Child Health Study Research Articles

DNA methylation as a potential mediator of the association between indoor air pollution and neurodevelopmental delay in a South African birth cohort

BackgroundExposure to indoor air pollution during pregnancy has been linked to neurodevelopmental delay in toddlers. Epigenetic modification, particularly DNA methylation (DNAm), may explain this link. In this study, we employed three high-dimensional mediation analysis methods (HIMA, DACT, and gHMA) followed by causal mediation analysis to identify differentially methylated CpG sites and genes that mediate the association between indoor air pollution and neurodevelopmental delay. Analyses were performed using data from 142 mother to child pairs from a South African birth cohort, the Drakenstein Child Health Study. DNAm from cord blood was measured using the Infinium MethylationEPIC and HumanMethylation450 arrays. Neurodevelopment was assessed at age 2 years using the Bayley Scores of Infant and Toddler Development, 3rd edition across four domains (cognitive development, general adaptive behavior, language, and motor function). Particulate matter with an aerodynamic diameter of 10 μm or less (PM10) was measured inside participants’ homes during the second trimester of pregnancy.ResultsA total of 29 CpG sites and 4 genes (GOPC, RP11-74K11.1, DYRK1A, RNMT) were identified as significant mediators of the association between PM10 and cognitive neurodevelopment. The estimated proportion mediated (95%-confidence interval) ranged from 0.29 [0.01, 0.86] for cg00694520 to 0.54 [0.11, 1.56] for cg05023582.ConclusionsOur findings suggest that DNAm may mediate the association between prenatal PM10 exposure and cognitive neurodevelopment. DYRK1A and several genes that our CpG sites mapped to, including CNKSR1, IPO13, IFNGR1, LONP2, and CDH1, are associated with biological pathways implicated in cognitive neurodevelopment and three of our identified CpG sites (cg23560546 [DAPL1], cg22572779 [C6orf218], cg15000966 [NT5C]) have been previously associated with fetal brain development. These findings are novel and add to the limited literature investigating the relationship between indoor air pollution, DNAm, and neurodevelopment, particularly in low- and middle-income country settings and non-white populations.

Metabolic Signatures of Youth Exposure to Mixtures of Per- and Polyfluoroalkyl Substances: A Multi-Cohort Study.

Exposure to per- and polyfluoroalkyl substances (PFAS) is ubiquitous and has been associated with an increased risk of several cardiometabolic diseases. However, the metabolic pathways linking PFAS exposure and human disease are unclear. We examined associations of PFAS mixtures with alterations in metabolic pathways in independent cohorts of adolescents and young adults. Three hundred twelve overweight/obese adolescents from the Study of Latino Adolescents at Risk (SOLAR) and 137 young adults from the Southern California Children's Health Study (CHS) were included in the analysis. Plasma PFAS and the metabolome were determined using liquid-chromatography/high-resolution mass spectrometry. A metabolome-wide association study was performed on log-transformed metabolites using Bayesian regression with a g-prior specification and g-computation for modeling exposure mixtures to estimate the impact of exposure to a mixture of six ubiquitous PFAS (PFOS, PFHxS, PFHpS, PFOA, PFNA, and PFDA). Pathway enrichment analysis was performed using Mummichog and Gene Set Enrichment Analysis. Significance across cohorts was determined using weighted -tests. In the SOLAR and CHS cohorts, PFAS exposure was associated with alterations in tyrosine metabolism (meta-analysis ) and de novo fatty acid biosynthesis (), among others. For example, when increasing all PFAS in the mixture from low (th percentile) to high (th percentile), thyroxine (T4), a thyroid hormone related to tyrosine metabolism, increased by 0.72 standard deviations (SDs; equivalent to a standardized mean difference) in the SOLAR cohort (95% Bayesian credible interval (BCI): 0.00, 1.20) and 1.60 SD in the CHS cohort (95% BCI: 0.39, 2.80). Similarly, when going from low to high PFAS exposure, arachidonic acid increased by 0.81 SD in the SOLAR cohort (95% BCI: 0.37, 1.30) and 0.67 SD in the CHS cohort (95% BCI: 0.00, 1.50). In general, no individual PFAS appeared to drive the observed associations. Exposure to PFAS is associated with alterations in amino acid metabolism and lipid metabolism in adolescents and young adults. https://doi.org/10.1289/EHP11372.

