during the prodromal period. Design, setting, and participants This 2-site, single rater-blinded randomized clinical trial of a preemptive intervention vs usual care was conducted at 2 Australian research centers (Perth, Melbourne). Community sampling was used to recruit 104 infants aged 9 to 14 months showing early behaviors associated with later ASD, as measured by the Social Attention and Communication Surveillance-Revised. Recruitment occurred from June 9, 2016, to March 30, 2018. Final follow-up data were collected on April 15, 2020. Interventions Infants were randomized on a 1:1 ratio to receive either a preemptive intervention plus usual care or usual care only over a 5-month period. The preemptive intervention group received a 10-session social communication intervention, iBASIS-Video Interaction to Promote Positive Parenting (iBASIS-VIPP). Usual care comprised services delivered by community clinicians. Main outcomes and measures Infants were assessed at baseline (approximate age, 12 months), treatment end point (approximate age, 18 months), age 2 years, and age 3 years. Primary outcome was the combined blinded measure of ASD behavior severity (the Autism Observation Scale for Infants and the Autism Diagnostic Observation Schedule, second edition) across the 4 assessment points. Secondary outcomes were an independent blinded clinical ASD diagnosis at age 3 years and measures of child development. Analyses were preregistered and comprised 1-tailed tests with an α level of .05. Results Of 171 infants assessed for eligibility, 104 were randomized; 50 infants (mean [SD] chronological age, 12.40 [1.93] months; 38 boys [76.0%]) received the iBASIS-VIPP preemptive intervention plus usual care (1 infant was excluded after randomization), and 53 infants (mean [SD] age, 12.38 [2.02] months; 32 boys [60.4%]) received usual care only. A total of 89 participants (45 in the iBASIS-VIPP group and 44 in the usual care group) were reassessed at age 3 years. The iBASIS-VIPP intervention led to a reduction in ASD symptom severity (area between curves, -5.53; 95% CI, -∞ to -0.28; P = .04). Reduced odds of ASD classification at age 3 years was found in the iBASIS-VIPP group (3 of 45 participants [6.7%]) vs the usual care group (9 of 44 participants [20.5%]; odds ratio, 0.18; 95% CI, 0-0.68; P = .02). Number needed to treat to reduce ASD classification was 7.2 participants. Improvements in caregiver responsiveness and language outcomes were also observed in the iBASIS-VIPP group. Conclusions and relevance Receipt of a preemptive intervention for ASD from age 9 months among a sample of infants showing early signs of ASD led to reduced ASD symptom severity across early childhood and reduced the odds of an ASD diagnosis at age 3 years. Trial registration http://anzctr.org.au identifier: ACTRN12616000819426.

Association of the COVID-19 Pandemic With Routine Childhood Vaccination Rates and Proportion Up to Date With Vaccinations Across 8 US Health Systems in the Vaccine Safety Datalink.

Abstract: Importance The COVID-19 pandemic has affected routine vaccine delivery in the US and globally. The magnitude of these disruptions and their association with childhood vaccination coverage are unclear. Objectives To compare trends in pediatric vaccination before and during the pandemic and to evaluate the proportion of children up to date (UTD) with vaccinations by age, race, and ethnicity. Design, Setting, and Participants This surveillance study used a prepandemic-postpandemic control design with data from 8 health systems in California, Oregon, Washington, Colorado, Minnesota, and Wisconsin in the Vaccine Safety Datalink. Children from age groups younger than 24 months and 4 to 6, 11 to 13, and 16 to 18 years were included if they had at least 1 week of health system enrollment from January 5, 2020, through October 3, 2020, over periods before the US COVID-19 pandemic (January 5, 2020, through March 14, 2020), during age-limited preventive care (March 15, 2020, through May 16, 2020), and during expanded primary care (May 17, 2020, through October 3, 2020). These individuals were compared with those enrolled during analogous weeks in 2019. Exposures This study evaluated UTD status among children reaching specific ages in February, May, and September 2020, compared with those reaching these ages in 2019. Main Outcomes and Measures Weekly vaccination rates for routine age-specific vaccines and the proportion of children UTD for all age-specific recommended vaccines. Results Of 1 399 708 children in 2019 and 1 402 227 in 2020, 1 371 718 were female (49.0%) and 1 429 979 were male (51.0%); 334 216 Asian individuals (11.9%), 900 226 were Hispanic individuals (32.1%), and 201 619 non-Hispanic Black individuals (7.2%). Compared with the prepandemic period and 2019, the age-limited preventive care period was associated with lower weekly vaccination rates, with ratios of rate ratios of 0.82 (95% CI, 0.80-0.85) among those younger than 24 months, 0.18 (95% CI, 0.16-0.20) among those aged 4 to 6 years, 0.16 (95% CI, 0.14-0.17) among those aged 11 to 13 years, and 0.10 (95% CI, 0.08-0.13) among those aged 16 to 18 years. Vaccination rates during expanded primary care remained lower for most ages (ratios of rate ratios: Conclusions and Relevance As of September 2020, childhood vaccination rates and the proportion who were UTD remained lower than 2019 levels. Interventions are needed to promote catch-up vaccination, particularly in populations at risk for underimmunization.

