Ethanol: Effect on Fetal Brain Growth and Development

  • Stanley E. Fisher


There is good evidence that heavy ethanol use has a detrimental effect on the unborn. In recent years, the medical community has become aware of a syndrome consisting of mental retardation, prenatal and postnatal growth retardation, and numerous congenital anomalies associated with heavy maternal ethanol ingestion. This collection of abnormalities has been coined the fetal alcohol syndrome (FAS). The FAS was “rediscovered” recently by Lemonie et al.1 in France and by Jones et al.2 in the United States. The term “rediscovered” is appropriate since there are biblical references to the importance of abstinence during pregnancy, and Aristotle observed that “foolish and drunken and harebrained women most often bring forth children like unto themselves, morose and languid.”3 Moreover, in the early eighteenth century, during the British “gin epidemic,” a report to Parliament pointed out that parental drinking was a cause of “weak, feeble and distempered children.” In addition, Sullivan,4 in 1899, found that the death rate among children of alcoholic mothers was more than twice that among infants of sober women of the same social status. As a counterpoint, Sullivan did indicate that the environment to which these children were born was also a factor. In general, observations made prior to the turn of this century were ignored until the works of Lemonie et al.1 and Jones et al.2 rekindled interest in the FAS.


Fetal Brain Alcohol Exposure Ethanol Exposure Fetal Alcohol Syndrome Postnatal Growth Retardation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Lemonie P, Harroussea H, Borteyru JP, et al: Les enfants de parents alcooliques: Anomalies observees a proposa de 127 cas. Quest med 25: 477–482, 1968Google Scholar
  2. 2.
    Jones KS, Smith DW, Ulleland CN, et al: Pattern of malformation in offspring of chronic alcoholic women. Lancet 1: 1267–1271, 1973PubMedCrossRefGoogle Scholar
  3. 3.
    Aristotle, cited by Burton: The Anatomy of Melancholy,1866 (first edition 1621)Google Scholar
  4. 4.
    Sullivan WC: J Ment Sci 45:489, 1899; cited by Streissguth AP, Landesman-Dwyer S, Martin JC, et al: Teratogenic effects of alcohol in humans and laboratory animals. Science 209: 353–361, 1980Google Scholar
  5. 5.
    Jones KL, Smith DW, Streissguth AP, et al: Outcome in offspring of chronic alcoholic women. Lancet 1.1076–1078, 1974Google Scholar
  6. 6.
    Ouellette EM, Rosett HL, Rosman NP, et al: Adverse effects on offspring of maternal alcohol abuse during pregnancy. N Engl J Med 297: 528–530Google Scholar
  7. 7.
    Sokol RI, Miller SI, Reed G: Alcohol abuse during pregnancy: An epidemiologic study. Alcoholism: Clin Exp Res 4: 135–145, 1980CrossRefGoogle Scholar
  8. 8.
    Leiber B: Warnhimweis von DOFONOS. Z Allgemeinmedizin 53: 2040–2043, 1977Google Scholar
  9. 9.
    Clarren SK, Smith DW: The fetal alcohol syndrome. N Engl J Med 298: 1063–1067, 1978PubMedCrossRefGoogle Scholar
  10. 10.
    Streissguth AP, Landesman-Dwyer S, Martin JC, et al: Teratogenic effects of alcohol in humans and laboratory animals. Science 209: 353–361, 1980PubMedCrossRefGoogle Scholar
  11. 11.
    Streissguth AP: Presented at the Fetal Alcohol Study Group, National Alcoholism Forum, Houston, Texas, 1983Google Scholar
  12. 12.
    Clarren SK, Alvoid EC, Sumi SM, et al: Brain malformations related to prenatal exposure to ethanol. J Pediatr 92: 6467, 1978Google Scholar
  13. 13.
    Gross MM, Goodenough DR, Tobin M, et al: Sleep disturbances and hallucinations in the acute alcoholic psychoses. J Nery Ment Dis 142: 493–498, 1966CrossRefGoogle Scholar
  14. 14.
