Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Primer
  • Published:

Fetal alcohol spectrum disorders

Nature Reviews Disease Primers volume 9, Article number: 11 (2023) Cite this article

Subjects

Abstract

Alcohol readily crosses the placenta and may disrupt fetal development. Harm from prenatal alcohol exposure (PAE) is determined by the dose, pattern, timing and duration of exposure, fetal and maternal genetics, maternal nutrition, concurrent substance use, and epigenetic responses. A safe dose of alcohol use during pregnancy has not been established. PAE can cause fetal alcohol spectrum disorders (FASD), which are characterized by neurodevelopmental impairment with or without facial dysmorphology, congenital anomalies and poor growth. FASD are a leading preventable cause of birth defects and developmental disability. The prevalence of FASD in 76 countries is >1% and is high in individuals living in out-of-home care or engaged in justice and mental health systems. The social and economic effects of FASD are profound, but the diagnosis is often missed or delayed and receives little public recognition. Future research should be informed by people living with FASD and be guided by cultural context, seek consensus on diagnostic criteria and evidence-based treatments, and describe the pathophysiology and lifelong effects of FASD. Imperatives include reducing stigma, equitable access to services, improved quality of life for people with FASD and FASD prevention in future generations.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Prevalence of alcohol use (any amount) during pregnancy among the general population (%).
Fig. 2: Prevalence of FASD among the general population (per 1,000 population).
Fig. 3: Pooled prevalence of FASD and FAS (shown in brackets) among selected subpopulations, by country, and in the general global population.
Fig. 4: Prenatal alcohol exposure during gastrulation in mice reproduces the facial phenotype of FAS.
Fig. 5: Mechanisms of alcohol teratogenesis.
Fig. 6: Sentinel facial features of fetal alcohol syndrome.
Fig. 7: Cultural, socioeconomic and environmental factors influencing alcohol use in pregnancy and strategies for prevention of FASD.

Similar content being viewed by others

References

  1. Gellius, A. & Beloe, W. The Attic Nights of Aulus Gellius (Johnson, J., 1795).

  2. Goodwin, W. W. (ed.) Plutarch’s Morals (Little & Brown, 1871).

  3. Lemoine, P., Harousseau, H., Borteyru, J. P. & Menuet, J. C. Children of alcoholic parents: observed anomalies: discussion of 127 cases. Ouest Med. 8, 476–482 (1968). This article describes FAS, beginning the modern era of understanding of the impact of PAE on development.

    Google Scholar 

  4. Jones, K., Smith, D., Ulleland, C. & Streissguth, A. Pattern of malformation in offspring of chronic alcoholic mothers. Lancet 301, 1267–1271 (1973). This article describes FAS, beginning the modern era of understanding of the impact of PAE on development.

    Article  Google Scholar 

  5. Jones, K. & Smith, D. Recognition of the fetal alcohol syndrome in early infancy. Lancet 302, 999–1001 (1973). This article describes FAS, beginning the modern era of understanding of the impact of PAE on development.

    Article  CAS  PubMed  Google Scholar 

  6. Warren, K. R. & Hewitt, B. G. Fetal alcohol spectrum disorders: when science, medicine, public policy, and laws collide. Dev. Disabil. Res. Rev. 15, 174 (2009).

    Article  Google Scholar 

  7. Brown, J. M., Bland, R., Jonsson, E. & Greenshaw, A. J. A brief history of awareness of the link between alcohol and fetal alcohol spectrum disorder. Can. J. Psychiatr. 64, 164–168 (2019).

    Article  Google Scholar 

  8. Armstrong, E. M. & Abel, E. L. Fetal alcohol syndrome: the origins of a moral panic. Alcohol Alcohol. 35, 276–282 (2000).

    Article  CAS  PubMed  Google Scholar 

  9. Sulik, K. K., Johnston, M. C. & Webb, M. A. Fetal alcohol syndrome: embryogenesis in a mouse model. Science 214, 936–938 (1981). This article demonstrates the replicability of the sentinel facial characteristics of FASD in a mouse model of PAE and the importance of the timing of PAE in determining dysmorphology.

    Article  CAS  PubMed  Google Scholar 

  10. Hoyme, H. E. et al. Updated clinical guidelines for diagnosing fetal alcohol spectrum disorders. Pediatrics 138, e20154256 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Bertrand, J. et al. Fetal Alcohol Syndrome: Guidelines for Referral and Diagnosis. Report by National Task Force on FAS & FAE (Centers for Disease Control and Prevention, 2004).

  12. Popova, S., Lange, S., Shield, K., Burd, L. & Rehm, J. Prevalence of fetal alcohol spectrum disorder among special subpopulations: a systematic review and meta‐analysis. Addiction 114, 1150–1172 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Popova, S. et al. Comorbidity of fetal alcohol spectrum disorder: a systematic review and meta-analysis. Lancet 387, 978–987 (2016).

    Article  PubMed  Google Scholar 

  14. Cook, J. C., Lynch, M. E. & Coles, C. D. Association analysis: fetal alcohol spectrum disorder and hypertension status in children and adolescents. Alcohol Clin. Exp. Res. 43, 1727–1733 (2019).

    Article  PubMed  Google Scholar 

  15. Popova, S. et al. Population-based prevalence of fetal alcohol spectrum disorder in Canada. BMC Public Health https://doi.org/10.1186/s12889-019-7213-3 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Phillips, N. L. et al. Impact of fetal alcohol spectrum disorder on families. Arch. Dis. Child. 107, 755–757 (2022).

    Article  PubMed  Google Scholar 

  17. Popova, S., Lange, S., Burd, L. & Rehm, J. The economic burden of fetal alcohol spectrum disorder in Canada in 2013. Alcohol Alcohol. 51, 367–375 (2016).

    Article  PubMed  Google Scholar 

  18. Popova, S., Stade, B., Bekmuradov, D., Lange, S. & Rehm, J. What do we know about the economic impact of fetal alcohol spectrum disorder? A systematic literature review. Alcohol Alcohol. 46, 490–497 (2011).

    Article  PubMed  Google Scholar 

  19. Charness, M. E., Riley, E. P. & Sowell, E. R. Drinking during pregnancy and the developing brain: Is any amount safe? Trends Cogn. Sci. 20, 80–82 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  20. Centers for Disease Control and Prevention. Advisory on Alcohol Use During Pregnancy. A 2005 Message to women from the US Surgeon General (CDC, 2005).

  21. Graves, L. et al. Guideline no. 405: Screening and counselling for alcohol consumption during pregnancy. J. Obstet. Gynaecol. Can. 42, 1158–1173.e1 (2020).

    Article  PubMed  Google Scholar 

  22. World Health Organization. Guidelines for the Identification and Management of Substance Use and Substance Use Disorders in Pregnancy (World Health Organization, 2014).

  23. National Health and Medical Research Council. Australian Guidelines to Reduce Health Risks from Drinking Alcohol (Australian Research Council and Universities Australia, Commonwealth of Australia, 2020).

  24. Popova, S., Lange, S., Probst, C., Gmel, G. & Rehm, J. Estimation of national, regional, and global prevalence of alcohol use during pregnancy and fetal alcohol syndrome: a systematic review and meta-analysis. Lancet Glob. Health 5, e290–e299 (2017). Presents the epidemiology of PAE and FAS.

    Article  PubMed  Google Scholar 

  25. Popova, S., Lange, S., Probst, C., Gmel, G. & Rehm, J. Global prevalence of alcohol use and binge drinking during pregnancy, and fetal alcohol spectrum disorder. Biochem. Cell Biol. 96, 237–240 (2018).

    Article  CAS  PubMed  Google Scholar 

  26. World Health Organization. Global Status Report on Alcohol and Health, 2018 (World Health Organization, 2018).

  27. Lange, S., Probst, C., Rehm, J. & Popova, S. Prevalence of binge drinking during pregnancy by country and World Health Organization region: systematic review and meta-analysis. Reprod. Toxicol. 73, 214–221 (2017).

    Article  CAS  PubMed  Google Scholar 

  28. Green, P. P., McKnight-Eily, L. R., Tan, C. H., Mejia, R. & Denny, C. H. Vital signs: alcohol-exposed pregnancies — United States, 2011-2013. MMWR Morb. Mortal. Wkly Rep. 65, 91–97 (2016).

    Article  PubMed  Google Scholar 

  29. Sedgh, G., Singh, S. & Hussain, R. Intended and unintended pregnancies worldwide in 2012 and recent trends. Stud. Fam. Plann. 45, 301–314 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  30. Muggli, E. et al. “Did you ever drink more?” A detailed description of pregnant women’s drinking patterns. BMC Public Health 16, 683 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  31. McCormack, C. et al. Prenatal alcohol consumption between conception and recognition of pregnancy. Alcohol Clin. Exp. Res. 41, 369–378 (2017).

    Article  PubMed  Google Scholar 

  32. Fitzpatrick, J. P. et al. Prevalence and patterns of alcohol use in pregnancy in remote western Australian communities: the Lililwan project. Drug Alcohol Rev. 34, 329–339 (2015).

    Article  PubMed  Google Scholar 

  33. Petersen Williams, P., Jordaan, E., Mathews, C., Lombard, C. & Parry, C. D. Alcohol and other drug use during pregnancy among women attending midwife obstetric units in the cape metropole, South Africa. Adv. Prev. Med. 2014, 871427 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  34. Allen, L. et al. Pregnant and early parenting Indigenous women who use substances in Canada: a scoping review of health and social issues, supports, and strategies. J. Ethn. Subst. Abus. https://doi.org/10.1080/15332640.2022.2043799 (2022).

    Article  Google Scholar 

  35. Gonzales, K. L. et al. An indigenous framework of the cycle of fetal alcohol spectrum disorder risk and prevention across the generations: historical trauma, harm and healing. Ethn. Health 26, 280–298 (2021).

