Maternal cigarette smoking during pregnancy and offspring DNA methylation in midlife.
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ABSTRACT:
SUBMITTER: Tehranifar P
PROVIDER: S-EPMC5873358 | biostudies-literature | 2018
REPOSITORIES: biostudies-literature
Publications
Maternal cigarette smoking during pregnancy and offspring DNA methylation in midlife.
Tehranifar Parisa P Wu Hui-Chen HC McDonald Jasmine A JA Jasmine Farzana F Santella Regina M RM Gurvich Irina I Flom Julie D JD Terry Mary Beth MB
Epigenetics 20180208 2
Maternal smoking in pregnancy (MSP) has been associated with DNA methylation in specific CpG sites (CpGs) in infants and children. We investigated whether MSP, independent of own personal active smoking, was associated with midlife DNA methylation in CpGs that were previously identified in studies of MSP-DNA methylation in children. We used data on MSP collected from pregnant mothers of 89 adult women born in 1959-1964 and measured DNA methylation in blood (granulocytes) collected in 2001-2007 ( ...[more]
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Project description:BackgroundWe examined whether the effect of maternal smoking during pregnancy on birthweight of the offspring was mediated by smoking-induced changes to DNA methylation in cord blood.MethodsFirst, we used cord blood of 129 Dutch children exposed to maternal smoking vs 126 unexposed to maternal and paternal smoking (53% male) participating in the GECKO Drenthe birth cohort. DNA methylation was measured using the Illumina HumanMethylation450 Beadchip. We performed an epigenome-wide association study for the association between maternal smoking and methylation followed by a mediation analysis of the top signals [false-discovery rate (FDR) < 0.05]. We adjusted both analyses for maternal age, education, pre-pregnancy BMI, offspring's sex, gestational age and white blood cell composition. Secondly, in 175 exposed and 1248 unexposed newborns from two independent birth cohorts, we replicated and meta-analysed results of eight cytosine-phosphate-guanine (CpG) sites in the GFI1 gene, which showed the most robust mediation. Finally, we performed functional network and enrichment analysis.ResultsWe found 35 differentially methylated CpGs (FDR < 0.05) in newborns exposed vs unexposed to smoking, of which 23 survived Bonferroni correction (P < 1 × 10(-7)). These 23 CpGs mapped to eight genes: AHRR, GFI1, MYO1G, CYP1A1, NEUROG1, CNTNAP2, FRMD4A and LRP5. We observed partial confirmation as three of the eight CpGs in GFI1 replicated. These CpGs partly mediated the effect of maternal smoking on birthweight (Sobel P < 0.05) in meta-analysis of GECKO and the two replication cohorts. Differential methylation of these three GFI1 CpGs explained 12-19% of the 202 g lower birthweight in smoking mothers. Functional enrichment analysis pointed towards activation of cell-mediated immunity.ConclusionsMaternal smoking during pregnancy was associated with cord blood methylation differences. We observed a potentially mediating role of methylation in the association between maternal smoking during pregnancy and birthweight of the offspring. Functional network analysis suggested a role in activating the immune system.
| S-EPMC4588868 | biostudies-literature
Project description:RATIONALE:Infants whose mothers smoked during pregnancy demonstrate lifelong decreases in pulmonary function. DNA methylation changes associated with maternal smoking during pregnancy have been described in placenta and cord blood at delivery, in fetal lung, and in buccal epithelium and blood during childhood. We demonstrated in a randomized clinical trial ( ClinicalTrials.gov identifier, NCT00632476) that vitamin C supplementation to pregnant smokers can lessen the impact of maternal smoking on offspring pulmonary function and decrease the incidence of wheeze at 1 year of age. OBJECTIVES:To determine whether vitamin C supplementation reduces changes in offspring methylation in response to maternal smoking and whether methylation at specific CpGs is also associated with respiratory outcomes. METHODS:Targeted bisulfite sequencing was performed with a subset of placentas, cord blood samples, and buccal samples collected during the NCT00632476 trial followed by independent validation of selected cord blood differentially methylated regions, using bisulfite amplicon sequencing. MEASUREMENTS AND MAIN RESULTS:The majority (69.03%) of CpGs with at least 10% methylation difference between placebo and nonsmoker groups were restored (by at least 50%) toward nonsmoker levels with vitamin C treatment. A significant proportion of restored CpGs were associated with phenotypic outcome with greater enrichment among hypomethylated CpGs. CONCLUSIONS:We identified a pattern of normalization in DNA methylation by vitamin C supplementation across multiple loci. The consistency of this pattern across tissues and time suggests a systemic and persistent effect on offspring DNA methylation. Further work is necessary to determine how genome-wide changes in DNA methylation may mediate or reflect persistent effects of maternal smoking on lung function.
