https://www.novareader.co Default RSS Feed en-us Newgen KnowledgeWorks https://www.novareader.co/book/isbn/10.1001/jamapediatrics.2021.0525 This cross-sectional study assesses inquiries to a child distress hotline during the COVID-19 pandemic compared with inquiries during the same period the previous year.

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Question

Are there potential harms associated with oral corticosteroid bursts (defined as the use of oral corticosteroids for 14 or fewer days) in children?

Findings

In this nationwide population-based study of 1 064 587 children who received a single corticosteroid burst, a burst was associated with 1.4- to 2.2-fold increased risk of gastrointestinal bleeding, sepsis, and pneumonia within the first month after corticosteroid initiation.

Meaning

This study suggests that clinicians should be aware of potentially severe adverse events associated with corticosteroid bursts in children.

Importance

The adverse effects from the long-term use of oral corticosteroids are known, but, to our knowledge, few studies have reported the risk of corticosteroid bursts, particularly among children.

Objective

To quantify the associations of corticosteroid bursts with severe adverse events, including gastrointestinal (GI) bleeding, sepsis, pneumonia, and glaucoma, in children.

Design, Setting, and Participants

This study used data derived from the National Health Insurance Research Database in Taiwan from January 1, 2013, to December 31, 2017, on children younger than 18 years of age and used a self-controlled case series design. Data were analyzed from January 1 to July 30, 2020.

Exposure

Oral corticosteroid bursts (defined as oral corticosteroid use for ≤14 days).

Main Outcomes and Measures

Incidence rates were calculated of 4 severe adverse events (GI bleeding, sepsis, pneumonia, and glaucoma) in children who did or did not receive corticosteroid bursts. Conditional fixed-effect Poisson regression was used to estimate incidence rate ratios (IRRs) of severe adverse events within 5 to 30 days and 31 to 90 days after initiation of corticosteroid bursts.

Results

Among 4 542 623 children, 23% (1 064 587; 544 268 boys [51.1%]; mean [SD] age, 9.7 [5.8] years) were prescribed a single corticosteroid burst. The most common indications were acute respiratory tract infections and allergic diseases. The incidence rate differences per 1000 person-years between children administered a single corticosteroid burst and those not prescribed corticosteroids were 0.60 (95% CI, 0.55-0.64) for GI bleeding, 0.03 (95% CI, 0.02-0.05) for sepsis, 9.35 (95% CI, 9.19-9.51) for pneumonia, and 0.01 (95% CI, 0.01-0.03) for glaucoma. The IRRs within 5 to 30 days after initiating corticosteroid bursts were 1.41 (95% CI, 1.27-1.57) for GI bleeding, 2.02 (95% CI, 1.55-2.64) for sepsis, 2.19 (95% CI, 2.13-2.25) for pneumonia, and 0.98 (95% CI, 0.85-1.13) for glaucoma; the IRRs within the subsequent 31 to 90 days were 1.10 (95% CI, 1.02-1.19) for GI bleeding, 1.08 (95% CI, 0.88-1.32) for sepsis, 1.09 (95% CI, 1.07-1.11) for pneumonia, and 0.95 (95% CI, 0.85-1.06) for glaucoma.

Conclusions and Relevance

This study suggests that corticosteroid bursts, which are commonly prescribed for children with respiratory and allergic conditions, are associated with a 1.4- to 2.2-fold increased risk of GI bleeding, sepsis, and pneumonia within the first month after initiation of corticosteroid therapy that is attenuated during the subsequent 31 to 90 days.

This study examines the associations of corticosteroid bursts with severe adverse events, including gastrointestinal bleeding, sepsis, pneumonia, and glaucoma, in children.

]]> https://www.novareader.co/book/isbn/10.1001/jamapediatrics.2021.1050 This cohort study assesses the association between COVID-19 and maternal and neonatal outcomes in pregnant women with COVID-19 diagnosis compared with concomitantly enrolled pregnant women without COVID-19 diagnosis.

Question

To what extent does COVID-19 in pregnancy alter the risks of adverse maternal and neonatal outcomes compared with pregnant individuals without COVID-19?