    Williams HL, Rundell OH Jr: Altered sleep physiology in chronic alcoholics: Reversal with abstinence. Alcoholism: Clin Exp Res 5: 318–325, 1981CrossRefGoogle Scholar
  15. 15.
    Shaywitz SE, Cohen DJ, Shaywitz BA: Behavior and learning difficulties in children of normal intelligence born to alcoholic mothers. J Pediatr 96: 978–982, 1980PubMedCrossRefGoogle Scholar
  16. 16.
    Shaywitz SE, Caparulo BK, Hodgson ES: Developmental language disability as a consequence of prenatal exposure to ethanol. Pediatrics 68: 850–855, 1981PubMedGoogle Scholar
  17. 17.
    Chemoff GF: The fetal alcohol syndrome in mice: Maternal variables. Teratology 22: 71–75, 1980CrossRefGoogle Scholar
  18. 18.
    Randall CL, Taylor WJ: Prenatal ethanol exposure in mice: Teratogenic effects. Teratology 19: 305–312, 1979PubMedCrossRefGoogle Scholar
  19. 19.
    Church MW, Holloway JA: Passive and active avoidance behaviors of rats prenatally exposed to ethanol and their untreated offspring. Alcoholism: Clin Exp Res 7: 107, 1983Google Scholar
  20. 20.
    Goodwin DW: Genetic component of alcoholism. Annu Rev Med 32: 93–99, 1981PubMedCrossRefGoogle Scholar
  21. 21.
    Hrubec Z, Omenn GS: Evidence of genetic predisposition to alcoholic cirrhosis and psychosis: Twin concordances for alcoholism and its biological end points by zygosity among male veterans. Alcoholism: Clin Exp Res 5: 207–215, 1981CrossRefGoogle Scholar
  22. 22.
    Stein Z, Susser M: The Dutch famine, 1944–1945, and the reproductive process. I. Effects on six indices at birth. Pediatr Res 9: 70–75, 1975PubMedGoogle Scholar
  23. 23.
    Stein Z, Susser M: The Dutch famine, 1944–1945, and the reproductive process. II. Interrelations of caloric rations and six indices at birth. Pediatr Res 9: 76–79, 1975PubMedGoogle Scholar
  24. 24.
    Stein Z, Susser M: Prenatal nutrition and mental competence, in Yloyd-Still JD (ed): Malnutrition and Intellectual Development. Littleton, Massachusetts, Publishing Sciences Group, 1976, pp 39–80Google Scholar
  25. 25.
    Ruth RE, Goldsmith SK: Interaction between zinc deprivation and acute ethanol intoxication during pregnancy in rats. J Nutr 111: 2034–2038, 1981PubMedGoogle Scholar
  26. 26.
    Flynn A, Martier SS, Sokol RJ, et al: Zinc status of pregnant alcoholic women: A determinant of fetal outcome. Lancet 1: 572–574, 1981PubMedCrossRefGoogle Scholar
  27. 27.
    Fisher SE, Atkinson M, Burnap JK, et al: Ethanol-associated selective fetal malnutrition: A contributing factor in the fetal alcohol syndrome. Alcoholism: Clin Exp Res 6: 197–201, 1982CrossRefGoogle Scholar
  28. 28.
    Munro NH: Placenta in relation to nutrition. Fed Proc 39: 236–238, 1980PubMedGoogle Scholar
  29. 29.
    Miller RK, Berndt WO: Mechanisms of transport across the placenta. An in vitro approach. Life Sci 15: 7–30, 1975CrossRefGoogle Scholar
  30. 30.
    Lin G: Effect of ethanol feeding during pregnancy on placental transfer of alpha-amino isobutyric acid in the rat. Life Sci 28: 595–601, 1981PubMedCrossRefGoogle Scholar
  31. 31.
