Maternal hemoglobin and iron status in early pregnancy and childhood cardiac outcomes.

BACKGROUND & AIMS: Dysregulation of iron homeostasis is associated with cardiac alterations in a sex-dependent manner in adults. It is unknown whether iron status during pregnancy has long-term impact on cardiovascular health, and if this association is influenced by sex. Therefore, this study aimed to evaluate sex-specific association between maternal iron status during early pregnancy and cardiac outcomes in children aged 10 years. METHODS: In a population-based cohort study among 1972 mother-child pairs, hemoglobin and ferritin were measured in early pregnancy (<18 weeks) and categorized into anemia (hemoglobin<11 g/dL), elevated hemoglobin (hemoglobin≥13.2 g/dL), iron deficiency (ferritin<15 µg/L), and iron overload (ferritin>150 µg/L). At 10 years of age, cardiac MRI was performed to measure right and left cardiac outcomes of function (ventricular end-diastolic volume (RVEDV and LVEDV) and ejection fraction (RVEF and LVEF)), and structure (left ventricular mass (LVM), and left ventricular mass-to-volume ratio (LMVR)). Results are presented for boys and girls separately and models were adjusted for confounders and multiple testing. RESULTS: In boys, one standard deviation score (SDS) increase in maternal hemoglobin was associated with lower RVEDV and LVEDV (difference (95%CI) -0.10 (-0.17, -0.03) SDS and -0.09 (-0.16, -0.03) SDS, respectively). In boys, maternal anemia, as compared to normal hemoglobin levels, was associated with higher LVEDV (difference 0.34 (0.10, 0.59) SDS). No associations were observed for other cardiac outcomes and for ferritin in boys. No associations were observed in girls. CONCLUSION: In boys, dysregulated iron status during early pregnancy might permanently alter cardiovascular RVEDV and LVEDV function. Underlying mechanisms need further study.

Green spaces and respiratory, cardiometabolic, and neurodevelopmental outcomes: An individual-participant data meta-analysis of >35.000 European children.

Studies evaluating the benefits and risks of green spaces on children's health are scarce. The present study aimed to examine the associations between exposure to green spaces during pregnancy and early childhood with respiratory, cardiometabolic, and neurodevelopmental outcomes in school-age children. We performed an Individual-Participant Data (IPD) meta-analysis involving 35,000 children from ten European birth cohorts across eight countries. For each participant, we calculated residential Normalized Difference Vegetation Index (NDVI) within a 300 m buffer and the linear distance to green spaces (meters) during prenatal life and childhood. Multiple harmonized health outcomes were selected: asthma and wheezing, lung function, body mass index, diastolic and systolic blood pressure, non-verbal intelligence, internalizing and externalizing problems, and ADHD symptoms. We conducted a two-stage IPD meta-analysis and evaluated effect modification by socioeconomic status (SES) and sex. Between-study heterogeneity was assessed via random-effects meta-regression. Residential surrounding green spaces in childhood, not pregnancy, was associated with improved lung function, particularly higher FEV1 (ß = 0.06; 95 %CI: 0.03, 0.09 I2 = 4.03 %, p < 0.001) and FVC (ß = 0.07; 95 %CI: 0.04, 0.09 I2 = 0 %, p < 0.001) with a stronger association observed in females (p < 0.001). This association remained robust after multiple testing correction and did not change notably after adjusting for ambient air pollution. Increased distance to green spaces showed an association with lower FVC (ß = -0.04; 95 %CI: -0.07, -0.02, I2 = 4.8, p = 0.001), with a stronger effect in children from higher SES backgrounds (p < 0.001). No consistent associations were found between green spaces and asthma, wheezing, cardiometabolic, or neurodevelopmental outcomes, with direction of effect varying across cohorts. Wheezing and neurodevelopmental outcomes showed high between-study heterogeneity, and the age at outcome assessment was only associated with heterogeneity in internalizing problems.. This large European meta-analysis suggests that childhood exposure to green spaces may lead to better lung function. Associations with other respiratory outcomes and selected cardiometabolic and neurodevelopmental outcomes remain inconclusive.