Findings

In this multinational cohort study of 2130 pregnant women in 18 countries, women with COVID-19 diagnosis were at increased risk of a composite maternal morbidity and mortality index. Newborns of women with COVID-19 diagnosis had significantly higher severe neonatal morbidity index and severe perinatal morbidity and mortality index compared with newborns of women without COVID-19 diagnosis.

Meaning

This study indicates a consistent association between pregnant individuals with COVID-19 diagnosis and higher rates of adverse outcomes, including maternal mortality, preeclampsia, and preterm birth compared with pregnant individuals without COVID-19 diagnosis.

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.

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Question

Can the evidence-based treatment of infants with bronchiolitis be improved by using targeted interventions to deimplement low-value care?

Findings

In this international cluster randomized clinical trial of 26 hospitals and 3727 infants, an absolute risk difference favoring intervention hospitals was seen in compliance with 5 evidence-based recommendations in the treatment of infants with bronchiolitis.

Meaning

Use of targeted interventions improved the treatment of infants with bronchiolitis by deimplementing the use of ineffective and potentially harmful therapies and management; these results are important for bronchiolitis management, deimplementation science, and future interventions in acute care pediatrics.

This cluster randomized clinical trial uses data from 26 hospitals to investigate whether evidence-based treatment of infants with bronchiolitis can be improved by using targeted interventions to deimplement low-value care.

Importance

In developed countries, bronchiolitis is the most common reason for infants to be admitted to the hospital, and all international bronchiolitis guidelines recommend supportive care; however, significant variation in practice continues with infants receiving non–evidence-based therapies. Deimplementation research aims to reduce the use of low-value care, and advancing science in this area is critical to delivering evidence-based care.

Objective

To determine the effectiveness of targeted interventions vs passive dissemination of an evidence-based bronchiolitis guideline in improving treatment of infants with bronchiolitis.

Design, Setting, and Participants

This international, multicenter cluster randomized clinical trial included 26 hospitals (clusters) in Australia and New Zealand providing tertiary or secondary pediatric care (13 randomized to intervention, 13 to control) during the 2017 bronchiolitis season. Data were collected on 8003 infants for the 3 bronchiolitis seasons (2014-2016) before the implementation period and 3727 infants for the implementation period (2017 bronchiolitis season, May 1-November 30). Data were analyzed from November 16, 2018, to December 9, 2020.

Interventions

Interventions were developed using theories of behavior change to target key factors that influence bronchiolitis management. These interventions included site-based clinical leads, stakeholder meetings, a train-the-trainer workshop, targeted educational delivery, other educational and promotional materials, and audit and feedback.

Main Outcomes and Measures

The primary outcome was compliance during the first 24 hours of care with no use of chest radiography, albuterol, glucocorticoids, antibiotics, and epinephrine, measured retrospectively from medical records of randomly selected infants with bronchiolitis who presented to the hospital. There were no patient-level exclusions.

Results

A total of 26 hospitals were randomized without dropouts. Analysis was by intention to treat. Baseline data collected on 8003 infants for 3 bronchiolitis seasons (2014-2016) before the implementation period were similar between intervention and control hospitals. Implementation period data were collected on 3727 infants, including 2328 boys (62%) and 1399 girls (38%), with a mean (SD) age of 6.0 (3.2) months. A total of 459 (12%) were Māori (New Zealand), and 295 (8%) were Aboriginal/Torres Strait Islander (Australia). Compliance with recommendations was 85.1% (95% CI, 82.6%-89.7%) in intervention hospitals vs 73.0% (95% CI, 65.3%-78.8%) in control hospitals (adjusted risk difference, 14.1%; 95% CI, 6.5%-21.7%; P < .001).

Conclusions and Relevance

Targeted interventions led to improved treatment of infants with bronchiolitis. This study has important implications for bronchiolitis management and the development of effective interventions to deimplement low-value care.

Trial Registration

Australian and New Zealand Clinical Trials Registry: ACTRN12616001567415.

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Question

What is the prevalence of autism spectrum disorder (ASD) in the total English state school population, and what are the social determinants associated with ASD status?

