Maternal smoking during pregnancy and offspring intellectual disability: sibling analysis in an intergenerational Danish cohort

Paul Madley-Dowd*, Amy E. Kalkbrenner, Hein P Heuvelman, Jon E Heron, Stanley Zammit, Dheeraj Rai, Diana Schendel

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

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Abstract

Background: Maternal smoking has known adverse effects on fetal development. However, research on the association between maternal smoking during pregnancy and offspring intellectual disability (ID) is limited, and whether any associations are due to a causal effect or residual confounding is unknown.
Method: Cohort study of all Danish births between 1995 and 2012 (1,066,989 persons from 658,335 families after exclusions), with prospectively recorded data for cohort members, parents and siblings. We assessed the association between maternal smoking during pregnancy (18.6% exposed, collected during prenatal visits) and offspring ID (8,051 cases, measured using ICD-10 diagnosis codes F70-F79) using logistic generalised estimating equation regression models. Models were adjusted for confounders including measures of socio-economic status and parental psychiatric diagnoses and were adjusted for family averaged exposure between full siblings. Adjustment for a family averaged exposure allows calculation of the within-family effect of smoking on child outcomes which is robust against confounders that are shared between siblings.
Results: We found increased odds of ID among those exposed to maternal smoking in pregnancy after confounder adjustment (OR=1.35, 95% CI: 1.28, 1.42) which attenuated to a null effect following adjustment for family averaged exposure (OR=0.91, 95% CI: 0.78, 1.06).
Conclusions: Our findings are inconsistent with a causal effect of maternal smoking during pregnancy on offspring ID risk. By estimating a within-family effect, our results suggest that prior associations were the result of unmeasured genetic or environmental characteristics of families in which the mother smokes during pregnancy.
Original languageEnglish
Number of pages10
JournalPsychological Medicine
DOIs
Publication statusPublished - 14 Oct 2020

Keywords

  • Confounding
  • Intellectual disability
  • Maternal smoking
  • Neurodevelopment
  • Tobacco
  • Sibling design

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