Age-specific SARS-CoV-2 transmission differed from human rhinovirus in households during the early COVID-19 pandemic.

OBJECTIVES: Children are generally considered main drivers of transmission for respiratory viruses, but the emergence of SARS-CoV-2 challenged this paradigm. Human rhinovirus (RV) continued to co-circulate throughout the pandemic, allowing for direct comparison of age-specific infectivity and susceptibility within households between these viruses during a time of low SARS-CoV-2 population immunity. METHODS: Households with children were prospectively monitored for ≥23 weeks between August 2020 and July 2021. Upon onset of respiratory symptoms in a household, an outbreak study was initiated, including questionnaires and repeated nasal self-sampling in all household members. Swabs were tested by PCR. Age-stratified within-household secondary attack rates (SARs) were compared between SARS-CoV-2 and RV. RESULTS: A total of 307 households participated, including 582 children and 627 adults. Overall, SAR was lower for SARS-CoV-2 than for RV (aOR 0.55) and age distributions differed between both viruses (p < 0.001). Following household exposure, children were significantly less likely to become infected with SARS-CoV-2 compared to RV (aOR 0.16), whereas this was opposite in adults (aOR 1.71). CONCLUSION: In households, age-specific susceptibility to SARS-CoV-2 and RV differs and drives differences in household transmission between these pathogens. This highlights the importance of characterizing age-specific transmission risks, particularly for emerging infections, to guide appropriate infection control interventions.

Early family socioeconomic status and asthma-related outcomes in school-aged children: Results from seven birth cohort studies.

OBJECTIVE: To examine the associations between maternal education and household income during early childhood with asthma-related outcomes in children aged 9-12 years in the UK, the Netherlands, Sweden, Australia, the USA and Canada. METHODS: Data on 31 210 children were obtained from 7 prospective birth cohort studies across six countries. Asthma-related outcomes included ever asthma, wheezing/asthma attacks and medication control for asthma. Relative social inequalities were estimated using pooled risk ratios (RRs) adjusted for potential confounders (child age, sex, mother ethnic background and maternal age) for maternal education and household income. The Slope Index of Inequality (SII) was calculated for each cohort to evaluate absolute social inequalities. RESULTS: Ever asthma prevalence ranged from 8.3% (Netherlands) to 29.1% (Australia). Wheezing/asthma attacks prevalence ranged from 3.9% (Quebec) to 16.8% (USA). Pooled RRs for low (vs high) maternal education and low (vs high) household income were: ever asthma (education 1.24, 95% CI 1.13 to 1.37; income 1.28, 95% CI 1.15 to 1.43), wheezing/asthma attacks (education 1.14, 95% CI 0.97 to 1.35; income 1.22, 95% CI 1.03 to 1.44) and asthma with medication control (education 1.16, 95% CI 0.97 to 1.40; income 1.25, 95% CI 1.01 to 1.55). SIIs supported the lower risk for children with more highly educated mothers and those from higher-income households in most cohorts, with few exceptions. CONCLUSIONS: Social inequalities by household income on the risk of ever asthma, wheezing/asthma attacks, and medication control for asthma were evident; the associations were attenuated for maternal education. These findings support the need for prevention policies to address the relatively high risks of respiratory morbidity in children in families with low socioeconomic status.

Early-life stress and the gut microbiome: A comprehensive population-based investigation.