Findings

In this ASD prevalence cohort study of 7 047 238 pupils, national English prevalence was 1.76%, with marked differences according to racial/ethnic group. The highest prevalence was found in Black pupils (2.11%) and the lowest in Roma/Irish Travelers (0.85%), with important variability across geographic areas.

Meaning

These results show differences in ASD prevalence estimates across racial/ethnic minority groups in England, which could be attributable to diagnostic biases, possible differences in detection and referral, or differential phenotypic prevalence for racial/ethnic minority groups.

This national cohort study evaluates whether socioeconomic disadvantage is associated with autism spectrum disorder prevalence and the likelihood of accessing autism services in racial/ethnic minority groups and disadvantaged groups among school pupils in England.

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 < .001) and 12.41% of indirect effects through this way.

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.

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Question

Is eviction during pregnancy associated with adverse birth outcomes, an important determinant of health across the life course?

Findings

In this case-control study of 88 862 births in Georgia, eviction during pregnancy, particularly during the second and third trimester, was associated with reductions in infants’ weight and gestational age at birth compared with maternal eviction at any other time.

Meaning

These findings suggest that housing, social, and medical assistance to pregnant women at risk for eviction might improve birth outcomes and health across the life course.

This case-control study assesses the association of eviction during pregnancy with birth outcomes among women in Georgia.

Importance

More than 2 million families face eviction annually, a number likely to increase due to the coronavirus disease 2019 pandemic. The association of eviction with newborns’ health remains to be examined.

Objective

To determine the association of eviction actions during pregnancy with birth outcomes.

Design

This case-control study compared birth outcomes of infants whose mothers were evicted during gestation with those whose mothers were evicted at other times. Participants included infants born to mothers who were evicted in Georgia from January 1, 2000, to December 31, 2016. Data were analyzed from March 1 to October 4, 2020.

Exposures

Eviction actions occurring during gestation.

Main Outcomes and Measures

Five metrics of neonatal health included birth weight (in grams), gestational age (in weeks), and dichotomized outcomes for low birth weight (LBW) (<2500 g), prematurity (gestational age <37.0 weeks), and infant death.

Results

A total of 88 862 births to 45 122 mothers (mean [SD] age, 26.26 [5.76] years) who experienced 99 517 evictions were identified during the study period, including 10 135 births to women who had an eviction action during pregnancy and 78 727 births to mothers who had experienced an eviction action when not pregnant. Compared with mothers who experienced eviction actions at other times, eviction during pregnancy was associated with lower infant birth weight (difference, −26.88 [95% CI, −39.53 to 14.24] g) and gestational age (difference, −0.09 [95% CI, −0.16 to −0.03] weeks), increased rates of LBW (0.88 [95% CI, 0.23-1.54] percentage points) and prematurity (1.14 [95% CI, 0.21-2.06] percentage points), and a nonsignificant increase in mortality (1.85 [95% CI, −0.19 to 3.89] per 1000 births). The association of eviction with birth weight was strongest in the second and third trimesters of pregnancy, with birth weight reductions of 34.74 (95% CI, −57.51 to −11.97) and 35.80 (95% CI, −52.91 to −18.69) g, respectively.

Conclusions and Relevance

These findings suggest that eviction actions during pregnancy are associated with adverse birth outcomes, which have been shown to have lifelong and multigenerational consequences. Ensuring housing, social, and medical assistance to pregnant women at risk for eviction may improve infant health.

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Question

Are specific phenotypes in preterm newborns associated with clinical, growth, and neurodevelopmental differences at age 2 years compared with term newborns?

Findings

In this cohort study of 6529 preterm and term newborns who were followed up from birth to age 2 years, 8 preterm-birth phenotypes were identified: no main maternal, fetal, or placental condition detected (35%); infections (21%); preeclampsia (12%); fetal distress (10%); intrauterine growth restriction (8%); severe maternal disease (6%); bleeding (5%); and congenital anomaly (4%). Each phenotype was associated with substantial differences in neonatal morbidity and infant outcomes.

Meaning

The study’s findings support the use of phenotypic classification for preterm births.

