Abstract
A meta-analysis was performed to evaluate the possible association between maternal alcohol drinking during pregnancy and autism spectrum disorder (ASD) in offspring. Twelve datasets from five observational studies were included. Results showed that maternal alcohol drinking during pregnancy was not independently associated with ASD (risk ratio: 0.90, 95% confidence interval: 0.78 to 1.04, p = 0.16, I2 = 0%). The results were consistent for heavy alcohol drinking versus no alcohol drinking during pregnancy, and for studies evaluating the influence of maternal alcohol consumption during different trimesters. In conclusion, current evidence does not support that maternal alcohol consumption during pregnancy is independently associated with ASD in offspring.
Similar content being viewed by others
References
Baxter, A. J., Brugha, T. S., Erskine, H. E., Scheurer, R. W., Vos, T., & Scott, J. G. (2015). The epidemiology and global burden of autism spectrum disorders. Psychological Medicine, 45, 601–613. https://doi.org/10.1017/S003329171400172X
Beavers, G. A., Iwata, B. A., & Lerman, D. C. (2013). Thirty years of research on the functional analysis of problem behavior. Journal of Applied Behavior Analysis, 46, 1–21. https://doi.org/10.1002/jaba.30
Cullen, C. L., Burne, T. H., Lavidis, N. A., & Moritz, K. M. (2013). Low dose prenatal ethanol exposure induces anxiety-like behaviour and alters dendritic morphology in the basolateral amygdala of rat offspring. PLoS ONE, 8, e54924. https://doi.org/10.1371/journal.pone.0054924
Egger, M., Davey Smith, G., Schneider, M., & Minder, C. (1997). Bias in meta-analysis detected by a simple, graphical test. BMJ, 315, 629–634.
Eliasen, M., Tolstrup, J. S., Nybo Andersen, A. M., Gronbaek, M., Olsen, J., & Strandberg-Larsen, K. (2010). Prenatal alcohol exposure and autistic spectrum disorders–A population-based prospective study of 80,552 children and their mothers. International Journal of Epidemiology, 39, 1074–1081. https://doi.org/10.1093/ije/dyq056
Elsabbagh, M. (2020). Linking risk factors and outcomes in autism spectrum disorder: Is there evidence for resilience? BMJ, 368, l6880. https://doi.org/10.1136/bmj.l6880
Gallagher, C., McCarthy, F. P., Ryan, R. M., & Khashan, A. S. (2018). Maternal alcohol consumption during pregnancy and the risk of autism spectrum disorders in offspring: A retrospective analysis of the Millennium Cohort Study. Journal of Autism and Developmental Disorders, 48, 3773–3782. https://doi.org/10.1007/s10803-018-3626-6
Gibson, L., & Porter, M. (2021). Alcohol and tobacco use while breastfeeding and risk of autism spectrum disorder or attention deficit/hyperactivity disorder. Journal of Autism and Developmental Disorders. https://doi.org/10.1007/s10803-021-05027-3
Gyawali, S., & Patra, B. N. (2019). Autism spectrum disorder: Trends in research exploring etiopathogenesis. Psychiatry and Clinical Neurosciences, 73, 466–475. https://doi.org/10.1111/pcn.12860
Halliday, J. L., et al. (2017). Alcohol consumption in a general antenatal population and child neurodevelopment at 2 years. Journal of Epidemiology and Community Health, 71, 990–998. https://doi.org/10.1136/jech-2017-209165
Hansen, S. N., Schendel, D. E., & Parner, E. T. (2015). Explaining the increase in the prevalence of autism spectrum disorders: The proportion attributable to changes in reporting practices. JAMA Pediatrics, 169, 56–62. https://doi.org/10.1001/jamapediatrics.2014.1893
Happe, F., Ronald, A., & Plomin, R. (2006). Time to give up on a single explanation for autism. Nature Neuroscience, 9, 1218–1220. https://doi.org/10.1038/nn1770
Hendricks, G., Malcolm-Smith, S., Adnams, C., Stein, D. J., & Donald, K. A. M. (2019). Effects of prenatal alcohol exposure on language, speech and communication outcomes: A review longitudinal studies. Acta Neuropsychiatrica, 31, 74–83. https://doi.org/10.1017/neu.2018.28
