Maternal and Child Health Journal

, Volume 19, Issue 12, pp 2605–2614 | Cite as

Dose and Timing of Prenatal Alcohol Exposure and Maternal Nutritional Supplements: Developmental Effects on 6-Month-Old Infants

  • Claire D. Coles
  • Julie A. Kable
  • Carl L. Keen
  • Kenneth Lyons Jones
  • Wladimir Wertelecki
  • Irina V. Granovska
  • Alla O. Pashtepa
  • Christina D. Chambers
  • the CIFASD



Fetal alcohol spectrum disorders are more common in disadvantaged populations. Environmental factors, like suboptimal nutrition, may potentiate the developmental effects of prenatal alcohol exposure. To evaluate the impact of micronutrients, including choline, on reduction of effects of exposure, we examined timing and dose of alcohol and effects of nutritional supplementation at two OMNI-Net sites in Western Ukraine that included high and low risk individuals.


Alcohol-using and nondrinking women were randomized to one of three multivitamin/mineral supplement groups: none, multivitamins/minerals (MVM), and multivitamin/minerals plus choline. Children (N = 367) were tested at 6 months with the Bayley Scales of Infant Development (2nd ED) yielding standard scores for Mental Development Index (MDI), Psychomotor Development Index (PDI) and Behavior.


Generalized linear modeling was used: (1) for factorial analysis of effects of alcohol group, multivitamin/minerals, and choline supplementation; and (2) to examine the relationship between amount and timing of alcohol (ounces of absolute alcohol/day [ozAA/day] peri-conception and on average in the second trimester) and MVM supplementation on developmental outcomes while controlling sex, social class, and smoking. MDI was significantly impacted by peri-conceptual alcohol dose (\(\upchi_{(1)}^{2} = 8.54\), p < .001) with more alcohol associated with lower scores and males more negatively affected than females (\(\upchi_{(3)}^{2} = 11.04\), p < .002). Micronutrient supplementation had a protective effect; those receiving supplements performed better (\(\upchi_{(1)}^{2} = 8.03\), p < .005). The PDI motor scores did not differ by group but were affected by peri-conceptual alcohol dose (\(\upchi_{(1)}^{2} = 4.17\), p < .04).

Conclusions for Practice

Multivitamin/mineral supplementation can reduce the negative impact of alcohol use during pregnancy on specific developmental outcomes.


Prenatal alcohol exposure Fetal alcohol spectrum disorders Multivitamin supplement Choline Infant development 



All or part of this work 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). Additional information about CIFASD can be found at Research described in this manuscript was supported by Contract #U01AA014835 funded by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the NIH Office of Dietary Supplements (ODS). We wish to acknowledge the contribution of: OMNI-Net, Ukraine, Participating families and staff in Rivne and Khmelnytsky, Ukraine.