| S-EPMC5620677 | biostudies-literature
Project description:Maternal smoking during pregnancy (MSDP) has detrimental effects on fetal development and on the health of the offspring into adulthood. Energy homeostasis through ATP production via the mitochondria (mt) plays a key role during pregnancy. This study aimed to determine if MSDP resulted in differences in DNA methylation to the placental mitochondrial chromosome at the transcription and replication control region, the D-Loop, and if these differences were also present in an alternate neonatal tissue (foreskin) in an independent birth cohort. We investigated mtDNA methylation by bisulfite-pyrosequencing in two sections of the D-Loop control region and in long interspersed nuclear element-1 (LINE-1) genomic sequences in placenta from 96 mother-newborn pairs that were enrolled in a Rhode Island birth cohort along with foreskin samples from 62 infants from a Kentucky birth cohort. In both placenta and foreskin, mtDNA methylation in the light chain D-Loop region 1 was positively associated with MSDP in placenta (difference+2.73%) (P=0.001) and foreskin (difference+1.22%) (P=0.08). Additionally, in foreskin, a second segment of the D-Loop-heavy chain region 1 showed a small but significant change in methylation with MSDP (+0.4%, P=0.04). No methylation changes were noted in either tissue at the LINE-1 repetitive element. We identified a similar pattern of epigenetic effect to mitochondria arising in cells from different primordial lineages and in different populations, associated with MSDP. These robust and consistent results build evidence that MSDP may impact mt D-Loop methylation, as one mechanism through which this exposure affects newborn health.
| S-EPMC5624552 | biostudies-literature
Project description:ObjectiveTo evaluate the possible association between maternal smoking during pregnancy and offspring outcomes of birth weight, pre-term birth, remediation, low scholastic achievement, regular smoking, attention deficit hyperactivity disorder and conduct problems while controlling for similar behaviors in parents.MethodsUsing telephone interviews, data were collected, in 2001 and 2004, as a part of two United States offspring-of-twins projects. Fathers, who were twins participating in the Vietnam Era Twin Registry, their female spouse and their offspring were interviewed - information on 1,342 unique pregnancies in mothers with a history of regular smoking was utilized for these analyses. The association between maternal smoking during pregnancy and birth weight, pre-term birth, remediation, low scholastic achievement, regular smoking, attention deficit hyperactivity disorder and conduct disorder while controlling for similar behaviors in parents, was examined using regression.ResultsMaternal smoking during pregnancy was associated with decreased birth weight, low scholastic achievement, regular smoking and attention deficit hyperactivity disorder. However, the association between maternal smoking during pregnancy and offspring attention deficit hyperactivity disorder was explained by maternal attention deficit hyperactivity disorder. Maternal smoking during pregnancy was also associated with earlier age of offspring initiation of smoking and onset of regular smoking.ConclusionsMaternal smoking during pregnancy may influence certain offspring outcomes via mechanisms that are independent from genetic risk attributable to comorbid conditions. Assisting expecting mothers with their smoking cessation efforts will likely provide widespread health benefits to both mother and offspring.
| S-EPMC2813884 | biostudies-literature
Project description:BackgroundMaternal smoking during pregnancy is associated with significant infant morbidity and mortality, and may influence later disease risk. One mechanism by which smoking (and other environmental factors) might have long-lasting effects is through epigenetic modifications such as DNA methylation.ObjectivesWe conducted an epigenome-wide association study (EWAS) investigating alterations in DNA methylation in infants exposed in utero to maternal tobacco smoke, using the Norway Facial Clefts Study.MethodsThe Illumina HumanMethylation450 BeadChip was used to assess DNA methylation in whole blood from 889 infants shortly after delivery. Of 889 mothers, 287 reported smoking-twice as many smokers as in any previous EWAS of maternal smoking. CpG sites related to maternal smoking during the first trimester were identified using robust linear regression.ResultsWe identified 185 CpGs with altered methylation in infants of smokers at genome-wide significance (q-value < 0.05; mean Δβ = ± 2%). These correspond to 110 gene regions, of which 7 have been previously reported and 10 are newly confirmed using publicly available results. Among these 10, the most noteworthy are FRMD4A, ATP9A, GALNT2, and MEG3, implicated in processes related to nicotine dependence, smoking cessation, and placental and embryonic development.ConclusionsOur study identified 10 genes with newly established links to maternal smoking. Further, we note differences between smoking-related methylation changes in newborns and adults, suggesting possible distinct effects of direct versus indirect tobacco smoke exposure as well as potential differences due to age. Further work would be needed to determine whether these small changes in DNA methylation are biologically or clinically relevant. The methylation changes identified in newborns may mediate the association between in utero maternal smoking exposure and later health outcomes.
