Dataset Information

Maternal anxiety during pregnancy and newborn epigenome-wide DNA methylation.

ABSTRACT: Maternal anxiety during pregnancy is associated with adverse foetal, neonatal, and child outcomes, but biological mechanisms remain unclear. Altered foetal DNA methylation (DNAm) has been proposed as a potential underlying mechanism. In the current study, we performed a meta-analysis to examine the associations between maternal anxiety, measured prospectively during pregnancy, and genome-wide DNAm from umbilical cord blood. Sixteen non-overlapping cohorts from 12 independent longitudinal studies of the Pregnancy And Childhood Epigenetics Consortium participated, resulting in a combined dataset of 7243 mother-child dyads. We examined prenatal anxiety in relation to genome-wide DNAm and differentially methylated regions. We observed no association between the general symptoms of anxiety during pregnancy or pregnancy-related anxiety, and DNAm at any of the CpG sites, after multiple-testing correction. Furthermore, we identify no differentially methylated regions associated with maternal anxiety. At the cohort-level, of the 21 associations observed in individual cohorts, none replicated consistently in the other cohorts. In conclusion, contrary to some previous studies proposing cord blood DNAm as a promising potential mechanism explaining the link between maternal anxiety during pregnancy and adverse outcomes in offspring, we found no consistent evidence for any robust associations between maternal anxiety and DNAm in cord blood. Larger studies and analysis of DNAm in other tissues may be needed to establish subtle or subgroup-specific associations between maternal anxiety and the foetal epigenome.

SUBMITTER: Sammallahti S

PROVIDER: S-EPMC8595870 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Maternal anxiety during pregnancy and newborn epigenome-wide DNA methylation.

Sammallahti Sara S Cortes Hidalgo Andrea P AP Tuominen Samuli S Malmberg Anni A Mulder Rosa H RH Brunst Kelly J KJ Alemany Silvia S McBride Nancy S NS Yousefi Paul P Heiss Jonathan A JA McRae Nia N Page Christian M CM Jin Jianping J Pesce Giancarlo G Caramaschi Doretta D Rifas-Shiman Sheryl L SL Koen Nastassja N Adams Charleen D CD Magnus Maria C MC Baïz Nour N Ratanatharathorn Andrew A Czamara Darina D Håberg Siri E SE Colicino Elena E Baccarelli Andrea A AA Cardenas Andres A DeMeo Dawn L DL Lawlor Deborah A DA Relton Caroline L CL Felix Janine F JF van IJzendoorn Marinus H MH Bakermans-Kranenburg Marian J MJ Kajantie Eero E Räikkönen Katri K Sunyer Jordi J Sharp Gemma C GC Houtepen Lotte C LC Nohr Ellen A EA Sørensen Thorkild I A TIA Téllez-Rojo Martha M MM Wright Robert O RO Annesi-Maesano Isabella I Wright John J Hivert Marie-France MF Wright Rosalind J RJ Zar Heather J HJ Stein Dan J DJ London Stephanie J SJ Cecil Charlotte A M CAM Tiemeier Henning H Lahti Jari J

Molecular psychiatry 20210107 6

Maternal anxiety during pregnancy is associated with adverse foetal, neonatal, and child outcomes, but biological mechanisms remain unclear. Altered foetal DNA methylation (DNAm) has been proposed as a potential underlying mechanism. In the current study, we performed a meta-analysis to examine the associations between maternal anxiety, measured prospectively during pregnancy, and genome-wide DNAm from umbilical cord blood. Sixteen non-overlapping cohorts from 12 independent longitudinal studies ...[more]

PMID: 33414500

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Project description:BackgroundUnbalanced iron homeostasis in pregnancy is associated with an increased risk of adverse birth and childhood health outcomes. DNA methylation has been suggested as a potential underlying mechanism linking environmental exposures such as micronutrient status during pregnancy with offspring health. We performed a meta-analysis on the association of maternal early-pregnancy serum ferritin concentrations, as a marker of body iron stores, and cord blood DNA methylation. We included 1286 mother-newborn pairs from two population-based prospective cohorts. Serum ferritin concentrations were measured in early pregnancy. DNA methylation was measured with the Infinium HumanMethylation450 BeadChip (Illumina). We examined epigenome-wide associations of maternal early-pregnancy serum ferritin and cord blood DNA methylation using robust linear regression analyses, with adjustment for confounders and performed fixed-effects meta-analyses. We additionally examined whether associations of any CpGs identified in cord blood persisted in the peripheral blood of older children and explored associations with other markers of maternal iron status. We also examined whether similar findings were present in the association of cord blood serum ferritin concentrations with cord blood DNA methylation.ResultsMaternal early-pregnancy serum ferritin concentrations were inversely associated with DNA methylation at two CpGs (cg02806645 and cg06322988) in PRR23A and one CpG (cg04468817) in PRSS22. Associations at two of these CpG sites persisted at each of the follow-up time points in childhood. Cord blood serum ferritin concentrations were not associated with cord blood DNA methylation levels at the three identified CpGs.ConclusionMaternal early-pregnancy serum ferritin concentrations were associated with lower cord blood DNA methylation levels at three CpGs and these associations partly persisted in older children. Further studies are needed to uncover the role of these CpGs in the underlying mechanisms of the associations of maternal iron status and offspring health outcomes.