Evaluation of Rooming-in Practice for Neonates Born to Mothers With Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Italy.

Abstract: Importance The management of mother-infant dyads during the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic constitutes a major issue for neonatologists. In mothers with SARS-CoV-2 infection, current recommendations suggest either to separate the dyad or encourage protected rooming-in under appropriate precautions. No data are available regarding the risk of mother-to-infant transmission of SARS-CoV-2 during rooming-in. Objective To evaluate the risk of postnatal transmission of SARS-CoV-2 from infected mothers to their neonates following rooming-in and breastfeeding. Design, Setting, and Participants A prospective, multicenter study enrolling mother-infant dyads from March 19 to May 2, 2020, followed up for 20 days of life (range, 18-22 days), was performed. The study was conducted at 6 coronavirus disease 2019 maternity centers in Lombardy, Northern Italy. Participants included 62 neonates born to 61 mothers with SARS-CoV-2 infection who were eligible for rooming-in practice based on the clinical condition of the mother and infants whose results of nasopharyngeal swabs were negative at birth. Exposures Mothers with SARS-CoV-2 infection were encouraged to practice rooming-in and breastfeeding under a standardized protocol to minimize the risk of viral transmission. Main Outcomes and Measures Clinical characteristics and real-time reverse transcriptase-polymerase chain reaction for SARS-CoV-2 on neonatal nasopharyngeal swabs at 0, 7, and 20 days of life. Results Of the 62 neonates enrolled (25 boys), born to 61 mothers (median age, 32 years; interquartile range, 28-36 years), only 1 infant (1.6%; 95% CI, 0%-8.7%) was diagnosed as having SARS-CoV-2 infection at postbirth checks. In that case, rooming-in was interrupted on day 5 of life because of severe worsening of the mother’s clinical condition. The neonate became positive for the virus on day 7 of life and developed transient mild dyspnea. Ninety-five percent of the neonates enrolled were breastfed. Conclusions and Relevance The findings of this cohort study provide evidence-based information on the management of mother-infant dyads in case of SARS-CoV-2 maternal infection suggesting that rooming-in and breastfeeding can be practiced in women who are able to care for their infants.

Short-term Outcomes of the Study of Refeeding to Optimize Inpatient Gains for Patients With Anorexia Nervosa: A Multicenter Randomized Clinical Trial.

