scholarly journals Mediation by Placental DNA Methylation of the Association of Prenatal Maternal Smoking and Birth Weight

2019 ◽  
Vol 188 (11) ◽  
pp. 1878-1886 ◽  
Author(s):  
Andres Cardenas ◽  
Sharon M Lutz ◽  
Todd M Everson ◽  
Patrice Perron ◽  
Luigi Bouchard ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Birth Weight ◽  
Maternal Smoking ◽  
Cell Types ◽  
Prenatal Smoking ◽  
Association Analyses ◽  
Lower Birth Weight ◽  
Cpg Sites ◽  
Prenatal Maternal Smoking ◽  
Infant Birth

Abstract Prenatal maternal smoking is a risk factor for lower birth weight. We performed epigenome-wide association analyses of placental DNA methylation (DNAm) at 720,077 cytosine-phosphate-guanine (CpG) sites and prenatal maternal smoking among 441 mother-infant pairs (2010–2014) and evaluated whether DNAm mediates the association between smoking and birth weight using mediation analysis. Mean birth weight was 3,443 (standard deviation, 423) g, and 38 mothers (8.6%) reported smoking at a mean of 9.4 weeks of gestation. Prenatal maternal smoking was associated with a 175-g lower birth weight (95% confidence interval (CI): −305.5, −44.8) and with differential DNAm of 71 CpGs in placenta, robust to latent-factor adjustment reflecting cell types (Bonferroni-adjusted P < 6.94 × 10−8). Of the 71 CpG sites, 7 mediated the association between prenatal smoking and birth weight (on MDS2, PBX1, CYP1A2, VPRBP, WBP1L, CD28, and CDK6 genes), and prenatal smoking × DNAm interactions on birth weight were observed for 5 CpG sites. The strongest mediator, cg22638236, was annotated to the PBX1 gene body involved in skeletal patterning and programming, with a mediated effect of 301-g lower birth weight (95% CI: −543, −86) among smokers but no mediated effect for nonsmokers (β = −38 g; 95% CI: −88, 9). Prenatal maternal smoking might interact with placental DNAm at specific loci, mediating the association with lower infant birth weight.

scholarly journals DNA methylation links prenatal smoking exposure to later life health outcomes in offspring

2018 ◽  
Author(s):  
Petri Wiklund ◽  
Ville Karhunen ◽  
Rebecca C Richmond ◽  
Alina Rodriguez ◽  
Maneka De Silva ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Health Outcomes ◽  
Maternal Smoking ◽  
Psychiatric Morbidity ◽  
Later Life ◽  
Prenatal Smoking ◽  
Smoking During Pregnancy ◽  
Mediation Analyses ◽  
Increased Risk ◽  
Prenatal Maternal Smoking

AbstractMaternal smoking during pregnancy is associated with adverse offspring health outcomes across their life course. We hypothesize that DNA methylation is a potential mediator of this relationship. To test this, we examined the association of prenatal maternal smoking with DNA methylation in 2,821 individuals (age 16 to 48 years) from five prospective birth cohort studies and perform Mendelian randomization and mediation analyses to assess, whether methylation markers have causal effects on disease outcomes in the offspring. We identify 69 differentially methylated CpGs in 36 genomic regions (P < 1×10−7), and show that DNA methylation may represent a biological mechanism through which maternal smoking is associated with increased risk of psychiatric morbidity in the exposed offspring.

scholarly journals Variable DNA methylation in neonates mediates the association between prenatal smoking and birth weight

2019 ◽  
Vol 374 (1770) ◽  
pp. 20180120 ◽  
Author(s):  
Eilis Hannon ◽  
Diana Schendel ◽  
Christine Ladd-Acosta ◽  
Jakob Grove ◽  
Christine Søholm Hansen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Birth Weight ◽  
Gestational Age ◽  
Maternal Smoking ◽  
Evolutionary Medicine ◽  
Prenatal Smoking ◽  
Smoking During Pregnancy ◽  
Significance Threshold ◽  
Birth Factors ◽  
Obstetric Factors

There is great interest in the role epigenetic variation induced by non-genetic exposures may play in the context of health and disease. In particular, DNA methylation has previously been shown to be highly dynamic during the earliest stages of development and is influenced by in utero exposures such as maternal smoking and medication. In this study we sought to identify the specific DNA methylation differences in blood associated with prenatal and birth factors, including birth weight, gestational age and maternal smoking. We quantified neonatal methylomic variation in 1263 infants using DNA isolated from a unique collection of archived blood spots taken shortly after birth (mean = 6.08 days; s.d. = 3.24 days). An epigenome-wide association study (EWAS) of gestational age and birth weight identified 4299 and 18 differentially methylated positions (DMPs) respectively, at an experiment-wide significance threshold of p < 1 × 10 −7 . Our EWAS of maternal smoking during pregnancy identified 110 DMPs in neonatal blood, replicating previously reported genomic loci, including AHRR . Finally, we tested the hypothesis that DNA methylation mediates the relationship between maternal smoking and lower birth weight, finding evidence that methylomic variation at three DMPs may link exposure to outcome. These findings complement an expanding literature on the epigenomic consequences of prenatal exposures and obstetric factors, confirming a link between the maternal environment and gene regulation in neonates. This article is part of the theme issue ‘Developing differences: early-life effects and evolutionary medicine’.