Early-life stress (ELS) has been robustly associated with a range of poor mental and physical health outcomes. Recent studies implicate the gut microbiome in stress-related mental, cardio-metabolic and immune health problems, but research on humans is scarce and thus far often based on small, selected samples, often using retrospective reports of ELS. We examined associations between ELS and the human gut microbiome in a large, population-based study of children. ELS was measured prospectively from birth to 10 years of age in 2,004 children from the Generation R Study. We studied overall ELS, as well as unique effects of five different ELS domains, including life events, contextual risk, parental risk, interpersonal risk, and direct victimization. Stool microbiome was assessed using 16S rRNA sequencing at age 10 years and data were analyzed at multiple levels (i.e. α- and ß-diversity indices, individual genera and predicted functional pathways). In addition, we explored potential mediators of ELS-microbiome associations, including diet at age 8 and body mass index at 10 years. While no associations were observed between overall ELS (composite score of five domains) and the microbiome after multiple testing correction, contextual risk - a specific ELS domain related to socio-economic stress, including risk factors such as financial difficulties and low maternal education - was significantly associated with microbiome variability. This ELS domain was associated with lower α-diversity, with ß-diversity, and with predicted functional pathways involved, amongst others, in tryptophan biosynthesis. These associations were in part mediated by overall diet quality, a pro-inflammatory diet, fiber intake, and body mass index (BMI). These results suggest that stress related to socio-economic adversity - but not overall early life stress - is associated with a less diverse microbiome in the general population, and that this association may in part be explained by poorer diet and higher BMI. Future research is needed to test causality and to establish whether modifiable factors such as diet could be used to mitigate the negative effects of socio-economic adversity on the microbiome and related health consequences.

Body composition and respiratory outcomes in children: a population-based prospective cohort study.

BACKGROUND: Body composition might influence lung function and asthma in children, but its longitudinal relations are unclear. We aimed to identify critical periods for body composition changes during childhood and adolescence in relation to respiratory outcomes in adolescents. METHODS: In a population-based prospective cohort study, we measured body mass index, fat mass index (FMI), lean mass index (LMI) and the ratio of android fat mass divided by gynoid fat mass (A/G ratio) by dual-energy X-ray absorptiometry at 6, 10 and 13 years. At 13 years, lung function was measured by spirometry, and current asthma was assessed by questionnaire. RESULTS: Most prominently and consistently, higher FMI and A/G ratio at age 13 years were associated with lower forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) and forced expiratory flow after exhaling 75% of FVC (FEF75) (range Z-score difference -0.13 (95% CI -0.16 to -0.10) to -0.08 (95% CI -0.11 to -0.05) per SD score increase), and higher LMI at all ages was associated with higher FEF75 (range Z-score difference 0.05 (95% CI 0.01 to 0.08) to 0.09 (95% CI 0.06 to 0.13)). Between the ages of 6 and 13 years, normal to high FMI and A/G ratio were associated with lower FEV1/FVC and FEF75 (range Z-score difference -0.20 (95% CI -0.30 to -0.10) to -0.17 (95% CI -0.28 to -0.06)) and high to high LMI with higher FEF75 (range Z-score difference0.32 (95% CI 0.23 to 0.41)). Body composition changes were not associated with asthma. CONCLUSION: Adolescents with higher total and abdominal fat indices may have impaired lung function, while those with a higher lean mass during childhood and adolescence may have better small airway function. Public health measures should focus on a healthy body composition in adolescents to minimise respiratory morbidity.

Estimation of introduction and transmission rates of SARS-CoV-2 in a prospective household study.

