Maternal smoking DNA methylation risk score associated with health outcomes in offspring of European and South Asian ancestry.

Background: Maternal smoking has been linked to adverse health outcomes in newborns but the extent to which it impacts newborn health has not been quantified through an aggregated cord blood DNA methylation (DNAm) score. Here, we examine the feasibility of using cord blood DNAm scores leveraging large external studies as discovery samples to capture the epigenetic signature of maternal smoking and its influence on newborns in White European and South Asian populations. Methods: We first examined the association between individual CpGs and cigarette smoking during pregnancy, and smoking exposure in two White European birth cohorts (n=744). Leveraging established CpGs for maternal smoking, we constructed a cord blood epigenetic score of maternal smoking that was validated in one of the European-origin cohorts (n=347). This score was then tested for association with smoking status, secondary smoking exposure during pregnancy, and health outcomes in offspring measured after birth in an independent White European (n=397) and a South Asian birth cohort (n=504). Results: Several previously reported genes for maternal smoking were supported, with the strongest and most consistent association signal from the GFI1 gene (6 CpGs with p<5 × 10-5). The epigenetic maternal smoking score was strongly associated with smoking status during pregnancy (OR = 1.09 [1.07, 1.10], p=5.5 × 10-33) and more hours of self-reported smoking exposure per week (1.93 [1.27, 2.58], p=7.8 × 10-9) in White Europeans. However, it was not associated with self-reported exposure (p>0.05) among South Asians, likely due to a lack of smoking in this group. The same score was consistently associated with a smaller birth size (-0.37±0.12 cm, p=0.0023) in the South Asian cohort and a lower birth weight (-0.043±0.013 kg, p=0.0011) in the combined cohorts. Conclusions: This cord blood epigenetic score can help identify babies exposed to maternal smoking and assess its long-term impact on growth. Notably, these results indicate a consistent association between the DNAm signature of maternal smoking and a small body size and low birth weight in newborns, in both White European mothers who exhibited some amount of smoking and in South Asian mothers who themselves were not active smokers. Funding: This study was funded by the Canadian Institutes of Health Research Metabolomics Team Grant: MWG-146332.

Impact of wheat sensitization on wheeze and T2 phenotypes in general population of children.

Background: The association between sensitization to specific aeroallergens and outcomes in patients with asthma is well researched; however, the association between childhood-onset wheeze/asthma and sensitization to various aeroallergens and food allergens in the general pediatric population remains poorly understood. Objective: We sought to investigate the association between sensitization to common aeroallergens and food allergens with wheeze and type 2 (T2) inflammation in the general pediatric population. Methods: Specific IgEs against 9 aeroallergens and 4 food allergens were measured in the prospective Hokkaido birth cohort of 428 school-age children (age ∼10 years). Wheeze and other allergic symptoms were assessed using the International Study of Asthma and Allergies in Childhood questionnaire. Blood eosinophil count and fractional exhaled nitric oxide level were assessed as T2 biomarkers. The Isle of Wight birth cohort in the United Kingdom was used for replication analysis (n = 1032). Results: The prevalence of sensitization to at least 1 aeroallergen and food allergen was 70.5% and 22.3%, respectively. A significant association between wheeze and sensitization to aeroallergens such as ragweed, Japanese cedar, mugwort, and pet dander was found. However, the association between wheeze and wheat sensitization was highly significant (Hokkaido birth cohort: odds ratio, 4.67; 95% CI, 1.98-11.01; Isle of Wight birth cohort, odds ratio, 4.01; 95% CI, 1.78-9.07). Sensitization to most aeroallergens, though not any food allergen, was associated with the T2-high phenotype. Conclusions: Sensitization to wheat may be an important risk factor for wheeze/asthma development, especially the pathogenesis of T2-non/low asthma, independent of aeroallergens, in the general pediatric population.

Associations of prenatal exposure to individual and mixed organophosphate esters with ADHD symptom trajectories in preschool children: The modifying effects of maternal Vitamin D.