Project description:BackgroundMaternal pre-pregnancy obesity is an established risk factor for childhood obesity. Investigating epigenetic alterations induced by maternal obesity during fetal development could gain mechanistic insight into the developmental origins of childhood obesity. While obesity disproportionately affects underrepresented racial and ethnic mothers and children in the USA, few studies investigated the role of prenatal epigenetic programming in intergenerational obesity of these high-risk populations.MethodsThis study included 903 mother-child pairs from the Boston Birth Cohort, a predominantly urban, low-income minority birth cohort. Mother-infant dyads were enrolled at birth and the children were followed prospectively to age 18 years. Infinium Methylation EPIC BeadChip was used to measure epigenome-wide methylation level of cord blood. We performed an epigenome-wide association study of maternal pre-pregnancy body mass index (BMI) and cord blood DNA methylation (DNAm). To quantify the degree to which cord blood DNAm mediates the maternal BMI-childhood obesity, we further investigated whether maternal BMI-associated DNAm sites impact birthweight or childhood overweight or obesity (OWO) from age 1 to age 18 and performed corresponding mediation analyses.ResultsThe study sample contained 52.8% maternal pre-pregnancy OWO and 63.2% offspring OWO at age 1-18 years. Maternal BMI was associated with cord blood DNAm at 8 CpG sites (genome-wide false discovery rate [FDR] < 0.05). After accounting for the possible interplay of maternal BMI and smoking, 481 CpG sites were discovered for association with maternal BMI. Among them 123 CpGs were associated with childhood OWO, ranging from 42% decrease to 87% increase in OWO risk for each SD increase in DNAm. A total of 14 identified CpG sites showed a significant mediation effect on the maternal BMI-child OWO association (FDR < 0.05), with mediating proportion ranging from 3.99% to 25.21%. Several of these 14 CpGs were mapped to genes in association with energy balance and metabolism (AKAP7) and adulthood metabolic syndrome (CAMK2B).ConclusionsThis prospective birth cohort study in a high-risk yet understudied US population found that maternal pre-pregnancy OWO significantly altered DNAm in newborn cord blood and provided suggestive evidence of epigenetic involvement in the intergenerational risk of obesity.

Project description:BackgroundPhysical activity (PA) prior to and during pregnancy may have intergenerational effects on offspring health through placental epigenetic modifications. We are unaware of epidemiologic studies on longitudinal PA and placental DNA methylation.ObjectivesWe evaluated the association between PA before and during pregnancy and placental DNA methylation.MethodsPlacental tissues were obtained at delivery and methylation was measured using HumanMethylation450 Beadchips for participants in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies-Singletons among 298 participants. Using the Pregnancy Physical Activity Questionnaire, women recalled periconception PA (past 12 mo) at 8-13 wk of gestation and PA since last visit at 4 follow-up visits at 16-22, 24-29, 30-33, and 34-37 wk. We conducted linear regression for associations of PA at each visit with methylation controlling for false discovery rate (FDR). Top 100 CpGs were queried for enrichment of functional pathways using Ingenuity Pathway Analysis.ResultsPericonception PA was significantly associated with 1 CpG site. PA since last visit for visits 1-4 was associated with 2, 2, 8, and 0 CpGs (log fold changes ranging from -0.0319 to 0.0080, after controlling for FDR). The largest change in methylation occurred at a site in TIMP2 , which is known to encode a protein critical for vasodilation, placentation, and uterine expansion during pregnancy (log fold change: -0.05; 95% CI: -0.06, -0.03 per metabolic equivalent of task-h/wk at 30-33 wk). Most significantly enriched pathways include cardiac hypertrophy signaling, B-cell receptor signaling, and netrin signaling. Significant CpGs and enriched pathways varied by visit.ConclusionsRecreational PA in the year prior and during pregnancy was associated with placental DNA methylation. The associated CpG sites varied based on timing of PA. If replicated, the findings may inform the mechanisms underlying the impacts of PA on placenta health. This study was registered at clinicaltrials.gov as NCT00912132.

Dataset Information

Maternal anxiety during pregnancy and newborn epigenome-wide DNA methylation.

Publications

Maternal anxiety during pregnancy and newborn epigenome-wide DNA methylation.

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