Abstract: Importance The standard of care for refeeding inpatients with anorexia nervosa, starting with low calories and advancing cautiously, is associated with slow weight gain and protracted hospital stay. Limited data suggest that higher-calorie refeeding improves these outcomes with no increased risk of refeeding syndrome. Objective To compare the short-term efficacy, safety, and cost of lower-calorie vs higher-calorie refeeding for malnourished adolescents and young adults with anorexia nervosa. Design, setting, and participants In this multicenter randomized clinical trial with prospective follow-up conducted at 2 inpatient eating disorder programs at large tertiary care hospitals, 120 adolescents and young adults aged 12 to 24 years hospitalized with anorexia nervosa or atypical anorexia nervosa and 60% or more of median body mass index were enrolled from February 8, 2016, to March 7, 2019. The primary analysis was a modified intent-to-treat approach. Interventions Higher-calorie refeeding, beginning at 2000 kcal/d and increasing by 200 kcal/d vs lower-calorie refeeding, beginning at 1400 k/cal and increasing by 200 kcal every other day. Main outcomes and measures Main outcomes were end-of-treatment outcomes; the primary end point of this trial will be clinical remission over 12 months. Short-term efficacy was defined a priori as time to restore medical stability in the hospital, measured by the following 6 indices: 24-hour heart rate of 45 beats/min or more, systolic blood pressure of 90 mm Hg or more, temperature of 35.6 °C or more, orthostatic increase in heart rate of 35 beats/min or less, orthostatic decrease in systolic blood pressure of 20 mm Hg or less, and 75% or more of median body mass index for age and sex. The prespecified safety outcome was incidence of electrolyte abnormalities; cost efficacy was defined as savings associated with length of stay. Results Because 9 participants withdrew prior to treatment, the modified intention-to-treat analyses included 111 participants (93%; 101 females [91%]; mean [SD] age, 16.4 [2.5] years). Higher-calorie refeeding restored medical stability significantly earlier than lower-calorie refeeding (hazard ratio, 1.67 [95% CI, 1.10-2.53]; P = .01). Electrolyte abnormalities and other adverse events did not differ by group. Hospital stay was 4.0 days shorter (95% CI, -6.1 to -1.9 days) among the group receiving higher-calorie refeeding, which was associated with a savings of $19 056 (95% CI, -$28 819 to -$9293) in hospital charges per participant. Conclusions and relevance In the first randomized clinical trial in the US to compare refeeding approaches in patients with anorexia nervosa and atypical anorexia nervosa, higher-calorie refeeding demonstrated short-term efficacy with no increase in safety events during hospitalization. Trial registration ClinicalTrials.gov Identifier: NCT02488109.

Association of Human Milk Antibody Induction, Persistence, and Neutralizing Capacity With SARS-CoV-2 Infection vs mRNA Vaccination.

Abstract: Importance Long-term effect of parental COVID-19 infection vs vaccination on human milk antibody composition and functional activity remains unclear. Objective To compare temporal IgA and IgG response in human milk and microneutralization activity against SARS-CoV-2 between lactating parents with infection and vaccinated lactating parents out to 90 days after infection or vaccination. Design, setting, and participants Convenience sampling observational cohort (recruited July to December 2020) of lactating parents with infection with human milk samples collected at days 0 (within 14 days of diagnosis), 3, 7, 10, 28, and 90. The observational cohort included vaccinated lactating parents with human milk collected prevaccination, 18 days after the first dose, and 18 and 90 days after the second dose. Exposures COVID-19 infection diagnosed by polymerase chain reaction within 14 days of consent or receipt of messenger RNA (mRNA) COVID-19 vaccine (BNT162b2 or mRNA-1273). Main outcomes and measures Human milk anti-SARS-CoV-2 receptor-binding domain IgA and IgG and microneutralization activity against live SARS-CoV-2 virus. Results Of 77 individuals, 47 (61.0%) were in the infection group (mean [SD] age, 29.9 [4.4] years), and 30 (39.0%) were in the vaccinated group (mean [SD] age, 33.0 [3.4] years; P = .002). The mean (SD) age of infants in the infection and vaccinated group were 3.1 (2.2) months and 7.5 (5.2) months, respectively (P Conclusions and relevance In this cohort study of a convenience sample of lactating parents, the pattern of IgA and IgG antibodies in human milk differed between COVID-19 infection vs mRNA vaccination out to 90 days. While infection was associated with a highly variable IgA-dominant response and vaccination was associated with an IgG-dominant response, both were associated with having human milk that exhibited neutralization activity against live SARS-CoV-2 virus.

Association Between Childhood Consumption of Ultraprocessed Food and Adiposity Trajectories in the Avon Longitudinal Study of Parents and Children Birth Cohort.

