CohortAutism research : official journal of the International Society for Autism Research2020

Familial confounding of the association between maternal smoking in pregnancy and autism spectrum disorder in offspring.

Amy E Kalkbrenner, Sandra M Meier, Paul Madley-Dowd and 4 others

PMID 31464107

WHAT IT FOUND

Maternal smoking in pregnancy is not a direct risk factor for autism when accounting for family-level confounders.

Population-level associations disappeared in sibling and family-based analyses, suggesting shared genetic or environmental factors drive observed links.

Key findings

01Maternal smoking in pregnancy is not a direct risk factor for autism independent of family-level factors.

02Conventional adjusted models showed an elevated risk (HR 1.17), but this association was attenuated to null in family-based models.

03Risk estimates for autism sub-phenotypes (with or without ADHD or intellectual disability) did not support a causal relationship after accounting for shared family factors.

STILL TO COME

How it was doneWhat they found

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What it does not show

The study only examined direct maternal smoking during pregnancy and cannot be generalized to second-hand smoke, paternal smoking, or grandparental exposure. Sibling comparisons are largely driven by the small proportion of families (26% in the discordant analysis) where the mother's smoking behavior changed between pregnancies, which may introduce bias if other unmeasured factors changed simultaneously. Self-reported smoking status was collected at a single antenatal visit, though it was validated against biomarkers in a separate sample.

Declared interests

The authors declare no financial or other conflicts of interest.

The easy way to misread this

Do not conclude that smoking during pregnancy is safe for neurodevelopment. This study addresses whether it causes autism specifically when controlling for family background, not whether it harms the fetus generally. The authors explicitly state that smoking has many other deleterious health impacts.

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The study

Participants
1,294,906 persons
Certainty of evidence
Low

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    Cite

    Amy E Kalkbrenner, Sandra M Meier, Paul Madley-Dowd, et al. Familial confounding of the association between maternal smoking in pregnancy and autism spectrum disorder in offspring. Autism research : official journal of the International Society for Autism Research. 2020.

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