Measured maternal prepregnancy anthropometry and newborn DNA methylation.
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ABSTRACT:
SUBMITTER: Yeung EH
PROVIDER: S-EPMC6371845 | biostudies-literature | 2019 Feb
REPOSITORIES: biostudies-literature
Publications
Measured maternal prepregnancy anthropometry and newborn DNA methylation.
Yeung Edwina H EH Guan Weihua W Mumford Sunni L SL Silver Robert M RM Zhang Cuilin C Tsai Michael Y MY Schisterman Enrique F EF
Epigenomics 20190108 2
<h4>Aim</h4>We examined maternal prepregnancy anthropometry and cord blood DNA methylation.<h4>Methods</h4>Associations between maternal measures (i.e., weight, height, waist circumference, hip circumference, skinfolds, leptin) and methylation β-values at each CpG (measured by the Infinium MethylationEPIC BeadChip) were estimated among 391 singletons.<h4>Results</h4>Total of 18% of mothers were obese (body mass index ≥ 30) and 27% centrally obese (waist-to-hip ratio ≥ 0.85). One Bonferroni signi ...[more]
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Project description:BackgroundPreconception nutrition sets the stage for a healthy pregnancy. Maternal fatty acids (FAs) are related to beneficial neonatal outcomes with DNA methylation proposed as a mechanism; however, few studies have investigated this association and none with preconception FAs.ObjectivesWe examined the relations of maternal plasma FA concentrations at preconception (n = 346) and 8 weeks of gestation (n = 374) with newborn DNA methylation.MethodsThe Effects of Aspirin in Gestation and Reproduction Trial (2006-2012) randomly assigned women with previous pregnancy loss to low dose aspirin or placebo prior to conception. We measured maternal plasma phospholipid FA concentration at preconception (on average 4 mo before pregnancy) and 8 weeks of gestation. Cord blood DNA from singletons was measured using the MethylationEPIC BeadChip. We used robust linear regression to test the associations of FA concentration with methylation ?-values of each CpG site, adjusting for estimated cell count using a cord blood reference, sample plate, maternal sociodemographic characteristics, cholesterol, infant sex, and epigenetic-derived ancestry. False discovery rate correction was used for multiple testing.ResultsMean ± SD concentrations of preconception marine (20:5n-3+22:6n-3+22:5n-3) and ?-6 PUFAs, SFAs, MUFAs, and trans FAs were 4.7 ± 1.2, 38.0 ± 2.0, 39.4 ± 1.8, 11.6 ± 1.1, and 1.0 ± 0.4 % of total FA, respectively; concentrations at 8 weeks of gestation were similar. Preconception marine PUFA concentration was associated with higher methylation at GRAMD2 (P = 1.1 × 10-8), LOXL1 (P = 5.5 × 10-8), SIK3 (P = 1.6 × 10-7), HTR1B (P = 1.9 × 10-7), and MCC (P = 2.1 × 10-7) genes. Preconception SFA concentration was associated with higher methylation at KIF25-AS1 and lower methylation at SLC39A14; other associations exhibited sensitivity to outliers. The trans FA concentration was related to lower methylation at 3 sites and higher methylation at 1 site. FAs at 8 weeks of gestation were largely unrelated to DNA methylation.ConclusionsMaternal preconception FAs are related to newborn DNA methylation of specific CpG sites, highlighting the importance of examining nutritional exposures preconceptionally. This trial was registered at clinicaltrials.gov as NCT00467363.