BACKGROUND: Organophosphate esters (OPEs) are a class of environmental chemicals with endocrine-disrupting properties. Epidemiologic studies have demonstrated that prenatal OPEs exposure is associated with neurodevelopmental disorders in offspring. However, studies assessing the effects of prenatal OPEs exposure on the dynamic changes in attention deficit hyperactivity disorder (ADHD) symptoms in preschoolers are scarce. Since vitamin D has been demonstrated to have a "neuroprotective" effect, the modifying effects of maternal vitamin D were estimated. METHODS: The present study included 2410 pregnant women from the Ma'anshan Birth Cohort. The levels of OPEs in the mothers' urine were examined in the three trimesters. The Chinese version of the Conners Abbreviated Symptom Questionnaire was used to examine preschoolers' ADHD symptoms at 3, 5, and 6 years of age. ADHD symptom trajectories were fitted via group-based trajectory modeling. We used multinomial logistic regression, Bayesian kernel machine regression, quantile-based g-computation, and generalized linear models to assess individual and mixed relationships between OPEs during pregnancy and preschoolers' ADHD symptoms and trajectories. RESULTS: Preschoolers' ADHD symptom scores were fitted to 3 trajectories, including the low-score, moderate-score, and high-score groups. First-trimester dibutyl phosphate (DBP), second-trimester bis(2-butoxyethyl) phosphate (BBOEP), and third-trimester diphenyl phosphate (DPHP) were associated with an increased risk in the high-score group (p < 0.05). BBOEP in the third trimester was associated with decreased risk in the moderate-score group (OR = 0.89, 95% CI: 0.79, 1.00). For mothers with 25(OH)D deficiency, a positive relationship was observed between OPEs during pregnancy and symptom trajectories. Our results did not reveal any mixed effects of OPEs on ADHD symptom trajectories. CONCLUSION: Prenatal exposure to OPEs had heterogeneous associations with ADHD symptom trajectories in preschoolers. Additionally, the effect of individual OPEs on symptom trajectories was intensified by vitamin D deficiency.

Long-term effects on growth in preterm and small for gestational age infants: A national birth cohort study.

BACKGROUND: Premature and small-for-gestational-age (SGA) infants tend to have long-term growth morbidities such as short stature, failure to thrive, and obesity. Although most of these infants show catch-up growth at 2-4 years of age, they are still more susceptible to childhood obesity and related metabolic disorders. Those who fail to achieve catch-up will suffer from pathological short stature and neurodevelopmental impairment through adulthood. This study aims to depict the growth pattern of premature or SGA infants and their growth morbidities in Taiwan. METHODS: Data were obtained from a nationally representative cohort of 24,200 pairs of postpartum women and newborns in the Taiwan Birth Cohort Study (TBCS), using structured questionnaire interviews. A total of 16,358 infants were included and three follow-up surveys were completed at 6, 18, and 36 months after the deliveries. We constructed growth curves to conduct an in-depth investigation into anthropometric data, applying a linear mixed model. Logistic regression was used to model the relevant outcomes, with adjustment for various potential confounding factors. RESULTS: Despite being born shorter and lighter, preterm and SGA infants generally showed catch-up growth and had no higher odds ratios (ORs) of developing short stature or failure to thrive compared to appropriate-for-gestational-age (AGA) term infants before 3 years of age. Preterm SGA infants, particularly females, had higher ORs for obesity at the 36-month follow-up. CONCLUSION: This is the first nationwide population-based study depicting the growth of SGA infants in Taiwan. The growth patterns of preterm and term SGA infants are different from those of preterm and term AGA infants. Further research is necessary to understand the growth trajectories of preterm and SGA infants and their associations with later diseases.

Association between high birth weight and dental caries at 4-5 years of age: a birth-cohort study.