| S-EPMC4181928 | biostudies-literature
Project description:BackgroundMaternal smoking during pregnancy, especially when sustained, leads to numerous adverse health outcomes in offspring. Pregnant women disproportionately underreport smoking and smokers tend to have lower follow-up rates to repeat questionnaires. Missing, incomplete, or inaccurate data on presence and duration of smoking in pregnancy impairs identification of novel health effects and limits adjustment for smoking in studies of other pregnancy exposures. An objective biomarker in newborns of maternal smoking during pregnancy would be valuable.ObjectivesWe developed a biomarker of sustained maternal smoking in pregnancy using common DNA methylation platforms.MethodsUsing a dimension reduction method, we developed and tested a numeric score in newborns to reflect sustained maternal smoking in pregnancy from data on cotinine, a short-term smoking biomarker measured mid-pregnancy, and Illumina450K cord blood DNA methylation from newborns in the Norwegian Mother and Child Cohort Study (MoBa).ResultsThis score reliably predicted smoking status in the training set (n = 1,057; accuracy = 96%, sensitivity = 80%, specificity = 98%). Sensitivity (58%) was predictably lower in the much smaller test set (n = 221), but accuracy (91%) and specificity (97%) remained high. Reduced birth weight, a well-known effect of maternal smoking, was as strongly related to the score as to cotinine. A three-site score had lower, but acceptable, performance (accuracytrain = 82%, accuracytest = 83%).ConclusionsOur smoking methylation score represents a promising novel biomarker of sustained maternal smoking during pregnancy easily calculated with Illumina450K or IlluminaEPIC data. It may help identify novel health impacts and improve adjustment for smoking when studying other risk factors with more subtle effects.
| S-EPMC5381987 | biostudies-literature
Project description:BACKGROUND:Prenatal smoking exposure affects fetal growth and development and is associated with increased risk of various neurodevelopmental disorders. Only one previous study has examined the association between maternal smoking during pregnancy and the risk of bipolar disorder (BPD). METHODS:In this nested case control study derived from all singleton live births in Finland between January 1st 1987 and December 31st 1998, we identified 724 children diagnosed and/or treated with BPD until 2008 and 1419 matched controls from four nationwide registers. Conditional logistic regression was used to examine the association between maternal smoking during pregnancy and BPD adjusting for potential confounding due to parental psychiatric history, maternal age and education level. RESULTS:18.5% of offspring were exposed to maternal smoking during pregnancy. In the unadjusted analysis, smoking during pregnancy was associated with a 1.41-fold (95% CI 1.12-1.79, P=0.004) increased risk of BPD. In the final model adjusting for potential covariates, the risk was 1.14-fold (95% CI 0.88-1.49, P=0.323). LIMITATIONS:The limitations of this study include: hospital based clinical diagnosis for case ascertainment, inclusion of early onset BPD cases, and lack of information on alcohol or other substance abuse during pregnancy. CONCLUSION:This study demonstrated that, in this sample, an increased risk of BPD among offspring of mothers who smoked during pregnancy is most likely due to confounding by familial background factors. Future studies including information on serological measures of smoking exposure in pregnancy e.g. cotinine are warranted to further clarify this association.
