Variation of DNA Methylation in Newborns Associated with Exhaled Carbon Monoxide during Pregnancy.

Ediane De Queiroz Andrade,Vanessa E Murphy,Gabriela Martins Costa Gomes,Adam Collison,Joerg Mattes,Wilfried Karmaus,Jane Grehan,Peter Gibson

doi:10.3390/ijerph18041597

Abstract

Fetal exposure to tobacco smoke is an adverse risk factor for newborns. A plausible mechanism of how this exposure may negatively impact long term health is differential methylation of deoxyribonucleic acid (DNAm) and its relation to birth weight. We examined whether self-reported gestational smoking status and maternal exhaled carbon monoxide (eCO) during early pregnancy were associated with methylation of cytosine by guanines (CpG) sites that themselves predicted birth weight. We focused first on CpGs associated with maternal smoking, and secondly, among these, on CpGs related to birth weight found in another cohort. Then in 94 newborns from the Breathing for Life Trial (BLT) DNAm levels in cord blood were determined using Infinium Methylation EPIC BeadChip measuring >850K CpGs. We regressed CpGs on eCO and tested via mediation analysis whether CpGs link eCO to birth weight. Nine smoking related CpG sites were significantly associated with birth weight. Among these nine CpGs the methylation of cg02264407 on the LMO7 gene was statistically significant and linked with eCO measurements. eCO greater than six ppm showed a 2.3% decrease in infant DNAm (p = 0.035) on the LMO7 gene. A 1% decrease in methylation at this site resulted in decreased birth weight by 44.8 g (p = 0.003). None of the nine CpGs tested was associated with self-reported smoking. This is the first study to report potential mediation of DNA methylation, linking eCO measurements during early pregnancy with birth weight.

Highlights

To reduce the number of cytosine-phosphate-guanine sites (CpGs) sites to be tested we focused on deoxyribonucleic acid (DNA) methylation sites related to smoking as reported by Joubert et al [29] based on a meta-analysis of multiple studies
A total of 94 participants were included in the analyses; exhaled carbon monoxide (eCO) was assessed in all participants
An analysis focusing on 520 smoking related CpGs sites was used to identify that CpGs associated with birth weight

Summary

Introduction

Fetal exposure to tobacco smoke throughout pregnancy is prevalent and a preventable risk for child morbidity and mortality [1,2]. Despite efforts of international health organisations to raise awareness for risk to the developing fetus, at least 15% to 20% of mothers do not quit smoking during pregnancy [3]. Previous research has described associations between in utero [4] tobacco smoke exposure with severe neonatal outcomes such as prematurity [5], stillbirth [6], congenital anomalies [7], low birth weight [8], and neonatal mortality [8]. One of the most widely reported effects is on birth weight [9,10,11]

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