Mother-Child Relationship Quality from Preschool to Adolescence: Variation by Maternal Education.

Using longitudinal data from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development (N = 1,088), we examine changes in maternal perception of closeness and conflict in the mother-child relationship from the child's preschool to adolescent years, with attention to variation by maternal education. Analyses using individual growth models show that mother-child closeness increases, while mother-child conflict decreases from preschool to first grade. From first grade to age 15, mother-child closeness decreases, while mother-child conflict increases, both gradually. The decrease in mother-child conflict from preschool to first grade and the increases in mother-child conflict from first to fifth grade, sixth grade, and age 15 are less steep for mothers with a college degree than for mothers without a college degree. These findings underscore the importance of examining changes in parent-child relationships using longitudinal data across children's developmental stages and their variations by parental social and economic status.

In-utero exposure to antibiotics and risk of colorectal cancer in a prospective cohort of 18 000 adult offspring.

Incidence rates of colorectal cancer (CRC) are increasing among younger adults and in mid-life, implicating exposures in early life as risk factors. We examined the association between in-utero exposure to antibiotics and risk of CRC in adult offspring. The Child Health and Development Studies is a prospective cohort of women receiving prenatal care between 1959 and 1966 in Oakland, California, with deliveries through June 1967. Diagnosed conditions and all prescribed medications were abstracted from mothers' medical records beginning 6 months prior to pregnancy through delivery. We identified mothers who received antibiotics in pregnancy, including penicillins, tetracyclines, short-acting sulfonamides and long-acting sulfonamides. Diagnoses of CRC in adult (age ≥18 years) offspring were ascertained through 2021 by linkage with the California Cancer Registry. Cox proportional models were used to estimate adjusted hazard ratios (aHR), with follow-up accrued from birth through cancer diagnosis, death or last contact. Of 18 751 liveborn offspring, about 15% (n = 2635) were exposed in utero to antibiotics: 5.4% (n = 1016) to tetracyclines, 4.9% (n = 918) to penicillins, 4.2% (n = 785) to short-acting sulfonamides and 1.5% (n = 273) to long-acting sulfonamides. Compared with offspring not exposed, associations between in-utero exposure and CRC in adult offspring were: aHR 1.03 (95% CI 0.32, 3.31) for tetracyclines; aHR 1.12 (95% CI 0.35, 3.58) for penicillins; aHR 0.83 (95% CI 0.20, 3.42) for short-acting sulfonamides; and aHR 4.40 (95% CI 1.63, 11.88) for long-acting sulfonamides. Our findings support an association between in-utero exposure to long-acting sulfonamides and CRC in adulthood.

Early Childhood Violence Exposure Patterns in The Drakenstein Child Health Study (DCHS)

Background: Research has highlighted high rates of exposure to violence among South African youth. However, work to date has been largely cross-sectional, focused on violence exposure during the adolescence period, and has been limited to specific types of violence exposure. We examined violence exposure in South African preschool children between 3 and 6 years of age, capturing both direct and indirect forms of violence, and tested for potential sex differences across the several types of exposures. Methods: Lifetime direct and indirect exposure to domestic and community violence was measured by parental report when children were 3.5 years (N = 530), 4.5 years (N = 749) and 6 years of age (N= 417) in a South African birth cohort located in a peri-urban community. Results: There are three main findings. First, a large proportion of children (72%-75%) were reported as having been exposed to some form of direct or indirect violent experience in their homes or communities from a young age. Second, there was significant polyvictimization, with 49% of the children being exposed to more than one type of violence by age 6. Third, by 4.5 years of age, there was evidence that boys were more likely than girls to be exposed to domestic victimisation (28% vs. 17%) and polyvictimization (38% vs. 28%). Conclusions: These findings highlight the high levels of violence exposure in young South African children, particularly among boys, and the need for prevention at both the community and individual levels.

Comparing youth with vs without outpatient mental health services on subsequent acute mental health care visits.