Household studies provide an efficient means to study transmission of infectious diseases, enabling estimation of susceptibility and infectivity by person-type. A main inclusion criterion in such studies is usually the presence of an infected person. This precludes estimation of the hazards of pathogen introduction into the household. Here we estimate age- and time-dependent household introduction hazards together with within household transmission rates using data from a prospective household-based study in the Netherlands. A total of 307 households containing 1,209 persons were included from August 2020 until March 2021. Follow-up of households took place between August 2020 and August 2021 with maximal follow-up per household mostly limited to 161 days. Almost 1 out of 5 households (59/307) had evidence of an introduction of SARS-CoV-2. We estimate introduction hazards and within-household transmission rates in our study population with penalized splines and stochastic epidemic models, respectively. The estimated hazard of introduction of SARS-CoV-2 in the households was lower for children (0-12 years) than for adults (relative hazard: 0.62; 95%CrI: 0.34-1.0). Estimated introduction hazards peaked in mid October 2020, mid December 2020, and mid April 2021, preceding peaks in hospital admissions by 1-2 weeks. Best fitting transmission models included increased infectivity of children relative to adults and adolescents, such that the estimated child-to-child transmission probability (0.62; 95%CrI: 0.40-0.81) was considerably higher than the adult-to-adult transmission probability (0.12; 95%CrI: 0.057-0.19). Scenario analyses indicate that vaccination of adults can strongly reduce household infection attack rates and that adding adolescent vaccination offers limited added benefit.

Urban environment during pregnancy and lung function, wheezing, and asthma in school-age children. The generation R study.

The urban environment during pregnancy may influence child's respiratory health, but scarce evidence exists on systematic evaluation of multiple urban exposures (e.g., air pollution, natural spaces, noise, built environment) on children's lung function, wheezing, and asthma development. We aimed to examine the association of the urban environment during pregnancy with lung function, preschool wheezing, and school-age asthma. We included 5624 mother-child pairs participating in a population-based prospective birth cohort. We estimated 30 urban environmental exposures including air pollution, road traffic noise, traffic, green spaces, blue spaces, and built environment during pregnancy. At 10 years of age, lung function was measured by spirometry. Information on preschool wheezing and physician-diagnosed school-age asthma was obtained from multiple questionnaires. We described single-exposure associations with respiratory outcomes using an exposome-wide association study. We also identified patterns of urban exposures with hierarchical clustering on principal components analysis and examined their associations with respiratory outcomes using multivariate regression models. Single-exposure analyses showed associations of higher particulate matter (PM) with lower mid-expiratory flow (FEF25-75%) (e.g., for PM < 2.5 µm of diameter [PM2.5] z-score = -0.06 [-0.09, -0.03]) and higher forced expiratory volume in 1s (FEV1) and forced vital capacity (FVC) (e.g., for PM2.5 FEV1 0.05 [0.02, 0.08]) after correction for multiple-hypothesis testing. Cluster analysis described three patterns of urban exposures during pregnancy and showed that the cluster characterised by higher levels of air pollution, noise, walkability, street connectivity, and lower levels of natural spaces were associated with lower FEF25-75% (-0.08 [-0.17, 0.00]), and higher odds of preschool wheezing (1.21 [1.03, 1.43]). This study shows that the characteristics of the urban environment during pregnancy are of relevance to the offspring's respiratory health during childhood.

Maternal hemoglobin and iron status in early pregnancy and risk of respiratory tract infections in childhood: A population-based prospective cohort study.

BACKGROUND: Maternal hemoglobin and iron status measures during pregnancy might affect the developing fetal respiratory system leading to adverse respiratory conditions. Our aim was to assess the associations of maternal hemoglobin and iron status measures during pregnancy with the risk of respiratory tract infections in children until 10 years of age. METHODS: In a population-based cohort study among 5134 mother-child pairs, maternal hemoglobin and iron status including ferritin, transferrin, and transferrin saturation were measured during early pregnancy. In children, physician-attended respiratory tract infections from age 6 months until 10 years were assessed by questionnaires. Confounder-adjusted generalized estimating equation modeling was applied. RESULTS: After taking multiple testing into account, high maternal ferritin concentrations and low maternal transferrin saturation during pregnancy were associated with an overall increased risk of upper, not lower, respiratory tract infections until age 10 years of the child [OR (95% CI: 1.23 (1.10, 1.38) and 1.28 (1.12, 1.47), respectively)]. High maternal transferrin saturation during pregnancy was associated with a decreased and increased risk of upper respiratory tract infections at 1 and 6 years, respectively, [OR (95% CI: 0.60 (0.44, 0.83) and 1.54 (1.17, 2.02))]. Observed associations were suggested to be U-shaped (p-values for non-linearity ≤.001). Maternal hemoglobin and iron status measures during pregnancy were not consistently associated with child's gastroenteritis and urinary tract infections, as proxies for general infection effects. CONCLUSION: High maternal ferritin and low transferrin saturation concentrations during early pregnancy were most consistently associated with an overall increased risk of child's upper, not lower, respiratory tract infections.