    Article  PubMed  Google Scholar 

  36. Mulat, B., Alemnew, W. & Shitu, K. Alcohol use during pregnancy and associated factors among pregnant women in sub-Saharan Africa: further analysis of the recent demographic and health survey data. BMC Pregnancy Childbirth 22, 361 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  37. Singal, D. et al. Prenatal care of women who give birth to children with fetal alcohol spectrum disorder in a universal health care system: a case–control study using linked administrative data. CMAJ Open 7, E63 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  38. Esper, L. H. & Furtado, E. F. Identifying maternal risk factors associated with fetal alcohol spectrum disorders: a systematic review. Eur. Child Adolesc. Psychiatry 23, 877–889 (2014).

    Article  PubMed  Google Scholar 

  39. Popova, S., Dozet, D., O’Hanlon, G., Temple, V. & Rehm, J. Maternal alcohol use, adverse neonatal outcomes and pregnancy complications in British Columbia, Canada: a population-based study. BMC Pregnancy Childbirth 21, 74 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  40. Poole, N. in Fetal Alcohol Spectrum Disorder: Management and Policy Perspectives of FASD Ch. 9 (eds Riley, E. P., Clarren, S., Weinberg, J. & Jonsson, E.) 161–173 (Weily, 2010).

  41. May, P. A. et al. Prevalence and characteristics of fetal alcohol spectrum disorders. Pediatrics 134, 855–866 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  42. Skagerstróm, J., Chang, G. & Nilsen, P. Predictors of drinking during pregnancy: a systematic review. J. Womens Health 20, 91–913 (2011).

    Article  Google Scholar 

  43. Colvin, L., Payne, J., Parsons, D., Kurinczuk, J. J. & Bower, C. Alcohol consumption during pregnancy in nonindigenous west Australian women. Alcohol Clin. Exp. Res. 31, 276–284 (2007).

    Article  PubMed  Google Scholar 

  44. Hutchinson, D. et al. Longitudinal prediction of periconception alcohol use: a 20-year prospective cohort study across adolescence, young adulthood and pregnancy. Addiction 117, 343–353 (2022).

    Article  PubMed  Google Scholar 

  45. Peadon, E. et al. Attitudes and behaviour predict women’s intention to drink alcohol during pregnancy: the challenge for health professionals. BMC Public Health 11, 584 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  46. Australian Institute of Health and Welfare. National Drug Strategy Household Survey 2016: Detailed Findings (Australian Institute of Health and Welfare, 2017).

  47. Tsang, T. W. et al. Predictors of alcohol use during pregnancy in Australian women. Drug Alcohol Rev. 41, 171–181 (2022).

    Article  PubMed  Google Scholar 

  48. Lange, S. et al. Global prevalence of fetal alcohol spectrum disorder among children and youth: a systematic review and meta-analysis. JAMA Pediatr. 171, 948–956 (2017). Presents the epidemiology of FASD.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Parker, S. E. et al. Updated national birth prevalence estimates for selected birth defects in the United States, 2004-2006. Birth Defects Res. A Clin. Mol. Teratol. 88, 1008–1016 (2010).

    Article  CAS  PubMed  Google Scholar 

  50. Zablotsky, B. et al. Prevalence and trends of developmental disabilities among children in the United States: 2009-2017. Pediatrics https://doi.org/10.1542/peds.2019-0811 (2019).

    Article  PubMed  Google Scholar 

  51. Popova, S., Dozet, D. & Burd, L. Fetal alcohol spectrum disorder: can we change the future? Alcohol Clin. Exp. Res. 44, 815–819 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  52. Mena, M., Navarrete, P., Avila, P., Bedregal, P. & Berríos, X. Alcohol drinking in parents and its relation with intellectual score of their children. Rev. Med. Chile 121, 98–105 (1993).

    CAS  PubMed  Google Scholar 

  53. Landgren, M., Svensson, L., Strömland, K. & Grönlund, M. A. Prenatal alcohol exposure and neurodevelopmental disorders in children adopted from eastern Europe. Pediatrics 125, e1178–e1185 (2010).

    Article  PubMed  Google Scholar 

  54. Colom, J. et al. Prevalence of fetal alcohol spectrum disorders (FASD) among children adopted from eastern European countries: Russia and Ukraine. Int. J. Environ. Res. Public Health https://doi.org/10.3390/ijerph18041388 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  55. Kuzmenkovienė, E., Prasauskienė, A. & Endzinienė, M. The prevalence of fetal alcohol spectrum disorders and concomitant disorders among orphanage children in Lithuania. J. Popul. Ther. Clin. Pharmacol. 19, e423 (2012).

    Google Scholar 

  56. Bower, C. et al. Fetal alcohol spectrum disorder and youth justice: a prevalence study among young people sentenced to detention in Western Australia. BMJ Open 8, e019605 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  57. Fast, D. K., Conry, J. & Loock, C. A. Identifying fetal alcohol syndrome among youth in the criminal justice system. J. Dev. Behav. Pediatr. 20, 370–372 (1999).

    Article  CAS  PubMed  Google Scholar 

  58. Bell, C. & Chimata, R. Prevalence of neurodevelopmental disorders among low-income African Americans at a clinic on Chicago’s south side. Psychiatr. Serv. 66, 539–542 (2015).

    Article  PubMed  Google Scholar 

  59. Fitzpatrick, J. P. et al. Prevalence and profile of neurodevelopment and fetal alcohol spectrum disorder (FASD) amongst Australian aboriginal children living in remote communities. Res. Dev. Disabil. 65, 114–126 (2017).

    Article  PubMed  Google Scholar 

  60. Legonkova, S. V. Clinical and Functional Characteristics of Fetal Alcohol Syndrome in Early Childhood [Russian] Thesis, St. Peterburg’s State Paediatric Medical Academy (2011).

  61. Heller, M. & Burd, L. Review of ethanol dispersion, distribution, and elimination from the fetal compartment. Birth Defects Res. A Clin. Mol. Teratol. 100, 277–283 (2014).

    Article  CAS  PubMed  Google Scholar 

  62. Dou, X., Lee, J. Y. & Charness, M. E. Neuroprotective peptide NAPVSIPQ antagonizes ethanol inhibition of L1 adhesion by promoting the dissociation of L1 and Ankyrin-G. Biol. Psychiatry 87, 656–665 (2020).

    Article  CAS  PubMed  Google Scholar 

  63. Lee, S. M., Yeh, P. W. L. & Yeh, H. H. L-type calcium channels contribute to ethanol-induced aberrant tangential migration of primordial cortical GABAergic interneurons in the embryonic medial prefrontal cortex. eNeuro https://doi.org/10.1523/eneuro.0359-21.2021 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  64. Ramanathan, R., Wilkemeyer, M. F., Mittal, B., Perides, G. & Charness, M. E. Alcohol inhibits cell-cell adhesion mediated by human L1. J. Cell Biol. 133, 381–390 (1996).

    Article  CAS  PubMed  Google Scholar 

  65. Kalinowski, A. & Humphreys, K. Governmental standard drink definitions and low-risk alcohol consumption guidelines in 37 countries. Addiction 111, 1293–1298 (2016).

    Article  PubMed  Google Scholar 

  66. Cuzon, V. C., Yeh, P. W., Yanagawa, Y., Obata, K. & Yeh, H. H. Ethanol consumption during early pregnancy alters the disposition of tangentially migrating GABAergic interneurons in the fetal cortex. J. Neurosci. 28, 1854–1864 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Muggli, E. et al. Association between prenatal alcohol exposure and craniofacial shape of children at 12 months of age. JAMA Pediatr. 171, 771–780 (2017). Shows the potential of 3D imaging in identifying individuals with FASD and PAE.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Long, X. & Lebel, C. Evaluation of brain alterations and behavior in children with low levels of prenatal alcohol exposure. JAMA Netw. Open 5, e225972 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  69. Lees, B. et al. Association of prenatal alcohol exposure with psychological, behavioral, and neurodevelopmental outcomes in children from the adolescent brain cognitive development study. Am. J. Psychiatry 177, 1060–1072 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  70. Lebel, C. et al. A longitudinal study of the long-term consequences of drinking during pregnancy: heavy in utero alcohol exposure disrupts the normal processes of brain development. J. Neurosci. 32, 15243–15251 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Kar, P. et al. Trajectories of brain white matter development in young children with prenatal alcohol exposure. Hum. Brain Mapp. https://doi.org/10.1002/hbm.25944 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  72. Eberhart, J. K. & Parnell, S. E. The genetics of fetal alcohol spectrum disorders. Alcohol Clin. Exp. Res. 40, 1154–1165 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  73. Kaminen-Ahola, N. Fetal alcohol spectrum disorders: genetic and epigenetic mechanisms. Prenat. Diagn. 40, 1185–1192 (2020).

    Article  CAS  PubMed  Google Scholar 

  74. Astley Hemingway, S. J. et al. Twin study confirms virtually identical prenatal alcohol exposures can lead to markedly different fetal alcohol spectrum disorder outcomes-fetal genetics influences fetal vulnerability. Adv. Pediatr. Res. https://doi.org/10.24105/apr.2019.5.23 (2018).

    Article  PubMed  Google Scholar 

  75. McCarthy, N. et al. Pdgfra protects against ethanol-induced craniofacial defects in a zebrafish model of FASD. Development 140, 3254–3265 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Kietzman, H. W., Everson, J. L., Sulik, K. K. & Lipinski, R. J. The teratogenic effects of prenatal ethanol exposure are exacerbated by sonic hedgehog or GLI2 haploinsufficiency in the mouse. PLoS ONE 9, e89448 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  77. Cobben, J. M. et al. DNA methylation abundantly associates with fetal alcohol spectrum disorder and its subphenotypes. Epigenomics 11, 767–785 (2019).