Use of acute care for mental health concerns has been increasing among youth in recent years. Improving access to outpatient mental health services may prevent downstream acute care visits. To examine differences in rates of acute mental health care visits among youth with- versus without prior outpatient mental health services. A total of 2,442 youth ages 14-17 years participated in a provincially representative cross-sectional epidemiological survey, the 2014 Ontario Child Health Study. This sample was individually linked to health administrative databases, with nearly universal coverage of all medically necessary physician and acute care visits. Our exposure was parent and youth reported outpatient mental health service use in the six-month period prior to completing the survey. Exposed youth (n=691) were matched with unexposed youth using a propensity score informed by a range of clinical and socio-demographic factors. Our outcome was acute mental health care visits in the 18-month period following completion of the survey, ascertained though the linked health administrative data. In our propensity score matched sample, we found no difference in rates of subsequent acute mental health care visits (HR= 1.14, 95%CI 0.44, 2.98) between youth with- versus without prior outpatient mental health services. There is a need to further understand the types of services youth are receiving in outpatient settings to determine if, and for whom, outpatient mental health services reduces the likelihood of future acute mental health care visits.

The combined effect of pre-pregnancy body mass index and gestational weight gain on the risk of pre-labour and intrapartum caesarean section-The ICE-MCH study.

Women who are obese before pregnancy have a higher risk of caesarean section than normal weight women. We investigated the combined effect of pre-pregnancy weight and gestational weight gain on pre-labour and intrapartum caesarean section risk. We collected data on 22,763 singleton, term, live deliveries in 2003-2014 from the Icelandic Maternal and Child Health Study (ICE-MCH), based on Icelandic registries. These were the Icelandic Medical Birth Registry and the Saga Maternal and Child Health Database. Pre-pregnancy body mass index was categorised into underweight, normal weight, overweight and obese. Gestational weight gain was classified according to the Institute of Medicine´s recommendation into below, within and above the recommended range. Logistic regression models, adjusted for maternal and gestational characteristics, were used to calculate adjusted odds ratios (AOR) and 95% confidence intervals (CI) for the risk of caesarean section. Obese women had a higher risk of pre-labour (AOR 1.56, 95% CI 1.34-1.81) and intrapartum caesarean section (AOR 1.92, 95% CI 1.70-2.17) than normal weight women in all categories of gestational weight gain. Gestational weight gain above the recommended range, compared to within the range, increased the risk of intrapartum caesarean section among normal weight (AOR 1.46, 95% CI 1.23-1.73) and overweight women (AOR 1.291, 95% CI 1.04-1.60). Gestational weight gain below the recommended range, compared to within the range, increased the risk of pre-labour caesarean section (AOR 1.64, 95% CI 1.20-2.25), but only among overweight women. Women who are obese before pregnancy have a high risk of caesarean section regardless of gestational weight gain. However, women who are normal weight or overweight before pregnancy and gain weight above the recommended range during pregnancy may also have an increased risk of caesarean section.

Neighborhood Socioeconomic Status and Women's Mental Health: A Longitudinal Study of Hurricane Katrina Survivors, 2005-2015.

There is limited knowledge on the relationship between neighborhood factors and mental health among displaced disaster survivors, particularly among women. Hurricane Katrina (Katrina) was the largest internal displacement in the United States (U.S.), which presented itself as a natural experiment. We examined the association between neighborhood socioeconomic status (SES) and mental health among women up to 10 years following Katrina (N = 394). We also investigated whether this association was modified by move status, comparing women who were permanently displaced to those who had returned to their pre-Katrina residence. We used hierarchical linear models to measure this association, using data from the American Community Survey and the Gulf Coast Child and Family Health study. Neighborhood SES was created as an index which represented social and economic characteristics of participants' neighborhoods. Mental health was measured using mental component summary (MCS) scores. Increased neighborhood SES was positively associated with mental health after controlling for age, race/ethnicity, economic positioning, time, and move status (19.6, 95% Confidence Interval: 5.8, 33.7). Neighborhood SES and mental health was also modified by move status. These findings underscore the need to better understand the impacts of socioeconomic conditions and health outcomes among women affected by natural disasters.

Racial socialization and discrimination-related psychological distress in middle-aged Black men and women.