Estimation of introduction and transmission rates of SARS-CoV-2 in a prospective household study.

Household studies provide an efficient means to study transmission of infectious diseases, enabling estimation of individual susceptibility and infectivity. A main inclusion criterion in such studies is often the presence of an infected person. This precludes estimation of the hazards of pathogen introduction into the household. Here we use data from a prospective household-based study to estimate SARS-CoV-2 age- and time-dependent household introduction hazards together with within household transmission rates in the Netherlands from August 2020 to August 2021. Introduction hazards and within-household transmission rates are estimated with penalized splines and stochastic epidemic models, respectively. The estimated hazard of introduction of SARS-CoV-2 in the households was lower for children (0-12 years) than for adults (relative hazard: 0.62; 95%CrI: 0.34-1.0). Estimated introduction hazards peaked in mid October 2020, mid December 2020, and mid April 2021, preceding peaks in hospital admissions by 1-2 weeks. The best fitting transmission models include increased infectivity of children relative to adults and adolescents, such that the estimated child-to-child transmission probability (0.62; 95%CrI: 0.40-0.81) was considerably higher than the adult-to-adult transmission probability (0.12; 95%CrI: 0.057-0.19). Scenario analyses show that vaccination of adults could have strongly reduced infection attack rates in households and that adding adolescent vaccination would have offered limited added benefit.

Bisphenol and phthalate exposure during pregnancy and the development of childhood lung function and asthma. The Generation R Study.

BACKGROUND: Fetal exposure to bisphenols and phthalates may lead to alterations in the respiratory and immune system development in children, and to adverse respiratory health. AIM: To study the associations of fetal bisphenols and phthalates exposure with lung function and asthma at age 13 years. STUDY DESIGN AND METHODS: This study among 1020 children was embedded in a population-based prospective cohort study. We measured maternal urine bisphenol and phthalate concentrations in the first, second and third trimester of pregnancy, and lung function by spirometry and asthma by questionnaires at age 13 years. Multivariable linear and logistic regression models were applied. RESULTS: Maternal urine bisphenol and phthalate concentrations averaged during pregnancy were not associated with childhood lung function or asthma. Associations of maternal urine bisphenol and phthalate concentrations in specific trimesters with respiratory outcomes showed that one interquartile range increase in the natural log-transformed maternal urine mono-isobutyl phthalate concentration in the second trimester was associated with a higher FEV1/FVC, but not with asthma, accounting for confounders and multiple-testing correction. Although there were associations of higher second trimester bisphenol S with a lower FVC and FEV1 in boys and girls, and of higher first trimester bisphenol S with a decreased risk of asthma in boys and an increased risk of asthma in girls, these results did not remain significant after correction for multiple testing. Results were not modified by maternal history of asthma or atopy. CONCLUSIONS: Maternal urine bisphenol and phthalate concentrations averaged or in specific trimesters during pregnancy were not strongly associated with childhood lung function and asthma at age 13 years. BPS, as a BPA substitute, tended to be associated with impaired lung function and altered risk of asthma, partly sex-dependent, but its strength was limited by a relatively low detection rate and should be queried in contemporary cohorts.

Key recommendations for primary care from the 2022 Global Initiative for Asthma (GINA) update.