scholarly journals Predicting Complex Traits and Exposures From Polygenic Scores and Blood and Buccal DNA Methylation Profiles

2021 ◽  
Vol 12 ◽  
Author(s):  
Veronika V. Odintsova ◽  
Valerie Rebattu ◽  
Fiona A. Hagenbeek ◽  
René Pool ◽  
Jeffrey J. Beck ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Birth Weight ◽  
Complex Traits ◽  
Maternal Smoking ◽  
Smoking Status ◽  
Association Studies ◽  
Methylation Data ◽  
Polygenic Scores ◽  
Prenatal Maternal Smoking ◽  
Variance Explained

We examined the performance of methylation scores (MS) and polygenic scores (PGS) for birth weight, BMI, prenatal maternal smoking exposure, and smoking status to assess the extent to which MS could predict these traits and exposures over and above the PGS in a multi-omics prediction model. MS may be seen as the epigenetic equivalent of PGS, but because of their dynamic nature and sensitivity of non-genetic exposures may add to complex trait prediction independently of PGS. MS and PGS were calculated based on genotype data and DNA-methylation data in blood samples from adults (Illumina 450 K; N = 2,431; mean age 35.6) and in buccal samples from children (Illumina EPIC; N = 1,128; mean age 9.6) from the Netherlands Twin Register. Weights to construct the scores were obtained from results of large epigenome-wide association studies (EWASs) based on whole blood or cord blood methylation data and genome-wide association studies (GWASs). In adults, MSs in blood predicted independently from PGSs, and outperformed PGSs for BMI, prenatal maternal smoking, and smoking status, but not for birth weight. The largest amount of variance explained by the multi-omics prediction model was for current vs. never smoking (54.6%) of which 54.4% was captured by the MS. The two predictors captured 16% of former vs. never smoking initiation variance (MS:15.5%, PGS: 0.5%), 17.7% of prenatal maternal smoking variance (MS:16.9%, PGS: 0.8%), 11.9% of BMI variance (MS: 6.4%, PGS 5.5%), and 1.9% of birth weight variance (MS: 0.4%, PGS: 1.5%). In children, MSs in buccal samples did not show independent predictive value. The largest amount of variance explained by the two predictors was for prenatal maternal smoking (2.6%), where the MSs contributed 1.5%. These results demonstrate that blood DNA MS in adults explain substantial variance in current smoking, large variance in former smoking, prenatal smoking, and BMI, but not in birth weight. Buccal cell DNA methylation scores have lower predictive value, which could be due to different tissues in the EWAS discovery studies and target sample, as well as to different ages. This study illustrates the value of combining polygenic scores with information from methylation data for complex traits and exposure prediction.

scholarly journals Birthweight DNA methylation signatures in infant saliva

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Chiara Moccia ◽  
Maja Popovic ◽  
Elena Isaevska ◽  
Valentina Fiano ◽  
Morena Trevisan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cord Blood ◽  
Gestational Age ◽  
Low Birthweight ◽  
Continuous Variable ◽  
Linear Regression Models ◽  
Association Analyses ◽  
Cpg Sites ◽  
Adverse Health Outcomes ◽  
The Look

Abstract Background Low birthweight has been repeatedly associated with long-term adverse health outcomes and many non-communicable diseases. Our aim was to look-up cord blood birthweight-associated CpG sites identified by the PACE Consortium in infant saliva, and to explore saliva-specific DNA methylation signatures of birthweight. Methods DNA methylation was assessed using Infinium HumanMethylation450K array in 135 saliva samples collected from children of the NINFEA birth cohort at an average age of 10.8 (range 7–17) months. The association analyses between birthweight and DNA methylation variations were carried out using robust linear regression models both in the exploratory EWAS analyses and in the look-up of the PACE findings in infant saliva. Results None of the cord blood birthweight-associated CpGs identified by the PACE Consortium was associated with birthweight when analysed in infant saliva. In saliva EWAS analyses, considering a false discovery rate p-values < 0.05, birthweight as continuous variable was associated with DNA methylation in 44 CpG sites; being born small for gestational age (SGA, lower 10th percentile of birthweight for gestational age according to WHO reference charts) was associated with DNA methylation in 44 CpGs, with only one overlapping CpG between the two analyses. Despite no overlap with PACE results at the CpG level, two of the top saliva birthweight CpGs mapped at genes associated with birthweight with the same direction of the effect also in the PACE Consortium (MACROD1 and RPTOR). Conclusion Our study provides an indication of the birthweight and SGA epigenetic salivary signatures in children around 10 months of age. DNA methylation signatures in cord blood may not be comparable with saliva DNA methylation signatures at about 10 months of age, suggesting that the birthweight epigenetic marks are likely time and tissue specific.

scholarly journals Prenatal smoking and childhood behavior problems: is the association mediated by birth weight?