    Article  CAS  PubMed  Google Scholar 

  78. Ernst, A. M. et al. Prenatal and postnatal choline supplementation in fetal alcohol spectrum disorder. Nutrients https://doi.org/10.3390/nu14030688 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  79. Smith, S. M. et al. Polymorphisms in SLC44A1 are associated with cognitive improvement in children diagnosed with fetal alcohol spectrum disorder: an exploratory study of oral choline supplementation. Am. J. Clin. Nutr. 114, 617–627 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  80. Wozniak, J. R., Riley, E. P. & Charness, M. E. Clinical presentation, diagnosis, and management of fetal alcohol spectrum disorder. Lancet Neurol. 18, 760–770 (2019). Outlines the key neurodevelopmental characteristics in children with PAE and FASD.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Steane, S. E. et al. Prenatal alcohol consumption and placental outcomes: a systematic review and meta-analysis of clinical studies. Am. J. Obstet. Gynecol. 225, 607.e1–607.e22 (2021).

    Article  PubMed  Google Scholar 

  82. Gårdebjer, E. M. et al. Effects of periconceptional maternal alcohol intake and a postnatal high-fat diet on obesity and liver disease in male and female rat offspring. Am. J. Physiol. Endocrinol. Metab. 315, E694–E704 (2018).

    Article  PubMed  Google Scholar 

  83. Lipinski, R. J. et al. Ethanol-induced face-brain dysmorphology patterns are correlative and exposure-stage dependent. PLoS ONE 7, e43067 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Kane, C. J. M. & Drew, P. D. Neuroinflammatory contribution of microglia and astrocytes in fetal alcohol spectrum disorders. J. Neurosci. Res. 99, 1973–1985 (2021).

    Article  CAS  PubMed  Google Scholar 

  85. Wilhelm, C. J. & Guizzetti, M. Fetal alcohol spectrum disorders: an overview from the glia perspective. Front. Integr. Neurosci. 9, 65 (2015).

    PubMed  Google Scholar 

  86. Burke, M. W., Ptito, M., Ervin, F. R. & Palmour, R. M. Hippocampal neuron populations are reduced in vervet monkeys with fetal alcohol exposure. Dev. Psychobiol. 57, 470–485 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Young, J. K., Giesbrecht, H. E., Eskin, M. N., Aliani, M. & Suh, M. Nutrition implications for fetal alcohol spectrum disorder. Adv. Nutr. 5, 675–692 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Jarmasz, J. S., Basalah, D. A., Chudley, A. E. & Del Bigio, M. R. Human brain abnormalities associated with prenatal alcohol exposure and fetal alcohol spectrum disorder. J. Neuropathol. Exp. Neurol. 76, 813–833 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  89. Marguet, F. et al. Prenatal alcohol exposure is a leading cause of interneuronopathy in humans. Acta Neuropathol. Commun. 8, 208 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Wang, X. et al. In utero MRI identifies consequences of early-gestation alcohol drinking on fetal brain development in rhesus macaques. Proc. Natl Acad. Sci. USA 117, 10035–10044 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Treit, S., Jeffery, D., Beaulieu, C. & Emery, D. Radiological findings on structural magnetic resonance imaging in fetal alcohol spectrum disorders and healthy controls. Alcohol Clin. Exp. Res. 44, 455–462 (2020).

    Article  CAS  PubMed  Google Scholar 

  92. Sullivan, E. V. et al. Graded cerebellar lobular volume deficits in adolescents and young adults with fetal alcohol spectrum disorders (FASD). Cereb. Cortex 30, 4729–4746 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  93. Lebel, C., Roussotte, F. & Sowell, E. R. Imaging the impact of prenatal alcohol exposure on the structure of the developing human brain. Neuropsychol. Rev. 21, 102–118 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  94. Nguyen, V. T. et al. Radiological studies of fetal alcohol spectrum disorders in humans and animal models: an updated comprehensive review. Magn. Reson. Imaging 43, 10–26 (2017).

    Article  PubMed  Google Scholar 

  95. De Guio, F. et al. A study of cortical morphology in children with fetal alcohol spectrum disorders. Hum. Brain Mapp. 35, 2285–2296 (2014).

    Article  PubMed  Google Scholar 

  96. Infante, M. A. et al. Atypical cortical gyrification in adolescents with histories of heavy prenatal alcohol exposure. Brain Res. 1624, 446–454 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Boronat, S. et al. Correlation between morphological MRI findings and specific diagnostic categories in fetal alcohol spectrum disorders. Eur. J. Med. Genet. 60, 65–71 (2017).

    Article  CAS  PubMed  Google Scholar 

  98. Yang, Y. et al. Callosal thickness reductions relate to facial dysmorphology in fetal alcohol spectrum disorders. Alcohol Clin. Exp. Res. 36, 798–806 (2012).

    Article  PubMed  Google Scholar 

  99. Yang, Y. et al. Abnormal cortical thickness alterations in fetal alcohol spectrum disorders and their relationships with facial dysmorphology. Cereb. Cortex 22, 1170–1179 (2012).

    Article  PubMed  Google Scholar 

  100. Donald, K. A. et al. Neuroimaging effects of prenatal alcohol exposure on the developing human brain: a magnetic resonance imaging review. Acta Neuropsychiatr. 27, 251–269 (2015).

    Article  PubMed  Google Scholar 

  101. Ghazi Sherbaf, F., Aarabi, M. H., Hosein Yazdi, M. & Haghshomar, M. White matter microstructure in fetal alcohol spectrum disorders: a systematic review of diffusion tensor imaging studies. Hum. Brain Mapp. 40, 1017–1036 (2019).

    Article  PubMed  Google Scholar 

  102. Biffen, S. C. et al. Compromised interhemispheric transfer of information partially mediates cognitive function deficits in adolescents with fetal alcohol syndrome. Alcohol Clin. Exp. Res. 46, 517–529 (2022).

    Article  CAS  PubMed  Google Scholar 

  103. Roussotte, F. F. et al. Regional brain volume reductions relate to facial dysmorphology and neurocognitive function in fetal alcohol spectrum disorders. Hum. Brain Mapp. 33, 920–937 (2012).

    Article  PubMed  Google Scholar 

  104. Marek, S. et al. Reproducible brain-wide association studies require thousands of individuals. Nature 603, 654–660 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Medina, A. E. Fetal alcohol spectrum disorders and abnormal neuronal plasticity. Neuroscientist 17, 274–287 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Marquardt, K. & Brigman, J. L. The impact of prenatal alcohol exposure on social, cognitive and affective behavioral domains: insights from rodent models. Alcohol 51, 1–15 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Harvey, R. E., Berkowitz, L. E., Hamilton, D. A. & Clark, B. J. The effects of developmental alcohol exposure on the neurobiology of spatial processing. Neurosci. Biobehav. Rev. 107, 775–794 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Stephen, J. M., Hill, D. E. & Candelaria-Cook, F. T. Examining the effects of prenatal alcohol exposure on corticothalamic connectivity: a multimodal neuroimaging study in children. Dev. Cogn. Neurosci. 52, 101019 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Candelaria-Cook, F. T., Schendel, M. E., Flynn, L., Hill, D. E. & Stephen, J. M. Altered resting-state neural oscillations and spectral power in children with fetal alcohol spectrum disorder. Alcohol Clin. Exp. Res. 45, 117–130 (2021).

    Article  CAS  PubMed  Google Scholar 

  110. Suttie, M. et al. Combined face-brain morphology and associated neurocognitive correlates in fetal alcohol spectrum disorders. Alcohol Clin. Exp. Res. 42, 1769–1782 (2018). Shows the potential of 3D imaging in identifying individuals with FASD and PAE.

    Article  PubMed  PubMed Central  Google Scholar 

  111. Ahlgren, S. C., Thakur, V. & Bronner-Fraser, M. Sonic hedgehog rescues cranial neural crest from cell death induced by ethanol exposure. Proc. Natl Acad. Sci. USA 99, 10476–10481 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Li, Y. et al. Sulforaphane protects against ethanol-induced apoptosis in human neural crest cells through diminishing ethanol-induced hypermethylation at the promoters of the genes encoding the inhibitor of apoptosis proteins. Front. Cell Dev. Biol. 9, 622152 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  113. Chen, S.-Y. & Sulik, K. K. Free radicals and ethanol-induced cytotoxicity in neural crest cells. Alcohol Clin. Exp. Res. 20, 1071–1076 (1996).

    Article  CAS  PubMed  Google Scholar 

  114. Chung, D. D. et al. Toxic and teratogenic effects of prenatal alcohol exposure on fetal development, adolescence, and adulthood. Int. J. Mol. Sci. 22, 8785 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Mitoma, H., Manto, M. & Shaikh, A. G. Mechanisms of ethanol-induced cerebellar ataxia: underpinnings of neuronal death in the cerebellum. Int. J. Environ. Res. Public Health https://doi.org/10.3390/ijerph18168678 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  116. Charness, M. E., Simon, R. P. & Greenberg, D. A. Ethanol and the nervous system. N. Engl. J. Med. 321, 442–454 (1989).

    Article  CAS  PubMed  Google Scholar 

  117. Harris, R. A., Trudell, J. R. & Mihic, S. J. Ethanol’s molecular targets. Sci. Signal. 1, re7 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  118. Gutherz, O. R. et al. Potential roles of imprinted genes in the teratogenic effects of alcohol on the placenta, somatic growth, and the developing brain. Exp. Neurol. 347, 113919 (2022).

    Article  CAS  PubMed  Google Scholar 

  119. Lussier, A. A., Bodnar, T. S. & Weinberg, J. Intersection of epigenetic and immune alterations: implications for fetal alcohol spectrum disorder and mental health. Front. Neurosci. 15, 788630 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  120. Cheedipudi, S., Genolet, O. & Dobreva, G. Epigenetic inheritance of cell fates during embryonic development. Front. Genet. https://doi.org/10.3389/fgene.2014.00019 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  121. Mews, P. et al. Alcohol metabolism contributes to brain histone acetylation. Nature 574, 717–721 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Cantacorps, L., Alfonso-Loeches, S., Guerri, C. & Valverde, O. Long-term epigenetic changes in offspring mice exposed to alcohol during gestation and lactation. J. Psychopharmacol. 33, 1562–1572 (2019).