OBJECTIVE: Early childhood caries has become a globally crucial oral health problem over the decades. Most studies have discussed the association between low birth weight and early childhood caries; however, studies focusing on high birth weight have been relatively limited. This study aimed to assess the impact of high birth weight on the incidence and severity of dental caries in 4-5-year-old children. SUBJECTS AND METHODS: Study subjects included 491 children from a birth cohort study at 4-5 years of age. Data on dental caries, prenatal and perinatal factors, and socio-demographic determinants were recorded. Logistic regression models adjusted for potential confounders were performed to analyze the data. Two-sided P-value < 0.05 was considered statistically significant. RESULTS: Of the 491 children, the prevalence of dental caries was 48.7%. High birth weight (≥ 4,000 g) was significantly associated with increased incidence of dental caries (OR, 2.000; CI 95% 1.062-3.765), and the relatively enhanced risk OR was further increased in subjects experiencing caries (dmft ≥ 3) (OR, 2.437; CI 95% 1.306-4.549) compared with the normal birth weight (2,500-3,999 g). CONCLUSIONS: High birth weight is a risk factor for early childhood caries. Particular attention should be paid to children with birth weight more than or equal to 4,000 g.

Maternal ozone exposure lowers infant's birthweight: A nationwide cohort of over 4 million livebirths in Iran.

BACKGROUND: Nationwide evidence linking maternal ozone exposure with fetal growth restriction (FGR) was extensively scarce, especially in the Middle East with dry climate and distinct religious culture. METHODS: We carried out a national retrospective birth cohort study using registry-based records from 749 hospitals across 31 provinces in Iran from 2013 to 2018. Monthly concentrations of maximum daily average 8-hour (MDA8) ozone at 0.125° × 0.125° resolution were extracted from well-validated spatiotemporal grid dataset. Linear and logistic regression models were employed to evaluate associations of maternal MDA8 ozone exposure with birthweight outcomes. Assuming causality, the comparative risk assessment framework was utilized to estimate the burden of low birthweight (LBW), small for gestational age (SGA), and birthweight loss per livebirth (BLL) attributable to ambient ozone pollution. RESULTS: Of 4030383 livebirths included in the study, 264304 (6.6%) were LBW and 484405 (12.0%) were SGA. Each 10-ppb increase in MDA8 ozone exposure was associated with an odds ratio of 1.123 (95% confidence interval [CI]: 1.104 to 1.142) for LBW and 1.210 (95% CI: 1.197 to 1.223) for SGA, and a 30.5-g (95% CI: 29.0 to 32.0) reduction in birthweight. We observed approximately linear exposure-response relationships of maternal MDA8 ozone exposure with LBW (Pnonlinear= 0.786), SGA (Pnonlinear= 0.156), and birthweight reduction (Pnonlinear= 0.104). Under the premise of causal association, we estimated 6.6% (95% CI: 5.7 to 7.5) of LBW, 10.1% (95% CI: 9.6 to 10.6) of SGA, and 18.8 g (95% CI: 17.9 to 19.7) of BLL could be attributable to maternal ozone exposure in Iran. Considerably greater risk and burden of ozone-related FGR were observed among younger, less-educated, and rural-dwelling mothers. CONCLUSIONS: Our study provided compelling evidence that maternal ozone exposure was associated with heightened FGR risk and burden, particularly among socioeconomically disadvantaged mothers. These findings underscored the urgent need for government to incorporate socioeconomic factors into future ozone-related health policies, not only to mitigate pollution, but also minimize inequality.

Life-course influences of poverty on violence and homicide: 30-year Brazilian birth cohort study.

BACKGROUND: Homicide is the leading cause of death among young people in Latin America, one of the world's most violent regions. Poverty is widely considered a key cause of violence, but theories suggest different effects of poverty, depending on when it is experienced in the life-course. Longitudinal studies of violence are scarce in Latin America, and very few prospective data are available worldwide to test different life-course influences on homicide. METHODS: In a prospective birth cohort study following 5914 children born in southern Brazil, we examined the role of poverty at birth, in early childhood, and in early adulthood on violence and homicide perpetration, in criminal records up to age 30 years. A novel Structured Life Course Modelling Approach was used to test competing life-course hypotheses about 'sensitive periods', 'accumulation of risk', and 'downward mobility' regarding the influence of poverty on violence and homicide. RESULTS: Cumulative poverty and poverty in early adulthood were the most important influences on violence and homicide perpetration. This supports the hypothesis that early adulthood is a sensitive period for the influence of poverty on lethal and non-lethal violence. Results were replicable using different definitions of poverty and an alternative outcome of self-reported fights. CONCLUSION: Cumulative poverty from childhood to adulthood was an important driver of violence and homicide in this population. However, poverty experienced in early adulthood was especially influential, suggesting the importance of proximal mechanisms for violence in this context, such as unemployment, organized crime, drug trafficking, and ineffective policing and justice systems.