Abstract: Importance Reports of associations between higher consumption of ultraprocessed foods (UPF) and elevated risks of obesity, noncommunicable diseases, and mortality in adults are increasing. However, associations of UPF consumption with long-term adiposity trajectories have never been investigated in children. Objective To assess longitudinal associations between UPF consumption and adiposity trajectories from childhood to early adulthood. Design, Setting, and Participants This prospective birth cohort study included children who participated in the Avon Longitudinal Study of Parents and Children (ALSPAC) in Avon County, southwest England. Children were followed up from 7 to 24 years of age during the study period from September 1, 1998, to October 31, 2017. Data were analyzed from March 1, 2020, to January 31, 2021. Exposures Baseline dietary intake data were collected using 3-day food diaries. Consumption of UPF (applying the NOVA food classification system) was computed as a percentage of weight contribution in the total daily food intake for each participant and categorized into quintiles. Main Outcomes and Measures Repeated recordings of objectively assessed anthropometrics (body mass index [BMI; calculated as weight in kilograms divided by height in meters squared], weight, and waist circumference) and dual-energy x-ray absorptiometry measurements (fat and lean mass indexes [calculated as fat and lean mass, respectively, divided by height in meters squared] and body fat percentage). Associations were evaluated using linear growth curve models and were adjusted for study covariates. Results A total of 9025 children (4481 [49.7%] female and 4544 [50.3%] male) were followed up for a median of 10.2 (interquartile range, 5.2-16.4) years. The mean (SD) UPF consumption at baseline was 23.2% (5.0%) in quintile 1, 34.7% (2.5%) in quintile 2, 43.4% (2.5%) in quintile 3, 52.7% (2.8%) in quintile 4, and 67.8% (8.1%) in quintile 5. Among those in the highest quintile of UPF consumption compared with their lowest quintile counterpart, trajectories of BMI increased by an additional 0.06 (95% CI, 0.04-0.08) per year; fat mass index, by an additional 0.03 (95% CI, 0.01-0.05) per year; weight, by an additional 0.20 (95% CI, 0.11-0.28) kg per year; and waist circumference, by an additional 0.17 (95% CI, 0.11-0.22) cm per year. Conclusions and Relevance These findings suggest that higher UPF consumption is associated with greater increases in adiposity from childhood to early adulthood. Robust public health measures that promote minimally processed foods and discourage UPF consumption among children are urgently needed to reduce obesity in England and globally.

Prevalence of SARS-CoV-2 Infection in Children Without Symptoms of Coronavirus Disease 2019.

Abstract: This cohort study examines the rate of positive test results for severe acute respiratory syndrome coronavirus 2 in children without symptoms who were treated in US hospitals for other conditions.

Assessment of School Anti-Bullying Interventions: A Meta-analysis of Randomized Clinical Trials.

Abstract: Importance Bullying is a prevalent and modifiable risk factor for mental health disorders. Although previous studies have supported the effectiveness of anti-bullying programs; their population impact and the association of specific moderators with outcomes are still unclear. Objective To assess the effectiveness of school anti-bullying interventions, their population impact, and the association between moderator variables and outcomes. Data sources A search of Ovid MEDLINE, ERIC, and PsycInfo databases was conducted using 3 sets of search terms to identify randomized clinical trials (RCTs) assessing anti-bullying interventions published from database inception through February 2020. A manual search of reference lists of articles included in previous systematic reviews and meta-analyses was also performed. Study selection The initial literature search yielded 34 798 studies. Included in the study were articles that (1) assessed bullying at school; (2) assessed the effectiveness of an anti-bullying program; (3) had an RCT design; (4) reported results; and (5) were published in English. Of 16 707 studies identified, 371 met the criteria for review of full-text articles; 77 RCTs were identified that reported data allowing calculation of effect sizes (ESs). Of these, 69 independent trials were included in the final meta-analysis database. Data extraction and synthesis Random-effects and meta-regression models were used to derive Cohen d values with pooled 95% CIs as estimates of ES and to test associations between moderator variables and ES estimates. Population impact number (PIN), defined as the number of children in the total population for whom 1 event may be prevented by an intervention, was used as an estimate of the population impact of universal interventions targeting all students, regardless of individual risk. Main outcomes and measures The main outcomes are the effectiveness (measured by ES) and the population impact (measured by the PIN) of anti-bullying interventions on the following 8 variable categories: overall bullying, bullying perpetration, bullying exposure, cyberbullying, attitudes that discourage bullying, attitudes that encourage bullying, mental health problems (eg, anxiety and depression), and school climate as well as the assessment of potential assocations between trial or intervention characteristics and outcomes. Results This study included 77 samples from 69 RCTs (111 659 participants [56 511 in the intervention group and 55 148 in the control group]). The weighted mean (range) age of participants in the intervention group was 11.1 (4-17) years and 10.8 (4-17) years in the control group. The weighted mean (range) proportion of female participants in the intervention group was 49.9% (0%-100%) and 50.5% (0%-100%) in the control group. Anti-bullying interventions were efficacious in reducing bullying (ES, -0.150; 95% CI, -0.191 to -0.109) and improving mental health problems (ES, -0.205; 95% CI, -0.277 to -0.133) at study end point, with PINs for universal interventions that target the total student population of 147 (95% CI, 113-213) and 107 (95% CI, 73-173), respectively. Duration of intervention was not statistically significantly associated with intervention effectiveness (mean [range] duration of interventions, 29.4 [1 to 144] weeks). The effectiveness of anti-bullying programs did not diminish over time during follow-up (mean [range] follow-up, 30.9 [2-104] weeks). Conclusions and relevance Despite the small ESs and some regional differences in effectiveness, the population impact of school anti-bullying interventions appeared to be substantial. Better designed trials that assess optimal intervention timing and duration are warranted.