Importance

The etiologic complexities of preterm birth remain inadequately understood, which may impede the development of better preventative and treatment measures.

Objective

To examine the association between specific preterm-birth phenotypes and clinical, growth, and neurodevelopmental differences among preterm newborns compared with term newborns up to age 2 years.

Design, Setting, and Participants

The INTERBIO-21st study included a cohort of preterm and term newborn singletons enrolled between March 2012 and June 2018 from maternity hospitals in 6 countries worldwide who were followed up from birth to age 2 years. All pregnancies were dated by ultrasonography. Data were analyzed from November 2019 to October 2020.

Exposures/Interventions

Preterm-birth phenotypes.

Main Outcomes and Measures

Infant size, health, nutrition, and World Health Organization motor development milestones assessed at ages 1 and 2 years; neurodevelopment evaluated at age 2 years using the INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA) tool.

Results

A total of 6529 infants (3312 boys [50.7%]) were included in the analysis. Of those, 1381 were preterm births (mean [SD] gestational age at birth, 34.4 [0.1] weeks; 5148 were term births (mean [SD] gestational age at birth, 39.4 [0] weeks). Among 1381 preterm newborns, 8 phenotypes were identified: no main maternal, fetal, or placental condition detected (485 infants [35.1%]); infections (289 infants [20.9%]); preeclampsia (162 infants [11.7%]); fetal distress (131 infants [9.5%]); intrauterine growth restriction (110 infants [8.0%]); severe maternal disease (85 infants [6.2%]); bleeding (71 infants [5.1%]); and congenital anomaly (48 infants [3.5%]). For all phenotypes, a previous preterm birth was a risk factor for recurrence. Each phenotype displayed differences in neonatal morbidity and infant outcomes. For example, infants with the no main condition detected phenotype had low neonatal morbidity but increased morbidity and hospitalization incidence at age 1 year (odds ratio [OR], 2.2; 95% CI, 1.8-2.7). Compared with term newborns, the highest risk of scoring lower than the 10th centile of INTER-NDA normative values was observed in the fine motor development domain among newborns with the fetal distress (OR, 10.6; 95% CI, 5.1-22.2) phenotype.

Conclusions and Relevance

Results of this study suggest that phenotypic classification may provide a better understanding of the etiologic factors and mechanisms associated with preterm birth than continuing to consider it an exclusively time-based entity.

This cohort study, part of the INTERBIO-21st Newborn Study, an extension of the INTERGROWTH-21st Project, examines the association between preterm-birth phenotypes and clinical, growth, and neurodevelopmental differences among preterm newborns compared with term newborns up to age 2 years.

]]> https://www.novareader.co/book/isbn/10.1001/jamapediatrics.2020.6721 This cohort study analyzes reductions in obesity rates at age 37 years among individuals who participated in a multisystemic Child-Parent Center preschool program.

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Question

Are hypertensive disorders of pregnancy (HDP) associated with poorer neurodevelopmental outcomes in offspring independently of shared familial confounding factors?

Findings

In this cohort study, offspring of HDP-complicated pregnancies had a somewhat higher incidence of autism spectrum disorders (ASDs), attention-deficit/hyperactivity disorder (ADHD), and intellectual disability (ID) and slightly lower overall cognitive performance. Analyses comparing siblings had less statistical power and indicated associations of a similar magnitude with ASDs and possibly ADHD only.

Meaning

This study suggests that HDP are associated with modestly increased risks of ASDs and possibly ADHD in offspring, whereas associations with ID and cognitive performance are likely the result of confounding by shared familial characteristics.

Importance

Hypertensive disorders of pregnancy (HDP) have been associated with poorer neurodevelopmental outcomes in offspring, but the role of familial confounding in these associations is unclear.

Objective

To investigate associations of maternal HDP with risks in offspring of autism spectrum disorders (ASDs), attention-deficit/hyperactivity disorder (ADHD), and intellectual disability (ID), as well as variation in overall cognitive performance in offspring.