    Patwardhan RV, Schenker S, Henderson GI, et al: Short term and long term ethanol administration inhibits the placental uptake and transport of valine in rats. J Lab Clin Med 98: 251–262, 1981PubMedGoogle Scholar
  32. 32.
    Henderson GI, Turner D, Patwardhan RV, et al: Inhibition of placental valine uptake after acute and chronic maternal ethanol consumption. J Pharmacol Exp Ther 216: 465–472, 1981PubMedGoogle Scholar
  33. 33.
    Henderson GI, Patwardhan RV, McLeroy S, et al: Inhibition of placental amino acid uptake in rats following acute and chronic ethanol exposure. Alcoholism: Clin Exp Res 6: 495–505, 1982CrossRefGoogle Scholar
  34. 34.
    Fisher SE, Atkinson M, Holzman I, et al: Effect of ethanol upon placental uptake of amino acids, in Messiha FS, Tyner GS (eds): Endocrinological Aspects of Alcoholism. Basel, Karger-Verlag, 1982, pp 216–223Google Scholar
  35. 35.
    Fisher SE, Atkinson M, Jacobson M, et al: Selective fetal malnutrition: The effect of in vivo ethanol exposure upon in vitro placental uptake of amino acids in the non-human primate. Pediatr Res 17: 704–707, 1983PubMedCrossRefGoogle Scholar
  36. 36.
    Fisher SE, Atkinson M, Van Thiel DH, et al: Selective fetal malnutrition: The effect of ethanol and acetaldehyde upon in vitro uptake of alpha amino isobutyric acid by human placenta. Life Sci 20: 1283–1288, 1981CrossRefGoogle Scholar
  37. 37.
    Henderson GI, Hoyumpa AM, McClain C, et al: The effects of chronic and acute alcohol administration on fetal development in the rat. Alcoholism: Clin Exp Res 3: 99–106, 1979CrossRefGoogle Scholar
  38. 38.
    Samson HH, Diaz J: Altered development of brain by neonatal ethanol exposure: Zinc levels during and after exposure. Alcoholism: Clin Exp Res 5: 563–569, 1981CrossRefGoogle Scholar
  39. 39.
    Jones PJH, Leichter J, Lee M: Uptake of zinc, folate and analogs of glucose and amino acid by the rat fetus exposed to alcohol in utero. Nutr Rep Int 24: 75–83, 1981Google Scholar
  40. 40.
    Suh SM, Firek AF: Magnesium and zinc deficiency and growth retardation in offspring of alcoholic rats. J Am Coll Nutr 1: 193–198, 1982Google Scholar
  41. 41.
    Ghishan FK, Patwardhan R, Greene HL: Fetal alcohol syndrome: Inhibition of placental zinc transport as a potential mechanism for fetal growth retardation in the rat. J Lab Clin Med 100: 45–52, 1981Google Scholar
  42. 42.
    Ghishan FK, Patwardhan R, Greene HL: Fetal alcohol syndrome: Failure of zinc supplementation to reverse the effect of ethanol on placental transport of zinc. Pediatr Res 17: 529–531, 1983PubMedCrossRefGoogle Scholar
  43. 43.
    Antony C, Utley C, Van Horne KC, et al: Isolation and characterization of a folate receptor from human placenta. J Biol Chem 256: 9684–9693, 1981PubMedGoogle Scholar
  44. 44.
    Lin GW: Fetal malnutrition: A possible cause of the fetal alcohol syndrome. Frog Biochem Pharmacol 18: 115–121, 1981Google Scholar
  45. 45.
    Fisher SE, Inselman LS, Duffy L, Atkinson M, Spencer H, Chang B: Ethanol and fetal nutrition: Effect of chronic ethanol exposure upon rat placental growth and membrane-associated folic acid receptor binding activity. J Pediatr Gastroenterol Nutr,in pressGoogle Scholar
  46. 46.
    Wunderlich SM, Baliga BS, Munro HN: Rat placental protein synthesis and peptide hormone secretion in relation to malnutrition from protein deficiency or alcohol administration. J Nutr 109: 1534–1541, 1979PubMedGoogle Scholar
  47. 47.