Association between physical activity and cardiovascular parameters in 7-year-old children: a Chinese cross-sectional study.

INTRODUCTION: Physical activity (PA) is believed to play an important part in many aspects during childhood and adolescence, especially cardiorespiratory fitness and cardiometabolic health. However, whether different levels of PA in daily life influence the structure or function of heart in school-aged children remains unknown. We aimed to investigate the association between PA and cardiovascular parameters in 7-year-old children. METHODS: Follow-up data from the Shanghai Prenatal Cohort Study and the Shanghai Birth Cohort was analyzed. Perinatal information including both maternal and offspring datum was recorded. A refined questionnaire was used to evaluate the frequency and duration of children's PA levels. Blood pressure, echocardiography, and anthropometry assessment were conducted during the follow-up of 7-year-old children. RESULTS: Overall, high PA level was associated with higher left ventricle posterior wall thickness in diastole (LVPWd, ß coefficient: 0.36, 95% CI: 0.12, 0.61), higher left ventricle mass index (LVMI, ß = 0.28, 95% CI: 0.07, 0.48), mitral E/a ratio (ß = 0.47, 95% CI: 0.22, 0.71) and slower heart rate (ß = -0.32, 95% CI: -0.57, -0.07), compared to low PA level. Medium PA level was associated with lower diastolic blood pressure (DBP, ß = -0.18, 95% CI: -0.35, -0.01). In subgroup analysis, increased relative wall thickness (RWT) was found in high PA level boys (ß = 0.36, 95% CI: 0.05, 0.67), and systolic blood pressure (SBP) showed a significant decrease in high PA level girls (ß = -0.42, 95% CI: -0.78, -0.06). CONCLUSIONS: This study suggested non-athlete children having higher PA level were associated with thicker left ventricle (LV) walls and better LV diastolic function, as well as slower heart rate and DBP at the age of 7. Furthermore, disparity in the association between PA level with morphological heart patterns and blood pressure existed in different sex category.

Trajectories of egg sensitization in childhood: Two birth cohorts in Asia and Europe.

BACKGROUND: Hen's egg exposure through impaired skin barrier is considered a major mechanism of sensitization to eggs. However, the impact of filaggrin (FLG) gene loss-of-function mutations on the natural history of egg sensitization lacks consensus among studies. OBJECTIVE: To evaluate the association between the natural course of egg sensitization and FLG mutations. METHODS: We used Japanese and the UK birth cohorts (CHIBA and MAAS) to identify the longitudinal patterns of egg sensitization until mid-school age and examined the relationship between the identified patterns and FLG mutations. Sensitization was assessed using egg white-specific IgE levels or skin prick tests (SPTs). Egg allergy was confirmed by parental reports and sensitization. Latent class growth analysis identified longitudinal patterns. RESULTS: Three similar patterns of egg sensitization (persistent, early-onset remitting, and no/low grade classes) were identified in both cohorts, with differing prevalence estimates. The proportion of children with egg allergy in the persistent class at 7 or 8 years of age was 23% (CHIBA) and 20% (MAAS). Consistently in both cohorts, FLG mutations were significantly associated only with the persistent class. Children with FLG mutations had an approximately four-fold increased risk of being in the persistent sensitization class (RRRs: 4.3, 95%C.I. (1.2-16.0), p = .03 in CHIBA; 4.3 (1.3-14.7), p = .02 in MAAS). CONCLUSION: FLG loss-of-function mutations are associated with persistent egg sensitization in both Japanese and European ethnicities, and the mutations might be a potential biomarker for identifying the risk of persistent egg sensitization/allergy in early infancy. Future studies should incorporate oral food challenges to confirm this relationship.