Our objectives were to evaluate gender-specific associations of racial discrimination with psychological sequelae among middle-aged Blacks and to evaluate the capacity of racial socialization to moderate the association between discrimination and psychological distress, accounting for relevant prospectively assessed childhood factors. We used data from the Child Health and Development Disparities Study that followed a Northern California-based group of Blacks from the prenatal period through midlife (N = 244, 49.6% female). Multiple regression analyses were performed separately by gender to assess (a) the main effects of racial socialization and racial discrimination on adult psychological distress, (b) racial socialization as a moderator of the association between racial discrimination and adult psychological distress, and (c) whether controls for prospectively assessed childhood factors changed conclusions regarding the role of racial socialization. Seventy percent of the middle-aged Blacks in our sample reported having at least one type of major experience of racial discrimination. Increased reports of racial discrimination were positively associated with psychological distress in men, but not in women. Similarly, racial socialization was associated with decreased overall distress for men, but not for women. Discrimination-related distress was attenuated for men who reported higher levels of racial socialization. These findings remained after adjustment for childhood socioeconomic status (SES), childhood internalizing symptoms, parental marital separation, and number of siblings. Findings suggest that racial socialization conferred a protective psychological effect through midlife to Black men who experienced racial discrimination, a commonplace experience in this cohort. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Exposição a metais em uma população infantil após rompimento de barragem de rejeitos da mineração. Projeto Bruminha

Objective: This study aimed to analyze the urinary concentrations of As, Cd, Pb, Hg, and Mn in children living in areas directly affected by the tailings of the Brumadinho disaster. Methods: We performed a cross-sectional descriptive study on a population of 217 children aged 0 to 6 years, living in Córrego do Feijão (CF), Parque da Cachoeira (PC), Aranha (AR), and Tejuco (TJ), enrolled in the Longitudinal Study of Child Health in Brumadinho (Minas Gerais) — Projeto Bruminha. Socioeconomic data and urine samples were collected to determine the concentration of selected metals. Results: Children living in locations not directly affected by the disaster (AR and TJ) had higher concentrations of As and Mn than those in directly affected areas (CF and PC). Additionally, children living in locations not potentially exposed to dust from tailings mud or mining activity (AR) showed higher urinary As concentrations than those potentially exposed (CF, PC, and TJ). Conclusion: Our results suggest the need to investigate possible sources of As exposure in children living in areas not directly affected by the disaster and not potentially exposed to dust.

Metal exposure in a child population after a mine tailings dam failure. Projeto Bruminha

This study aimed to analyze the urinary concentrations of As, Cd, Pb, Hg, and Mn in children living in areas directly affected by the tailings of the Brumadinho disaster. We performed a cross-sectional descriptive study on a population of 217 children aged 0 to 6 years, living in Córrego do Feijão (CF), Parque da Cachoeira (PC), Aranha (AR), and Tejuco (TJ), enrolled in the Longitudinal Study of Child Health in Brumadinho (Minas Gerais) - Projeto Bruminha. Socioeconomic data and urine samples were collected to determine the concentration of selected metals. Children living in locations not directly affected by the disaster (AR and TJ) had higher concentrations of As and Mn than those in directly affected areas (CF and PC). Additionally, children living in locations not potentially exposed to dust from tailings mud or mining activity (AR) showed higher urinary As concentrations than those potentially exposed (CF, PC, and TJ). Our results suggest the need to investigate possible sources of As exposure in children living in areas not directly affected by the disaster and not potentially exposed to dust.

Social Disparities in Mental Health Service Use Among Children and Youth in Ontario: Evidence From a General, Population-Based Survey.