| S-EPMC7049533 | biostudies-literature
Project description:BackgroundMaternal obesity prior to or during pregnancy influences fetal growth, predisposing the offspring to increased risk for obesity across the life course. Placental epigenetic mechanisms may underlie these associations. We conducted an epigenome-wide association study to identify placental DNA methylation changes associated with maternal prepregnancy body mass index (BMI) and rate of gestational weight gain at first (GWG1), second (GWG2), and third trimester (GWG3).MethodParticipants of the NICHD Fetal Growth Studies with genome-wide placental DNA methylation (n = 301) and gene expression (n = 75) data were included. Multivariable-adjusted regression models were used to test the associations of 1 kg/m2 increase in prepregnancy BMI or 1 kg/week increase in GWG with DNA methylation levels. Genes harboring top differentially methylated CpGs (FDR P < 0.05) were evaluated for placental gene expression. We assessed whether DNA methylation sites known to be associated with BMI in child or adult tissues, were also associated with maternal prepregnancy BMI in placenta.ResultsPrepregnancy BMI was associated with DNA methylation at cg14568196[EGFL7], cg15339142[VETZ], and cg02301019[AC092377.1] (FDR P < 0.05, P ranging from 1.4 × 10-10 to 1.7 × 10-9). GWG1 or GWG2 was associated with DNA methylation at cg17918270[MYT1L], cg20735365[DLX5], and cg17451688[SLC35F3] (FDR P < 0.05, P ranging from 6.4 × 10-10 to 1.2 × 10-8). Both prepregnancy BMI and DNA methylation at cg1456819 [EGFL7] were negatively correlated with EGFL7 expression in placenta (P < 0.05). Several CpGs previously implicated in obesity traits in children and adults were associated with prepregnancy BMI in placenta. Functional annotations revealed that EGFL7 is highly expressed in placenta and the differentially methylated CpG sites near EGFL7 and VEZT were cis-meQTL targets in blood.ConclusionsWe identified placental DNA methylation changes at novel loci associated with prepregnancy BMI and GWG. The overlap between CpGs associated with obesity traits in placenta and other tissues in children and adults suggests that epigenetic mechanisms in placenta may give insights to early origins of obesity.
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Project description:Around 15–65% of women globally experience depression during pregnancy, prevalence being particularly high in low- and middle-income countries. Prenatal depression has been associated with adverse birth and child development outcomes. DNA methylation (DNAm) may aid in understanding this association. In this project, we analyzed associations between prenatal depression and DNAm from cord blood from participants of the South African Drakenstein Child Health Study. We examined DNAm in an epigenome-wide association study (EWAS) of 248 mother-child pairs. DNAm was measured using the Infinium MethylationEPIC (N = 145) and the Infinium HumanMethylation450 (N = 103) arrays. Prenatal depression scores, obtained with the Edinburgh Postnatal Depression Scale (EPDS) and the Beck Depression Inventory-II (BDI-II), were analyzed as continuous and dichotomized variables. We used linear robust models to estimate associations between depression and newborn DNAm, adjusted for measured (smoking status, household income, sex, preterm birth, cell type proportions, and genetic principal components) and unmeasured confounding using Cate and Bacon algorithms. Bonferroni correction was used to adjust for multiple testing. DMRcate and dmrff were used to test for differentially methylated regions (DMRs). Differential DNAm was significantly associated with BDI-II variables, in cg16473797 (Δ beta = −1.10E-02, p = 6.87E-08), cg23262030 (Δ beta per BDI-II total IQR = 1.47E-03, p = 1.18E-07), and cg04859497 (Δ beta = −6.42E-02, p = 1.06E-09). Five DMRs were associated with at least two depression variables. Further studies are needed to replicate these findings and investigate their biological impact.
| S-EPMC8576002 | biostudies-literature
Project description: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.
| S-EPMC8595870 | biostudies-literature
Project description:Background: Changes in DNA methylation patterns with age frequently have been observed and implicated in the normal aging process and its associated increasing risk of disease, particularly cancer. Additionally, the offspring of older parents are at significantly increased risk of cancer, diabetes, and neurodevelopmental disorders. Only a proportion of these increased risks among the children of older parents can be attributed to nondisjunction and chromosomal rearrangements. Results: Using a genome-wide survey of 27,578 CpG dinucleotides in a cohort of 168 newborns, we examined the relationship between DNA methylation in newborns and a variety of parental and newborn traits. We found that methylation levels of 144 CpGs belonging to 142 genes were significantly correlated with maternal age. A weaker correlation was observed with paternal age. Among these genes, processes related to cancer were over-represented, as were functions related to neurological regulation, glucose/carbohydrate metabolism, nucleocytoplasmic transport, and transcriptional regulation. CpGs exhibiting gender differences in methylation were overwhelmingly located on the X chromosome, although a small subset of autosomal CpGs were found in genes previously shown to exhibit gender-specific differences in methylation levels. Conclusions: These results indicate that there are differences in CpG methylation levels at birth that are related to parental age and that could influence disease risk in childhood and throughout life. 168 newborn umbilical cord buffy coat samples run singly as a cross-sectional study, not case-control.
