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

ABSTRACT: 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.

SUBMITTER: Parker SE

PROVIDER: S-EPMC6734934 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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

Parker S E SE Collett B R BR Speltz M L ML Werler M M MM

Journal of developmental origins of health and disease 20160216 3

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 ass ...[more]

PMID: 26880155

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Project description:BACKGROUND:Cigarette smoking has severe adverse health consequences in adults and in the offspring of mothers who smoke during pregnancy. One of the most widely reported effects of smoking during pregnancy is reduced birth weight which is in turn associated with chronic disease in adulthood. Epigenome-wide association studies have revealed that smokers show a characteristic "smoking methylation pattern", and recent authors have proposed that DNA methylation mediates the impact of maternal smoking on birth weight. The aims of the present study were to replicate previous reports that methylation mediates the effect of maternal smoking on birth weight, and for the first time to investigate whether the observed mediation effects are sex-specific in order to account for known sex-specific differences in methylation levels. METHODS:Methylation levels in the cord blood of 313 newborns were determined using the Illumina HumanMethylation450K Beadchip. A total of 5,527 CpG sites selected on the basis of evidence from the literature were tested. To determine whether the observed association between maternal smoking and birth weight was attributable to methylation, mediation analyses were performed for significant CpG sites. Separate analyses were then performed in males and females. RESULTS:Following quality control, 282 newborns eventually remained in the analysis. A total of 25 mothers had smoked consistently throughout the pregnancy. The birthweigt of newborns whose mothers had smoked throughout pregnancy was reduced by >200g. After correction for multiple testing, 30 CpGs showed differential methylation in the maternal smoking subgroup including top "smoking methylation pattern" genes AHRR, MYO1G, GFI1, CYP1A1, and CNTNAP2. The effect of maternal smoking on birth weight was partly mediated by the methylation of cg25325512 (PIM1); cg25949550 (CNTNAP2); and cg08699196 (ITGB7). Sex-specific analyses revealed a mediating effect for cg25949550 (CNTNAP2) in male newborns. CONCLUSION:The present data replicate previous findings that methylation can mediate the effect of maternal smoking on birth weight. The analysis of sex-dependent mediation effects suggests that the sex of the newborn may have an influence. Larger studies are warranted to investigate the role of both the identified differentially methylated loci and the sex of the newborn in mediating the association between maternal smoking during pregnancy and birth weight.

Project description:IntroductionDevelopment of the primary tooth bud commences at the end of the 5th week of gestation, with mineralization starting at about the 13th week and continuing throughout pregnancy to the end of the first year of life. During this critical period, exposure to maternal lifestyle factors, specifically, prenatal smoking can negatively affect the quality (i.e., tooth calcification and mineralization) and timing of tooth eruption.MethodsThis study evaluated the association between the trimester of smoking and offspring caries experience at 3 time points (31, 43, and 61 months) by analyzing data from 1,429 mother-offspring participants in the 1991/92 Avon Longitudinal Study of Parents and Children, conducted in Bristol, England. Prenatal smoking in the first, second, and third trimesters were self-reported during pregnancy while offspring caries experience was determined by clinical oral examinations. Adjusted for confounders, log-binomial regression estimated the risk ratio (RR) and 95% confidence interval (CI) of the association between trimester of smoking and the risk of offspring caries.ResultsTwenty percent smoked in the first trimester of their pregnancy, 15% in the second, and 17% in the third. Forty-six percent of children whose mothers smoked during pregnancy had caries experience (i.e., dmft ≥1) with a mean dmft count of 1.58, versus children whose mothers did not smoke during pregnancy (33% of whom had dmft ≥1 with a mean dmft count of 0.33). Smoking in the first, second, and third trimesters were independently associated with a higher adjusted RR (95% CI) of caries experience at 61 months, i.e., 1.16 (0.93-1.43), 1.11 (0.75-1.65), and 1.60 (1.09-2.32), respectively.ConclusionsWithin the limitations of covariates adjusted for, with the caveat that residual confounding and bias from unmeasured covariates are likely present, our findings suggest that smoking during pregnancy may be harmful to the oral health of the offspring irrespective of the trimester during which the smoking occurred. Nevertheless, these results should be interpreted cautiously because the findings might not generalize broadly.

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

Publications

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

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