    Article  CAS  PubMed  Google Scholar 

  123. Gangisetty, O., Chaudhary, S., Palagani, A. & Sarkar, D. K. Transgenerational inheritance of fetal alcohol effects on proopiomelanocortin gene expression and methylation, cortisol response to stress, and anxiety-like behaviors in offspring for three generations in rats: evidence for male germline transmission. PLoS ONE 17, e0263340 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Jarmasz, J. S. et al. Global DNA Methylation and histone posttranslational modifications in human and nonhuman primate brain in association with prenatal alcohol exposure. Alcohol Clin. Exp. Res. 43, 1145–1162 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  125. Lussier, A. A. et al. DNA methylation as a predictor of fetal alcohol spectrum disorder. Clin. Epigenetics 10, 5 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  126. Ehrhart, F. et al. Review and gap analysis: molecular pathways leading to fetal alcohol spectrum disorders. Mol. Psychiatry 24, 10–17 (2019).

    Article  CAS  PubMed  Google Scholar 

  127. Shabtai, Y., Bendelac, L., Jubran, H., Hirschberg, J. & Fainsod, A. Acetaldehyde inhibits retinoic acid biosynthesis to mediate alcohol teratogenicity. Sci. Rep. 8, 347 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  128. Yan, T., Zhao, Y., Jiang, Z. & Chen, J. Acetaldehyde induces cytotoxicity via triggering mitochondrial dysfunction and overactive mitophagy. Mol. Neurobiol. 59, 3933–3946 (2022).

    Article  CAS  PubMed  Google Scholar 

  129. Weeks, O. et al. Embryonic alcohol exposure disrupts the ubiquitin-proteasome system. JCI Insight https://doi.org/10.1172/jci.insight.156914 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  130. Petrelli, B., Bendelac, L., Hicks, G. G. & Fainsod, A. Insights into retinoic acid deficiency and the induction of craniofacial malformations and microcephaly in fetal alcohol spectrum disorder. Genesis 57, e23278 (2019).

    Article  PubMed  Google Scholar 

  131. Boschen, K. E., Fish, E. W. & Parnell, S. E. Prenatal alcohol exposure disrupts sonic hedgehog pathway and primary cilia genes in the mouse neural tube. Reprod. Toxicol. 105, 136–147 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Fish, E. W. et al. Cannabinoids exacerbate alcohol teratogenesis by a CB1-hedgehog interaction. Sci. Rep. 9, 16057 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  133. Burton, D. F. et al. Pharmacological activation of the sonic hedgehog pathway with a Smoothened small molecule agonist ameliorates the severity of alcohol-induced morphological and behavioral birth defects in a zebrafish model of fetal alcohol spectrum disorder. J. Neurosci. Res. 100, 1585–1601 (2022).

    Article  CAS  PubMed  Google Scholar 

  134. Li, Y. X. et al. Fetal alcohol exposure impairs hedgehog cholesterol modification and signaling. Lab. Invest. 87, 231–240 (2007).

    Article  CAS  PubMed  Google Scholar 

  135. Boronat, S. et al. Seizures and electroencephalography findings in 61 patients with fetal alcohol spectrum disorders. Eur. J. Med. Genet. 60, 72–78 (2017).

    Article  CAS  PubMed  Google Scholar 

  136. Maness, P. F. & Schachner, M. Neural recognition molecules of the immunoglobulin superfamily: signaling transducers of axon guidance and neuronal migration. Nat. Neurosci. 10, 19–26 (2007).

    Article  CAS  PubMed  Google Scholar 

  137. Arevalo, E. et al. An alcohol binding site on the neural cell adhesion molecule L1. Proc. Natl Acad. Sci. USA 105, 371–375 (2008).

    Article  CAS  PubMed  Google Scholar 

  138. Dou, X. et al. L1 coupling to ankyrin and the spectrin-actin cytoskeleton modulates ethanol inhibition of L1 adhesion and ethanol teratogenesis. FASEB J. 32, 1364–1374 (2018).

    Article  CAS  PubMed  Google Scholar 

  139. Wilkemeyer, M. F. et al. Differential effects of ethanol antagonism and neuroprotection in peptide fragment NAPVSIPQ prevention of ethanol-induced developmental toxicity. Proc. Natl Acad. Sci. USA 100, 8543–8548 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Delatour, L. C., Yeh, P. W. & Yeh, H. H. Ethanol exposure in utero disrupts radial migration and pyramidal cell development in the somatosensory cortex. Cereb. Cortex 29, 2125–2139 (2019).

    Article  PubMed  Google Scholar 

  141. Salem, N. A. et al. A novel Oct4/Pou5f1-like non-coding RNA controls neural maturation and mediates developmental effects of ethanol. Neurotoxicol. Teratol. 83, 106943 (2021).

    Article  CAS  PubMed  Google Scholar 

  142. Mohammad, S. et al. Kcnn2 blockade reverses learning deficits in a mouse model of fetal alcohol spectrum disorders. Nat. Neurosci. 23, 533–543 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Tseng, A. M. et al. Ethanol exposure increases miR-140 in extracellular vesicles: implications for fetal neural stem cell proliferation and maturation. Alcohol Clin. Exp. Res. 43, 1414–1426 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Chung, D. D. et al. Dose-related shifts in proteome and function of extracellular vesicles secreted by fetal neural stem cells following chronic alcohol exposure. Heliyon 8, e11348 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Rubert, G., Miñana, R., Pascual, M. & Guerri, C. Ethanol exposure during embryogenesis decreases the radial glial progenitorpool and affects the generation of neurons and astrocytes. J. Neurosci. Res. 84, 483–496 (2006).

    Article  CAS  PubMed  Google Scholar 

  146. Darbinian, N. et al. Ethanol-mediated alterations in oligodendrocyte differentiation in the developing brain. Neurobiol. Dis. 148, 105181 (2021).

    Article  CAS  PubMed  Google Scholar 

  147. Creeley, C. E., Dikranian, K. T., Johnson, S. A., Farber, N. B. & Olney, J. W. Alcohol-induced apoptosis of oligodendrocytes in the fetal macaque brain. Acta Neuropathol. Commun. 1, 23 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  148. Bodnar, T. S. et al. Immune network dysregulation associated with child neurodevelopmental delay: modulatory role of prenatal alcohol exposure. J. Neuroinflammation 17, 39 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Bodnar, T. S. et al. Modulatory role of prenatal alcohol exposure and adolescent stress on the response to arthritis challenge in adult female rats. EBioMedicine 77, 103876 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Bodnar, T. S. et al. Evidence for long-lasting alterations in the fecal microbiota following prenatal alcohol exposure. Alcohol Clin. Exp. Res. 46, 542–555 (2022).

    Article  CAS  PubMed  Google Scholar 

  151. Virdee, M. S. et al. An enriched biosignature of gut microbiota-dependent metabolites characterizes maternal plasma in a mouse model of fetal alcohol spectrum disorder. Sci. Rep. 11, 248 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Lo, J. O. et al. Effects of early daily alcohol exposure on placental function and fetal growth in a rhesus macaque model. Am. J. Obstet. Gynecol. 226, 130.e1–130.e11 (2022).

    Article  CAS  PubMed  Google Scholar 

  153. Naik, V. D. et al. Mechanisms underlying chronic binge alcohol exposure-induced uterine artery dysfunction in pregnant rat. Alcohol Clin. Exp. Res. 42, 682–690 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Balaraman, S. et al. Plasma miRNA profiles in pregnant women predict infant outcomes following prenatal alcohol exposure. PLoS ONE 11, e0165081 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  155. Mahnke, A. H. et al. Infant circulating microRNAs as biomarkers of effect in fetal alcohol spectrum disorders. Sci. Rep. 11, 1429 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Tseng, A. M. et al. Maternal circulating miRNAs that predict infant FASD outcomes influence placental maturation. Life Sci. Alliance https://doi.org/10.26508/lsa.201800252 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  157. Elliott, A. J. et al. Concurrent prenatal drinking and smoking increases risk for SIDS: safe passage study report. EClinicalMedicine 19, 100247–100247 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  158. Page, K. et al. Prevalence of marijuana use in pregnant women with concurrent opioid use disorder or alcohol use in pregnancy. Addict. Sci. Clin. Pract. 17, 3 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  159. Lowe, J. R. et al. Early developmental trajectory of children with prenatal alcohol and opioid exposure. Pediatr. Res. https://doi.org/10.1038/s41390-022-02252-z (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  160. Siqueira, M. & Stipursky, J. Blood brain barrier as an interface for alcohol induced neurotoxicity during development. Neurotoxicology 90, 145–157 (2022).

    Article  CAS  PubMed  Google Scholar 

  161. Chudley, A. E. & Longstaffe, S. E. in Management of Genetic Syndromes Ch. 25 (eds Cassidy, S. B. & Allanson, J. E.) 363–380 (Wiley, 2010).

  162. Clarren, S. K., Lutke, J. & Sherbuck, M. The Canadian guidelines and the interdisciplinary clinical capacity of Canada to diagnose fetal alcohol spectrum disorder. J. Popul. Ther. Clin. Pharmacol. 18, e494–e499 (2011).

    PubMed  Google Scholar 

  163. Chasnoff, I. J., Wells, A. M. & King, L. Misdiagnosis and missed diagnoses in foster and adopted children with prenatal alcohol exposure. Pediatrics 135, 264–270 (2015).

    Article  PubMed  Google Scholar 

  164. May, P. A. et al. Prevalence of fetal alcohol spectrum disorders in 4 US communities. JAMA 319, 474–482 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  165. Astley, S. J. Validation of the fetal alcohol spectrum disorder (FASD) 4-digit diagnostic code. J. Popul. Ther. Clin. Pharmacol. 20, e416–e467 (2013).

    PubMed  Google Scholar 

  166. Astley, S. J. Diagnostic Guide for Fetal Alcohol Spectrum Disorders: The 4-Digit Diagnostic Code (Univ. Washington, 2004).