To examine differences in mental health-related service contacts between immigrant, refugee, racial and ethnic minoritized children and youth, and the extent to which social, and economic characteristics account for group differences. The sample for analyses includes 10,441 children and youth aged 4-17 years participating in the 2014 Ontario Child Health Study. The primary caregiver completed assessments of their child's mental health symptoms, perceptions of need for professional help, mental health-related service contacts, experiences of discrimination and sociodemographic and economic characteristics. Adjusting for mental health symptoms and perceptions of need for professional help, children and youth from immigrant, refugee and racial and ethnic minoritized backgrounds were less likely to have mental health-related service contacts (adjusted odds ratios ranged from 0.54 to 0.79), compared to their non-immigrant peers and those who identified as White. Group differences generally remained the same or widened after adjusting for social and economic characteristics. Large differences in levels of perceived need were evident across non-migrant and migrant children and youth. Lower estimates of mental health-related service contacts among immigrant, refugee and racial and ethnic minoritized children and youth underscore the importance and urgency of addressing barriers to recognition and treatment of mental ill-health among children and youth from minoritized backgrounds.

Self-regulation linking the quality of early parent-child relationship to adolescents' obesity risk and food consumption.

The quality of parent-child relationships has been examined as a contributor to children's healthy behaviours and weight outcomes, but the mechanisms accounting for associations remain understudied. This study examined whether the quality of early parent-child relationship is associated with adolescent obesity risk and whether self-regulation and (un)healthful food consumption mediate these associations. Employing structural equation modelling, two theory-driven models were examined using a large sample (N=1237) drawn from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development. Indicators of the quality of parent-child relationship included assessments of child attachment security and observational assessments of maternal sensitivity (15, 24, and 36 months). Self-regulation at 54 months was assessed using behavioural and computerized tasks and, at ages 11-12 and 15 years, using parental ratings of self-control. Food consumption was self-reported at age 11-12. Height and weight measures in early/middle childhood and adolescence were used to compute BMI z-scores. No direct associations between the quality of parent-child relationship and adolescent obesity risk were found in either model. Instead, child self-regulation was found to mediate the associations between the quality of parent-child relationship and both unhealthy food consumption and higher adolescent BMI status. The findings highlight how the nature of parent-child relationships impacts developing regulatory processes in children which, in turn, have implications for obesity-related behaviours and outcomes. Interventions to reduce childhood obesity should consider self-regulation skills across multiple domains, and early parenting practices that foster these capacities.

Association of Maternal and Child Anemia With Brain Structure in Early Life in South Africa

Anemia affects millions of pregnant women and their children worldwide, particularly in low- and middle-income countries. Although anemia in pregnancy is a well-described risk factor for cognitive development, the association with child brain structure is poorly understood. To explore the association of anemia during pregnancy and postnatal child anemia with brain structure in early life. This neuroimaging nested cohort study was embedded within the Drakenstein Child Health Study (DCHS), a population-based birth cohort in South Africa. Pregnant individuals were enrolled into the DCHS between 2012 and 2015 from 2 clinics in a periurban setting. Mother-child pairs were assessed prospectively; follow-up is ongoing. A subgroup of children had brain magnetic resonance imaging (MRI) at age 2 to 3 years from 2015 to 2018. This study focused on the 147 pairs with structural neuroimaging and available hemoglobin data. Data analyses were conducted in 2021 and 2022. Mothers had hemoglobin measurements during pregnancy, and a subgroup of children had hemoglobin measurements during early life. Anemia was classified as hemoglobin levels less than 11 g/dL based on World Health Organization guidelines; children younger than 6 months were classified using local guidelines. Child brain volumes of global, subcortical, and corpus callosum structures were quantified using T1-weighted MRI. Linear regression models were used to analyze the associations between maternal and child anemia with child brain volumes, accounting for potential confounders. Of 147 children (mean [SD] age at MRI, 34 [2] months; 83 [56.5%] male) with high-resolution MRI scans, prevalence of maternal anemia in pregnancy was 31.3% (46 of 147; median [IQR] gestation of measurement: 13 [9-20] weeks). Maternal anemia during pregnancy was significantly associated with smaller volumes of the child caudate bilaterally (adjusted percentage difference, -5.30% [95% CI, -7.01 to -3.59]), putamen (left hemisphere: -4.33% [95% CI, -5.74 to -2.92]), and corpus callosum (-7.75% [95% CI, -11.24 to -4.26]). Furthermore, antenatal maternal hemoglobin levels were also associated with brain volumes in the caudate (left hemisphere: standardized β = 0.15 [95% CI, 0.02 to 0.28]; right hemisphere: β = 0.15 [95% CI, 0.02 to 0.27]), putamen left hemisphere (β = 0.21 [95% CI, 0.07 to 0.35]), and corpus callosum (β = 0.24 [95% CI, 0.09 to 0.39]). Prevalence of child anemia was 52.5% (42 of 80; median [IQR] age of measurement: 8.0 [2.7 to 14.8] months). Child anemia was not associated with brain volumes, nor did it mediate the association of maternal anemia during pregnancy with brain volumes. In this cohort study, anemia in pregnancy was associated with altered child brain structural development. Given the high prevalence of antenatal maternal anemia worldwide, these findings suggest that optimizing interventions during pregnancy may improve child brain outcomes.

