Meta-Analyses of Externalizing Disorders: Genetics or Prenatal Alcohol Exposure?
- Authors
- Wetherill, Leah; Foroud, Tatiana; Goodlett, Charles
- Year
- 2018
- Journal
- Alcoholism, clinical and experimental research
- PMID
- 29063614
- DOI
- 10.1111/acer.13535
- PMCID
- PMC5750073
BACKGROUND: Externalizing disorders are heritable precursors to alcohol dependence, common in children of alcoholics (COA), and in children with prenatal alcohol exposure (PAE). Pregnancies involving alcohol exposure sufficient to affect the fetus may involve women with genetic risk for alcohol dependence. We hypothesized that known PAE will increase the odds of having an externalizing disorder compared to COA. METHODS: The odds ratios of 3 externalizing disorders (attention-deficit hyperactivity disorder [ADHD], conduct disorder [CD], and oppositional defiant disorder [ODD]) were obtained for 2 domains: (i) PAE and (ii) COA, by estimating the logged odds ratio (LOR) for each study. Permutation tests were implemented to compare LORs for PAE versus COA studies within each disorder, including PAE versus an alcohol dependent (AD) mother and PAE versus an AD father. RESULTS: In PAE studies, the odds of ADHD and CD were elevated. Rates of all 3 disorders were elevated in COA studies. Permutation tests revealed that the mean LOR for ADHD was significantly higher in PAE studies compared to: COA (p = 0.01), AD mother (p < 0.05), and AD father (p = 0.03). No differences were found for ODD (p = 0.09) or CD (p = 0.21). CONCLUSIONS: These results provide compelling evidence of an increased risk of ADHD in those with PAE beyond that due to parental alcohol dependence or a genetic liability, consistent with a unique etiology most likely due to direct alcohol exposure during prenatal development.
Visualization of the dual burden of maternal alcohol consumption and alcohol dependence.
Forest plots including heterogeneity and random effects LOR for attention deficit disorder for (A) PAE studies, and (B) COA studies; conduct disorder for (C) PAE studies and (D) COA studies; and oppositional defiant disorder for (E) PAE studies and (F) COA studies. Each square plots the natural log of the odds ratio calculated from the study (depicted as a plus sign in the center of the square), comparing the odds of having the disorder in alcohol-ascertained samples (prenatal alcohol exposure or children of alcoholics) compared to normal controls (non-exposed or families with no genetic loading for alcohol dependence). Size of the square indicates sample size, with larger squares reflecting larger samples. The 95% confidence interval of the log odds ratio is represented by bars on each side of the plus sign. For visualization purposes, white bars are used when the confidence interval lies completely within the square, and black bars are used when the confidence interval extends beyond the square. PAE = prenatal alcohol exposure, COA = children of alcoholics.Figure 2A: Attention Deficit Hyperactivity Disorder Forest Plot of PAE StudiesFigure 2B: Attention Deficit Hyperactivity Disorder Forest Plot of COA StudiesFigure 2C: Conduct Disorder Forest Plot of PAE StudiesFigure 2D: Conduct Disorder Forest Plot of COA Studies; ASIAN = Asian sample, PI = Pacific Islander sample, CAUC = Caucasian sampleFigure 2E: Oppositional Defiant Disorder Forest Plot of PAE StudiesFigure 2F: Oppositional Defiant Disorder Forest Plot of COA Studies
Mean log odds ratios for each parent of interest within each domain and standard error bars. The number of studies used to compute the mean is provided above each bar. OR = odds ratio, ADHD = attention deficit hyperactivity disorder, CD = conduct disorder, ODD = oppositional defiance disorder, AD = alcohol dependence, PAE = prenatal alcohol exposure, COA = children of alcoholics, OR = odds ratio
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External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Correction: Implications for the Prevention of Poverty-Related Environmental Risks for Childhood ADHD: A Narrative Review. | İçen S | — | 2026 | → |
| Implications for the Prevention of Poverty-Related Environmental Risks for Childhood ADHD: A Narrative Review. | İçen S | — | 2026 | → |
| Environmental Risk Factors of Conduct Disorder: An Overview of Meta-Analyses. | Salmanian M et al. | — | 2025 | → |
| Advances in the etiology and neuroimaging of children with attention deficit hyperactivity disorder. | Shen F et al. | — | 2024 | → |
| An overview on neurobiology and therapeutics of attention-deficit/hyperactivity disorder. | da Silva BS et al. | — | 2023 | → |
| Alcohol and Tobacco use While Breastfeeding and Risk of Autism Spectrum Disorder or Attention Deficit/Hyperactivity Disorder. | Gibson L et al. | — | 2022 | → |