Design, Setting, and Participants

This Swedish register-based study used data from a birth cohort divided into 1 085 024 individuals born between 1987 and 1996 and followed up until December 31, 2014, and 285 901 men born between 1982 and 1992 who attended assessments for military conscription, including a cognitive function test. Statistical analysis was performed from April 1, 2019, to June 1, 2020.

Exposures

Diagnoses of HDP, which were provided by the Medical Birth Register.

Main Outcomes and Measures

Diagnoses of ASDs, ADHD, and ID were extracted from the National Patient Register. Cognitive function was assessed using written tests and summarized as a single 9-point score. Whole-cohort and within-sibship analyses were performed; the latter accounted for unmeasured familial confounding factors shared by siblings.

Results

The study included 1 085 024 individuals (556 912 male participants [51.3%]) born between 1987 and 1996 and 285 901 men born between 1982 and 1992 who attended assessments for military conscription. The prevalence of maternal HDP was 4.0% in the 1987-1996 birth cohort (n = 42 980) and 5.1% in the military conscription cohort (n = 14 515). A total of 15 858 participants received a diagnosis of ASD, 36 852 received a diagnosis of ADHD, and 8454 received a diagnosis of ID. The mean (SD) cognitive score among the men in the conscription cohort was 5.1 (1.9). In whole-cohort analyses with multivariable adjustment, HDP were associated with offspring ASDs (hazard ratio [HR], 1.22; 95% CI, 1.13-1.31), ADHD (HR, 1.10; 95% CI, 1.05-1.16), and ID (HR, 1.39; 95% CI, 1.27-1.53). Analyses comparing siblings discordant for HDP were less statistically powered but indicated estimates of similar magnitude for ASDs (HR, 1.19; 95% CI, 1.00-1.42) and possibly ADHD (HR, 1.09; 95% CI, 0.95-1.24), but not for ID (HR, 1.04; 95% CI, 0.83-1.29). Hypertensive disorders of pregnancy were associated with somewhat lower cognitive scores in whole-cohort analysis (mean difference comparing offspring exposed with those unexposed, −0.10; 95% CI, −0.13 to −0.07), but in within-sibship analysis, the association was null (mean difference, 0.00; 95% CI, −0.09 to 0.08).

Conclusions and Relevance

The study results suggest that HDP are associated with small increased risks of ASDs and possibly ADHD in offspring, whereas associations with ID and cognitive performance are likely confounded by shared familial (environmental or genetic) factors.

This cohort study investigates associations of maternal hypertensive disorders of pregnancy with risks in offspring of autism spectrum disorders, attention-deficit/hyperactivity disorder, and intellectual disability, as well as variation in overall cognitive performance in offspring.

]]> https://www.novareader.co/book/isbn/10.1001/jamapediatrics.2021.0001

Question

What is the rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and the seroprevalence of SARS-CoV-2 antibodies in children aged 1 to 10 years and a corresponding parent in a population-based sample in southwest Germany?

Findings

This large-scale, multicenter, cross-sectional investigation of 4964 participants accurately determined anti–SARS-CoV-2 seropositivity by combining the results of enzyme-linked immunosorbent assay and immunofluorescence tests. The estimated SARS-CoV-2 seroprevalence was low in parents (1.8%) and 3-fold lower in children (0.6%).

Meaning

The low seroprevalence of SARS-CoV-2 antibodies in young children in this study may indicate that they do not play a key role in SARS-CoV-2 spreading during the current pandemic.

This cross-sectional investigation conducted in southwest Germany describes the rate of severe acute respiratory syndrome coronavirus 2 infections and the seroprevalence of antibodies in children aged 1 to 10 years, compared with a parent of each child, in a population-based sample.

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 BaWü 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.

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Question

Can screening for adverse childhood experiences (ACEs) accurately predict individual risk for later health problems?

Findings

In 2 population-based birth cohorts (with a total of 2927 individuals) growing up 20 years and 20 000 km apart, ACE scores were associated with mean group differences in health problems independent of other information available to clinicians. However, ACE scores had low accuracy in predicting health problems at the individual level.

Meaning

ACE scores can forecast mean group differences in later health problems; however, ACE scores have poor accuracy in identifying individuals at high risk for future health problems.

