Obstet Gynecol Sci.  2022 Sep;65(5):385-394. 10.5468/ogs.22123.

Prenatal maternal alcohol exposure: diagnosis and prevention of fetal alcohol syndrome

• Hur YM
• Choi J
• Park S
• Oh SS
• Kim YJ

• KMID: 2533812
• DOI: http://doi.org/10.5468/ogs.22123

Abstract

Fetal alcohol syndrome (FAS) is a developmental and congenital disorder characterized by neurocognitive impairment, structural defects, and growth restriction due to prenatal alcohol exposure. The estimated global prevalence of alcohol use during pregnancy is 9.8%, and the estimated prevalence of FAS in the general population is 14.6 per 10,000 people. In Korea, the estimated prevalence of alcohol use during pregnancy is 16%, and the prevalence of FAS is 18-51 per 10,000 women, which is higher than the global prevalence. Women’s alcohol consumption rates have increased, especially in women of childbearing age. This could increase the incidence of FAS, leading to higher medical expenses and burden on society. Alcohol is the single most important teratogen that causes FAS, and there is no safe trimester to drink alcohol and no known safe amount of alcohol consumption during pregnancy. Thus, physicians should assess women’s drinking patterns in detail and provide education on FAS to women by understanding its pathophysiology. Moreover, the prevention of FAS requires long-term care with a multidisciplinary approach.

Keyword

Fetal alcohol syndrome; Fetal alcohol spectrum disorders; Pregnancy; Alcohols

Figure

• 

  Fig. 1 Typical appearance associated with fetal alcohol syndrome (FAS) [12].

• 

  Fig. 2 Conceptual framework for fetal alcohol syndrome. There are variable processes in the effects of alcohol on the fetus. These influences produce variable outcomes, from stillbirths, structural anomaly in infancy to neurobehavioral disorders in adolescence. ALDH, aldehyde dehydrogenase.

Reference

References

1. Seo BA, Kim SG, Huh SY, Lee DH, An SH, Lee SY, et al. Changes of drinking behavior in Korean pregnancy women for the last 20 year. J Public Health (Oxf). 2021; 43:e632–6.

2. Öztürk HNO, Türker PF. Fetal programming: could intrauterin life affect health status in adulthood? Obstet Gynecol Sci. 2021; 64:473–83.

3. Lee S, Kwon EJ, You YA, Du JE, Jo I, Kim YJ. Long-term effects of pro-opiomelanocortin methylation induced in food-restricted dams on metabolic phenotypes in male rat offspring. Obstet Gynecol Sci. 2020; 63:239–50.

4. 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. 2017; 5:e290–99.

5. Persson A, Lindmark S, Petersson K, Gabriel E, Thorsell M, Lindström K, et al. Alcohol and illicit and non-medical prescription drug use before and during pregnancy in Stockholm, Sweden: a cross-sectional study. Sex Reprod Healthc. 2021; 29:100622.

6. Miyake Y, Tanaka K, Okubo H, Sasaki S, Arakawa M. Alcohol consumption during pregnancy and birth outcomes: the Kyushu Okinawa maternal and child health study. BMC Pregnancy Childbirth. 2014; 14:79.

7. May PA, Blankenship J, Marais AS, Gossage JP, Kalberg WO, Barnard R, et al. Approaching the prevalence of the full spectrum of fetal alcohol spectrum disorders in a South African population-based study. Alcohol Clin Exp Res. 2013; 37:818–30.

8. Lee HG. Development of diagnostic system for fetal alcohol spectrum disorders (2011E6100200). cheongju: Korea Disease Control and Prevention Agency;c2011. [cited 2022 Apr 24]. Available from: https://nih.go.kr/board.es?mid=a40801000000&cbid=0050&act=view&list_no=20485 .

9. Lee SH, Shin SJ, Won SD, Kim EJ, Oh DY. Alcohol use during pregnancy and related risk factors in Korea. Psychiatry Investig. 2010; 7:86–92.

10. Lemoine P, Harousseau H, Borteyru JP, Menuet JC. Children of alcoholic parents--observed anomalies: discussion of 127 cases. Ther Drug Monit. 2003; 25:132–6.

11. Calhoun F, Warren K. Fetal alcohol syndrome: historical perspectives. Neurosci Biobehav Rev. 2007; 31:168–71.

12. Hoyme HE, Kalberg WO, Elliott AJ, Blankenship J, Buckley D, Marais AS, et al. Updated clinical guidelines for diagnosing fetal alcohol spectrum disorders. Pediatrics. 2016; 138:e20154256.