2011-08-31 | E-GEOD-27317 | biostudies-arrayexpress
Project description:Background: Changes in DNA methylation patterns with age frequently have been observed and implicated in the normal aging process and its associated increasing risk of disease, particularly cancer. Additionally, the offspring of older parents are at significantly increased risk of cancer, diabetes, and neurodevelopmental disorders. Only a proportion of these increased risks among the children of older parents can be attributed to nondisjunction and chromosomal rearrangements. Results: Using a genome-wide survey of 27,578 CpG dinucleotides in a cohort of 168 newborns, we examined the relationship between DNA methylation in newborns and a variety of parental and newborn traits. We found that methylation levels of 144 CpGs belonging to 142 genes were significantly correlated with maternal age. A weaker correlation was observed with paternal age. Among these genes, processes related to cancer were over-represented, as were functions related to neurological regulation, glucose/carbohydrate metabolism, nucleocytoplasmic transport, and transcriptional regulation. CpGs exhibiting gender differences in methylation were overwhelmingly located on the X chromosome, although a small subset of autosomal CpGs were found in genes previously shown to exhibit gender-specific differences in methylation levels. Conclusions: These results indicate that there are differences in CpG methylation levels at birth that are related to parental age and that could influence disease risk in childhood and throughout life.
2011-09-01 | GSE27317 | GEO
Project description:Long-chain omega-3 fatty acid status during pregnancy may influence newborn anthropometry and duration of gestation. Evidence from high-quality trials from low- and middle-income countries (LMICs) is limited. We conducted a double-blind, randomized, placebo-controlled trial among 957 pregnant women (singleton gestation, 14-20 weeks' gestation at enrollment) in India to test the effectiveness of 400 mg/day algal docosahexaenoic acid (DHA) compared to placebo provided from enrollment through delivery. Among 3379 women who were screened, 1171 were found eligible; 957 were enrolled and were randomized. The intervention was two microencapsulated algal DHA (200 × 2 = 400 mg/day) or two microencapsulated soy and corn oil placebo tablets to be consumed daily from enrollment (≤20 weeks) through delivery. The primary outcome was newborn anthropometry (birth weight, length, head circumference). Secondary outcomes were gestational age and 1 and 5 min Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) score. The groups (DHA; n = 478 and placebo; n = 479) were well balanced at baseline. There were 902 live births. Compliance with the intervention was similar across groups (DHA: 88.5%; placebo: 87.1%). There were no significant differences between DHA and placebo groups for birth weight (2750.6 ± 421.5 vs. 2768.2 ± 436.6 g, p = 0.54), length (47.3 ± 2.0 vs. 47.5 ± 2.0 cm, p = 0.13), or head circumference (33.7 ± 1.4 vs. 33.8 ± 1.4 cm, p = 0.15). The mean gestational age at delivery was similar between groups (DHA: 38.8 ± 1.7 placebo: 38.8 ± 1.7 wk, p = 0.54) as were APGAR scores at 1 and 5 min. Supplementing mothers through pregnancy with 400 mg/day DHA did not impact the offspring's birthweight, length, or head circumference.