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, 1.14 [95% CI, 1.10-1.18] per each additional ACE; any physical health problem: relative risk, 1.09 [95% CI, 1.07-1.12] 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, 0.58 [95% CI, 0.56-0.61]; any physical health problem: area under the receiver operating characteristic curve, 0.60 [95% CI, 0.58-0.63]; chance prediction: area under the receiver operating characteristic curve, 0.50). 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.

This cohort study uses data from 2 birth cohorts to test the predictive accuracy of adverse childhood experience screening for later health problems.

]]> https://www.novareader.co/book/isbn/10.1001/jamapediatrics.2020.5441 This cohort study assesses the sensitivity of dried blood spots polymerase chain reaction for newborn screening for congenital cytomegalovirus infection using saliva as the reference standard for screening, followed by collection of a urine sample for confirmation of congenital infection

Question

What is the sensitivity of polymerase chain reaction testing for congenital cytomegalovirus deployed on dried blood spots obtained for universal newborn screening using current best methods?

Findings

This cohort study of 12 554 newborns screened in a multisite study in Minnesota included 56 (4.5 per 1000) with confirmed congenital cytomegalovirus infection. The sensitivity of dried blood spots polymerase chain reaction testing was 85.7% with results of 2 laboratory results combined, which is substantially higher than reported in past studies.

Meaning

The relatively high sensitivity of dried blood spots in the interim analysis of this study suggests their potential usefulness for universal cytomegalovirus screening as DNA extraction and polymerase chain reaction methodologies continue to improve.

Importance

The sensitivity of dried blood spots (DBS) to identify newborns with congenital cytomegalovirus (cCMV) infection has not been evaluated in screening studies using the current, higher-sensitivity methods for DBS processing.

Objective

To assess the sensitivity of DBS polymerase chain reaction (PCR) for newborn screening for cCMV infection using saliva as the reference standard for screening, followed by collection of a urine sample for confirmation of congenital infection.

Design, Setting, and Participants

This population-based cohort study took place at 5 newborn nurseries and 3 neonatal intensive care units in the Minneapolis/Saint Paul area in Minnesota from April 2016 to June 2019. Newborns enrolled with parental consent were screened for cCMV using DBS obtained for routine newborn screening and saliva collected 1 to 2 days after birth. Dried blood spots were tested for CMV DNA by PCR at both the University of Minnesota (UMN) and the US Centers for Disease Control and Prevention (CDC). Saliva swabs were tested by CMV DNA PCR at the UMN laboratory only. Newborns who screened positive by saliva or DBS had a diagnostic urine sample obtained by primary care professionals, tested by PCR within 3 weeks of birth. Analysis began July 2019.

Exposures

Detection of CMV from a saliva swab using a PCR assay.

Main Outcomes and Measures

Number of children with urine-confirmed cCMV and the proportion of them who were CMV positive through DBS screening.

Results

Of 12 554 individuals enrolled through June 2019 (of 25 000 projected enrollment), 56 newborns were confirmed to have cCMV (4.5 per 1000 [95% CI, 3.3-5.7]). Combined DBS results from either UMN or CDC had a sensitivity of 85.7% (48 of 56; 95% CI, 74.3%-92.6%), specificity of 100.0% (95% CI, 100.0%-100.0%), positive predictive value (PPV) of 98.0% (95% CI, 89.3%-99.6%), and negative predictive value (NPV) of 99.9% (95% CI, 99.9%-100.0%). Dried blood spot results from UMN had a sensitivity of 73.2% (95% CI, 60.4%-83.0%), specificity of 100.0% (100.0%-100.0%), PPV of 100.0% (95% CI, 91.4%-100.0%), and NPV of 99.9% (95% CI, 99.8%-99.9%). Dried blood spot results from CDC had a sensitivity of 76.8% (95% CI, 64.2%-85.9%), specificity of 100.0% (95% CI, 100.0%-100.0%), PPV of 97.7% (95% CI, 88.2%-99.6%), and NPV of 99.9% (95% CI, 99.8%-99.9%). Saliva swab results had a sensitivity of 92.9% (52 of 56; 95% CI, 83.0%-97.2%), specificity of 99.9% (95% CI, 99.9%-100.0%), PPV of 86.7% (95% CI, 75.8%-93.1%), and NPV of 100.0% (95% CI, 99.9%-100.0%).