    Mukherjee AB, Hodgen GD: Maternal ethanol exposure induces transient impairment of umbilical circulation and fetal hypoxia in monkeys. Science 218: 700–702, 1982PubMedCrossRefGoogle Scholar
  48. 48.
    Baldwin VJ, MacLeon PM, Benirschke K: Placental findings in alcohol abuse in pregnancy. Birth Defects 18: 89–94, 1982PubMedGoogle Scholar
  49. 49.
    Winick M: Nutrition and central nervous system development. Prog Brain Res 53: 93–97, 1980PubMedCrossRefGoogle Scholar
  50. 50.
    Henderson GI: Fetal alcohol syndrome. An overview. Neurobehav Toxicol Teratol 3: 73–80, 1981PubMedGoogle Scholar
  51. 51.
    Thadani PC: Fetal alcohol syndrome: Neurochemical and endocrinological abnormalities. Prog Biochem Pharmacol 18: 83–98, 1981PubMedGoogle Scholar
  52. 52.
    Detering N, Collins RM, Hawkins RL, et al: Comparative effects of ethanol and malnutrition on development of catecholamine neurons: A long-lasting effect in the hypothalamus. J Neurochem 36: 2094–2096, 1981PubMedCrossRefGoogle Scholar
  53. 53.
    Chernoff GF: The fetal alcohol syndrome in mice: An animal model. Teratology 15: 223–230, 1978CrossRefGoogle Scholar
  54. 54.
    Sulik K, Johnston MS, Webb MA: Fetal alcohol syndrome: Embryogenesis in a mouse model. Science 214: 936–938, 1981PubMedCrossRefGoogle Scholar
  55. 55.
    Abel EL, Dintcheff BA: Effects of prenatal alcohol exposure on growth and development in rats. J Pharmacol Exp Ther 207: 916–921, 1978PubMedGoogle Scholar
  56. 56.
    Ellis FW, Pick JR: An animal model of the fetal alcohol syndrome in beagles. Alcoholism: Clin Exp Res 4: 123–134, 1980CrossRefGoogle Scholar
  57. 57.
    Dexter JD, Tumbleson ME, Decker JD, et al: Fetal alcohol syndrome in Sinclair (S-1) miniature swine. Alcoholism: Clin Exp Res 4: 146–151, 1980CrossRefGoogle Scholar
  58. 58.
    Jacobson S, Sehgal P, Bronson R, et al: Comparison between an oral and an intravenous method to demonstrate the in utero effects of ethanol in the monkey. Neurobehav Toxicol 2: 253–259, 1980Google Scholar
  59. 59.
    Clarren SK, Bowden DM: Fetal alcohol syndrome: A new primate model for binge drinking and its relevance to human ethanol teratogeneis. J Pediatr 101: 819–824, 1982PubMedCrossRefGoogle Scholar
  60. 60.
    Altschuler HL, Amirian JA, Osei-Frimpong J: The development of a subhuman primate model of the fetal alcohol syndrome. Alcoholism: Clin Exp Res 6: 134, 1982Google Scholar
  61. 61.
    Altschuler HL, Amirian JA, Osei-Frimpong J: The fetal alcohol syndrome in rhesus monkeys. Alcoholism: Clin Exp Res 7: 104, 1983CrossRefGoogle Scholar
  62. 62.
    Hall W: Weaning and growth of artificially reared rats. Science 190: 1313–1315, 1975PubMedCrossRefGoogle Scholar
  63. 63.
    Diaz J, Samson HH: Impaired brain growth in neonatal rats exposed to ethanol. Science 208: 751–753, 1980PubMedCrossRefGoogle Scholar
  64. 64.
    Altschuler HL: Data presented to the Fetal Alcohol Study Group, National Alcoholism Forum, Houston, Texas, 1983Google Scholar
  65. 65.
