Prenatal smoking, alcohol and caffeine exposure and offspring externalizing disorders: a systematic review and meta-analysis

Elis Haan, Kirsten E Westmoreland, Laura Schellhas, Hannah M Sallis, Gemma Taylor, Luisa Zuccolo, Marcus R Munafò

Research output: Contribution to journalReview articlepeer-review

4 Citations (SciVal)


BACKGROUND AND AIMS: Several studies have indicated an association between maternal prenatal substance use and offspring externalizing disorders; however, it is uncertain whether this relationship is causal. We conducted a systematic review to determine: (1) if the literature supports a causal role of maternal prenatal substance use on offspring externalizing disorders diagnosis and (2) whether these associations differ across externalizing disorders.

METHODS: We searched Web of Science, Embase, PsycINFO and Medline databases. Risk of bias assessment was conducted using the Newcastle-Ottawa Scale (NOS), and where possible meta-analysis was conducted for studies classed as low risk of bias. We included studies of any design that examined prenatal smoking, alcohol or caffeine use. Studies in non-English language, fetal alcohol syndrome and comorbid autism spectrum disorders were excluded. Participants in the included studies were mothers and their offspring. Measurements included prenatal smoking, alcohol or caffeine use as an exposure, and diagnosis of attention-deficit hyperactivity disorder (ADHD), conduct disorder (CD) and oppositional defiant disorder (ODD) in offspring as an outcome.

RESULTS: We included 63 studies, 46 of which investigated smoking and ADHD. All studies were narratively synthesized, and seven studies on smoking and ADHD were meta-analysed. The largest meta-analysis based on genetically sensitive design included 1 011 546 participants and did not find evidence for an association [odds ratio (OR)1-9 cigarettes  = 0.90, 95% confidence interval (CI) = 0.83-1.11; OR > 10 cigarettes  = 1.04, 95% CI = 0.79-1.36). Studies on alcohol exposure in all the outcomes reported inconsistent findings and no strong conclusions on causality can be made. Studies on caffeine exposure were mainly limited to ADHD and these studies do not support a causal effect.

CONCLUSIONS: There appears to be no clear evidence to support a causal relationship between maternal prenatal smoking and offspring attention-deficit hyperactivity disorder. Findings with alcohol and caffeine exposures and conduct disorder and oppositional-defiant disorder need more research, using more genetically sensitive designs.

Original languageEnglish
Pages (from-to)2602-2613
Number of pages12
Issue number10
Early online date6 Apr 2022
Publication statusPublished - 31 Oct 2022

Bibliographical note

Funding Information:
This research was performed in the UK Medical Research Council Integrative Epidemiology Unit (grant number MC_UU_00011/7) and also supported by the National Institute for Health Research (NIHR) Bristol Biomedical Research Centre at University Hospitals Bristol NHS Foundation Trust and the University of Bristol. L.Z. was supported by a UK Medical Research Council fellowship (grant number G0902144). H.M.S. is supported by the European Research Council (Grant ref: 758813 MHINT). The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health and Social Care. This research was also conducted as part of the CAPICE (Childhood and Adolescence Psychopathology: unravelling the complex etiology by a large Interdisciplinary Collaboration in Europe) project, funded by the European Union's Horizon 2020 research and innovation programme, Marie Sklodowska Curie Actions—MSCA‐ITN‐2016—Innovative Training Networks under grant agreement number 721567.


  • ADHD
  • ODD
  • alcohol
  • caffeine
  • conduct disorder
  • meta-analysis
  • smoking
  • systematic review

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Psychiatry and Mental health


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