Conclusions and Relevance

This study demonstrates relatively high analytical sensitivity for DBS compared with previous studies that performed population-based screening. As more sensitive DNA extraction and PCR methods continue to emerge, DBS-based testing should remain under investigation as a potential low-cost, high-throughput option for cCMV screening.

]]> https://www.novareader.co/book/isbn/10.1001/jamapediatrics.2020.5653

Question

Does enteral fatty acid supplementation with arachidonic acid (AA) and docosahexaenoic acid (DHA) from birth to 40 weeks’ postmenstrual age reduce severe retinopathy of prematurity (ROP) in extremely preterm infants?

Findings

This randomized clinical trial found that enteral AA and DHA supplementation lowered the risk of severe ROP by 50%. In addition, the group that received enteral AA and DHA supplementation showed higher serum levels of both AA and DHA compared with controls.

Meaning

Supplementing the diet of the most immature infants born at less than 27 weeks’ gestational age with an enteral lipid solution with AA:DHA had no significant adverse effects and seems to be a promising intervention to prevent sight-threatening ROP and thereby reduce visual impartment and blindness.

Importance

Lack of arachidonic acid (AA) and docosahexaenoic acid (DHA) after extremely preterm birth may contribute to preterm morbidity, including retinopathy of prematurity (ROP).

Objective

To determine whether enteral supplementation with fatty acids from birth to 40 weeks’ postmenstrual age reduces ROP in extremely preterm infants.

Design, Setting, and Participants

The Mega Donna Mega trial, a randomized clinical trial, was a multicenter study performed at 3 university hospitals in Sweden from December 15, 2016, to December 15, 2019. The screening pediatric ophthalmologists were masked to patient groupings. A total of 209 infants born at less than 28 weeks’ gestation were tested for eligibility, and 206 infants were included. Efficacy analyses were performed on as-randomized groups on the intention-to-treat population and on the per-protocol population using as-treated groups. Statistical analyses were performed from February to April 2020.

Interventions

Infants received either supplementation with an enteral oil providing AA (100 mg/kg/d) and DHA (50 mg/kg/d) (AA:DHA group) or no supplementation within 3 days after birth until 40 weeks’ postmenstrual age.

Main Outcomes and Measures

The primary outcome was severe ROP (stage 3 and/or type 1). The secondary outcomes were AA and DHA serum levels and rates of other complications of preterm birth.

Results

A total of 101 infants (58 boys [57.4%]; mean [SD] gestational age, 25.5 [1.5] weeks) were included in the AA:DHA group, and 105 infants (59 boys [56.2%]; mean [SD] gestational age, 25.5 [1.4] weeks) were included in the control group. Treatment with AA and DHA reduced severe ROP compared with the standard of care (16 of 101 [15.8%] in the AA:DHA group vs 35 of 105 [33.3%] in the control group; adjusted relative risk, 0.50 [95% CI, 0.28-0.91]; P = .02). The AA:DHA group had significantly higher fractions of AA and DHA in serum phospholipids compared with controls (overall mean difference in AA:DHA group, 0.82 mol% [95% CI, 0.46-1.18 mol%]; P < .001; overall mean difference in control group, 0.13 mol% [95% CI, 0.01-0.24 mol%]; P = .03). There were no significant differences between the AA:DHA group and the control group in the rates of bronchopulmonary dysplasia (48 of 101 [47.5%] vs 48 of 105 [45.7%]) and of any grade of intraventricular hemorrhage (43 of 101 [42.6%] vs 42 of 105 [40.0%]). In the AA:DHA group and control group, respectively, sepsis occurred in 42 of 101 infants (41.6%) and 53 of 105 infants (50.5%), serious adverse events occurred in 26 of 101 infants (25.7%) and 26 of 105 infants (24.8%), and 16 of 101 infants (15.8%) and 13 of 106 infants (12.3%) died.

