A meta-analysis of epigenome-wide association studies on pregnancy vitamin B12 concentrations and offspring DNA methylation

This is the final version. Available on open access from Routledge via the DOI in this record. Data availability statement: Analysis plan and R code for cohort-specific analyses and meta-analyses are available via https://github.com/GiuliettaMonasso/PACE-B12-meta-analysis-of-EWAS. The dataset(s) supporting the conclusions of this article is available in the [Zenodo repository]. All further relevant data supporting the key findings of this study are available within the article and its Supplementary Information files or from the corresponding author upon reasonable request and subject to the study-specific data access procedures. Requests for access to the individual-level data for ALSPAC can be directed to GCS: [email protected]. Requests for access to the individual-level data for GENR can be directed to JFF: [email protected]. Requests for access to the individual-level data for INMA can be directed to MB: [email protected]. Requests for access to the individual-level data for MARBLES can be directed to RJS: [email protected]. Requests for access to the individual-level data for MoBa1 and MoBa2 can be directed to SEH: [email protected] vitamin B12 concentrations during pregnancy are associated with offspring health. Foetal DNA methylation changes could underlie these associations. Within the Pregnancy And Childhood Epigenetics Consortium, we meta-analysed epigenome-wide associations of circulating vitamin B12 concentrations in mothers during pregnancy (n = 2,420) or cord blood (n = 1,029), with cord blood DNA methylation. Maternal and newborn vitamin B12 concentrations were associated with DNA methylation at 109 and 7 CpGs, respectively (False Discovery Rate P-value <0.05). Persistent associations with DNA methylation in the peripheral blood of up to 482 children aged 4-10 y were observed for 40.7% of CpGs associated with maternal vitamin B12 and 57.1% of CpGs associated with newborn vitamin B12. Of the CpGs identified in the maternal meta-analyses, 4.6% were associated with either birth weight or gestational age in a previous work. For the newborn meta-analysis, this was the case for 14.3% of the identified CpGs. Also, of the CpGs identified in the newborn meta-analysis, 14.3% and 28.6%, respectively, were associated with childhood cognitive skills and nonverbal IQ. Of the 109 CpGs associated with maternal vitamin B12, 18.3% were associated with nearby gene expression. In this study, we showed that maternal and newborn vitamin B12 concentrations are associated with DNA methylation at multiple CpGs in offspring blood (PFDR<0.05). Whether this differential DNA methylation underlies associations of vitamin B12 concentrations with child health outcomes, such as birth weight, gestational age, and childhood cognition, should be further examined in future studies.Medical Research Council (MRC)European Research Council (ERC

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

Higher adherence to the Mediterranean diet during pregnancy may be related to offspring cord blood DNA methylation. In a meta-analysis of epigenome-wide association studies (EWAS) in 2802 mother-child pairs from 5 cohorts we calculated the relative Mediterranean diet (rMED) score and an adjusted rMED excluding alcohol (rMEDp). rMEDp was associated with cord blood DNA methylation at cg23757341

Circulating n-3 fatty acid levels and total and cause-specific mortality: A de novo pooled analysis from 17 prospective studies

The health effects of omega-3 fatty acids (n-3 FAs) have been controversial. A de novo pooled analysis was conducted with 17 prospective cohort studies examining the associations between blood n-3 FAs levels and risk for all-cause mortality. Over a median of 15 years of follow-up, 15,720 deaths occurred among 42,466 individuals. After adjustment for relevant risk factors, risk for death from all causes was significantly lower (by 15-18%) in the highest vs the lowest quintile for circulating long chain (20-22 carbon) n-3 FAs, but not for the 18-carbon n-3 FA. These novel findings suggest that higher circulating levels of marine n-3 PUFA may be associated with a lower risk of premature death.The EPIC Norfolk study (DOI 10.22025/2019.10.105.00004) has received funding from the Medical Research Council (MR/N003284/1 and MC-UU_12015/1) and Cancer Research UK (C864/A14136). NJW, NGF, and FI were supported by the Medical Research Council Epidemiology Unit core funding [MC_UU_12015/1 and MC_UU_12015/5]. NJW and NGF acknowledge support from the National Institute for Health Research Cambridge Biomedical Research Centre [IS-BRC-1215-20014] and NJW is an NIHR Senior Investigator

Impact of maternal body mass index and gestational weight gain on pregnancy complications: an individual participant data meta‐analysis of European, North American and Australian cohorts

ObjectiveTo assess the separate and combined associations of maternal pre-pregnancy body mass index (BMI) and gestational weight gain with the risks of pregnancy complications and their population impact.DesignIndividual participant data meta-analysis of 39 cohorts.SettingEurope, North America, and Oceania.Population265&nbsp;270 births.MethodsInformation on maternal pre-pregnancy BMI, gestational weight gain, and pregnancy complications was obtained. Multilevel binary logistic regression models were used.Main outcome measuresGestational hypertension, pre-eclampsia, gestational diabetes, preterm birth, small and large for gestational age at birth.ResultsHigher maternal pre-pregnancy BMI and gestational weight gain were, across their full ranges, associated with higher risks of gestational hypertensive disorders, gestational diabetes, and large for gestational age at birth. Preterm birth risk was higher at lower and higher BMI and weight gain. Compared with normal weight mothers with medium gestational weight gain, obese mothers with high gestational weight gain had the highest risk of any pregnancy complication (odds ratio 2.51, 95% CI 2.31- 2.74). We estimated that 23.9% of any pregnancy complication was attributable to maternal overweight/obesity and 31.6% of large for gestational age infants was attributable to excessive gestational weight gain.ConclusionsMaternal pre-pregnancy BMI and gestational weight gain are, across their full ranges, associated with risks of pregnancy complications. Obese mothers with high gestational weight gain are at the highest risk of pregnancy complications.&nbsp;Promoting a healthy pre-pregnancy BMI and gestational weight gain may reduce the burden of pregnancy complications and ultimately the risk of maternal and neonatal morbidity.Tweetable abstractPromoting a healthy body mass index and gestational weight gain might reduce the population burden of pregnancy complications