Biomarkers of maternal smoking during pregnancy associated with decreased epigenetic age acceleration at birth Público
Tynan, Timothy (Fall 2021)
Abstract
Maternal smoking during pregnancy (MSDP), or the use of smoking tobacco during pregnancy, is a relatively common behavior despite decades of public health recommendations to avoid cigarettes during this time period. MSDP is associated with a wide range of health outcomes, including intrauterine growth restriction, preterm birth, stillbirth, low birth weight, congenital malformations, increased perinatal mortality as well as several other obstetrical disorders. Epigenetic biomarkers of biological aging, known as age acceleration, have been posited as an effective mechanism to measure the health and development of offspring, but few have examined the impact of smoking during pregnancy on offspring epigenetic age.
We aimed to test the relationship between maternal smoking during pregnancy and epigenetic gestational age acceleration (GAA) at birth, using both the Bohlin and Knight epigenetic clocks. The New Hampshire Birth Cohort Study (NHBCS) was utilized and includes data on cord blood DNA methylation, self-report surveys, as well as cotinine and NNAL biomarkers for tobacco use. Study participants consisted of 255 mother-offspring pairs with both epigenetic and exposure data. We used multiple linear regression to test for differences in GAA at birth, associated with self-reported and biomarker-indicated maternal smoking during pregnancy, while adjusting for potential confounders.
We observed statistically significant decreases in GAAKnight with a beta coefficient of -0.894 (95% CI (-1.743, -0.045)) and in GAABohlin (beta coefficient of -0.557, 95% CI (-1.087, -0.027)) associated with biomarker-indicated maternal smoking. When adjusting for confounders (maternal age at enrollment, maternal BMI, sex, labor type, and cell types), the observed associations were unperturbed and remained statistically significant for both GAAKnight (beta coefficient of -0.951 (95% CI = -1.752, -0.149) and GAABohlin (beta coefficient of -0.567, 95% CI = -1.075, -0.059). Self-reported smoking during pregnancy exhibited the same direction of effect, but the effect sizes were smaller and confidence intervals crossed the null.
Our study provides supporting evidence that MSDP is associated with decreased GAA. These findings were particularly pronounced for when smoking status was determined via higher concentrations of cotinine and NNAL.
Table of Contents
Introduction……………………………………………………………………………………….1
Epidemiology of Maternal Smoking During Pregnancy………………………………….1
Epigenetic Mechanisms and Prenatal Exposures…………………………………………2
Effects of Maternal Smoking During Pregnancy on Epigenetic Mechanisms……………3
Epigenetic Age as Surrogate Measure for Biological Age………………………………..4
Tobacco Smoke Appears to Alter Epigenetic Aging……………………………………...6
Current Gaps in the Research……………………………………………………………..7
Objectives and Hypotheses………………………………………………………………..8
Methods……………………………………………………………………………………………9
Study Populations and Inclusion/Exclusion Criteria……………………………………...9
Institutional Review Board (IRB) Approval………………………………………………9
Cord Blood and DNA Methylation………………………………………………………..9
Epigenetic Age Estimation Methods…………………………………………………….10
Smoking Variables……………………………………………………………………….11
Statistical Analysis……………………………………………………………………….11
Results……………………………………………………………………………………………12
Characteristics of the Study Population………………………………………………….12
Relationship between DNA Methylation Age and Chronological Age………………….12
Age Acceleration Associations…………………………………………………………..13
Secondary Analyses……………………………………………………………………...16
Summary of Results……………………………………………………………………...17
Discussion………………………………………………………………………………………..17
Public Health Significance……………………………………………………………….20
Conclusions and Future Directions………………………………………………………21
References………………………………………………………………………………………..22
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