The Global Initiative for Asthma (GINA) was established in 1993 by the World Health Organization and the US National Heart Lung and Blood Institute to improve asthma awareness, prevention and management worldwide. GINA develops and publishes evidence-based, annually updated resources for clinicians. GINA guidance is adopted by national asthma guidelines in many countries, adapted to fit local healthcare systems, practices, and resource availability. GINA is independent of industry, funded by the sale and licensing of its materials. This review summarizes key practical guidance for primary care from the 2022 GINA strategy report. It provides guidance on confirming the diagnosis of asthma using spirometry or peak expiratory flow. GINA recommends that all adults, adolescents and most children with asthma should receive inhaled corticosteroid (ICS)-containing therapy to reduce the risk of severe exacerbations, either taken regularly, or (for adults and adolescents with "mild" asthma) as combination ICS-formoterol taken as needed for symptom relief. For patients with moderate-severe asthma, the preferred regimen is maintenance-and-reliever therapy (MART) with ICS-formoterol. Asthma treatment is not "one size fits all"; GINA recommends individualized assessment, adjustment, and review of treatment. As many patients with difficult-to-treat or severe asthma are not referred early for specialist review, we provide updated guidance for primary care on diagnosis, further investigation, optimization and treatment of severe asthma across secondary and tertiary care. While the GINA strategy has global relevance, we recognize that there are special considerations for its adoption in low- and middle-income countries, particularly the current poor access to inhaled medications.

Maternal iron status in early pregnancy and childhood body fat measures and cardiometabolic risk factors: A population-based prospective cohort.

BACKGROUND: Whether maternal iron status during pregnancy is associated with cardiometabolic health in the offspring is poorly known. OBJECTIVES: We aimed to assess the associations of maternal iron status during early pregnancy with body fat measures and cardiometabolic risk factors in children aged 10 y. METHODS: In a population-based cohort study among 3718 mother-child pairs, we measured ferritin, transferrin, and transferrin saturation during early pregnancy. We obtained child BMI, fat mass index, and android/gynoid fat mass ratio by DXA, subcutaneous fat index, visceral fat index, pericardial fat index, and liver fat fraction by magnetic resonance imaging and assessed systolic and diastolic blood pressure, serum lipids, glucose, insulin, and CRP at 10 y. RESULTS: A one-standard deviation score (SDS) higher maternal ferritin was associated with lower fat mass index [difference -0.05 (95% CI: -0.08, -0.02) SDS] and subcutaneous fat index [difference -0.06 (95% CI: -0.10, -0.02) SDS] in children. One-SDS higher maternal transferrin was associated with higher fat mass index [difference 0.04 (95% CI: 0.01, 0.07) SDS], android/gynoid fat mass ratio [difference 0.05 (95% CI: 0.02, 0.08) SDS], and subcutaneous fat index [difference 0.06 (95% CI: 0.02, 0.10) SDS] in children. Iron status during pregnancy was not consistently associated with organ fat and cardiometabolic risk factors at 10 y. CONCLUSIONS: Maternal lower ferritin and higher transferrin in early pregnancy are associated with body fat accumulation and distribution but are not associated with cardiometabolic risk factors in childhood. Underlying mechanisms and long-term consequences warrant further study.

The impact of variant and vaccination on SARS-CoV-2 symptomatology; three prospective household cohorts.

OBJECTIVES: We compared age-stratified SARS-CoV-2 symptomatology of wild-type/Alpha vs Omicron BA.1/BA.2 variant infected individuals and the impact of COVID-19 booster vaccination on Omicron symptom burden. METHODS: Data from three European prospective household cohorts were used (April 2020 to April 2021 and January to March 2022). Standardized outbreak protocols included (repeated) polymerase chain reaction testing, paired serology, and daily symptom scoring for all household members. Comparative analyses were performed on 346 secondary household cases from both periods. RESULTS: Children <12 years (all unvaccinated) experienced more symptoms and higher severity scores during Omicron compared with wild-type/Alpha period (P ≤0.01). In adults, Omicron disease duration and severity were reduced (P ≤ 0.095). Omicron was associated with lower odds for loss of smell or taste (adjusted odds ratio [aOR]: 0.14; 95% CI 0.03-0.50) and higher but non-significant odds for upper respiratory symptoms, fever, and fatigue (aORs: 1.85-2.23). No differences were observed in disease severity or duration between primary vs booster series vaccinated adults (P ≥0.12). CONCLUSION: The Omicron variant causes higher symptom burden in children compared with wild-type/Alpha and lower in adults, possibly due to previous vaccination. A shift in symptoms occurred with reduction in loss of smell/taste for Omicron. No additional effect of booster vaccination on Omicron symptom burden was observed.