2016 ◽  
Vol 7 (3) ◽  
pp. 273-281 ◽  
Author(s):  
S. E. Parker ◽  
B. R. Collett ◽  
M. L. Speltz ◽  
M. M. Werler
Keyword(s):  
Birth Weight ◽  
Behavior Problems ◽  
Child Behavior ◽  
Maternal Smoking ◽  
Behavioral Outcomes ◽  
Attention Problems ◽  
Prenatal Smoking ◽  
Teacher Report ◽  
Smoking During Pregnancy ◽  
Maternal Smoking During Pregnancy

Maternal smoking during pregnancy is associated with both reduced birth weight and adverse neurobehavioral outcomes. The aim of this study was to investigate longitudinal associations between maternal smoking during pregnancy and childhood behavioral outcomes, and to determine the role of birth weight in mediating such associations. The study included 489 mother–child pairs. Prenatal exposures were assessed via maternal interviews conducted on average 1 year after delivery and child behavior assessments were completed at 5–12 years of age using the Child Behavior Checklist (CBCL) and Teacher Report Form (TRF). Maternal smoking during pregnancy was associated with externalizing and total behavior problems according to both mother and teacher report. Maternal smoking was also associated with the following percentage increases in scores: 41% (CBCL) and 44% (TRF) for aggressive behavior and 65% (CBCL) and 47% (TRF) for attention problems. Associations with behavior problems were attenuated or no longer observed for mothers that quit smoking in early pregnancy. The proportion of the total effect of maternal smoking on behavioral outcomes explained by differences in birth weight was small and ranged from 6.6% for externalizing behavior on the CBCL to 20.1% for rule-breaking behavior on the CBCL. Our results suggest that birth weight differences explain only a small proportion of the magnitude of association between maternal smoking during pregnancy and selected behavioral outcomes.

Placental Dna Methylation Is Associated With Birth Weight And Maternal Smoking: An Epigenome-Wide Association Study

2015 ◽  
Vol 2015 (1) ◽  
pp. 3156
Author(s):  
Johanna Lepeule ◽  
Emilie Abraham ◽  
Lise Giorgis-Allemand ◽  
Jorg Tost ◽  
Daniel Vaiman ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Birth Weight ◽  
Association Study ◽  
Maternal Smoking

Maternal prenatal state anxiety symptoms and birth weight: A pilot study

Open Medicine ◽  
2012 ◽  
Vol 7 (6) ◽  
pp. 747-752 ◽  
Author(s):  
Rima Azar ◽  
Samahra Singer
Keyword(s):  
Birth Weight ◽  
Pilot Study ◽  
State Anxiety ◽  
Statistical Significance ◽  
Anxiety Symptoms ◽  
State Trait Anxiety Inventory ◽  
Hierarchical Multiple Regression ◽  
Early Gestation ◽  
Lower Birth Weight ◽  
Infant Birth

AbstractMany women suffer from new or worsening anxiety during pregnancy. In this pilot study, we investigated the effect of timing and severity of prenatal state anxiety symptoms on reduced birth weight. We hypothesized that: (1) Women with state anxiety symptoms during mid-gestation would deliver newborns with lower birth weight in comparison to participants with symptoms in early gestation and (2) compared to women with lower anxiety symptoms (< 50th percentile), women with medium-to-high state anxiety symptoms (> 50th percentile) would have lower birth weight offspring. The sample consisted of the first 30 pregnant women who agreed to participate in this pilot study. We assessed anxiety symptoms, using the State-Trait Anxiety Inventory during early and mid-gestation. We obtained birth weight from clinical charts. A hierarchical multiple regression showed that, after controlling for covariates, state anxiety symptoms in mid-gestation were associated with lower infant birth weight [F(9, 7) = 20.30, p<.001]. However, birth weight did not differ as a function of the severity of maternal state anxiety [F(1, 23)=.14, p=.71 and F(1, 24)=1.76, p=.20., respectively]. Clearly, our pilot data need replication. Once statistical significance is established with larger samples, it will be informative to examine the clinical significance of those findings.

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