Early maternal sensitivity and markers of physical health: Enduring or transient associations from childhood to adulthood?

Individual differences in the quality of early experiences with primary caregivers have been reliably implicated in the development of socioemotional adjustment and, more recently, physical health. However, few studies have examined the development of such associations with physical health into the adult years. To that end, the current study used prospective, longitudinal data from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development (N = 1,306, 52% male, 77% White/non-Hispanic) to investigate whether associations between direct observations of maternal sensitivity in the first 3 years of life and repeated assessments of two commonly used, objective indicators of physical health (i.e., body mass and mean arterial blood pressure) remained stable or diminished in magnitude over time. Associations between early maternal sensitivity and lower body mass remained relatively stable from age 54 months to 26 years and were robust to the modeling of autoregressive and second-order stability processes as well as the inclusion of potential demographic confounders. In contrast, although associations between early caregiving and lower mean arterial pressure remained relatively stable from Grade 4 to age 15 years (the oldest age for which mean arterial pressure was assessed thus far), these associations were not robust to the inclusion of covariates and the modeling of second-order stability processes. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Personal monitoring of fine particulate matter (PM2.5) exposure in mothers and young children in a South African birth cohort study – A pilot study

Air pollution is a recognized risk factor for impaired lung health and increased morbidity and mortality globally. Fine particulate matter (PM2.5) has been linked to respiratory illness, but assessing personal PM2.5 exposure remains difficult, especially in children. The MicroPEM™ and Enhanced Children's MicroPEM™ (ECM) are personal fine particulate matter exposure monitors that have not been well-evaluated for young children. We aimed to assess compliance and acceptability of these monitors and to investigate risk factors associated with fine particulate matter in mother-child pairs. MethodsMother-child pairs, enrolled in a South African birth cohort, the Drakenstein Child Health Study, were recruited. A MicroPEM (mother) and ECM (child), issued to each participant and worn over 24 h, quantified PM2.5 exposure. Home environment, wearability, and wearing compliance were assessed. Linear regression identified associations between variables characterising the home environment and PM2.5 levels. ResultsFrom August to November 2016, 86 mothers and 75 children (age 1–4 years) had results. Fossil fuels were used in 21% of homes; maternal smoking (37%) and exposure to household tobacco smoke (89%) was high. Waking wearing compliance of the devices was 59% in children and 56% in mothers. PM2.5 exposures were above the World Health Organization recommend 24-h interim target (IT-4 25 μg/m3) in 38/75 (51%) children, and in 44/86 (51%) mothers. Winter, smoking and public transport were associated with higher concentrations of PM2.5 in mothers. Whereas, for the children higher concentrations of PM2.5 were associated with winter and two or more household smokers; while lower concentrations were associated with age, weight-for-age z-score and households that had fewer than two basic dimensions. Wearability for children was reported as “very easy” in the majority (n = 54, 63%) with similar acceptability in mothers (n = 55, 64%). ConclusionThe MicroPEM and ECM provide wearable low-burden personal exposure monitoring tools for women and children with reasonable rates of acceptability. High exposure to fine particulate matter in children is concerning; strategies to minimise exposure need to be strengthened.