  167. Cook, J. L. et al. Fetal alcohol spectrum disorder: a guideline for diagnosis across the lifespan. CMAJ Open 188, 191–197 (2016).

    Article  Google Scholar 

  168. Bower, C. & Elliott, E. J. Australian Guide to the Diagnosis of FASD (Australian Government Department of Health, 2020).

  169. Scottish Intercollegiate Guidelines Network. Children and Young People Exposed Prenatally to Alcohol (SIGN publication no. 156) (SIGN, 2019).

  170. Gibbs, A. & Sherwood, K. Putting fetal alcohol spectrum disorder (FASD) on the map in New Zealand: a review of health, social, political, justice and cultural developments. Psychiatr. Psychol. Law 24, 825–842 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  171. Centres for Disease Control. Fetal Alcohol Syndrome: Guidelines for Referral and Diagnosis (US Department of Health and Human Services, 2004).

  172. Okulicz-Kozaryn, K., Maryniak, A., Borkowska, M., Śmigiel, R. & Dylag, K. A. Diagnosis of fetal alcohol spectrum disorders (FASDs): guidelines of interdisciplinary group of Polish professionals. Int. J. Environ. Res. Public Health 18, 7526 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  173. Landgraf, M. N., Nothacker, M. & Heinen, F. Diagnosis of fetal alcohol syndrome (FAS): German guideline version 2013. Eur. J. Paediatr. Neurol. 17, 437–446 (2013).

    Article  PubMed  Google Scholar 

  174. Chudley, A. E. et al. Fetal alcohol spectrum disorder: Canadian guidelines for diagnosis. Can. Med. Assoc. J. 172 (Suppl. 5), S1–S21 (2005).

    Article  Google Scholar 

  175. Bush, K., Kivlahan, D. R., McDonell, M. B., Fihn, S. D. & Bradley, K. A. The AUDIT alcohol consumption questions (AUDIT-C): an effective brief screening test for problem drinking. Arch. Intern. Med. 158, 1789–1795 (1998).

    Article  CAS  PubMed  Google Scholar 

  176. Sokol, R. J., Martier, S. S. & Ager, J. W. The T-ACE questions: practical prenatal detection of risk-drinking. Am. J. Obstet. Gynecol. 160, 863–870 (1989).

    Article  CAS  PubMed  Google Scholar 

  177. Chiodo, L. M. et al. Increased cut-point of the TACER-3 screen reduces false positives without losing sensitivity in predicting risk alcohol drinking in pregnancy. Alcohol Clin. Exp. Res. 38, 1401–1408 (2014).

    Article  PubMed  Google Scholar 

  178. Tsang, T. W. et al. Digital assessment of the fetal alcohol syndrome facial phenotype: reliability and agreement study. BMJ Paediatr. 1, e000137 (2017).

    Article  Google Scholar 

  179. Hemingway, S. J. A. et al. Comparison of the 4-digit code, Canadian 2015, Australian 2016 and Hoyme 2016 fetal alcohol spectrum disorder diagnostic guidelines. Adv. Pediatr. Res. https://doi.org/10.35248/2385-4529.19.6.31 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  180. Coles, C. D. et al. A comparison among 5 methods for the clinical diagnosis of fetal alcohol spectrum disorders. Alcohol Clin. Exp. Res. 40, 1000–1009 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  181. Coles, C. D. et al. Comparison of three systems for the diagnosis of fetal alcohol spectrum disorders in a community sample. Alcohol Clin. Exp. Res. https://doi.org/10.1111/acer.14999 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  182. Leibson, T., Neuman, G., Chudley, A. E. & Koren, G. The differential diagnosis of fetal alcohol spectrum disorder. J. Popul. Ther. Clin. Pharmacol. 21, e1–e30 (2014).

    PubMed  Google Scholar 

  183. Pearson, M. A., Hoyme, H. E., Seaver, L. H. & Rimsza, M. E. Toluene embryopathy: delineation of the phenotype and comparison with fetal alcohol syndrome. Pediatrics 93, 211–215 (1994).

    Article  CAS  PubMed  Google Scholar 

  184. Abdelmalik, N. et al. Diagnostic outcomes of 27 children referred by pediatricians to a genetics clinic in the Netherlands with suspicion of fetal alcohol spectrum disorders. Am. J. Med. Genet. A 161A, 254–260 (2013).

    Article  PubMed  Google Scholar 

  185. Douzgou, S. et al. Diagnosing fetal alcohol syndrome: new insights from newer genetic technologies. Arch. Dis. Child. 97, 812 (2012).

    Article  PubMed  Google Scholar 

  186. Malinowski, J. et al. Systematic evidence-based review: outcomes from exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability. Genet. Med. 22, 986–1004 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  187. McKay, L., Petrelli, B., Chudley, A. E. & Hicks, G. G. In Fetal Alcohol Spectrum Disorder: Advances in Research and Practice Vol. 188 (eds Chudley, A. E. & Hicks, G. G.) 77–117 (Springer USA, 2022).

  188. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5 5th edn (American Psychiatric Association, 2013).

  189. Mattson, S. N., Bernes, G. A. & Doyle, L. R. Fetal alcohol spectrum disorders: a review of the neurobehavioral deficits associated with prenatal alcohol exposure. Alcohol Clin. Exp. Res. 43, 1046–1062 (2019). This article outlines the key neurodevelopmental characteristics in children with PAE and FASD.

    PubMed  PubMed Central  Google Scholar 

  190. Klug, M. G., O’Connell, A. M., Palme, A., Kobrinsky, N. & Burd, L. A validation study of the alcohol related neurodevelopmental disorders behavioral checklist. Alcohol Clin. Exp. Res. 45, 765–772 (2021).

    Article  PubMed  Google Scholar 

  191. Kable, J. A. et al. Characteristics of the symptoms of the proposed ND-PAE disorder in first grade children in a community sample. Child Psychiatry Hum. Dev. https://doi.org/10.1007/s10578-022-01414-8 (2022).

    Article  PubMed  Google Scholar 

  192. World Health Organization. International Classification of Diseases, Eleventh Revision (ICD-11), for mortality and morbidity statistics. WHO https://icd.who.int/browse11/l-m/en#/http://id.who.int/icd/entity/362980699-11 (2022).

  193. Kambeitz, C., Klug, M. G., Greenmyer, J., Popova, S. & Burd, L. Association of adverse childhood experiences and neurodevelopmental disorders in people with fetal alcohol spectrum disorders (FASD) and non-FASD controls. BMC Pediatrics 19, 498 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  194. May, P. A. et al. Case management reduces drinking during pregnancy among high risk women. Int. J. Alcohol Drug Res. 2, 61–70 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  195. Poole, N., Schmidt, R. A., Bocking, A., Bergeron, J. & Fortier, I. The potential for fetal alcohol spectrum disorder prevention of a harmonized approach to data collection about alcohol use in pregnancy cohort studies. Int. J. Environ. Res. Public Health 16, 2019 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  196. Dozet, D., Burd, L. & Popova, S. Screening for alcohol use in pregnancy: a review of current practices and perspectives. Int. J. Ment. Health Addict. https://doi.org/10.1007/s11469-021-00655-3 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  197. Arnold, K. et al. Fetal alcohol spectrum disorders: knowledge and screening practices of university hospital medical students and residents. J. Popul. Ther. Clin. Pharmacol. 20, e18–e25 (2013).

    PubMed  Google Scholar 

  198. Payne, J. et al. Health professionals’ knowledge, practice and opinions about fetal alcohol syndrome and alcohol consumption in pregnancy. Aust. NZ J. Public Health 29, 558–564 (2005).

    Article  Google Scholar 

  199. Furtwængler, N. A. F. F. & de Visser, R. O. Lack of international consensus in low-risk drinking guidelines. Drug Alcohol Rev. 32, 11–18 (2013).

    Article  PubMed  Google Scholar 

  200. Wangberg, S. C. Norwegian midwives’ use of screening for and brief interventions on alcohol use in pregnancy. Sex. Reprod. Healthc. 6, 186–190 (2015).

    Article  PubMed  Google Scholar 

  201. France, K. et al. Health professionals addressing alcohol use with pregnant women in western Australia: Barriers and strategies for communication. Subst. Use Misuse 45, 1474–1490 (2010).

    Article  PubMed  Google Scholar 

  202. Doi, L., Cheyne, H. & Jepson, R. Alcohol brief interventions in Scottish antenatal care: a qualitative study of midwives’ attitudes and practices. BMC Pregnancy Childbirth 14, 170 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  203. Doi, L., Jepson, R. & Cheyne, H. A realist evaluation of an antenatal programme to change drinking behaviour of pregnant women. Midwifery 31, 965–972 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  204. Oni, H. T. et al. Barriers and facilitators in antenatal settings to screening and referral of pregnant women who use alcohol or other drugs: a qualitative study of midwives’ experience. Midwifery 81, 102595 (2020).

    Article  PubMed  Google Scholar 

  205. Lange, S., Shield, K., Koren, G., Rehm, J. & Popova, S. A comparison of the prevalence of prenatal alcohol exposure obtained via maternal self-reports versus meconium testing: a systematic literature review and meta-analysis. BMC Pregnancy Childbirth 14, 127 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  206. Szewczyk, Z. et al. Cost, cost-consequence and cost-effectiveness evaluation of a practice change intervention to increase routine provision of antenatal care addressing maternal alcohol consumption. Implement. Sci. 17, 14 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  207. Floyd, R. L. et al. Preventing alcohol-exposed pregnancies: a randomized controlled trial. Am. J. Prev. Med. 32, 1–10 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  208. Tzilos, G. K., Sokol, R. J. & Ondersma, S. J. A randomized phase I trial of a brief computer-delivered intervention for alcohol use during pregnancy. J. Womens Health 20, 1517–1524 (2011).

    Article  Google Scholar 

  209. Wouldes, T. A., Crawford, A., Stevens, S. & Stasiak, K. Evidence for the effectiveness and acceptability of e-SBI or e-SBIRT in the management of alcohol and illicit substance use in pregnant and post-partum women. Front. Psychiatr. 12, 634805 (2021).

