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Maternal smoking during pregnancy and autism: using causal inference methods in a birth cohort study.

ABSTRACT: An association between maternal smoking in pregnancy and autism may be biologically plausible, but the evidence to date is inconsistent. We aimed to investigate the causal relationship between maternal smoking during pregnancy and offspring autism using conventional analysis and causal inference methods. In the Avon Longitudinal Study of Parents and Children we investigated the association of maternal smoking during pregnancy (exposure) with offspring autism spectrum disorder (ASD) or possible ASD diagnosis (n?=?11,946) and high scores on four autism-related traits (outcomes) (n?=?7402-9152). Maternal smoking was self-reported and also measured using an epigenetic score (n?=?866-964). Partner's smoking was used as a negative control for intrauterine exposure (n?=?6616-10,995). Mendelian randomisation (n?=?1002-2037) was carried out using a genetic variant at the CHRNA3 locus in maternal DNA as a proxy for heaviness of smoking. In observational analysis, we observed an association between smoking during pregnancy and impairments in social communication [OR?=?1.56, 95% CI?=?1.29, 1.87] and repetitive behaviours, but multivariable adjustment suggested evidence for confounding. There was weaker evidence of such association for the other traits or a diagnosis of autism. The magnitude of association for partner's smoking with impairments in social communication was similar [OR?=?1.56, 95% CI?=?1.30, 1.87] suggesting potential for shared confounding. There was weak evidence for an association of the epigenetic score or genetic variation at CHRNA3 with ASD or any of the autism-related traits. In conclusion, using several analytic methods, we did not find enough evidence to support a causal association between maternal smoking during pregnancy and offspring autism or related traits.

SUBMITTER: Caramaschi D

PROVIDER: S-EPMC6265272 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Maternal smoking during pregnancy and autism: using causal inference methods in a birth cohort study.

Caramaschi Doretta D Taylor Amy E AE Richmond Rebecca C RC Havdahl Karoline Alexandra KA Golding Jean J Relton Caroline L CL Munafò Marcus R MR Davey Smith George G Rai Dheeraj D

Translational psychiatry 20181129 1

An association between maternal smoking in pregnancy and autism may be biologically plausible, but the evidence to date is inconsistent. We aimed to investigate the causal relationship between maternal smoking during pregnancy and offspring autism using conventional analysis and causal inference methods. In the Avon Longitudinal Study of Parents and Children we investigated the association of maternal smoking during pregnancy (exposure) with offspring autism spectrum disorder (ASD) or possible A ...[more]

PMID: 30498225

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Project description:There has been a growing interest in the association between maternal levels of vitamin D during pregnancy and offspring autism. However, whether any associations reflect causal effects is still inconclusive. We used data from a UK-based pregnancy cohort study (Avon Longitudinal Study of Parents and Children) comprising 7689 births between 1991 and 1992 with maternal blood vitamin D levels recorded during pregnancy and at least one recorded outcome measure, including autism diagnosis and autism-associated traits. The association between each outcome with seasonal and gestational age-adjusted maternal serum 25-hydroxyvitamin D during pregnancy was estimated using confounder-adjusted regression models. Multiple imputation was used to account for missing data, and restricted cubic splines were used to investigate nonlinear associations. Mendelian randomization was used to strengthen causal inference. No strong evidence of an association between maternal serum 25-hydroxyvitamin D during pregnancy and any offspring autism-associated outcome was found using multivariable regression analysis (autism diagnosis: adjusted OR = 0.98, 95% CI = 0.90-1.06), including with multiple imputation (autism diagnosis: adjusted OR = 0.99, 95% CI = 0.93-1.06), and no evidence of a causal effect was suggested by Mendelian randomization (autism diagnosis: causal OR = 1.08, 95% CI = 0.46-2.55). Some evidence of increased odds of autism-associated traits at lower levels of maternal serum 25-hydroxyvitamin D was found using spline analysis. Our study was potentially limited by low power, particularly for diagnosed autism cases as an outcome. The cohort may not have captured the extreme lows of the distribution of serum 25-hydroxyvitamin D, and our analyses may have been biased by residual confounding and missing data. The present study found no strong evidence of a causal link between maternal vitamin D levels in pregnancy and offspring diagnosis or traits of autism.

Project description:BackgroundSmoking is one of the modifiable risk factors for adverse maternal and neonatal outcomes and is associated with low birth weight, preterm birth, respiratory, antepartum and intrapartum stillbirth, and perinatal death as well as long-term morbidity in offspring and sudden unexpected infant death. The rate of smoking in low- and middle-income countries is still relevantly high, and Jordan is no exception.ObjectiveTo investigate the effect of active and passive smoking during pregnancy on adverse pregnancy outcomes.MethodsThe case-control study was conducted in Jordan in June 2020. Healthy women with full-term singleton pregnancy (n = 180) were interviewed and stratified into three groups: Group I, active smokers; Group II, passive smokers; and Group III, nonsmokers. The study variables included demographic data, current pregnancy history, cotinine level of mothers and newborns, and perinatal outcomes. Statistical analysis was performed using the application package IBM SPSS 25. Various algorithms of statistical analysis were used depending on the type of distribution of feature and data quality. The threshold for statistical significance was set at p < 0.05.ResultsActive smokers had significantly lower gestational age at delivery compared to passive and nonsmoking women (p = 0.038 and p = 0.003, respectively). Neonates from active smoking mothers had significantly lower birth weight compared to neonates from passive and nonsmoking women (p = 0.016 and p = 0.019, respectively), significantly lower head and chest circumferences compared to babies from passive smokers (p < 0.001 and p = 0.036, respectively), and significantly lower first-minute Apgar score compared to those from nonsmoking women (p = 0.023). The urine cotinine level was significantly higher in both active and passive smoking women (both p < 0.01), and it was significantly higher in newborns who had been exposed to smoking in utero despite maternal active or passive smoking status (both p < 0.001). There was a weak negative correlation between urine cotinine level and birth weight: r = -0.14 for maternal cotinine level and r = -0.15 for neonate cotinine level.ConclusionsThe current study illustrated that smoking during pregnancy leads to offspring with reduced birth weight, birth length, and head and chest circumference; reduces delivery gestational age; and lowers the first-minute Apgar score. Our study findings highlight the need for further research issued to smoking effects on perinatal outcomes, the implementation of actions to develop cessation interventions in the preconception period, and an evaluation of useful interventions to enhance a smoking-free environment during pregnancy.

Dataset Information

Maternal smoking during pregnancy and autism: using causal inference methods in a birth cohort study.

Publications

Maternal smoking during pregnancy and autism: using causal inference methods in a birth cohort study.

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