Early childhood wheezing phenotypes and determinants in a South African birth cohort: longitudinal analysis of the Drakenstein Child Health Study

Developmental trajectories of childhood wheezing in low-income and middle-income countries (LMICs) have not been well described. We aimed to derive longitudinal wheeze phenotypes from birth to 5 years in a South African birth cohort and compare those with phenotypes derived from a UK cohort. We used data from the Drakenstein Child Health Study (DCHS), a longitudinal birth cohort study in a peri-urban area outside Cape Town, South Africa. Pregnant women (aged ≥18 years) were enrolled during their second trimester at two public health clinics. We followed up children from birth to 5 years to derive six multidimensional indicators of wheezing (including duration, temporal sequencing, persistence, and recurrence) and applied Partition Around Medoids clustering to derive wheeze phenotypes. We compared phenotypes with a UK cohort (the Avon Longitudinal Study of Parents and Children [ALSPAC]). We investigated associations of phenotypes with early-life exposures, including all-cause lower respiratory tract infection (LRTI) and virus-specific LRTI (respiratory syncytial virus, rhinovirus, adenovirus, influenza, and parainfluenza virus) up to age 5 years. We investigated the association of phenotypes with lung function at 6 weeks and 5 years. Between March 5, 2012, and March 31, 2015, we enrolled 1137 mothers and there were 1143 livebirths. Four wheeze phenotypes were identified among 950 children with complete data: never (480 children [50%]), early transient (215 children [23%]), late onset (104 children [11%]), and recurrent (151 children [16%]). Multivariate adjusted analysis indicated that LRTI and respiratory syncytial virus-LRTI, but not other respiratory viruses, were associated with increased risk of recurrent wheeze (odds ratio [OR] 2·79 [95% CI 2·05-3·81] for all LTRIs; OR 2·59 [1·30-5·15] for respiratory syncytial virus-LRTIs). Maternal smoking (1·88 [1·12-3·02]), higher socioeconomic status (2·46 [1·23-4·91]), intimate partner violence (2·01 [1·23-3·29]), and male sex (2·47 [1·50-4·04]) were also associated with recurrent wheeze. LRTI and respiratory syncytial virus-LRTI were also associated with early transient and late onset clusters. Wheezing illness architecture differed between DCHS and ALSPAC; children included in ALSPAC in the early transient cluster wheezed for a longer period before remission and late-onset wheezing started at an older age, and no persistent phenotype was identified in DCHS. At 5 years, airway resistance was higher in children with early or recurrent wheeze compared with children who had never wheezed. Airway resistance increased from 6 weeks to 5 years among children with recurrent wheeze. Effective strategies to reduce maternal smoking and psychosocial stressors and new preventive interventions for respiratory syncytial virus are urgently needed to optimise child health in LMICs. UK Medical Research Council; The Bill & Melinda Gates Foundation; National Institutes of Health Human Heredity and Health in Africa; South African Medical Research Council; Wellcome Trust.

Maternal Consumption of Dairy Products during Pregnancy Is Associated with Decreased Risk of Emotional Problems in 5-Year-Olds: The Kyushu Okinawa Maternal and Child Health Study.

Milk is a good source of fats, minerals, and vitamins. The present prebirth cohort study examined the association between maternal dairy product intake during pregnancy and the risk of childhood behavioral problems in 5-year-old Japanese children. Study subjects were 1199 mother-child pairs. Dietary intake was assessed using a diet history questionnaire. Emotional problems, conduct problems, hyperactivity problems, peer problems, and low prosocial behavior were assessed using the parent-reported version of the Strengths and Difficulties Questionnaire. Adjustments were made for a priori selected non-dietary confounders and potentially related dietary factors. A significant inverse exposure-response association was observed between maternal total dairy intake during pregnancy and the risk of childhood emotional problems (adjusted odds ratio [OR] between extreme quartiles, 0.62; 95% confidence interval [CI]: 0.36-1.03, p for trend, 0.04). The greater maternal consumption of cow's milk, but not yogurt or cheese, during pregnancy was independently related to a reduced risk of emotional problems in children (adjusted OR between extreme quartiles, 0.41; 95% CI: 0.23-0.70, p for trend, 0.003). Higher maternal consumption levels of total dairy products, especially cow's milk, during pregnancy may be associated with a decreased risk of emotional problems in 5-year-old children.