    Marin-Padilla M: Abnormal neuronal differentiation (functional maturation) in mental retardation. Birth Defects 11:133–153, 1975Google Scholar
  66. 66.
    Jones KL, Smith DW: Recognition of the fetal alcohol syndrome in early infancy. Lancet 2: 999–1001, 1973CrossRefGoogle Scholar
  67. 67.
    Peiffer J, Majewski F, Fischback JR, et al: Alcohol, embryo and fetopathy: Neuropathology of three children and three fetuses. J Neural Sci 41: 125–137, 1979CrossRefGoogle Scholar
  68. 68.
    Hammer RP Jr, Scheibe! AB: Morphologic evidence for a delay of neuronal maturation in fetal alcohol exposure. Exp Neural 74: 587–596, 1981CrossRefGoogle Scholar
  69. 69.
    Volk B, Maletz J, Tiedemann M, et al: Impaired maturation of purkinje cells in the fetal alcohol syndrome of the rat. Acta Neuropathol 54: 19–29, 1981PubMedCrossRefGoogle Scholar
  70. 70.
    West JR, Hodges CA, Black AC Jr: Prenatal exposure to ethanol alters the organization of hippocampal mossy fibers in rats. Science 211: 957–959, 1981PubMedCrossRefGoogle Scholar
  71. 71.
    Martin JC, Marin DC, Sigman G, et al: Maternal ethanol consumption and hyperactivity in cross-fostering offspring. Physiol Psycho! 6: 362–365, 1978Google Scholar
  72. 72.
    Shaywitz BA, Griffieth GG, Warshaw JB: Hyperactivity and cognitive deficits in developing rat pups born to alcoholic mothers: An experimental model of the expanded fetal alcohol syndrome (EFAS). Neurobehav Toxicol 1: 113–122, 1979Google Scholar
  73. 73.
    Abel EL: Prenatal effects of alcohol on open-field behavior, stop-down latencies, and “sleep time.” Behav Neurol Biol 25: 406–410, 1979CrossRefGoogle Scholar
  74. 74.
    Bond NW, DiGuisto EL: Effects of prenatal alcohol consumption on open-field behavior and alcohol preference in rats. Psychopharmacologia 46: 163–165, 1976PubMedCrossRefGoogle Scholar
  75. 75.
    Abel EL: Prenatal effects of alcohol on adult learning in rats. Pharmacol Biochem Behav 10: 239–243, 1979PubMedCrossRefGoogle Scholar
  76. 76.
    Auroux M, Dehaupas M: Influence on maternal nutrition on the development of the central nervous system of offspring. 1. Improvement of learning ability in the rat offspring of alcohol-treated mothers. C R Soc Biol (Paris) 164: 1432–1436, 1970Google Scholar
  77. 77.
    Bond NW, Diguisto EL: Avoidance conditioning and Hebb—Williams maze performance in rats treated prenatally with alcohol. Psychopharmacologia 58: 69–71, 1978CrossRefGoogle Scholar
  78. 78.
    Phillips DS, Stainbrook GL: Effects of early alcohol exposure upon adult learning ability and taste preferences. Physiol Psychol 4: 473–475, 1976Google Scholar
  79. 79.
    Abel EL: In utero alcohol exposure and developmental delay of response inhibition. Alcoholism: Clin Exp Res 6: 369–376, 1982CrossRefGoogle Scholar
  80. 80.
    Riley EP, Lochry EA, Shapiro NR: Lack of response inhibition in rats prenatally exposed to alcohol. Psychopharmacologia 62: 47–52, 1979CrossRefGoogle Scholar
  81. 81.
    Riley EP, Lochry EA, Shapiro NR, et al: Response perseveration in rats exposed to alcohol prenatally. Pharmacol Biochem Behav 10: 255–259, 1979PubMedCrossRefGoogle Scholar
  82. 82.
    Rawat AL: Ribosomal protein synthesis in the fetal and neonatal rat brain as influenced by maternal ethanol consumption. Res Commun Chem Pathol Pharmacol 12: 723–732, 1975PubMedGoogle Scholar
  83. 83.