13. Cunningham FG, Leveno KJ, Bloom SL, Dashe JS, Hoffman BL, Casey BM, et al. Williams obstetrics. 25th ed. New York (NY): McGraw-Hill;2018.

14. Denny L, Coles S, Blitz R. Fetal alcohol syndrome and fetal alcohol spectrum disorders. Am Fam Physician. 2017; 96:515–22.

15. Moberg DP, Bowser J, Burd L, Elliott AJ, Punyko J, Wilton G. Fetal alcohol syndrome surveillance: age of syndrome manifestation in case ascertainment. Birth Defects Res A Clin Mol Teratol. 2014; 100:663–69.

16. Astley SJ, Clarren SK. Diagnostic guide for fetal alcohol syndrome and related conditions: the 4-digit diagnostic code. Seattle (WA): University of Washington;1999.

17. Astley SJ, Clarren SK. Diagnosing the full spectrum of fetal alcohol-exposed individuals: introducing the 4-digit diagnostic code. Alcohol Alcohol. 2000; 35:400–10.

18. Chudley AE, Conry J, Cook JL, Loock C, Rosales T, LeBlanc N. Fetal alcohol spectrum disorder: Canadian guidelines for diagnosis. CMAJ. 2005; 172(5 suppl):S1–21.

19. Cook JL, Green CR, Lilley CM, Anderson SM, Baldwin ME, Chudley AE, et al. Fetal alcohol spectrum disorder: a guideline for diagnosis across the lifespan. CMAJ. 2016; 188:191–7.

20. Burd L, Klug MG, Li Q, Kerbeshian J, Martsolf JT. Diagnosis of fetal alcohol spectrum disorders: a validity study of the fetal alcohol syndrome checklist. Alcohol. 2010; 44:605–14.

21. Douzgou S, Breen C, Crow YJ, Chandler K, Metcalfe K, Jones E, et al. Diagnosing fetal alcohol syndrome: new insights from newer genetic technologies. Arch Dis Child. 2012; 97:812–17.

22. Adams DJ, Clark DA. Common genetic and epigenetic syndromes. Pediatr Clin North Am. 2015; 62:411–26.

23. Adibi JJ, Marques ETA Jr, Cartus A, Beigi RH. Teratogenic effects of the Zika virus and the role of the placenta. Lancet. 2016; 387:1587–90.

24. Maier SE, West JR. Drinking patterns and alcohol-related birth defects. Alcohol Res Health. 2001; 25:168–74.

25. Bonthius DJ, West JR. Alcohol-induced neuronal loss in developing rats: increased brain damage with binge exposure. Alcohol Clin Exp Res. 1990; 14:107–18.

26. Strandberg-Larsen K, Nielsen NR, Grønbaek M, Andersen PK, Olsen J, Andersen AM. Binge drinking in pregnancy and risk of fetal death. Obstet Gynecol. 2008; 111:602–9.

27. Gursky ZH, Savage LM, Klintsova AY. Executive functioning-specific behavioral impairments in a rat model of human third trimester binge drinking implicate prefrontal-thalamo-hippocampal circuitry in fetal alcohol spectrum disorders. Behav Brain Res. 2021; 405:113208.

28. National Institute on Alcohol Abuse and Alcoholism. What is a standard drink? [Internet]. Bethesda (MD): National Institute on Alcohol Abuse and Alcoholism;c2021. [cited 2021 Aug 26]. Available from: https://www.niaaa.nih.gov/alcohols-effects-health/overview-alcohol-consumption/what-standard-drink .

29. Breunis LJ, Wassenaar S, Sibbles BJ, Aaldriks AA, Bijma HH, Steegers EA, et al. Objective assessment of alcohol consumption in early pregnancy using phosphatidylethanol: a cross-sectional study. BMC Pregnancy Childbirth. 2021; 21:1–7.

30. Maugeri A, Barchitta M, Magnano San Lio R, La Rosa MC, La Mastra C, Favara G, et al. The effect of alcohol on telomere length: a systematic review of epidemiological evidence and a pilot study during pregnancy. Int J Environ Res Public Health. 2021; 18:5038.

31. Adler J, Rissmann A, Kropf S, Mohnicke K, Taneva E, Ansorge T, et al. Estimated prevalence of harmful alcohol consumption in pregnant and nonpregnant women in Saxony-Anhalt (NorthEast Germany) using biomarkers. Alcohol Clin Exp Res. 2021; 45:819–27.

32. Mahnke AH, Sideridis GD, Salem NA, Tseng AM, Carter RC, Dodge NC, et al. Infant circulating microRNAs as biomarkers of effect in fetal alcohol spectrum disorders. Sci Rep. 2021; 11:1429.