Higgins, J., et al. (2021). Cochrane handbook for systematic reviews of interventions version 6.2. The Cochrane Collaboration. http://www.training.cochrane.org/handbook. Accessed 5 Jan 2022
Higgins, J. P., & Thompson, S. G. (2002). Quantifying heterogeneity in a meta-analysis. Statistics in Medicine, 21, 1539–1558. https://doi.org/10.1002/sim.1186
Hodges, H., Fealko, C., & Soares, N. (2020). Autism spectrum disorder: Definition, epidemiology, causes, and clinical evaluation. Translational Pediatrics, 9, S55–S65. https://doi.org/10.21037/tp.2019.09.09
Huang, Y., Li, Y., Zheng, S., Yang, X., Wang, T., & Zeng, J. (2017). Moderate alcohol consumption and atherosclerosis: Meta-analysis of effects on lipids and inflammation. Wiener Klinische Wochenschrift, 129, 835–843. https://doi.org/10.1007/s00508-017-1235-6
Imhof, A., Froehlich, M., Brenner, H., Boeing, H., Pepys, M. B., & Koenig, W. (2001). Effect of alcohol consumption on systemic markers of inflammation. The Lancet, 357, 763–767. https://doi.org/10.1016/S0140-6736(00)04170-2
India. (2020). The burden of mental disorders across the states of India: The Global Burden of Disease Study 1990–2017. Lancet Psychiatry, 7, 148–161. https://doi.org/10.1016/S2215-0366(19)30475-4
Jiang, N. M., Cowan, M., Moonah, S. N., & Petri, W. A., Jr. (2018). The impact of systemic inflammation on neurodevelopment. Trends in Molecular Medicine, 24, 794–804. https://doi.org/10.1016/j.molmed.2018.06.008
Kodak, T., & Bergmann, S. (2020). Autism spectrum disorder: Characteristics, associated behaviors, and early intervention. Pediatric Clinics of North America, 67, 525–535. https://doi.org/10.1016/j.pcl.2020.02.007
Lord, C., et al. (2020). Autism spectrum disorder. Nature Reviews. Disease Primers, 6, 5. https://doi.org/10.1038/s41572-019-0138-4
Lord, C., Elsabbagh, M., Baird, G., & Veenstra-Vanderweele, J. (2018). Autism spectrum disorder. The Lancet, 392, 508–520. https://doi.org/10.1016/S0140-6736(18)31129-2
Lyall, K., et al. (2017). The changing epidemiology of autism spectrum disorders. Annual Review of Public Health, 38, 81–102. https://doi.org/10.1146/annurev-publhealth-031816-044318
Mamluk, L., et al. (2017). Low alcohol consumption and pregnancy and childhood outcomes: Time to change guidelines indicating apparently ‘safe’ levels of alcohol during pregnancy? A systematic review and meta-analyses. British Medical Journal Open, 7, e015410. https://doi.org/10.1136/bmjopen-2016-015410
Manoli, D. S., & State, M. W. (2021). Autism spectrum disorder genetics and the search for pathological mechanisms. American Journal of Psychiatry, 178, 30–38. https://doi.org/10.1176/appi.ajp.2020.20111608
Masi, A., DeMayo, M. M., Glozier, N., & Guastella, A. J. (2017). An overview of autism spectrum disorder, heterogeneity and treatment options. Neuroscience Bulletin, 33, 183–193. https://doi.org/10.1007/s12264-017-0100-y
Modabbernia, A., Velthorst, E., & Reichenberg, A. (2017). Environmental risk factors for autism: An evidence-based review of systematic reviews and meta-analyses. Molecular Autism, 8, 13. https://doi.org/10.1186/s13229-017-0121-4
Nadeem, M. S., et al. (2020). Multiple risk factors: A challenge in the management of autism. Current Pharmaceutical Design, 26, 743–754. https://doi.org/10.2174/1381612826666200226101218
Oei, J. L. (2020). Alcohol use in pregnancy and its impact on the mother and child. Addiction, 115, 2148–2163. https://doi.org/10.1111/add.15036
Page, M. J., et al. (2021a). The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ, 372, n71. https://doi.org/10.1136/bmj.n71
Page, M. J., et al. (2021b). PRISMA 2020 explanation and elaboration: Updated guidance and exemplars for reporting systematic reviews. BMJ, 372, n160. https://doi.org/10.1136/bmj.n160
