Familial confounding of the association between maternal smoking during pregnancy and ADHD in offspring
Open accessAbstract
Background: Maternal Smoking During Pregnancy ( SDP ) has consistently been associated with increased risk of attention‐deficit/hyperactivity disorder ( ADHD ) in offspring, but recent studies indicate that this association might be due to unmeasured familial confounding. Methods: A total of 813,030 individuals born in Sweden between 1992 and 2000 were included in this nationwide population‐based cohort study. Data on maternal SDP and ADHD diagnosis were obtained from national registers and patients were followed up from the age of 3 to the end of 2009. Hazard Ratios ( HR s) were estimated using stratified Cox regression models. Cousin and sibling data were used to control for unmeasured familial confounding. Results: At the population level maternal SDP predicted ADHD in offspring ( HR M oderate SDP = 1.89; HR H igh SDP = 2.50). This estimate gradually attenuated toward the null when adjusting for measured confounders ( HR M oderate SDP = 1.62; HR H igh SDP = 2.04), unmeasured confounders shared within the extended family (i.e., cousin comparison) ( HR M oderate SDP = 1.45; HR H igh SDP = 1.69), and unmeasured confounders within the nuclear family (i.e., sibling comparison) ( HR M oderate SDP = 0.88; HR H igh SDP = 0.84). Conclusions: Our results suggest that the association between maternal SDP and offspring ADHD are due to unmeasured familial confounding.
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Adjusting for family history of ADHD removes the maternal-smoking association, suggesting familial or genetic confounding.
“it disappears after adjusting for family history of ADHD which indicates that the association between maternal smoking during pregnancy and ADHD is due to familial or genetic factors that increase the risk for both smoking and ADHD”
From The World Federation of ADHD International Consensus Statement: 208 Evidence-based conclusions about the disorder (2021) · cites this paper as Skoglund et al., 2014
The Results report that the smoking–ADHD association disappeared in sibling comparisons, supporting familial confounding. But the Methods list no adjustment for family history of ADHD, and the association remained significant after adjustment for measured covariates. The paper therefore does not show that adjusting for ADHD family history specifically removes it, or establish that genetic factors are the cause. (LLM, conf=0.90)
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- Authors
- Skoglund, C., Chen, Q., D′Onofrio, B. M., Lichtenstein, P., & Larsson, H.
- Affiliations
- Karolinska Institutet (SE)
- Department of Psychological and Brain Sciences Indiana University Bloomington IN USA
- Corresponding author
- Skoglund, Charlotte
- Venue
- Journal of Child Psychology and Psychiatry
- Publisher
- Wiley
- Published
- 2013-07-30
- Volume
- 55
- Issue
- 1
- Pages
- 61-68
- ISSN
- 0021-9630 (ISSN-L)
- 1469-7610
- PMC
- PMC4217138
- OpenAlex
- W2129258898
- Cited by
- 136
- References
- 41
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 10 · 2023: 11 · 2022: 12 · 2021: 10 · 2020: 12 · 2019: 13 · 2018: 14 · 2017: 16 · 2016: 14 · 2015: 11 · 2014: 2
- FWCI
- 6.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Child Psychology and Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Figshare (submittedVersion)
- Open Archive (Karolinska Institutet) (submittedVersion)
- Funders
- Swedish Council for Working Life and Social Research
- Swedish Research Council (2010-3184, 2011-2492)
- National Institute of Child Health and Human Development (HD061817)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Keywords
- smoking during pregnancy, attention deficit hyperactivity disorder, familial confounding, unmeasured confounding, sibling comparison, prenatal tobacco exposure, ADHD risk
- MeSH terms
- Adolescent, Adult, Attention Deficit Disorder with Hyperactivity, Child, Child, Preschool, Family, Female, Humans, Male, Mothers, Pregnancy, Prenatal Exposure Delayed Effects, Risk Factors, Smoking, Sweden, Cohort Studies, Confounding Factors, Epidemiologic, Proportional Hazards Models, Genetic Predisposition to Disease, Siblings, Young Adult
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