Maternal smoking during pregnancy, offspring smoking, adverse childhood events, and risk of major depression: a sibling design study
Abstract
Background: Evidence of a biologically plausible association between maternal smoking during pregnancy (MSP) and the risk of depression is discounted by null findings from two sibling studies. However, valid causal inference from sibling studies is subject to challenges inherent to human studies of MSP and biases particular to this design. We addressed these challenges in the first sibling study of MSP and depression conducted among adults past the peak age for the onset of depression, utilizing a prospectively collected and biologically validated measure of MSP and accounting for non-shared as well as mediating factors. Methods: We fit GEE binomial regression models to correct for dependence in the risk of depression across pregnancies of the same mother. We also fit marginal structural models (MSM) to estimate the controlled direct effect of MSP on depression that is not mediated by the offspring's smoking status. Both models allow the estimation of within- and between-sibling risk ratios. Results: The adjusted within-sibling risk ratios (RR W) from both models (GEE: RR W = 1.97, CI 1.16–3.32; MSM: RR W = 2.08, CI 1.04–4.17) evinced an independent association between MSP and risk of depression. The overall effects from a standard model evinced lower associations (GEE: RR T = 1.12, CI 0.98–1.28; MSM: RR T = 1.18, CI 1.01–1.37). Conclusions: Based on within-sibling information free of unmeasured shared confounders and accounting for a range of unshared factors, we found an effect of MSP on the offspring's risk of depression. Our findings, should they be replicated in future studies, highlight the importance of considering challenges inherent to human studies of MSP and affective disorders.
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PTE predicted progression from weekly smoking to nicotine dependence (OR=1.4, 95% CI=1.2-1.8) in sibling-pairs discordant for maternal smoking during pregnancy.
“One study with sibling-pairs discordant for maternal smoking during pregnancy (n = 1,783), for example, found that PTE predicted progression from weekly smoking to nicotine dependence (OR = 1.4 [95% CI = 1.2, 1.8])”
From Prenatal nicotine exposure during pregnancy results in adverse neurodevelopmental alterations and neurobehavioral deficits (2023) · cites this paper as [158]
PTE did not predict progression to marijuana dependence in the exposed sibling.
“but did not predict progression to marijuana dependence in the exposed sibling [158].”
From Prenatal nicotine exposure during pregnancy results in adverse neurodevelopmental alterations and neurobehavioral deficits (2023) · cites this paper as [158]
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- Authors
- Shenassa, E. D., Rogers, M. L., & Buka, S. L.
- Affiliations
- University of Maryland, Baltimore (US)
- Brown University (US)
- Corresponding author
- Shenassa, Edmond D.
- Venue
- Psychological Medicine
- Publisher
- Cambridge University Press (CUP)
- Published
- 2021-04-26
- Volume
- 53
- Issue
- 1
- Pages
- 206-216
- ISSN
- 0033-2917 (ISSN-L)
- 1469-8978
- OpenAlex
- W3159735419
- Cited by
- 13
- References
- 48
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 1
- FWCI
- 1.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Psychological Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Keywords
- smoking during pregnancy, major depressive disorder, adverse childhood experiences, causal inference, nonshared environment, mediation, controlled direct effect, generalized estimating equations, marginal structural models, prenatal tobacco exposure
- MeSH terms
- Adult, Child, Depression, Major Depressive Disorder, Depressive Disorder, Major, Female, Humans, Pregnancy, Prenatal Exposure Delayed Effects, Risk Factors, Smoking, Siblings
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