    Article  Google Scholar 

  210. Coons, K. D., Watson, S. L., Yantzi, N. M., Lightfoot, N. E. & Larocque, S. Health care students’ attitudes about alcohol consumption during pregnancy: responses to narrative vignettes. Glob. Qual. Nurs. Res. 4, 2333393617740463 (2017).

    PubMed  PubMed Central  Google Scholar 

  211. Greenmyer, J. R. et al. Pregnancy status is associated with screening for alcohol and other substance use in the emergency department. J. Addict. Med. 14, e64–e69 (2020).

    Article  PubMed  Google Scholar 

  212. United Nations. The UN Sustainable Development Goals (United Nations, 2015).

  213. Schölin, L. Prevention of Harm Caused by Alcohol Exposure in Pregnancy: Rapid Review and Case Studies from Member States (World Health Organization, Regional Office for Europe, 2016).

  214. Poole, N., Schmidt, R. A., Green, C. & Hemsing, N. Prevention of fetal alcohol spectrum disorder: current Canadian efforts and analysis of gaps. J. Subst. Abus. Treat. 2016, 1–11 (2016).

    Google Scholar 

  215. Poole, N. Fetal alcohol spectrum disorder (FASD) prevention: Canadian perspectives. Public Health Agency of Canada https://www.phac-aspc.gc.ca/hp-ps/dca-dea/prog-ini/fasd-etcaf/publications/cp-pc/pdf/cp-pc-eng.pdf (2008).

  216. Jacobsen, B., Lindemann, C., Petzina, R. & Verthein, U. The universal and primary prevention of foetal alcohol spectrum disorders (FASD): a systematic review. J. Prev. 43, 297–316 (2022).

    Article  Google Scholar 

  217. Centers for Disease Control and Prevention. Alcohol & public health — preventing excessive alcohol use. CDC https://www.cdc.gov/alcohol/fact-sheets/prevention.htm (2022).

  218. Jernigan, D. H. & Trangenstein, P. J. What’s next for WHO’s global strategy to reduce the harmful use of alcohol? Bull. World Health Organ. 98, 222–223 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  219. Babor, T. et al. Who is responsible for the public’s health? The role of the alcohol industry in the WHO global strategy to reduce the harmful use of alcohol. Addiction 108, 2045–2047 (2013).

    Article  PubMed  Google Scholar 

  220. Driscoll, D. L., Barnes, V. R., Johnston, J. M., Windsor, R. & Ray, R. A formative evaluation of two FASD prevention communication strategies. Alcohol Alcohol. 53, 461–469 (2018).

    Article  PubMed  Google Scholar 

  221. Thomas, G., Gonneau, G., Poole, N. & Cook, J. The effectiveness of alcohol warning labels in the prevention of fetal alcohol spectrum disorder: a brief review. Int. J. Alcohol Drug Res. 3, 91–103 (2014).

    Article  Google Scholar 

  222. Choate, P., Badry, D., MacLaurin, B., Ariyo, K. & Sobhani, D. Fetal alcohol spectrum disorder: what does public awareness tell us about prevention programming? Int. J. Environ. Res. Public Health https://doi.org/10.3390/ijerph16214229 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  223. Reid, N. et al. Preconception interventions to reduce the risk of alcohol‐exposed pregnancies: a systematic review. Alcohol Clin. Exp. Res. 45, 2414–2429 (2021).

    Article  PubMed  Google Scholar 

  224. Symons, M., Pedruzzi, R. A., Bruce, K. & Milne, E. A systematic review of prevention interventions to reduce prenatal alcohol exposure and fetal alcohol spectrum disorder in indigenous communities. BMC Public Health 18, 1227 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  225. Montag, A., Clapp, J. D., Calac, D., Gorman, J. & Chambers, C. A review of evidence-based approaches for reduction of alcohol consumption in Native women who are pregnant or of reproductive age. Am. J. Drug Alcohol Abuse 38, 436–443 (2012).

    Article  PubMed  Google Scholar 

  226. O’Connor, E. A. et al. Screening and behavioral counseling interventions to reduce unhealthy alcohol use in adolescents and adults: updated evidence report and systematic review for the US preventive services task force. JAMA 320, 1910–1928 (2018).

    Article  PubMed  Google Scholar 

  227. Erng, M. N., Smirnov, A. & Reid, N. Prevention of alcohol‐exposed pregnancies and fetal alcohol spectrum disorder among pregnant and postpartum women: a systematic review. Alcohol Clin. Exp. Res. 44, 2431–2448 (2020).

    Article  PubMed  Google Scholar 

  228. Thanh, N. X. et al. An economic evaluation of the parent–child assistance program for preventing fetal alcohol spectrum disorder in Alberta, Canada. Adm. Policy Ment. Health 42, 10–18 (2015).

    Article  PubMed  Google Scholar 

  229. Keen, C. L. et al. The plausibility of maternal nutritional status being a contributing factor to the risk for fetal alcohol spectrum disorders: the potential influence of zinc status as an example. BioFactors 36, 125–135 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  230. McQuire, C., Daniel, R., Hurt, L., Kemp, A. & Paranjothy, S. The causal web of foetal alcohol spectrum disorders: a review and causal diagram. Eur. Child Adolesc. Psychiatr. 29, 575–594 (2020).

    Article  Google Scholar 

  231. Samawi, L., Williams, P. P., Myers, B. & Fuhr, D. C. Effectiveness of psychological interventions to reduce alcohol consumption among pregnant and postpartum women: a systematic review. Arch. Womens Ment. Health 24, 557–568 (2021).

    Article  PubMed  Google Scholar 

  232. Greenmyer, J. R., Popova, S., Klug, M. G. & Burd, L. Fetal alcohol spectrum disorder: a systematic review of the cost of and savings from prevention in the United States and Canada. Addiction 115, 409–417 (2020).

    Article  PubMed  Google Scholar 

  233. Wolfson, L. et al. Collaborative action on fetal alcohol spectrum disorder prevention: Principles for enacting the truth and reconciliation commission call to action #33. Int. J. Environ. Res. Public Health https://doi.org/10.3390/ijerph16091589 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  234. Reid, N., Crawford, A., Petrenko, C., Kable, J. & Olson, H. C. A family-directed approach for supporting individuals with fetal alcohol spectrum disorders. Curr. Dev. Disord. Rep. 9, 9–18 (2022).

    Article  Google Scholar 

  235. Bertrand, J. Interventions for children with fetal alcohol spectrum disorders (FASDs): overview of findings for five innovative research projects. Res. Dev. Disabil. 30, 986–1006 (2009).

    Article  PubMed  Google Scholar 

  236. Streissguth, A. P., Barr, H. M., Kogan, J. & Bookstein, F. L. Understanding the Occurrence of Secondary Disabilities in Clients with Fetal Alcohol Syndrome (FAS) and Fetal Alcohol Effects (FAE). Final Report to the Centers for Disease Control and Prevention (CDC). Report No. 96-06 (Univ. Washington, Fetal Alcohol & Drug Unit, 1996).

  237. Reid, N. et al. Systematic review of fetal alcohol spectrum disorder interventions across the life span. Alcohol Clin. Exp. Res. 39, 2283–2295 (2015).

    Article  PubMed  Google Scholar 

  238. Ordenewitz, L. K. et al. Evidence-based interventions for children and adolescents with fetal alcohol spectrum disorders — a systematic review. Eur. J. Paediatr. Neurol. 33, 50–60 (2021).

    Article  PubMed  Google Scholar 

  239. Carr, E. G. et al. Positive behavior support: evolution of an applied science. J. Posit. Behav. Inter. 4, 4–16 (2002).

    Article  Google Scholar 

  240. Kable, J. A., Taddeo, E., Strickland, D. & Coles, C. D. Improving FASD children’s self-regulation: piloting phase 1 of the GoFAR intervention. Child Fam. Behav. Ther. 38, 124–141 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  241. Kable, J. A., Coles, C. D. & Taddeo, E. Socio-cognitive habilitation using the math interactive learning experience program for alcohol-affected children. Alcohol Clin. Exp. Res. 31, 1425–1434 (2007).

    Article  PubMed  Google Scholar 

  242. Petrenko, C. L., Parr, J., Kautz, C., Tapparello, C. & Olson, H. C. A mobile health intervention for fetal alcohol spectrum disorders (families moving forward connect): development and qualitative evaluation of design and functionalities. JMIR mHealth uHealth 8, e14721 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  243. Coles, C. D., Kable, J. A., Taddeo, E. & Strickland, D. GoFAR: improving attention, behavior and adaptive functioning in children with fetal alcohol spectrum disorders: brief report. Dev. Neurorehabil. 21, 345–349 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  244. Coles, C. D., Kable, J. A. & Taddeo, E. Math performance and behavior problems in children affected by prenatal alcohol exposure: intervention and follow-up. J. Dev. Behav. Pediatr. 30, 7–15 (2009).

    Article  PubMed  Google Scholar 

  245. Kully-Martens, K. et al. Mathematics intervention for children with fetal alcohol spectrum disorder: a replication and extension of the math interactive learning experience (MILE) program. Res. Dev. Disabil. 78, 55–65 (2018).

    Article  PubMed  Google Scholar 

  246. Williams, M. S. & Shellenberger, S. How Does Your Engine Run?: A Leader’s Guide to the Alert Program for Self-Regulation (TherapyWorks, Inc., 1996).

  247. Soh, D. W. et al. Self-regulation therapy increases frontal gray matter in children with fetal alcohol spectrum disorder: evaluation by voxel-based morphometry. Front. Hum. Neurosci. 9, 108 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  248. Wells, A. M., Chasnoff, I. J., Schmidt, C. A., Telford, E. & Schwartz, L. D. Neurocognitive habilitation therapy for children with fetal alcohol spectrum disorders: an adaptation of the Alert Program®. Am. J. Occup. Ther. 66, 24–34 (2012).