Association Between Race and COVID-19 Outcomes Among 2.6 Million Children in England.

Abstract: Importance Although children mainly experience mild COVID-19 disease, hospitalization rates are increasing, with limited understanding of underlying factors. There is an established association between race and severe COVID-19 outcomes in adults in England; however, whether a similar association exists in children is unclear. Objective To investigate the association between race and childhood COVID-19 testing and hospital outcomes. Design, Setting, Participants In this cohort study, children (0-18 years of age) from participating family practices in England were identified in the QResearch database between January 24 and November 30, 2020. The QResearch database has individually linked patients with national SARS-CoV-2 testing, hospital admission, and mortality data. Exposures The main characteristic of interest is self-reported race. Other exposures were age, sex, deprivation level, geographic region, household size, and comorbidities (asthma; diabetes; and cardiac, neurologic, and hematologic conditions). Main Outcomes and Measures The primary outcome was hospital admission with confirmed COVID-19. Secondary outcomes were SARS-CoV-2–positive test result and any hospital attendance with confirmed COVID-19 and intensive care admission. Results Of 2 576 353 children (mean [SD] age, 9.23 [5.24] years; 48.8% female), 410 726 (15.9%) were tested for SARS-CoV-2 and 26 322 (6.4%) tested positive. A total of 1853 children (0.07%) with confirmed COVID-19 attended hospital, 343 (0.01%) were admitted to the hospital, and 73 (0.002%) required intensive care. Testing varied across race. White children had the highest proportion of SARS-CoV-2 tests (223 701/1 311 041 [17.1%]), whereas Asian children (33 213/243 545 [13.6%]), Black children (7727/93 620 [8.3%]), and children of mixed or other races (18 971/147 529 [12.9%]) had lower proportions. Compared with White children, Asian children were more likely to have COVID-19 hospital admissions (adjusted odds ratio [OR], 1.62; 95% CI, 1.12-2.36), whereas Black children (adjusted OR, 1.44; 95% CI, 0.90-2.31) and children of mixed or other races (adjusted OR, 1.40; 95% CI, 0.93-2.10) had comparable hospital admissions. Asian children were more likely to be admitted to intensive care (adjusted OR, 2.11; 95% CI, 1.07-4.14), and Black children (adjusted OR, 2.31; 95% CI, 1.08-4.94) and children of mixed or other races (adjusted OR, 2.14; 95% CI, 1.25-3.65) had longer hospital admissions (≥36 hours). Conclusions and Relevance In this large population-based study exploring the association between race and childhood COVID-19 testing and hospital outcomes, several race-specific disparities were observed in severe COVID-19 outcomes. However, ascertainment bias and residual confounding in this cohort study should be considered before drawing any further conclusions. Overall, findings of this study have important public health implications internationally.