| S-EPMC7996222 | biostudies-literature
Project description:OBJECTIVE:To characterize the association of longitudinal changes in maternal anthropometric measures with neonatal anthropometry and to assess to what extent late-gestational changes in maternal anthropometry are associated with neonatal body composition. DESIGN:In a prospective cohort of pregnant women, maternal anthropometry was measured at six study visits across pregnancy and after birth, neonates were measured and fat and lean mass calculated. We estimated maternal anthropometric trajectories and separately assessed rate of change in the second (15-28 weeks) and third trimester (28-39 weeks) in relation to neonatal anthropometry. We investigated the extent to which tertiles of third-trimester maternal anthropometry change were associated with neonatal outcomes. SETTING:Women were recruited from twelve US sites (2009-2013).ParticipantsNon-obese women with singleton pregnancies (n 2334). RESULTS:A higher rate of increase in gestational weight gain was associated with larger-birth-weight infants with greater lean and fat mass. In contrast, higher rates of increase in maternal anthropometry measures were not associated with infant birth weight but were associated with decreased neonatal lean mass. In the third trimester, women in the tertile of lowest change in triceps skinfold (-0·57 to -0·06 mm per week) had neonates with 35·8 g more lean mass than neonates of mothers in the middle tertile of rate of change (-0·05 to 0·06 mm per week). CONCLUSIONS:The rate of change in third-trimester maternal anthropometry measures may be related to neonatal lean and fat mass yet have a negligible impact on infant birth weight, indicating that neonatal anthropometry may provide additional information over birth weight alone.
| S-EPMC6440828 | biostudies-literature
Project description:ObjectiveMaternal gestational diabetes mellitus (GDM) has been associated with adverse outcomes in the offspring. Growing evidence suggests that the epigenome may play a role, but most previous studies have been small and adjusted for few covariates. The current study meta-analyzed the association between maternal GDM and cord blood DNA methylation in the Pregnancy and Childhood Epigenetics (PACE) consortium.Research design and methodsSeven pregnancy cohorts (3,677 mother-newborn pairs [317 with GDM]) contributed results from epigenome-wide association studies, using DNA methylation data acquired by the Infinium HumanMethylation450 BeadChip array. Associations between GDM and DNA methylation were examined using robust linear regression, with adjustment for potential confounders. Fixed-effects meta-analyses were performed using METAL. Differentially methylated regions (DMRs) were identified by taking the intersection of results obtained using two regional approaches: comb-p and DMRcate.ResultsTwo DMRs were identified by both comb-p and DMRcate. Both regions were hypomethylated in newborns exposed to GDM in utero compared with control subjects. One DMR (chr 1: 248100345-248100614) was located in the OR2L13 promoter, and the other (chr 10: 135341870-135342620) was located in the gene body of CYP2E1. Individual CpG analyses did not reveal any differentially methylated loci based on a false discovery rate-adjusted P value threshold of 0.05.ConclusionsMaternal GDM was associated with lower cord blood methylation levels within two regions, including the promoter of OR2L13, a gene associated with autism spectrum disorder, and the gene body of CYP2E1, which is upregulated in type 1 and type 2 diabetes. Future studies are needed to understand whether these associations are causal and possible health consequences.
| S-EPMC6925578 | biostudies-literature
Project description:Measurements of neonatal metabolites are commonly used in newborn screening (NBS) programs to detect inborn errors of metabolism. Variation in these metabolites, particularly in infants born preterm (<37 weeks gestation), can result from multiple etiologies. We sought to evaluate the impact of maternal complications of pregnancy and environmental stressors on NBS metabolites.We examined 49 metabolic biomarkers obtained from routine NBS in 452 infants born preterm for association with maternal environmental stressors and complications of pregnancy.Neonatal free carnitine (C0, p = 1.4 × 10(-7)), acetylcarnitine (C2, p = 2.7 × 10(-7)), octenoylcarnitine (C8:1, p = 5.2 × 10(-11)) and linoleoylcarnitine (C18:2, p = 9.1 × 10(-7)) were elevated in infants born to preeclamptic mothers. Similar elevations were observed in small for gestational age infants and in infants where labor was not initiated prior to delivery. When accounting for all three factors, associations remained strongest between acylcarnitines and preeclampsia.We observed that maternal conditions, particularly preeclampsia, influence NBS biomarkers. This is important for identifying maternal conditions that influence metabolites measured during routine NBS that are also markers of fetal growth and overall health.
| S-EPMC3753672 | biostudies-literature