The gut microbiome and child mental health: A population-based study.

The link between the gut microbiome and the brain has gained increasing scientific and public interest for its potential to explain psychiatric risk. While differences in gut microbiome composition have been associated with several mental health problems, evidence to date has been largely based on animal models and human studies with modest sample sizes. In this cross-sectional study in 1,784 ten-year-old children from the multi-ethnic, population-based Generation R Study, we aimed to characterize associations of the gut microbiome with child mental health problems. Gut microbiome was assessed from stool samples using 16S rRNA sequencing. We focused on overall psychiatric symptoms as well as with specific domains of emotional and behavioral problems, assessed via the maternally rated Child Behavior Checklist. While we observed lower gut microbiome diversity in relation to higher overall and specific mental health problems, associations were not significant. Likewise, we did not identify any taxonomic feature associated with mental health problems after multiple testing correction, although suggestive findings indicated depletion of genera previously associated with psychiatric disorders, including Hungatella, Anaerotruncus and Oscillospiraceae. The identified compositional abundance differences were found to be similar across all mental health problems. Finally, we did not find significant enrichment for specific microbial functions in relation to mental health problems. In conclusion, based on the largest sample examined to date, we do not find clear evidence of associations between gut microbiome diversity, taxonomies or functions and mental health problems in the general pediatric population. In future, the use of longitudinal designs with repeated measurements of microbiome and psychiatric outcomes will be critical to identify whether and when associations between the gut microbiome and mental health emerge across development and into adulthood.

Longitudinal Household Assessment of Respiratory Illness in Children and Parents During the COVID-19 Pandemic.