Association of Maternal Caffeine Consumption During Pregnancy With Child Growth

Greater caffeine consumption in pregnancy is associated with reduced birth size, but potential associations with childhood growth are unclear. To evaluate the associations of pregnancy caffeine and paraxanthine measures with child growth in a contemporary cohort with low caffeine consumption and a historical cohort with high caffeine consumption. The Environmental Influences on Child Health Outcomes cohort of the National Institute of Child Health and Human Development Fetal Growth Studies (ECHO-FGS; 10 sites, 2009-2013) was a pregnancy cohort with 1 child measurement between ages 4 and 8 years (follow-up in 2017-2019). The Collaborative Perinatal Project (CPP) was a pregnancy cohort (12 sites, 1959-1965) with child follow-up through 8 years (1960-1974). The current secondary analysis was conducted in 2021 and 2022. Concentrations of caffeine and its primary metabolite, paraxanthine, were quantified from plasma (ECHO-FGS) and serum (CPP) collected in the first trimester. Cut points for analyses were defined by quartiles in ECHO-FGS and quintiles in CPP. Child z scores for body mass index, weight, and height were evaluated, as well as fat mass index and percentage and obesity risk measured at 1 time between age 4 and 8 years in ECHO-FGS. In a secondary analysis of the CPP cohort, child z scores and obesity risk longitudinally through age 8 years were evaluated. In ECHO-FGS (median caffeine intake <50 mg/d), 788 children (mean [SD] age, 6.8 [1.0] years; 411 boys [52.2%]) of women in the fourth vs first quartile of plasma caffeine concentrations had lower height z scores (β = -0.21; 95% CI, -0.41 to -0.02), but differences in weight z scores were only observed in the third quartile (β = -0.27; 95% CI, -0.47 to -0.07). In CPP, beginning at age 4 years, 1622 children (805 boys [49.7%]) of women in the highest caffeine quintile group had lower height z scores than their peers from the lowest group, with the gap widening with each successive year of age (β = -0.16 [95% CI, -0.31 to -0.01] at 4 years; β = -0.37 [95% CI, -0.57 to -0.16] at 8 years). There were slight reductions in weight at ages 5 to 8 years for children in the third vs first caffeine quintile (β = -0.16 to -0.22). Results were consistent for paraxanthine concentrations in both cohorts. Intrauterine exposure to increasing levels of caffeine and paraxanthine, even in low amounts, was associated with shorter stature in early childhood. The clinical implication of reductions in height and weight is unclear; however, the reductions were apparent even with levels of caffeine consumption below clinically recommended guidelines of less than 200 mg per day.

In-utero HIV exposure and cardiometabolic health among children 5-8 years: findings from a prospective birth cohort in South Africa.

To evaluate if in-utero HIV exposure is associated with adverse cardiometabolic health outcomes at 5-8 years of age. Prospective cohort study. We enrolled a random sample of HIV-exposed but uninfected (HEU) and HIV-unexposed children from the Drakenstein Child Health study, a longitudinal birth cohort study in Cape Town, South Africa, in a cardiometabolic health pilot study. Outcomes were assessed by trained study staff and included: anthropometry, body composition and size, blood pressure, fasting plasma glucose, HbA1c, lipids, and insulin resistance using HOMA-IR. We used multivariable linear and log-binomial regression to estimate associations between HIV-exposure and cardiometabolic outcomes, adjusted for child age, sex, height, body size, and maternal factors as appropriate. We included 260 children (HEU n = 100, HIV-unexposed n = 160). HEU children had older mothers (median age 30 vs. 26 years), with minimal differences in gestational age and size at birth by HIV-exposure status. In multivariable analyses, HEU children had lower weight-for-age (mean difference -0.35, 95% confidence interval -0.66, -0.05), and height-for-age (mean difference -0.29, 95% confidence interval -0.56, -0.03; z-scores). There were no differences in adiposity, impaired glucose metabolism, or lipid levels by HIV-exposure status. Overall, 12% of children had blood pressure more than 90th percentile, with no differences by HIV-exposure status. Overall, there were few differences in cardiometabolic outcomes between HEU and HIV-unexposed children in this South African cohort. Although these findings are reassuring, monitoring of cardiometabolic health is important as HEU and HIV-unexposed children enter adolescence and cardiometabolic risk trajectories become established.