Proteomic analysis of serum in a population-based cohort did not reveal a biomarker for Modic changes.

Introduction: Modic changes (MC) are bone marrow lesions of vertebral bones, which can be detected with magnetic resonance imaging (MRI) adjacent to degenerated intervertebral discs. Defined by their appearance on T1 and T2 weighted images, there are three interconvertible types: MC1, MC2, and MC3. The inter-observer variability of the MRI diagnosis is high, therefore a diagnostic serum biomarker complementing the MRI to facilitate diagnosis and follow-up would be of great value. Methods: We used a highly sensitive and reproducible proteomics approach: DIA/SWATH-MS to find serum biomarkers in a subset of the Northern Finland Birth Cohort 1966. Separately, we measured a panel of factors involved in inflammation and angiogenesis to confirm some potential biomarkers published before with an ELISA-based method called V-Plex. Results: We found neither an association between the serum concentrations of the proteins detected with DIA/SWATH-MS with the presence of MC, nor a correlation with the size of the MC lesions. We did not find any association between the factors measured with the V-Plex and the presence of MC or their size. Conclusion: Altogether, our study suggests that a robust and generally usable biomarker to facilitate the diagnosis of MC cannot readily be found in serum.

Associations of prenatal exposure to PM2.5 and its components with offsprings' neurodevelopmental and behavioral problems: A prospective cohort study from China.

Prenatal exposure to fine particulate matter (PM2.5) has been linked with increased neurodevelopmental disorders. However, the most detrimental component of PM2.5 and the most vulnerable exposure time windows remain undetermined, especially in areas with high PM2.5 levels. In a prospective cohort study involving 4494 mother-child dyads, we examined the associations of prenatal exposure to PM2.5 and its four main components with children's neurodevelopmental and behavioral problems (NBPs), separately in three pregnancy trimesters. Poisson regression and generalized additive models were used to depict the linear and nonlinear associations, respectively. Weighted quantile sum and Bayesian kernel machine regression models were applied to examine the effects of exposure to both mixed and individual components. Results showed that exposure to PM2.5 and its components throughout the three trimesters increased the risk of children's NBPs (Risk ratio for PM2.5: 1.16, 95 % confidence interval 1.14-1.18 per µg/m3 in the first trimester; 1.15, 1.12-1.17 in the second trimester; 1.06, 1.04-1.08 in the third trimester), with associations gradually diminishing as pregnancy progressed (P values for trends < 0.05). Among the four main components of PM2.5, exposure to SO42- posed the highest risks on children's NBPs, while organic matter contributed the largest proportion to the overall impacts of PM2.5 exposure. These results underscore the significance of mitigating PM2.5 exposure in pregnant women to reduce the risk of neurodevelopmental disorders in offspring. Our findings would inform risk assessment of PM2.5 exposure and facilitate the development of precision preventive strategies targeting specific components of PM2.5 in similar areas with high levels of exposure.

Children's nocturnal awakenings and sleep duration during the first two years of life in the NASCITA cohort study.