    Article  PubMed  Google Scholar 

  249. Wagner, B. et al. School-based intervention to address self-regulation and executive functioning in children attending primary schools in remote Australian Aboriginal communities. PLoS ONE 15, e0234895 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  250. Frankel, F. D. & Myatt, R. J. Children’s Friendship Training (Routledge, 2013).

  251. Petrenko, C. L. M., Pandolfino, M. E. & Robinson, L. K. Findings from the families on track intervention pilot trial for children with fetal alcohol spectrum disorders and their families. Alcohol Clin. Exp. Res. 41, 1340–1351 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  252. Petrenko, C. L. M. & Alto, M. E. Interventions in fetal alcohol spectrum disorders: an international perspective. Eur. J. Med. Genet. 60, 79–91 (2017).

    Article  PubMed  Google Scholar 

  253. Ritfeld, G. J., Kable, J. A., Holton, J. E. & Coles, C. D. Psychopharmacological treatments in children with fetal alcohol spectrum disorders: a review. Child Psychiatry Hum. Dev. 53, 268–277 (2022).

    Article  PubMed  Google Scholar 

  254. Coles, C. D. et al. A comparison of children affected by prenatal alcohol exposure and attention deficit, hyperactivity disorder. Alcohol Clin. Exp. Res. 21, 150–161 (1997).

    Article  CAS  PubMed  Google Scholar 

  255. Young, S. et al. Guidelines for identification and treatment of individuals with attention deficit/hyperactivity disorder and associated fetal alcohol spectrum disorders based upon expert consensus. BMC Psychiatry 16, 324 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  256. Mela, M. et al. Treatment algorithm for the use of psychopharmacological agents in individuals prenatally exposed to alcohol and/or with diagnosis of fetal alcohol spectrum disorder (FASD). J. Popul. Ther. Clin. Pharmacol. 27, e1–e13 (2020).

    Article  PubMed  Google Scholar 

  257. Akison, L. K., Kuo, J., Reid, N., Boyd, R. N. & Moritz, K. M. Effect of choline supplementation on neurological, cognitive, and behavioral outcomes in offspring arising from alcohol exposure during development: a quantitative systematic review of clinical and preclinical studies. Alcohol Clin. Exp. Res. 42, 1591–1611 (2018).

    Article  PubMed  Google Scholar 

  258. Wozniak, J. R. et al. Four-year follow-up of a randomized controlled trial of choline for neurodevelopment in fetal alcohol spectrum disorder. J. Neurodev. Disord. 12, 9 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  259. Hemingway, S. J. A., Davies, J. K., Jirikowic, T. & Olson, E. M. What proportion of the brain structural and functional abnormalities observed among children with fetal alcohol spectrum disorder is explained by their prenatal alcohol exposure and their other prenatal and postnatal risks? Adv. Pediatr. Res. 7, 41 (2020).

    PubMed  PubMed Central  Google Scholar 

  260. McSherry, D. & McAnee, G. Exploring the relationship between adoption and psychological trauma for children who are adopted from care: a longitudinal case study perspective. Child Abus. Negl. 130, 105623 (2022).

    Article  Google Scholar 

  261. Koponen, A. M., Kalland, M. & Autti-Rämö, I. Caregiving environment and socio-emotional development of foster-placed FASD-children. Child. Youth Serv. Rev. 31, 1049–1056 (2009).

    Article  Google Scholar 

  262. Coggins, T. E., Timler, G. R. & Olswang, L. B. A state of double jeopardy: impact of prenatal alcohol exposure and adverse environments on the social communicative abilities of school-age children with fetal alcohol spectrum disorder. Lang. Speech Hear. Serv. Sch. 38, 117–127 (2007).

    Article  PubMed  Google Scholar 

  263. Joseph, J. J., Mela, M. & Pei, J. Aggressive behaviour and violence in children and adolescents with FASD: a synthesizing review. Clin. Psychol. Rev. 94, 102155 (2022).

    Article  PubMed  Google Scholar 

  264. Perry, B. D. Examining child maltreatment through a neurodevelopmental lens: clinical applications of the neurosequential model of therapeutics. J. Loss Trauma 14, 240–255 (2009).

    Article  Google Scholar 

  265. Cheung, M. M. Y. et al. Ear abnormalities among children with fetal alcohol spectrum disorder: a systematic review and meta-analysis. J. Pediatr. 242, 113–120.e16 (2022).

    Article  PubMed  Google Scholar 

  266. Tsang, T. W. et al. Eye abnormalities in children with fetal alcohol spectrum disorders: a systematic review. Ophthalmic Epidemiol. https://doi.org/10.1080/09286586.2022.2123004 (2022).

    Article  PubMed  Google Scholar 

  267. Streissguth, A. P. et al. Risk factors for adverse life outcomes in fetal alcohol syndrome and fetal alcohol effects. J. Dev. Behav. Pediatr. 25, 228–238 (2004).

    Article  PubMed  Google Scholar 

  268. Oh, S. S. et al. Hospitalizations and mortality among patients with fetal alcohol spectrum disorders: a prospective study. Sci. Rep. 10, 19512 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  269. Greenmyer, J. R., Klug, M. G., Kambeitz, C., Popova, S. & Burd, L. A multicountry updated assessment of the economic impact of fetal alcohol spectrum disorder: costs for children and adults. J. Addict. Med. 12, 466–473 (2018).

    Article  PubMed  Google Scholar 

  270. Petrenko, C., Tahir, N., Mahoney, E. & Chin, N. Prevention of secondary conditions in fetal alcohol spectrum disorders: identification of systems-level barriers. Matern. Child Health J. 18, 1496–1505 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  271. Flannigan, K. et al. Balancing the story of fetal alcohol spectrum disorder: a narrative review of the literature on strengths. Alcohol Clin. Exp. Res. 45, 2448–2464 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  272. Mukherjee, R., Wray, E., Commers, M., Hollins, S. & Curfs, L. The impact of raising a child with FASD upon carers: findings from a mixed methodology study in the UK. Adopt. Foster. 37, 43–56 (2013).

    Article  Google Scholar 

  273. Burd, L., Klug, M. & Martsolf, J. Increased sibling mortality in children with fetal alcohol syndrome. Addict. Biol. 9, 179–186 (2004).

    Article  CAS  PubMed  Google Scholar 

  274. Li, Q., Fisher, W. W., Peng, C.-Z., Williams, A. D. & Burd, L. Fetal alcohol spectrum disorders: a population based study of premature mortality rates in the mothers. Matern. Child Health J. 16, 1332–1337 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  275. Thanh, N. X. & Jonsson, E. Life expectancy of people with fetal alcohol syndrome. J. Popul. Ther. Clin. Pharmacol. 23, e53–e59 (2016).

    PubMed  Google Scholar 

  276. Burd, L. et al. Mortality rates in subjects with fetal alcohol spectrum disorders and their siblings. Birth Defects Res. Part. A Clin. Mol. Teratol. 82, 217–223 (2008).

    Article  CAS  Google Scholar 

  277. Thompson, A., Hackman, D. & Burd, L. Mortality in fetal alcohol spectrum disorders. Open J. Pediatr. 4, 21–33 (2014).

    Article  Google Scholar 

  278. O’Connor, M. J., Portnoff, L. C., Lebsack-Coleman, M. & Dipple, K. M. Suicide risk in adolescents with fetal alcohol spectrum disorders. Birth Defects Res. 111, 822–828 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  279. Bobbitt, S. A. et al. Caregiver needs and stress in caring for individuals with fetal alcohol spectrum disorder. Res. Dev. Disabil. 55, 100–113 (2016).

    Article  PubMed  Google Scholar 

  280. Domeij, H. et al. Experiences of living with fetal alcohol spectrum disorders: a systematic review and synthesis of qualitative data. Dev. Med. Child Neurol. 60, 741–752 (2018).

    Article  PubMed  Google Scholar 

  281. Reid, N. & Moritz, K. M. Caregiver and family quality of life for children with fetal alcohol spectrum disorder. Res. Dev. Disabil. 94, 103478 (2019).

    Article  CAS  PubMed  Google Scholar 

  282. Connolly, S. L., Miller, C. J., Gifford, A. L. & Charness, M. E. Perceptions and use of telehealth among mental health, primary, and specialty care clinicians during the COVID-19 pandemic. JAMA Netw. Open https://doi.org/10.1001/jamanetworkopen.2022.16401 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  283. Petrenko, C. L. A review of intervention programs to prevent and treat behavioral problems in young children with developmental disabilities. J. Dev. Phys. Disabil. https://doi.org/10.1007/s10882-013-9336-2 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  284. Bager, H., Christensen, L. P., Husby, S. & Bjerregaard, L. Biomarkers for the detection of prenatal alcohol exposure: a review. Alcohol Clin. Exp. Res. 41, 251–261 (2017).

    Article  CAS  PubMed  Google Scholar 

  285. Suttie, M. et al. Facial dysmorphism across the fetal alcohol spectrum. Pediatrics 131, e779–e788 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  286. Indiana Alliance on Prenatal Substance Exposure. BRAIN-online. Indiana Alliance on Prenatal Substance Exposure https://inalliancepse.org/brain-online/ (2023).

  287. Goh, P. K. et al. A decision tree to identify children affected by prenatal alcohol exposure. J. Pediatr. 177, 121–127.e1 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  288. Mattson, S. N. et al. Validation of the FASD-Tree as a screening tool for fetal alcohol spectrum disorders. Alcohol Clin. Exp. Res. 1-10 https://doi.org/10.1111/acer.14987 the CIFASD (2022).

  289. Bernes, G. A. et al. Development and validation of a postnatal risk score that identifies children with prenatal alcohol exposure. Alcohol Clin. Exp. Res. 46, 52–65 (2022).

    Article  PubMed  Google Scholar 

  290. Mooney, S. M., Petrenko, C. L. M., Hamre, K. M. & Brigman, J. Proceedings of the 2021 annual meeting of the fetal alcohol spectrum disorders study group. Alcohol 102, 23–33 (2022).