Conclusions and Relevance

This study found that, compared with standard of care, enteral AA:DHA supplementation lowered the risk of severe ROP by 50% and showed overall higher serum levels of both AA and DHA. Enteral lipid supplementation with AA:DHA is a novel preventive strategy to decrease severe ROP in extremely preterm infants.

Trial Registration

ClinicalTrials.gov Identifier: NCT03201588

This randomized clinical trial examines whether enteral supplementation with arachidonic acid and docosahexaenoic acid from birth to 40 weeks’ postmenstrual age reduces retinopathy of prematurity in extremely preterm infants.

]]> https://www.novareader.co/book/isbn/10.1001/jamapediatrics.2020.5227 This study assesses a 2-gene RNA signature that can be translated into a rapid (<25 minutes) and portable laboratory-on-a-chip platform suitable for development as a point-of-care test.

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Question

How common is opioid use in the early decades of life, and which childhood risk factors are associated with opioid use in young adulthood?

Findings

This cohort study assessed opioid use among 1252 non-Hispanic White individuals and American Indian individuals in rural counties in the central Appalachia region of North Carolina from January 1993 to December 2015. By age 30 years, approximately one-quarter of participants had used opioids, and the findings revealed that childhood tobacco use and depression were associated with later nonheroin opioid use in general, weekly nonheroin opioid use, and heroin use.

Meaning

Childhood tobacco use and depression may be associated with impaired reward system functioning, which may increase young adults’ vulnerability to opioid-associated euphoria.

This cohort study documents age-related changes in opioid use and analyzes childhood antecedents of opioid use among non-Hispanic White individuals and American Indian individuals.

Importance

Opioid use disorder and opioid deaths have increased dramatically in young adults in the US, but the age-related course or precursors to opioid use among young people are not fully understood.

Objective

To document age-related changes in opioid use and study the childhood antecedents of opioid use by age 30 years in 6 domains of childhood risk: sociodemographic characteristics; school or peer problems; parental mental illness, drug problems, or legal involvement; substance use; psychiatric illness; and physical health.

Design, Setting, and Participants

This community-representative prospective longitudinal cohort study assessed 1252 non-Hispanic White individuals and American Indian individuals in rural counties in the central Appalachia region of North Carolina from January 1993 to December 2015. Data were analyzed from January 2019 to January 2020.

Exposures

Between ages 9 and 16 years, participants and their parents were interviewed up to 7 times using the Child and Adolescent Psychiatric Assessment and reported risk factors in 6 risk domains.

Main Outcomes and Measures

Participants were assessed again at ages 19, 21, 25, and 30 years for nonheroin opioid use (any and weekly) and heroin use using the structured Young Adult Psychiatric Assessment.

Results

Of 1252 participants, 342 (27%) were American Indian. By age 30 years, 322 participants had used a nonheroin opioid (24.2%; 95% CI, 21.8-26.5), 155 had used a nonheroin opioid weekly (8.8%; 95% CI, 7.2-10.3), and 95 had used heroin (6.6%; 95% CI, 5.2-7.9). Childhood risk markers for later opioid use included male sex, tobacco use, depression, conduct disorder, cannabis use, having peers exhibiting social deviance, parents with legal involvement, and elevated systemic inflammation. In final models, childhood tobacco use, depression, and cannabis use were most robustly associated with opioid use in young adulthood (ages 19 to 30 years). Chronic depression and dysthymia were strongly associated with any nonheroin opioid use (OR. 5.43; 95% CI, 2.35-12.55 and OR, 7.13; 95% CI, 1.99-25.60, respectively) and with weekly nonheroin opioid use (OR, 8.89; 95% CI, 3.61-21.93 and OR, 11.51; 95% CI, 3.05-42.72, respectively). Among young adults with opioid use, those with heroin use had the highest rates of childhood psychiatric disorders and comorbidities.

Conclusions and Relevance

Childhood tobacco use and chronic depression may be associated with impaired reward system functioning, which may increase young adults’ vulnerability to opioid-associated euphoria. Preventing and treating early substance use and childhood mental illness may help prevent later opioid use.

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