PURPOSE: Previous studies have analyzed the characteristics and prevalence of sleep disturbances among Italian children. Less attention has been paid, however, to the factors involved in sleep disturbances in the first two years of life. The goals of the present study were, therefore: 1) to provide a developmental trajectory of Italian infants' night awakenings and duration during the first two years of life and 2) to analyze which factors affect night awakenings the most over time. METHODS: Data for this study were collected in the NASCITA cohort. During the well-child visits conducted at 6, 12, and 24 months, pediatricians asked parents to report if the child had any sleep disturbances, especially frequent night awakenings. Univariate and multivariable analyses were performed to test the association between child and family variables and the likelihood of frequent awakenings. RESULTS: 2973 toddlers, out of 5054 initially enrolled newborns, were included in this study; 875 (29.4 %) of whom presented frequent awakenings in at least one visit (peak of prevalence of 19.8 % at 12 months). Bed-sharing (adjusted OR 2.53; 95%CI:2.05-3.12) and living in the northern Italy (aOR 2.25; 95%CI:1.80-2.81) were the variables more strongly associated with an increased likelihood of frequent awakenings in the binomial logistic regression, while sleeping alone was associated with a decreased chance (aOR 0.62; 95%CI 0.45-0.89). A short sleep duration (<11 h/day) was reported for 801 (26.9 %) at 12 months, for 743 (25.0 %) at 24 months of age; in 383 cases, the short sleep duration was reported at both time points. An association was observed between frequent awakenings at 12 or 24 months and short sleep duration (OR 1.23; 95%CI 1.05-1.44 -ꭓ2 6.25, p = 0.012). CONCLUSIONS: The current study identified some early predictors of frequent awakenings during the first two years of life. Since optimal sleep practices in children are essential for their development, effective, early interventions must be defined and integrated into pediatric care practices.

Childhood Nutritional Factors and Cardiometabolic Outcomes at 9-11 y of Age: Findings from the ROLO Longitudinal Birth Cohort Study.

BACKGROUND: Childhood represents a critical period of nutritional risk in the programming of later chronic disease. Few longitudinal studies have explored repeated measures of nutrition throughout the first decade of life in relation to preteen cardiometabolic outcomes. OBJECTIVES: This research aimed to explore associations of early feeding practices (human milk exposure and duration and timing of introduction to solids) and childhood dietary quality and inflammatory scores (at 5 and 9-11 y and change during childhood) on preteen cardiometabolic outcomes. METHODS: This is an analysis of children from the ROLO longitudinal birth cohort study (n = 399). Information on early feeding practices were obtained at postnatal study visits. Food frequency questionnaires collected maternal-reported dietary intakes for each child at 5 and 9-11 y of age. Healthy Eating Index (HEI)-2015 and the Children's Dietary Inflammatory Index (C-DII) scores were calculated. Anthropometry, body composition, blood pressure, heart rate, cardiorespiratory endurance, and blood biomarkers were obtained at 9-11 y. Crude and adjusted linear regression models examined nutritional exposure associations with preteen cardiometabolic outcomes. RESULTS: In the adjusted model, any human milk exposure was associated with lower body fat (%) at 9-11 y (ß: -2.86; 95% confidence interval [CI]: -5.46, -0.27; P = 0.03), than never receiving human milk. At 5 y, diet scores were favorably associated with lean mass at 9-11 y (P < 0.05 for both). Higher preteen HEI-2015 scores were associated with lower preteen leptin levels (tertile 3 compared with tertile 1-ß: -2.92; 95% CI: -5.64, -0.21; P = 0.03). Diet quality significantly deteriorated (HEI-2015 score decreased) and became more proinflammatory (C-DII score increased) from 5 to 9-11 y of age. Diet quality/inflammation deterioration (compared with improvement) or overall change in dietary scores were not related to preteen cardiometabolic outcomes. CONCLUSIONS: Exposure to human milk in early life was associated with lower preteen adiposity, irrespective of duration. Diet quality/inflammatory potential deteriorated between early childhood and the preteen years, highlighting a potential period for intervention.

Prenatal exposure to metal mixtures, body mass index trajectories in early life and effect modifiers: Insights from a prospective birth cohort study.