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Project description:BackgroundExisting evidence on the link between smoking and appendicitis is scarce and ambiguous. We therefore conducted a population-based cohort study in Denmark to investigate whether smoking during pregnancy is associated with an increased risk of appendicitis in offspring.MethodsWe used the Danish Birth Registry to include all singletons born during 1991-2017 and to identify maternal smoking status during pregnancy. We followed the children from birth until date of appendicitis, emigration, death, or administrative end of study (31 December 2018), whichever came first. We calculated crude and adjusted hazard ratios (HRs) of appendicitis with 95% confidence intervals (CIs) comparing children of mothers who smoked during pregnancy to children of nonsmokers. Further, we conducted a bias analysis and sibling analysis.ResultsWe included 1,659,526 singletons of whom 19% were born to mothers who smoked during pregnancy. After maximum 28 years of follow-up, hazard rates for children of smokers were slightly higher than for children of nonsmokers [adjusted HR: 1.07 (95% CI = 1.04, 1.10)]. Stratification by sex revealed no association for males [adjusted HR: 1.02 (95% CI = 0.99, 1.06)], but a higher HR for females [adjusted HR: 1.13 (95% CI = 1.09, 1.18)]. This association increased with increasing length of follow-up, indicating that the association may be mediated by later-life exposures. The bias analysis indicated that misclassification of maternal smoking could attenuate a true association, while the sibling analysis showed no association.ConclusionsMaternal smoking during pregnancy and appendicitis in the offspring may be associated.
| S-EPMC9891296 | biostudies-literature
Project description:ObjectiveMaternal smoking during pregnancy (MSDP) has been associated with offspring internalizing and externalizing disorders. The purpose of this research is to examine whether MSDP is also associated with variations in normal personality traits in childhood and adulthood.MethodThis study uses four independent samples (total N = 16,323) to examine whether there are mean-level differences in offspring personality traits by MSDP, controlling for relevant sociodemographic factors. Two samples are of children (Ns = 3,782 and 3,841) and two samples are of adults (Ns = 1,786 and 6,914).ResultsA meta-analysis across the four samples indicated that offspring of mothers who did smoke during pregnancy scored higher in Neuroticism (p = .000) and Extraversion (p = .003) and lower in Conscientiousness (p = .002) than offspring of mothers who did not smoke during pregnancy. The association between MSDP and Neuroticism and Conscientiousness held across both childhood and adulthood and when propensity score matching was used, whereas the association with Extraversion was only apparent in adulthood and did not hold with propensity scores.ConclusionsThese results suggest that MSDP is associated with individual differences in psychological traits in childhood and adulthood and may be one prenatal factor that contributes to trait Neuroticism and Conscientiousness.
| S-EPMC5817044 | biostudies-literature
Project description:To assess whether associations between maternal smoking during pregnancy and offspring smoking initiation are due to intrauterine mechanisms.Comparison of associations of maternal and partner smoking behaviour during pregnancy with offspring smoking initiation using partner smoking as a negative control (n?=?6484) and a Mendelian randomization analysis (n?=?1020), using a genetic variant in the mothers as a proxy for smoking cessation during pregnancy.A longitudinal birth cohort in South West England.Participants of the Avon Longitudinal Study of Parents and Children (ALSPAC).Smoking status during pregnancy was self-reported by mother and partner in questionnaires administered at pregnancy. Latent classes of offspring smoking initiation (non-smokers, experimenters, late-onset regular smokers and early-onset regular smokers) were previously developed from questionnaires administered at 14-16 years. A genetic variant, rs1051730, was genotyped in the mothers.Both mother and partner smoking were similarly positively associated with offspring smoking initiation classes, even after adjustment for confounders. Odds ratios (OR) [95% confidence interval (CI)] for class membership compared with non-smokers were: experimenters: mother OR?=?1.33 (95% CI?=?1.06, 1.67), partner OR?=?1.28 (95% CI?=?1.06, 1.55), late-onset regular smokers: mother OR?=?1.80 (95% CI?=?1.43, 2.26), partner OR?=?1.86 (95% CI?=?1.52, 2.28) and early-onset regular smokers: mother OR?=?2.89 (95% CI?=?2.12, 3.94), partner OR?=?2.50 (95% CI?=?1.85, 3.37). There was no clear evidence for a dose-response effect of either mother or partner smoking heaviness on class membership. Maternal rs1051730 genotype was not clearly associated with offspring smoking initiation class in pre-pregnancy smokers (P?=?0.35).The association between smoking during pregnancy and offspring smoking initiation does not appear to operate through intrauterine mechanisms.
| S-EPMC4114534 | biostudies-literature