    Fisher SE, Bamicle MA, Steis B, et al: Effects of acute ethanol exposure upon in vivo leucine uptake and protein synthesis in the fetal rat. Pediatr Res 15: 335–339, 1981PubMedCrossRefGoogle Scholar
  84. 84.
    Khawaja JA, Lindholm DB: Neuronal protein synthesis in vitro: Influence of ethanol consumed with low or adequate dietary protein. Res Commun Subs! Abuse 3: 355–361, 1982Google Scholar
  85. 85.
    Ellis J. Krsiak M, Poschlova N: Effect of alcohol given at different periods of gestation on brain serotonin in offspring. Acta Nery Super 20: 287–288, 1978Google Scholar
  86. 86.
    Rawat AK: Effects of maternal ethanol consumption in the fetal and neonatal cerebral neurotransmitters, in Lindros KO, Eriksson CJP (eds): The Role of Acetaldehyde, Actions of Ethanol, Vol 23. Helsinki, Finnish Foundation for Alcohol Studies, 1975, pp 159–176Google Scholar
  87. 87.
    Thadani PV, Lau C, Slotkin TA, et al: Effects of maternal ethanol on amine uptake into synaptosomes of fetal and neonatal rat brain. J Pharmacol Exp Ther 200: 292–297, 1977PubMedGoogle Scholar
  88. 88.
    Jacobson S, Rich JA, Tobsky NJ: Delayed myelination and lamination in the cerebral cortex of the albino rat as a result of the fetal alcohol syndrome. Curr Alcoholism 5: 123–133, 1978Google Scholar
  89. 89.
    Druse MJ, Hofteigh JH: The effect of chronic maternal alcohol consumption on the development of central nervous system myelin subfractions in rat offspring. Drug Alcohol Depend 2: 421–429, 1977PubMedCrossRefGoogle Scholar
  90. 90.
    Hofteig JH, Druse MJ: Central nervous system myelination in rats exposed to ethanol in utero. Drug Alcohol Depend 3: 429–434, 1978PubMedCrossRefGoogle Scholar
  91. 91.
    Sedmak PA, Sedmak D, Fritz HI, et al: Myelination in chronically-alcoholic mice. Experientia 34: 1058–1060, 1978CrossRefGoogle Scholar
  92. 92.
    Church MW, Holloway JA: Postnatal development of brainstem auditory evoked potentials in rat pups prenatally exposed to ethanol: A preliminary report. Alcohol Tech Rep 9: 7–12, 1980Google Scholar
  93. 93.
    Porjesz B, Begleiter H: Human evoked brain potentials and alcohol. Alcoholism: Clin Exp Res 5: 304–318, 1981CrossRefGoogle Scholar
  94. 94.
    Stibler H, Bums E, Krukeberg T, et al: Effect of ethanol on symptosomal scalic acid metabolism in the developing rat brain. J Neurol Sci 59: 21–35, 1983PubMedCrossRefGoogle Scholar
  95. 95.
    Hanson JW, Streissguth AP, Smith DW: The effects of moderate alcohol consumption during pregnancy on fetal growth and morphogensis. J Pediatr 92: 457–460, 1978PubMedCrossRefGoogle Scholar
  96. 96.
    Smith DW: The fetal alcohol syndrome. Hosp Prac 14: 121–128, 1979Google Scholar
  97. 97.
    Mau G: Moderate alcohol consumption during pregnancy and child development. Eur J Pediatr 133: 233–237, 1980PubMedCrossRefGoogle Scholar
  98. 98.
    Meyer, MB, Tonascia JA: Maternal cigarette smoking, pregnancy complications, and perinatal risks. Am J Obstet Gynecol 128: 494–502, 1977PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1985

Authors and Affiliations

  • Stanley E. Fisher
    • 1
  1. 1.Department of PediatricsNorth Shore University Hospital, Cornell University Medical CollegeManhassetUSA

Personalised recommendations