Current scientific knowledge is insufficient on the effects of metal mixtures on early life growth trajectories. This study included 7118 mother-infant pairs from a Chinese birth cohort. Concentrations of 18 maternal urinary metals were quantified, and growth trajectories were conducted based on standardized body mass index (BMI) for up to eight times from 0 to 2 years. A three-phase analytical framework was applied to explore the risk ratios (RR) and 95 % confidence intervals (95 % CI) of co-exposure to metals on dynamic growth, along with potential modifiers. Five growth trajectory groups were identified. Exposure to metal mixtures driven by thallium (Tl, 34.8 %) and aluminum (Al, 16.2 %) was associated with an increased risk of low-rising trajectory (RR=1.58, 95 % CI: 1.25, 2.00); however, exposure to mixtures driven by strontium (Sr, 49.5 %) exhibited an inverse correlation (RR = 0.81, 95 % CI: 0.67, 0.97). Furthermore, infants with varying levels of Tl, Al and Sr, as well as modifiers including pre-pregnancy BMI and infant sex faced distinct risks of low-rising trajectory. Our findings highlighted the Tl, Al, and Sr as key metals in relation to the low-rising trajectory in early life characterized as catch-up growth, with pre-pregnancy BMI and infant sex exerting as potential modifiers.

Prenatal Parental Exposure to Metals and Birth Defects: A Prospective Birth Cohort Study.

While maternal exposure to high metal levels during pregnancy is an established risk factor for birth defects, the role of paternal exposure remains largely unknown. We aimed to assess the associations of prenatal paternal and maternal metal exposure and parental coexposure with birth defects in singletons. This study conducted within the Jiangsu Birth Cohort recruited couples in early pregnancy. We measured their urinary concentrations for 25 metals. A total of 1675 parent-offspring trios were included. The prevalence of any birth defects among infants by one year of age was 7.82%. Paternal-specific gravity-corrected urinary concentrations of titanium, vanadium, chromium, manganese, cobalt, nickel, copper, and selenium and maternal vanadium, chromium, nickel, copper, selenium, and antimony were associated with a 21-91% increased risk of birth defects after adjusting for covariates. These effects persisted after mutual adjustment for the spouse's exposure. Notably, when assessing the parental mixture effect by Bayesian kernel machine regression, paternal and maternal chromium exposure ranked the highest in relative importance. Parental coexposure to metal mixture showed a pronounced joint effect on the risk of overall birth defects, as well as for some specific subtypes. Our findings suggested a couple-based prevention strategy for metal exposure to reduce birth defects in offspring.

Intrauterine exposure to long-chain perfluorocarboxylic acids (PFCAs) were associated with reduced primary bile acids in three-year-old children: Findings from a prospective birth cohort study.

Bile acids (BAs) play a crucial role in lipid metabolism of children. However, the association between per- and polyfluoroalkyl substance (PFAS) exposure and BAs in children is scarce. To address this need, we selected 252 children from the Maoming Birth Cohort and measured 32 PFAS, encompassing short- and long-chain perfluorocarboxylic acids (PFCAs) and perfluorosulfonic acids (PFSAs) in the cord blood. Additionally, we analyzed nine primary and eight secondary BAs in the serum of three-year-old children. Generalized linear models with FDR-adjusted and Bayesian kernel machine regression (BKMR) were used to explore the associations of individual and mixture effects of PFAS and BAs. We found negative associations between cord blood long-chain PFCAs exposure and serum primary BAs in three-year-old children. For example, one ln-unit (ng/mL) increase of perfluoro-n-tridecanoic acid (PFTrDA), perfluoro-n-undecanoic acid (PFUnDA) and perfluoro-n-decanoic acid (PFDA) were associated with decreased taurochenodeoxycholic acid, with estimated percentage change of -24.28% [95% confidence interval (CI): -36.75%, -9.35%], -25.84% (95% CI: -39.67%, -8.83%), and -22.97% (95% CI: -34.45%, -9.47%) respectively. Notably, the observed associations were more pronounced in children with lower vegetable intake. Additionally, the BKMR model also demonstrated a monotonical decline in primary BAs as the PFAS mixture increased. We provided the first evidence of the association between intrauterine exposure to PFAS and its mixture with BAs in children. Further large-sample-size studies are needed to verify this finding.

Younger Older Americans and Sarcopenic Obesity: The Moderating Role of Living Alone.

OBJECTIVES: Previous studies have indicated that compared to older adults, younger older adults (e.g., baby boomers) are more susceptible to obesity, but their risk decreases as they age. However, there is a lack of research on how individuals experience sarcopenic obesity, which increases in later life and is a mortality risk factor. This study examined how younger cohorts of older Americans and their demographic traits are related to sarcopenic obesity. METHODS: Generalized estimating equations were used to analyze participants aged 65 years and older, stratified by sex using data from the 2006-2016 Health and Retirement Study, with survey weights (n = 2,896 men and n = 4,268 women). RESULTS: The findings indicate that the youngest cohort (born between 1948 and 1953) had greater odds of sarcopenic obesity than older cohorts (born before 1931). However, the youngest cohort did not have significantly different risks from those born between 1931 and 1947. Unexpectedly, the youngest cohort of older women living alone tended not to have sarcopenic obesity compared to the older cohorts living alone. These results remained significant even after adjusting for various covariates, including marital status, race, education level, wealth, and other factors. DISCUSSION: This paper contributes to the existing literature on population health and demographic change in 2 ways. First, the risk of sarcopenic obesity is higher among younger cohorts of older Americans relative to older cohorts (born before 1931). Second, living alone may not necessarily be considered a worse health condition, particularly for younger female cohorts.

Combination of taking neuropsychiatric medications and psychological distress in pregnant women, with behavioral problems in children at 2 years of age: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

Aim: To examine the association of the combination of taking neuropsychiatric medications from the onset of pregnancy to mid-pregnancy and maternal psychological distress at mid-pregnancy, with children's behavioral problems. Methods: Neuropsychiatric medication use from the onset of pregnancy to mid-pregnancy was defined by the self-reported name of the neuropsychiatric medication in the questionnaire in early and mid-pregnancy. Maternal psychological distress was defined by the Kessler Psychological Distress Scale (K6) ≥13 on the questionnaire in mid-pregnancy. We classified the participants into four categories based on the combination of taking neuropsychiatric medications and psychological distress: "None," "Medications only," "K6 ≥ 13 only," and "Both." Children's behavioral problems were assessed using the Child Behavior Checklist for Ages 1½-5 (CBCL) at 2 years of age. The clinical ranges of the internalizing and externalizing scales of the CBCL were defined as behavioral problems. We conducted a multivariable logistic regression analysis to examine the associations between the four categories of maternal exposure and children's behavioral problems. Results: Compared with the "None" category (n = 9873), the "K6 ≥ 13 only" category (n = 308) was statistically significantly associated with internalizing and externalizing problems. In contrast, the "Medications only" (n = 93) and "Both" (n = 22) categories were not statistically significantly associated with internalizing and externalizing problems, although the point estimates of the odds ratio in the "Both" category were relatively high (1.58 for the internalizing problem and 2.50 for the externalizing problem). Conclusion: The category of mothers taking neuropsychiatric medications and having no psychological distress during pregnancy was not associated with children's behavioral problems in the present population.

Pre-pregnancy shift work's influence on postpartum weight retention: Body mass index's role.

Shift work is a prevalent workplace exposure, which increases the possibility of unhealthy behaviours and circadian rhythm disruptions and elevates the risk of metabolic diseases and adverse reproductive outcomes. But its potential of increasing the risk of postpartum weight retention remains uncertain. This study aimed to investigate the association between maternal shift work prior to conception and postpartum weight retention, and to identify modifiable factors during pregnancy for prevention. We analysed data from the Taiwan Birth Cohort Study, a prospective cohort of Taiwanese women who gave birth in 2005. We examined the pre-conceptional shift work status of 13,575 mothers and their body weight before pregnancy, before delivery, six and eighteen months after delivery. We used multivariable linear models to examine associations and effect modifications. Maternal shift work before pregnancy was significantly associated with increased postpartum weight retention at six and eighteen months (ß-estimate for six months: 0.19-kilogram, 95% CI: 0.03-0.34; eighteen months: 0.23-kilogram, 95% CI: 0.04-0.40). The association between shift work and weight retention at six months postpartum was stronger among mothers who were overweight or obese before pregnancy than mothers with normal weight. This study showed the impact of shift work on postpartum weight retention and suggested a stronger association among mothers with overweight or obesity before pregnancy.