    Article  PubMed  Google Scholar 

  291. Himmelreich, M., Lutke, C., Hargrove, E., Begun, A. & Murray, M. in The Routledge Handbook of Social Work and Addictive Behaviors (eds Begun, A. L. & Murray, M. M.) (Routledge, 2020).

  292. Altimus, C. M. et al. The next 50 years of neuroscience. J. Neurosci. 40, 101–106 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  293. Brown, S. A. & Tapert, S. F. Adolescence and the trajectory of alcohol use: basic to clinical studies. Ann. NY Acad. Sci. 1021, 234–244 (2004).

    Article  PubMed  Google Scholar 

  294. World Health Organization. Global Action Plan for the Prevention and Control of NCDs 2013–2020 (World Health Organization, 2013).

  295. World Health Organization. Global Strategy to Reduce the Harmful Use of Alcohol (World Health Organization, 2010).

  296. Yanaguita, M. Y. et al. Pregnancy outcome in ethanol-treated mice with folic acid supplementation in saccharose. Childs Nerv. Syst. 24, 99–104 (2008).

    Article  CAS  PubMed  Google Scholar 

  297. Helfrich, K. K., Saini, N., Kling, P. J. & Smith, S. M. Maternal iron nutriture as a critical modulator of fetal alcohol spectrum disorder risk in alcohol-exposed pregnancies. Biochem. Cell Biol. 96, 204–212 (2018).

    Article  CAS  PubMed  Google Scholar 

  298. Joya, X., Garcia-Algar, O., Salat-Batlle, J., Pujades, C. & Vall, O. Advances in the development of novel antioxidant therapies as an approach for fetal alcohol syndrome prevention. Birth Defects Res. A Clin. Mol. Teratol. 103, 163–177 (2015).

    Article  CAS  PubMed  Google Scholar 

  299. Zhang, Y., Wang, H., Li, Y. & Peng, Y. A review of interventions against fetal alcohol spectrum disorder targeting oxidative stress. Int. J. Dev. Neurosci. 71, 140–145 (2018).

    Article  CAS  PubMed  Google Scholar 

  300. Zheng, D. et al. The protective effect of astaxanthin on fetal alcohol spectrum disorder in mice. Neuropharmacology 84, 13–18 (2014).

    Article  CAS  PubMed  Google Scholar 

  301. Peng, Y. et al. Ascorbic acid inhibits ROS production, NF-κB activation and prevents ethanol-induced growth retardation and microencephaly. Neuropharmacology 48, 426–434 (2005).

    Article  CAS  PubMed  Google Scholar 

  302. Shirpoor, A., Nemati, S., Ansari, M. H. K. & Ilkhanizadeh, B. The protective effect of vitamin E against prenatal and early postnatal ethanol treatment-induced heart abnormality in rats: a 3-month follow-up study. Int. Immunopharmacol. 26, 72–79 (2015).

    Article  CAS  PubMed  Google Scholar 

  303. Wentzel, P., Rydberg, U. & Eriksson, U. J. Antioxidative treatment diminishes ethanol-induced congenital malformations in the rat. Alcohol Clin. Exp. Res. 30, 1752–1760 (2006).

    Article  CAS  PubMed  Google Scholar 

  304. Luo, G. et al. Resveratrol attenuates excessive ethanol exposure induced insulin resistance in rats via improving NAD+/NADH ratio. Mol. Nutr. Food Res. 61, 1700087 (2017).

    Article  Google Scholar 

  305. Yuan, H. et al. Neuroprotective effects of resveratrol on embryonic dorsal root ganglion neurons with neurotoxicity induced by ethanol. Food Chem. Toxicol. 55, 192–201 (2013).

    Article  CAS  PubMed  Google Scholar 

  306. Cantacorps, L., Montagud-Romero, S. & Valverde, O. Curcumin treatment attenuates alcohol-induced alterations in a mouse model of foetal alcohol spectrum disorders. Prog. Neuropsychopharmacol. Biol. Psychiatry 100, 109899 (2020).

    Article  CAS  PubMed  Google Scholar 

  307. Tiwari, V. & Chopra, K. Protective effect of curcumin against chronic alcohol-induced cognitive deficits and neuroinflammation in the adult rat brain. Neuroscience 244, 147–158 (2013).

    Article  CAS  PubMed  Google Scholar 

  308. Gupta, K. K., Gupta, V. K. & Shirasaka, T. An update on fetal alcohol syndrome-pathogenesis, risks, and treatment. Alcohol Clin. Exp. Res. 40, 1594–1602 (2016).

    Article  CAS  PubMed  Google Scholar 

  309. Popova, S. et al. Health, social and legal outcomes of individuals with diagnosed or at risk for fetal alcohol spectrum disorder: Canadian example. Drug Alcohol Depend. 219, 108487 (2021).

    Article  PubMed  Google Scholar 

  310. Popova, S., Lange, S., Bekmuradov, D., Mihic, A. & Rehm, J. Fetal alcohol spectrum disorder prevalence estimates in correctional systems: a systematic literature review. Can. J. Public Health 102, 336–340 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  311. Weeks, O. et al. Fetal alcohol spectrum disorder predisposes to metabolic abnormalities in adulthood. J. Clin. Invest. 130, 2252–2269 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  312. Carson, G. et al. No. 245-Alcohol use and pregnancy consensus clinical guidelines. J. Obstet. Gynaecol. Can. 39, e220–e254 (2017).

    Article  PubMed  Google Scholar 

  313. Gomez, D., Petrenko, C., Monteiro, M. & Rahman, O. Assessment of Fetal Alcohol Spectrum Disorders. Report No. 978-92-75-12224-2 (Pan American Health Organization, 2020).

Download references

Acknowledgements

M.E.C. and E.P.R.: part of the work on mechanisms of alcohol harm was done in conjunction with the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD), which is funded by grants from the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Support was provided by U24 AA014811 (E.P.R. and M.E.C.). Additional information about CIFASD, including information on how to request data, can be found at www.cifasd.org. H.E.H.: the section on diagnostic guidelines was partially supported by the National Institute on Alcohol Abuse and Alcoholism grants R01 AA11685, R01/U01 AA01115134, and U01 AA019879-01/NIH-NIAAA (Collaboration on Fetal Alcohol Spectrum Disorders Prevalence (CoFASP)), and by the Oxnard Foundation, Newport Beach, CA, USA. E.J.E. is supported by an Australian Medical Research Futures Fund Next Generation Fellowship (#MRF1135959) and National Health and Medical Research Council of Australia funding for a Centre of Research Excellence in FASD (#GNT1110341).

Author information

Authors and Affiliations

  1. Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada

    Svetlana Popova

  2. VA Boston Healthcare System, West Roxbury, MA, USA

    Michael E. Charness

  3. Department of Neurology, Harvard Medical School, Boston, MA, USA

    Michael E. Charness

  4. Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA

    Michael E. Charness

  5. Department of Neurology, Brigham and Women’s Hospital, Boston, MA, USA

    Michael E. Charness

  6. North Dakota Fetal Alcohol Syndrome Center, Department of Pediatrics, University of North Dakota School of Medicine and Health Sciences, Pediatric Therapy Services, Altru Health System, Grand Forks, ND, USA

    Larry Burd

  7. Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand

    Andi Crawford

  8. Sanford Children’s Genomic Medicine Consortium, Sanford Health, and University of South Dakota Sanford School of Medicine, Sioux Falls, SD, USA

    H. Eugene Hoyme

  9. National UK FASD Clinic, Surrey and Borders Partnership NHS Foundation Trust, Redhill, Surrey, UK

    Raja A. S. Mukherjee

  10. Center for Behavioral Teratology, San Diego State University, San Diego, CA, USA

    Edward P. Riley

  11. Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia

    Elizabeth J. Elliott

  12. New South Wales FASD Assessment Service, CICADA Centre for Care and Intervention for Children and Adolescents affected by Drugs and Alcohol, Sydney Children’s Hospitals Network, Westmead, Sydney, New South Wales, Australia

    Elizabeth J. Elliott

Authors
  1. Svetlana Popova
    View author publications

    Search author on:PubMed Google Scholar

  2. Michael E. Charness
    View author publications

    Search author on:PubMed Google Scholar

  3. Larry Burd
    View author publications

    Search author on:PubMed Google Scholar

  4. Andi Crawford
    View author publications

    Search author on:PubMed Google Scholar

  5. H. Eugene Hoyme
    View author publications

    Search author on:PubMed Google Scholar

  6. Raja A. S. Mukherjee
    View author publications

    Search author on:PubMed Google Scholar

  7. Edward P. Riley
    View author publications

    Search author on:PubMed Google Scholar

  8. Elizabeth J. Elliott
    View author publications

    Search author on:PubMed Google Scholar

Contributions

Introduction (E.P.R. and E.J.E.); Epidemiology (S.P.); Mechanisms/pathophysiology (M.E.C.); Diagnosis, screening and prevention (E.J.E., M.E.C., H.E.H., E.P.R., S.P., A.C. and L.B.); Management (R.A.S.M., A.C. and E.J.E.); Quality of life (S.P., L.B. and R.A.S.M.); Outlook (E.J.E. and M.E.C.); Overview of Primer (S.P. and E.J.E.).

Corresponding author

Correspondence to Svetlana Popova.

Ethics declarations

Competing interests

The authors declare no competing interests

Peer review

Peer review information

Nature Reviews Disease Primers thanks C. Chambers, O. Garcia-Algar, J. Kable, C. Valenzuela and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Informed consent

The authors affirm that human research participants provided informed consent, for publication of the images in Figure 4.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Popova, S., Charness, M.E., Burd, L. et al. Fetal alcohol spectrum disorders. Nat Rev Dis Primers 9, 11 (2023). https://doi.org/10.1038/s41572-023-00420-x

Download citation

  • Accepted:

  • Published:

  • Version of record:

  • DOI: https://doi.org/10.1038/s41572-023-00420-x

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing