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Prenatal exposure to maternal cigarette smoking and DNA methylation: epigenome-wide association in a discovery sample of adolescents and replication in an independent cohort at birth through 17 years of age.

ABSTRACT: BACKGROUND:Prenatal exposure to maternal cigarette smoking (prenatal smoke exposure) had been associated with altered DNA methylation (DNAm) at birth. OBJECTIVE:We examined whether such alterations are present from birth through adolescence. METHODS:We used the Infinium HumanMethylation450K BeadChip to search across 473,395 CpGs for differential DNAm associated with prenatal smoke exposure during adolescence in a discovery cohort (n = 132) and at birth, during childhood, and during adolescence in a replication cohort (n = 447). RESULTS:In the discovery cohort, we found five CpGs in MYO1G (top-ranking CpG: cg12803068, p = 3.3 × 10-11) and CNTNAP2 (cg25949550, p = 4.0 × 10-9) to be differentially methylated between exposed and nonexposed individuals during adolescence. The CpGs in MYO1G and CNTNAP2 were associated, respectively, with higher and lower DNAm in exposed versus nonexposed adolescents. The same CpGs were differentially methylated at birth, during childhood, and during adolescence in the replication cohort. In both cohorts and at all developmental time points, the differential DNAm was in the same direction and of a similar magnitude, and was not altered appreciably by adjustment for current smoking by the participants or their parents. In addition, four of the five EWAS (epigenome-wide association study)-significant CpGs in the adolescent discovery cohort were also among the top sites of differential methylation in a previous birth cohort, and differential methylation of CpGs in CYP1A1, AHRR, and GFI1 observed in that study was also evident in our discovery cohort. CONCLUSIONS:Our findings suggest that modifications of DNAm associated with prenatal maternal smoking may persist in exposed offspring for many years-at least until adolescence.

SUBMITTER: Lee KW

PROVIDER: S-EPMC4314251 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Prenatal exposure to maternal cigarette smoking and DNA methylation: epigenome-wide association in a discovery sample of adolescents and replication in an independent cohort at birth through 17 years of age.

Lee Ken W K KW Richmond Rebecca R Hu Pingzhao P French Leon L Shin Jean J Bourdon Celine C Reischl Eva E Waldenberger Melanie M Zeilinger Sonja S Gaunt Tom T McArdle Wendy W Ring Susan S Woodward Geoff G Bouchard Luigi L Gaudet Daniel D Smith George Davey GD Relton Caroline C Paus Tomas T Pausova Zdenka Z

Environmental health perspectives 20141017 2

<h4>Background</h4>Prenatal exposure to maternal cigarette smoking (prenatal smoke exposure) had been associated with altered DNA methylation (DNAm) at birth.<h4>Objective</h4>We examined whether such alterations are present from birth through adolescence.<h4>Methods</h4>We used the Infinium HumanMethylation450K BeadChip to search across 473,395 CpGs for differential DNAm associated with prenatal smoke exposure during adolescence in a discovery cohort (n = 132) and at birth, during childhood, an ...[more]

PMID: 25325234

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Project description:ImportanceCigarette smoking during pregnancy increases the risk of preterm birth, low birth weight, and infant mortality.ObjectiveTo assess the probability of preterm birth among expectant mothers who smoked cigarettes before pregnancy and quit smoking at the start or during pregnancy.Design, setting, and participantsThis cross-sectional study analyzed information provided on live birth certificates from 2011 through 2017 that were obtained from US states that implemented the 2003 revision of the US live birth certificate. In total, 25?233?503 expectant mothers who delivered live neonates and had known prepregnancy and trimester-specific cigarette smoking frequency were included in the analyses.ExposuresCigarette smoking frequency (1-9, 10-19, and ?20 cigarettes per day) 3 months prior to pregnancy and for each trimester during pregnancy.Main outcomes and measuresCigarette smoking cessation throughout pregnancy, after the first trimester, after the second trimester, and during the third trimester irrespective of first and second trimester smoking. Probability of preterm birth (<37 weeks' gestation).ResultsOf 25?233?503 expectant mothers who delivered live neonates between 2011 and 2017, the modal age at delivery was 25 to 29 years; 52.9% were non-Hispanic white, 23.6% were Hispanic, and 14.2% were non-Hispanic black women; 22?600?196 mothers did not smoke during the 3 months prior to pregnancy, and 2?633?307 smoked during the 3 months prior to pregnancy. The proportion of prepregnancy smokers who quit throughout pregnancy was 24.3% in 2011 and 24.6% in 2017. The proportion of prepregnancy smokers who quit during the third trimester was 39.5% in 2011 and 39.7% in 2017. High-frequency cigarette smoking often occurred among expectant mothers who smoked during pregnancy (eg, 46.9% of third-trimester smokers smoked ?10 cigarettes per day in 2017). The probability of preterm birth decreased more the earlier smoking cessation occurred in pregnancy. For example, the probability of preterm birth was 9.8% (95% CI, 9.7%-10.0%) among 25- to 29-year-old, non-Hispanic white, primigravida and primiparous expectant mothers (ie, pregnant for the first time and not yet delivered) who smoked 1 to 9 cigarettes per day prior to pregnancy and maintained this frequency throughout their pregnancy. The probability of preterm birth was 9.0% (95% CI, 8.8%-9.1%) if smoking cessation occurred at the start of the second trimester (an 8.9% relative decrease), and 7.8% (95% CI, 7.7%-8.0%) if cessation occurred at the start of pregnancy (a 20.3% relative decrease).Conclusions and relevanceQuitting smoking-and quitting early in pregnancy-was associated with reduced risk of preterm birth even for high-frequency cigarette smokers.

Project description:IntroductionTobacco smoking and alcohol consumption during pregnancy are particularly prevalent in low socioeconomic status populations, with an adverse association with birth outcomes and cardiometabolic risk factors. However, the direct and indirect effects of prenatal cigarette smoking and alcohol consumption during pregnancy on cardiometabolic risk in offspring have been rather inconsistent. This may be attributed to multiple factors, such as the amount and timing of exposure to tobacco smoking and alcohol during pregnancy; the influence of maternal, environmental and socioeconomic factors; or how risk factors were defined by individual researchers and studies. Therefore, this review aims to provide a summary of the most recent evidence on birth outcomes and cardiometabolic risk in children associated with alcohol and/or tobacco exposure in utero.Methods and analysisPubMed, Scopus and Web of Science will be searched to identify published articles from 1 January 2001. Clinical studies that investigate the association between maternal cigarette smoking or alcohol consumption and birth weight and cardiometabolic risk factors in infants, children and adolescents will be included. Prospective cohort, case-control studies and birth cohort studies will be eligible for inclusion. Grey literature will be searched including conference proceedings, Google Scholar and the ProQuest Dissertation and Theses database. Only studies published in English will be included, with no restrictions regarding country, race or gender. Two independent reviewers will conduct the literature search and article screening. Eligibility criteria will be based on the population (infants, children, adolescents), exposure (maternal cigarette smoking, alcohol consumption or both), comparator (control group with no exposure during pregnancy) and outcomes (birth weight and cardiometabolic risk factors). Quality assessment and risk of bias will be assessed using a risk of bias tool for observational studies, and data will be extracted for analysis using a researcher-generated data extraction form. A meta-analysis will be performed to estimate pooled effect sizes if there are sufficient good-quality studies available. Sources of heterogeneity will be explored using subgroup analysis.Ethics and disseminationEthical clearance will not be required as this review will extract publicly available secondary data. Findings from this review will be disseminated via publication in a peer-review journal.Prospero registration numberCRD42021286630.

Project description:BACKGROUND:Maternal mood disorders and their treatment during pregnancy may have effects on the offspring epigenome. We aim to evaluate associations of maternal prenatal antidepressant use, anxiety, and depression with cord blood DNA methylation across the genome at birth and test for persistence of associations in early and mid-childhood blood DNA. METHODS:A discovery phase was conducted in Project Viva, a prospective pre-birth cohort study with external replication in an independent cohort, the Generation R Study. In Project Viva, pregnant women were recruited between 1999 and 2002 in Eastern Massachusetts, USA. In the Generation R Study, pregnant women were recruited between 2002 and 2006 in Rotterdam, the Netherlands. In Project Viva, 479 infants had data on maternal antidepressant use, anxiety, depression, and cord blood DNA methylation, 120 children had DNA methylation measured in early childhood (~ 3 years), and 460 in mid-childhood (~ 7 years). In the Generation R Study, 999 infants had data on maternal antidepressants and cord blood DNA methylation. The prenatal antidepressant prescription was obtained from medical records. At-mid pregnancy, symptoms of anxiety and depression were assessed with the Pregnancy-Related Anxiety Scale and the Edinburgh Postnatal Depression Scale in Project Viva and with the Brief Symptom Inventory in the Generation R Study. Genome-wide DNA methylation was measured using the Infinium HumanMethylation450 BeadChip in both cohorts. RESULTS:In Project Viva, 2.9% (14/479) pregnant women were prescribed antidepressants, 9.0% (40/445) experienced high pregnancy-related anxiety, and 8.2% (33/402) reported symptoms consistent with depression. Newborns exposed to antidepressants in pregnancy had 7.2% lower DNA methylation (95% CI, - 10.4, - 4.1; P = 1.03 × 10-8) at cg22159528 located in the gene body of ZNF575, and this association replicated in the Generation R Study (β = - 2.5%; 95% CI - 4.2, - 0.7; P = 0.006). In Project Viva, the association persisted in early (β = - 6.2%; 95% CI - 10.7, - 1.6) but not mid-childhood. We observed cohort-specific associations for maternal anxiety and depression in Project Viva that did not replicate. CONCLUSIONS:The ZNF575 gene is involved in transcriptional regulation but specific functions are largely unknown. Given the widespread use of antidepressants in pregnancy, as well as the effects of exposure to anxiety and depression, implications of potential fetal epigenetic programming by these risk factors and their impacts on development merit further investigation.

Project description:Despite awareness of negative health outcomes associated with smoking, pregnant smokers might reduce their tobacco consumption thinking that a low smoking rate reduces smoking-related negative birth outcomes. We aimed to assess in a clinical sample whether there is a smoking rate that would not impact on birth weight (BW).Pregnant smokers ?18 years, gestational age of 9-20 weeks of amenorrhea, motivated to quit smoking, smoking ?5 cigarettes/day (cpd) and their newborns (381 singleton, live births) were included in this secondary analysis of a French smoking cessation trial.The mean BW when the mother quit smoking was 3417 g (95 % CI: 3098-3738 g); when smoking >0<5 cpd, 3081g (3003-3159 g); when smoking 5-9 cpd, 3043 g (2930-3157 g); and when smoking ?10 cpd, 2831 g (2596-3157 g) (p = .006). The corresponding effect sizes ranged from medium to large (Cohen's d for BW: 0.54, 0.57 and 0.85) compared to BW when the mother quit. In the multivariable analysis, adjusted for all significant confounders, when the mother smoked on average >0<5 cpd, the loss in BW was 228 g; when smoking 5-9 cpd, 251 g; and when smoking ?10 cpd, 262 g (all p ? .02) compared to newborns' BW of mothers who stopped smoking since quit date.Even low cigarette consumption during pregnancy is associated with BW loss. All efforts should be made to help pregnant smokers quit completely during their pregnancy.As an alternative to quitting smoking, pregnant smokers reduce their smoking rate thinking that this diminishes smoking-related negative health outcomes. No study has established whether low smoking rate (more than 0 but less than 5 cpd) during pregnancy impacts BW compared to abstinence from smoking. Among treatment-seeking pregnant smokers BW of newborns of mothers who smoked even less than 5 cpd was significantly lower than of those whose mothers quit; effect sizes of different consumption levels on BW ranged from moderate (>0<5 cpd) to large (?10 cpd). Even low smoking rate is associated with reduced BW compared to complete maternal smoking abstinence.

Dataset Information

Prenatal exposure to maternal cigarette smoking and DNA methylation: epigenome-wide association in a discovery sample of adolescents and replication in an independent cohort at birth through 17 years of age.

Publications

Prenatal exposure to maternal cigarette smoking and DNA methylation: epigenome-wide association in a discovery sample of adolescents and replication in an independent cohort at birth through 17 years of age.

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