Popova, S., Lange, S., Probst, C., Gmel, G., & Rehm, J. (2017). Estimation of national, regional, and global prevalence of alcohol use during pregnancy and fetal alcohol syndrome: A systematic review and meta-analysis. The Lancet Global Health, 5, e290–e299. https://doi.org/10.1016/S2214-109X(17)30021-9
Prata, J., et al. (2019). The contribution of inflammation to autism spectrum disorders: Recent clinical evidence. Methods in Molecular Biology, 2011, 493–510. https://doi.org/10.1007/978-1-4939-9554-7_29
Pyman, P., Collins, S. E., Muggli, E., Testa, R., & Anderson, P. J. (2021). Cognitive and behavioural attention in children with low-moderate and heavy doses of prenatal alcohol exposure: A systematic review and meta-analysis. Neuropsychology Review, 31, 610–627. https://doi.org/10.1007/s11065-021-09490-8
Roberts, A. L., Lyall, K., Rich-Edwards, J. W., Ascherio, A., & Weisskopf, M. G. (2013). Association of maternal exposure to childhood abuse with elevated risk for autism in offspring. JAMA Psychiatry, 70, 508–515. https://doi.org/10.1001/jamapsychiatry.2013.447
Roos, A., et al. (2021). Central white matter integrity alterations in 2–3-year-old children following prenatal alcohol exposure. Drug and Alcohol Dependence, 225, 108826. https://doi.org/10.1016/j.drugalcdep.2021.108826
Roseman, C., Truedsson, L., & Kapetanovic, M. C. (2012). The effect of smoking and alcohol consumption on markers of systemic inflammation, immunoglobulin levels and immune response following pneumococcal vaccination in patients with arthritis. Arthritis Research & Therapy, 14, R170. https://doi.org/10.1186/ar3923
Schneider, M. L., Moore, C. F., & Kraemer, G. W. (2001). Moderate alcohol during pregnancy: Learning and behavior in adolescent rhesus monkeys. Alcoholism, Clinical and Experimental Research, 25, 1383–1392.
Singer, A. B., et al. (2017). Prenatal alcohol exposure in relation to autism spectrum disorder: Findings from the Study to Explore Early Development (SEED). Paediatric and Perinatal Epidemiology, 31, 573–582. https://doi.org/10.1111/ppe.12404
Stolakis, V., et al. (2015). Exposure to ethanol during neurodevelopment modifies crucial offspring rat brain enzyme activities in a region-specific manner. Metabolic Brain Disease, 30, 1467–1477. https://doi.org/10.1007/s11011-015-9730-9
Sundermann, A. C., et al. (2019). Alcohol use in pregnancy and miscarriage: A systematic review and meta-analysis. Alcoholism, Clinical and Experimental Research, 43, 1606–1616. https://doi.org/10.1111/acer.14124
Wells, G.A., et al. (2010). The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed 5 Jan 2022
Zuccolo, L., et al. (2009). A non-synonymous variant in ADH1B is strongly associated with prenatal alcohol use in a European sample of pregnant women. Human Molecular Genetics, 18, 4457–4466. https://doi.org/10.1093/hmg/ddp388
Zuo, L., et al. (2013). Association between common alcohol dehydrogenase gene (ADH) variants and schizophrenia and autism. Human Genetics, 132, 735–743. https://doi.org/10.1007/s00439-013-1277-4
Author information
Authors and Affiliations
Contributions
ZL, CY, and XZ designed the study. ZL and CY performed database search, study identification, data collection, and quality evaluation. TC, JL, YL, and BL performed statistical analyses and interpreted the results. ZL and CY drafted the manuscript. XZ revised the manuscript. All authors approved the submission of the manuscript.
Corresponding author
Ethics declarations
Conflict of Interest
The authors declare no competing interests.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Luo, Z., Yang, C., Cai, T. et al. Maternal Alcohol Consumption During Pregnancy and Autism Spectrum Disorder in Offspring: a Meta-analysis. Rev J Autism Dev Disord (2022). https://doi.org/10.1007/s40489-022-00336-4
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s40489-022-00336-4