33. Shepard TH. Annual commentary on human teratogens. Teratology. 2002; 66:275.

34. Paintner A, Williams AD, Burd L. Fetal alcohol spectrum disorders--implications for child neurology, part 2: diagnosis and management. J Child Neurol. 2012; 27:355–62.

35. Kim JY, Lee DY, Lee YJ, Park KJ, Kim KH, Kim JW, et al. Chronic alcohol consumption potentiates the development of diabetes through pancreatic β-cell dysfunction. World J Biol Chem. 2015; 6:1–15.

36. Lee YJ, Kim JY, Lee DY, Park KJ, Kim GH, Kim JE, et al. Alcohol consumption before pregnancy causes detrimental fetal development and maternal metabolic disorders. Sci Rep. 2020; 10:10054.

37. Abel EL, Hannigan JH. Maternal risk factors in fetal alcohol syndrome: provocative and permissive influences. Neurotoxicol Teratol. 1995; 17:445–62.

38. Davis WL, Crawford LA, Cooper OJ, Farmer GR, Thomas DL, Freeman BL. Ethanol induces the generation of reactive free radicals by neural crest cells in vitro. J Craniofac Genet Dev Biol. 1990; 10:277–93.

39. Sulik KK. Genesis of alcohol-induced craniofacial dysmorphism. Exp Biol Med (Maywood). 2005; 230:366–75.

40. Jones KL, Smith DW. Recognition of the fetal alcohol syndrome in early infancy. Lancet. 1973; 302:999–1001.

41. Olney J. Fetal alcohol syndrome at the cellular level. Addict Biol. 2006; 9:137–49.

42. Guerri C, Bazinet A, Riley EP. Foetal alcohol spectrum disorders and alterations in brain and behaviour. Alcohol Alcohol. 2009; 44:108–14.

43. Roediger DJ, Krueger AM, de Water E, Mueller BA, Boys CA, Hendrickson TJ, et al. Hippocampal subfield abnormalities and memory functioning in children with fetal alcohol spectrum disorders. Neurotoxicol Teratol. 2021; 83:106944.

44. Bayih WA, Belay DM, Ayalew MY, Tassew MA, Chanie ES, Feleke DG, et al. The effect of substance use during pregnancy on neonatal outcomes in Ethiopia: a systematic review and meta-analysis. Heliyon. 2021; 7:e06740.

45. Warren KR, Li TK. Genetic polymorphisms: impact on the risk of fetal alcohol spectrum disorders. Birth Defects Res A Clin Mol Teratol. 2005; 73:195–203.

46. Ehrenstein V, Sørensen HT, Bakketeig LS, Pedersen L. Medical databases in studies of drug teratogenicity: methodological issues. Clin Epidemiol. 2010; 2:37–43.

47. Mullally A, Cleary BJ, Barry J, Fahey TP, Murphy DJ. Prevalence, predictors and perinatal outcomes of peri-conceptional alcohol exposure--retrospective cohort study in an urban obstetric population in Ireland. BMC Pregnancy Childbirth. 2011; 11:27.

48. Auriacombe M, Moriceau S, Serre F, Denis C, Micoulaud-Franchi JA, de Sevin E, et al. Development and validation of a virtual agent to screen tobacco and alcohol use disorders. Drug Alcohol Depend. 2018; 193:1–6.

49. O’Keeffe LM, Kearney PM, McCarthy FP, Khashan AS, Greene RA, North RA, et al. Prevalence and predictors of alcohol use during pregnancy: findings from international multicentre cohort studies. BMJ Open. 2015; 5:3006323.

50. Lee JY, Lee YS, Kim DH, Lee HS, Yang BR, Kim MG. The use of social media in detecting drug safety-related new black box warnings, labeling changes, or withdrawals: scoping review. JMIR Public Health Surveill. 2021; 7:e30137.

51. May PA, Baete A, Russo J, Elliott AJ, Blankenship J, Kalberg WO, et al. Prevalence and characteristics of fetal alcohol spectrum disorders. Pediatrics. 2014; 134:855–66.

52. Jasper JD, Goel R, Einarson A, Gallo M, Koren G. Effects of framing on teratogenic risk perception in pregnant women. Lancet. 2001; 358:1237–8.

53. FAS Diagnostic & Prevention Network. FAS DPN [Internet]. Seattle (WA): FAS Diagnostic & Prevention Network;c2021. [cited 2021 Aug 26]. Available from: https://depts.washington.edu/fasdpn .