Perfluoroalkyl Substances in Pregnancy and the Risk of Preeclampsia

Perfluoroalkyl substances (PFASs) are persistent, ubiquitous environmental contaminants and may be related to preeclampsia, a common pregnancy complication. Previous studies have found serum concentrations of PFASs to be positively associated with serum cholesterol in non-pregnant individuals, and also associated with pregnancy-induced hypertension, including preeclampsia. Using data from the large, population-based Norwegian Mother and Child Cohort (MoBa) Study, we estimated associations between PFAS concentrations measured during pregnancy and an independently validated diagnosis of preeclampsia. Additionally, we estimated associations between mid-pregnancy PFAS concentrations and plasma lipid concentrations in order to evaluate one possible mechanism of association between PFASs and preeclampsia. A case-cohort study was conducted to estimate associations between mid-pregnancy plasma PFAS concentrations and preeclampsia. In proportional hazards models adjusted for maternal age, pre-pregnancy body mass index, education and smoking, we observed no positive associations between PFASs and preeclampsia. However, we found an inverse association between perfluoroundecanoic acid (PFUnDA) and preeclampsia, with a hazard ratio of 0.8 (95% confidence interval [CI]=0.7, 0.9) per natural-log unit increase in PFUnDA. In a separate cross-sectional analysis, we found positive associations between mid-pregnancy plasma concentrations of seven PFASs and high-density lipoprotein cholesterol (HDL). The greatest change in HDL per natural-log unit of exposure was associated with PFUnDA. HDL increased 3.7 mg/dL per interquartile shift in PFUnDA (95% CI=2.5, 4.9). A multi-pollutant model for HDL including seven PFAS exposures also showed the strongest association with PFUnDA compared with the other six PFASs. Additionally, perfluorooctane sulfonate (PFOS) was positively associated with plasma total cholesterol. Total cholesterol increased 4.2 mg/dL per interquartile shift in PFOS (95% CI=0.8, 7.7) in adjusted models. We found positive associations between certain PFASs and plasma lipid parameters, and we observed that different PFASs may have different strengths of association with lipid parameters during pregnancy. We did not observe any positive associations between mid-pregnancy plasma PFAS concentrations and a validated diagnosis of preeclampsia. The plasma concentrations of PFOA in this study, while within the range of previous studies of non-occupationally exposed populations, are substantially lower than exposure levels in the previous study that found associations between PFOA and preeclampsia.Doctor of Philosoph

Behavioural risks in female dogs with minimal lifetime exposure to gonadal hormones

Spaying of female dogs is a widespread practice, performed primarily for population control. While the consequences of early spaying for health are still being debated, the consequences for behaviour are believed to be negligible. The current study focused on the reported behaviour of 8981 female dogs spayed before 520 weeks (ten years) of life for reasons other than behavioural management, and calculated their percentage lifetime exposure to gonadal hormones (PLGH) as a proportion of their age at the time of being reported to the online Canine Behavioral Assessment and Research Questionnaire (C-BARQ). We found that 23 behaviours differed between entire and spayed dogs, of which 12 were associated with PLGH and 5 with age-at-spay (AAS). Two behaviours, chewing and howling, were significantly more likely in dogs with longer PLGH. In contrast, longer PLGH was associated with significantly reduced reporting of 10 (mostly unwelcome) behaviours. Of these, one related to fearfulness and three to aggression. The current data suggest that dogs’ tendency to show numerous behaviours can be influenced by the timing of spaying. They indicate how female dog behaviour matures when gonadal hormones are allowed to have their effect. The differences reported here between undesirable behaviours of spayed and entire dogs were in the range of 5.33% and 7.22%, suggesting that, for some dogs, partial or complete denial of maturation may reduce howling and chewing and improve retrieval and recall, but have other undesirable consequences. Veterinarians may take these data into account to discuss the risks and benefits of spaying with clients, and the timing of the procedure

Pesticide use and incident diabetes among wives of farmers in the Agricultural Health Study

To estimate associations between use of specific agricultural pesticides and incident diabetes in women

An epigenome-wide association study of child appetitive traits and DNA methylation

The etiology of childhood appetitive traits is poorly understood. Early-life epigenetic processes may be involved in the developmental programming of appetite regulation in childhood. One such process is DNA methylation (DNAm), whereby a methyl group is added to a specific part of DNA, where a cytosine base is next to a guanine base, a CpG site. We meta-analyzed epigenome-wide association studies (EWASs) of cord blood DNAm and early-childhood appetitive traits. Data were from two independent cohorts: the Generation R Study (n = 1,086, Rotterdam, the Netherlands) and the Healthy Start study (n = 236, Colorado, USA). DNAm at autosomal methylation sites in cord blood was measured using the Illumina Infinium HumanMethylation450 BeadChip. Parents reported on their child's food responsiveness, emotional undereating, satiety responsiveness and food fussiness using the Children's Eating Behaviour Questionnaire at age 4–5 years. Multiple regression models were used to examine the association of DNAm (predictor) at the individual site- and regional-level (using DMRff) with each appetitive trait (outcome), adjusting for covariates. Bonferroni-correction was applied to adjust for multiple testing. There were no associations of DNAm and any appetitive trait when examining individual CpG-sites. However, when examining multiple CpGs jointly in so-called differentially methylated regions, we identified 45 associations of DNAm with food responsiveness, 7 associations of DNAm with emotional undereating, 13 associations of DNAm with satiety responsiveness, and 9 associations of DNAm with food fussiness. This study shows that DNAm in the newborn may partially explain variation in appetitive traits expressed in early childhood and provides preliminary support for early programming of child appetitive traits through DNAm. Investigating differential DNAm associated with appetitive traits could be an important first step in identifying biological pathways underlying the development of these behaviors.</p

Associations of maternal BMI and gestational weight gain with neonatal adiposity in the Healthy Start study

Background: Maternal obesity and weight gain during pregnancy are risk factors for child obesity. Associations may be attributable to causal effects of the intrauterine environment or genetic and postnatal environmental factors

Prenatal metal(loid) mixtures and birth weight for gestational age: A pooled analysis of three cohorts participating in the ECHO program

Background: A growing number of studies have identified both toxic and essential metals which influence fetal growth. However, most studies have conducted single-cohort analyses, which are often limited by narrow exposure ranges, and evaluated metals individually. The objective of the current study was to conduct an environmental mixture analysis of metal impacts on fetal growth, pooling data from three geographically and demographically diverse cohorts in the United States participating in the Environmental Influences on Child Health Outcomes program. Methods: The pooled sample (N = 1,002) included participants from the MADRES, NHBCS, and PROTECT cohorts. Associations between seven metals (antimony, cadmium, cobalt, mercury, molybdenum, nickel, tin) measured in maternal urine samples collected during pregnancy (median: 16.0 weeks gestation) and birth weight for gestational age z-scores (BW for GA) were investigated using Bayesian Kernel Machine Regression (BKMR). Models were also stratified by cohort and infant sex to investigate possible heterogeneity. Chromium and uranium concentrations fell below the limits of detection for most participants and were evaluated separately as binary variables using pooled linear regression models. Results: In the pooled BKMR analysis, antimony, mercury, and tin were inversely and linearly associated with BW for GA, while a positive linear association was identified for nickel. The inverse association between antimony and BW for GA was observed in both males and females and for all three cohorts but was strongest for MADRES, a predominantly low-income Hispanic cohort in Los Angeles. A reverse j-shaped association was identified between cobalt and BW for GA, which was driven by female infants. Pooled associations were null for cadmium, chromium, molybdenum, and uranium, and BKMR did not identify potential interactions between metal pairs. Conclusions: Findings suggest that antimony, an understudied metalloid, may adversely impact fetal growth. Cohort- and/or sex-dependent associations were identified for many of the metals, which merit additional investigation

Maternal Mediterranean diet in pregnancy and newborn DNA methylation:a meta-analysis in the PACE Consortium

Data de publicació electrònica: 02-03-2022Higher adherence to the Mediterranean diet during pregnancy is related to a lower risk of preterm birth and to better offspring cardiometabolic health. DNA methylation may be an underlying biological mechanism. We evaluated whether maternal adherence to the Mediterranean diet was associated with offspring cord blood DNA methylation.We meta-analysed epigenome-wide association studies (EWAS) of maternal adherence to the Mediterranean diet during pregnancy and offspring cord blood DNA methylation in 2802 mother-child pairs from five cohorts. We calculated the relative Mediterranean diet (rMED) score with range 0-18 and an adjusted rMED excluding alcohol (rMEDp, range 0-16). DNA methylation was measured using Illumina 450K arrays. We used robust linear regression modelling adjusted for child sex, maternal education, age, smoking, body mass index, energy intake, batch, and cell types. We performed several functional analyses and examined the persistence of differential DNA methylation into childhood (4.5-7.8 y).rMEDp was associated with cord blood DNA methylation at cg23757341 (0.064% increase in DNA methylation per 1-point increase in the rMEDp score, SE = 0.011, P = 2.41 × 10-8). This cytosine-phosphate-guanine (CpG) site maps to WNT5B, associated with adipogenesis and glycaemic phenotypes. We did not identify associations with childhood gene expression, nor did we find enriched biological pathways. The association did not persist into childhood.In this meta-analysis, maternal adherence to the Mediterranean diet (excluding alcohol) during pregnancy was associated with cord blood DNA methylation level at cg23757341. Potential mediation of DNA methylation in associations with offspring health requires further study.This work was supported by the Foundation for the National Institutes of Health [R01 HD034568, UH3 OD023286, R01 NR013945, R01 HL111108]; Joint Programming Initiative A healthy diet for a healthy life [529051023, MR/S036520/1, 529051022, MR/S036520/1, MR/S036520/1]; National Institute of Environmental Health Sciences [R00ES025817]; National institute of diabetes and digestive and kidney diseases [R01DK076648]; National Institutes of Health Office of the Director [UH3OD023248]; Horizon 2020 research and innovation [874739, 733206, 848158, 824989]; Medical Research Council [MR/S009310/1]

Association between Perfluoroalkyl substances and thyroid stimulating hormone among pregnant women: a cross-sectional study

BackgroundPerfluoroalkyl substances (PFASs) are a group of highly persistent chemicals that are widespread contaminants in wildlife and humans. Exposure to PFAS affects thyroid homeostasis in experimental animals and possibly in humans. The objective of this study was to examine the association between plasma concentrations of PFASs and thyroid stimulating hormone (TSH) among pregnant women.MethodsA total of 903 pregnant women who enrolled in the Norwegian Mother and Child Cohort Study from 2003 to 2004 were studied. Concentrations of thirteen PFASs and TSH were measured in plasma samples collected around the 18th week of gestation. Linear regression models were used to evaluate associations between PFASs and TSH.ResultsAmong the thirteen PFASs, seven were detected in more than 60% of samples and perfluorooctane sulfonate (PFOS) had the highest concentrations (median, 12.8ng/mL; inter-quartile range [IQR], 10.1 -16.5ng/mL). The median TSH concentration was 3.5 (IQR, 2.4 - 4.8) μIU/mL. Pregnant women with higher PFOS had higher TSH levels. After adjustment, with each 1ng/mL increase in PFOS concentration, there was a 0.8% (95% confidence interval: 0.1%, 1.6%) rise in TSH. The odds ratio of having an abnormally high TSH, however, was not increased, and other PFASs were unrelated to TSH.ConclusionsOur results suggest an association between PFOS and TSH in pregnant women that is small and may be of no clinical significance

Longitudinal associations of DNA methylation and sleep in children : a meta-analysis

Publisher Copyright: © 2022, The Author(s).Background: Sleep is important for healthy functioning in children. Numerous genetic and environmental factors, from conception onwards, may influence this phenotype. Epigenetic mechanisms such as DNA methylation have been proposed to underlie variation in sleep or may be an early-life marker of sleep disturbances. We examined if DNA methylation at birth or in school age is associated with parent-reported and actigraphy-estimated sleep outcomes in children. Methods: We meta-analysed epigenome-wide association study results. DNA methylation was measured from cord blood at birth in 11 cohorts and from peripheral blood in children (4–13 years) in 8 cohorts. Outcomes included parent-reported sleep duration, sleep initiation and fragmentation problems, and actigraphy-estimated sleep duration, sleep onset latency and wake-after-sleep-onset duration. Results: We found no associations between DNA methylation at birth and parent-reported sleep duration (n = 3658), initiation problems (n = 2504), or fragmentation (n = 1681) (p values above cut-off 4.0 × 10–8). Lower methylation at cg24815001 and cg02753354 at birth was associated with longer actigraphy-estimated sleep duration (p = 3.31 × 10–8, n = 577) and sleep onset latency (p = 8.8 × 10–9, n = 580), respectively. DNA methylation in childhood was not cross-sectionally associated with any sleep outcomes (n = 716–2539). Conclusion: DNA methylation, at birth or in childhood, was not associated with parent-reported sleep. Associations observed with objectively measured sleep outcomes could be studied further if additional data sets become available.Peer reviewe