Importance: In the early COVID-19 pandemic, SARS-CoV-2 testing was only accessible and recommended for symptomatic persons or adults. This restriction hampered assessment of the true incidence of SARS-CoV-2 infection in children as well as detailed characterization of the SARS-CoV-2 disease spectrum and how this spectrum compared with that of other common respiratory illnesses. Objective: To estimate the community incidence of SARS-CoV-2 infection in children and parents and to assess the symptoms and symptom severity of respiratory illness episodes involving SARS-CoV-2-positive test results relative to those with SARS-CoV-2-negative test results. Design, Setting, and Participants: This cohort study randomly selected Dutch households with at least 1 child younger than 18 years. A total of 1209 children and adults from 307 households were prospectively followed up between August 25, 2020, and July 29, 2021, covering the second and third waves of the COVID-19 pandemic. Participation included SARS-CoV-2 screening at 4- to 6-week intervals during the first 23 weeks of participation (core study period; August 25, 2020, to July 29, 2021). Participants in all households finishing the core study before July 1, 2021, were invited to participate in the extended follow-up and to actively report respiratory symptoms using an interactive app until July 1, 2021. At new onset of respiratory symptoms or a SARS-CoV-2 positive test result, a household outbreak study was initiated, which included daily symptom recording, repeated polymerase chain reaction testing (nose-throat swabs and saliva and fecal samples), and SARS-CoV-2 antibody measurement (paired dried blood spots) in all household members. Outbreaks, households, and episodes of respiratory illness were described as positive or negative depending on SARS-CoV-2 test results. Data on participant race and ethnicity were not reported because they were not uniformly collected in the original cohorts and were therefore not representative or informative. Exposures: SARS-CoV-2-positive and SARS-CoV-2-negative respiratory illness episodes. Main Outcomes and Measures: Age-stratified incidence rates, symptoms, and symptom severity for SARS-CoV-2-positive and SARS-CoV-2-negative respiratory illness episodes. Results: Among 307 households including 1209 participants (638 female [52.8%]; 403 [33.3%] aged <12 years, 179 [14.8%] aged 12-17 years, and 627 [51.9%] aged ≥18 years), 183 household outbreaks of respiratory illness were observed during the core study and extended follow-up period, of which 63 (34.4%) were SARS-CoV-2 positive (59 outbreaks [32.2%] during the core study and 4 outbreaks [2.2%] during follow-up). SARS-CoV-2 incidence was similar across all ages (0.24/person-year [PY]; 95% CI, 0.21-0.28/PY). Overall, 33 of 134 confirmed SARS-CoV-2 episodes (24.6%) were asymptomatic. The incidence of SARS-CoV-2-negative respiratory illness episodes was highest in children younger than 12 years (0.94/PY; 95% CI, 0.89-0.97/PY). When comparing SARS-CoV-2-positive vs SARS-CoV-2-negative respiratory illness episodes in children younger than 12 years, no differences were observed in number of symptoms (median [IQR], 2 [2-4] for both groups), symptom severity (median [IQR] maximum symptom severity score, 6 [4-9] vs 7 [6-13]), or symptom duration (median [IQR], 6 [5-12] days vs 8 [4-13] days). However, among adults, SARS-CoV-2-positive episodes had a significantly higher number (median [IQR], 6 [4-8] vs 3 [2-4]), severity (median [IQR] maximum symptom severity score, 15 [9-19] vs 7 [6-11]), and duration (median [IQR] 13 [8-29] days vs 5 [3-11] days; P < .001 for all comparisons) of symptoms vs SARS-CoV-2-negative episodes. Conclusions and Relevance: In this cohort study, during the first pandemic year when mostly partial or full in-person learning occurred, the SARS-CoV-2 incidence rate in children was substantially higher than estimated from routine testing or seroprevalence data and was similar to that of adult household members. Unlike in unvaccinated adults, SARS-CoV-2 symptoms and symptom severity in children were similar to other common respiratory illnesses. These findings may prove useful when developing pediatric COVID-19 vaccine recommendations.

Predictors of maternal dietary quality and dietary inflammation during pregnancy: An individual participant data meta-analysis of seven European cohorts from the ALPHABET consortium.

BACKGROUND & AIMS: Maternal diet during pregnancy is a modifiable behaviour which plays an important role in maternal, neonatal and child health outcomes. Thus, knowledge of predictors of dietary quality and dietary inflammatory potential in European countries may contribute to developing maternal diet-related public health policies that target specific at-risk populations in Europe. METHODS: We used harmonised data from >26,000 pregnant women enrolled in the ALSPAC, EDEN, Generation R, Lifeways, REPRO_PL, ROLO and SWS cohorts, as part of the ALPHABET consortium. Maternal dietary quality and inflammatory potential were assessed using the Dietary Approaches to Stop Hypertension (DASH) and the energy-adjusted Dietary Inflammatory Index (E-DII). We conducted an individual participant data meta-analysis to investigate the maternal sociodemographic, health and behavioural predictors of maternal diet before and during pregnancy. RESULTS: DASH and E-DII scores were moderately correlated: from -0.63 (95% CI: -0.66, -0.59) to -0.48 (95% CI: -0.49, -0.47) across cohorts. Higher maternal age, education, household income, and physical activity during pregnancy were associated with a better dietary quality and a more anti-inflammatory diet. Conversely, multiparity and smoking during pregnancy were associated with a poorer dietary quality and a more proinflammatory diet. Women with obesity had a poorer pregnancy dietary quality than women with a normal body mass index range. CONCLUSIONS: The results will help identify population subgroups who may benefit from targeted public health strategies and interventions aimed at improving women's dietary quality during pregnancy.