  1. 1.
    Riley, E. P., Infante, M. A., & Warren, K. R. (2011). Fetal alcohol spectrum disorders: An overview. Neuropsychology Review, 21(2), 73–80.PubMedCentralCrossRefPubMedGoogle Scholar
  2. 2.
    Mattson, S. N., Crocker, N., & Nguyen, T. T. (2011). Fetal alcohol spectrum disorders: Neuropsychological and behavioral features. Neuropsychology Review, 21(2), 81–101.PubMedCentralCrossRefPubMedGoogle Scholar
  3. 3.
    Centers for Disease Control and Prevention (CDC). (2002). Fetal alcohol syndrome—Alaska, Arizona, Colorado, and New York, 1995–1997. Morbidity and Mortality Reports, 51(20), 433–435.Google Scholar
  4. 4.
    May, P. A., et al. (2014). Prevalence and characteristics of fetal alcohol spectrum disorders. Pediatrics, 134(5), 855–866.PubMedCentralCrossRefPubMedGoogle Scholar
  5. 5.
    Jacobson, S. W., et al. (2002). Validity of maternal report of prenatal alcohol, cocaine, and smoking in relation to neurobehavioral outcome. Pediatrics, 109(5), 815–825.CrossRefPubMedGoogle Scholar
  6. 6.
    Niclasen, J. (2014). Drinking or not drinking in pregnancy: The multiplicity of confounding influences. Alcohol and Alcoholism, 49(3), 349–355.CrossRefPubMedGoogle Scholar
  7. 7.
    Abel, E. L. (1998). Fetal alcohol abuse syndrome. New York, NY: Plenum Press.CrossRefGoogle Scholar
  8. 8.
    Weiss, L. A., & Chambers, C. D. (2013). Associations between multivitamin supplement use and alcohol consumption before pregnancy: Pregnancy risk assessment monitoring system, 2004 to 2008. Alcoholism, Clinical and Experimental Research, 37(9), 1595–1600.PubMedCentralCrossRefPubMedGoogle Scholar
  9. 9.
    Keen, C. L., et al. (2010). 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(2), 125–135.PubMedCentralPubMedGoogle Scholar
  10. 10.
    Jiang, X., West, A. A., & Caudill, M. A. (2014). Maternal choline supplementation: A nutritional approach for improving offspring health? Trends in Endocrinology and Metabolism, 25(5), 263–273.CrossRefPubMedGoogle Scholar
  11. 11.
    Thomas, J. D., Abou, E. J., & Dominguez, H. D. (2009). Prenatal choline supplementation mitigates the adverse effects of prenatal alcohol exposure on development in rats. Neurotoxicology and Teratology, 31(5), 303–311.PubMedCentralCrossRefPubMedGoogle Scholar
  12. 12.
    Thomas, J. D., et al. (2010). Prenatal choline supplementation mitigates behavioral alterations associated with prenatal alcohol exposure in rats. Birth Defects Research Part A: Clinical and Molecular Teratology, 88(10), 827–837.CrossRefGoogle Scholar
  13. 13.
    Thomas, J. D., et al. (2000). Neonatal choline supplementation ameliorates the effects of prenatal alcohol exposure on a discrimination learning task in rats. Neurotoxicology and Teratology, 22(5), 703–711.CrossRefPubMedGoogle Scholar
  14. 14.
    Strain, J. J., et al. (2013). Choline status and neurodevelopmental outcomes at 5 years of age in the Seychelles Child Development Nutrition Study. British Journal of Nutrition, 110(2), 330–336.PubMedCentralCrossRefPubMedGoogle Scholar
  15. 15.
    Villamor, E., et al. (2012). Maternal intake of methyl-donor nutrients and child cognition at 3 years of age. Paediatric and Perinatal Epidemiology, 26(4), 328–335.PubMedCentralCrossRefPubMedGoogle Scholar
  16. 16.
    Cheatham, C. L., et al. (2012). Phosphatidylcholine supplementation in pregnant women consuming moderate-choline diets does not enhance infant cognitive function: a randomized, double-blind, placebo-controlled trial. American Journal of Clinical Nutrition, 96(6), 1465–1472.PubMedCentralCrossRefPubMedGoogle Scholar
  17. 17.
    anomalies, E.s.o.c. (2014). EUROCAT Prevalence Data Tables: A5—Fetal alcohol syndrome § (per 10,000 births) for the following registries: All Registries, from 2008–2012.Google Scholar
  18. 18.
    Bakhireva, L. N., et al. (2011). Paternal drinking, intimate relationship quality, and alcohol consumption in pregnant Ukrainian women. Journal of Studies on Alcohol and Drugs, 72(4), 536–544.PubMedCentralCrossRefPubMedGoogle Scholar
  19. 19.
    Chambers, C. D., et al. (2014). Prevalence and predictors of maternal alcohol consumption in 2 regions of Ukraine. Alcoholism, Clinical and Experimental Research, 38(4), 1012–1019.PubMedCentralCrossRefPubMedGoogle Scholar
  20. 20.
    Sobell, L. C., & Sobell, M. B. (2000). Alcohol timeline followback (TLFB). In American Psychiatric Association (Ed.), Handbook of psychiatric measures (pp. 477–479). Washington, DC: American Psychiatric Association.Google Scholar
  21. 21.
    Barr, H. M., & Streissguth, A. P. (2001). Identifying maternal self-reported alcohol use associated with fetal alcohol spectrum disorders. Alcoholism, Clinical and Experimental Research, 25(2), 283–287.CrossRefPubMedGoogle Scholar
  22. 22.
    Hollingshead, A. B. (2011). Four factor index of social status. Yale Journal of Sociology, 8, 21–51.Google Scholar
  23. 23.
    Holm, P. I., et al. (2003). Determination of choline, betaine, and dimethylglycine in plasma by a high-throughput method based on normal-phase chromatography-tandem mass spectrometry. Clinical Chemistry, 49(2), 286–294.CrossRefPubMedGoogle Scholar
  24. 24.
    Innis, S. M., & Hasman, D. (2006). Evidence of choline depletion and reduced betaine and dimethylglycine with increased homocysteine in plasma of children with cystic fibrosis. Journal of Nutrition, 136(8), 2226–2231.PubMedGoogle Scholar
  25. 25.
    Bayley, N. (1993). Bayley scales of infant development (BSID-2). San Antonio, TX: Psychological Corporation.Google Scholar
  26. 26.
    Moore, T., et al. (2012). Relationship between test scores using the second and third editions of the Bayley Scales in extremely preterm children. Journal of Pediatrics, 160(4), 553–558.CrossRefPubMedGoogle Scholar
  27. 27.
    Jones, K. L., et al. (1973). Pattern of malformation in offspring of chronic alcoholic mothers. Lancet, 1(7815), 1267–1271.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Claire D. Coles
    • 1
    • 7
  • Julie A. Kable
    • 1
  • Carl L. Keen
    • 2
  • Kenneth Lyons Jones
    • 3
  • Wladimir Wertelecki
    • 3
    • 4
    • 5
    • 6
  • Irina V. Granovska
    • 5
  • Alla O. Pashtepa
    • 6
  • Christina D. Chambers
    • 3
  • the CIFASD
  1. 1.Departments of Psychiatry and PediatricsEmory University School of MedicineAtlantaUSA
  2. 2.Department of NutritionUniversity of California-DavisDavisUSA
  3. 3.Department of PediatricsUniversity of California, San DiegoLa JollaUSA
  4. 4.University of South AlabamaMobileUSA
  5. 5.OMNI-Net for Children International Charitable FundRivne Regional Medical Diagnostic CenterRivneUkraine
  6. 6.OMNI-Net for Children International Charitable FundKhmelnytsky Perinatal CenterKhmelnytskyUkraine
  7. 7.Department of Psychiatry and Behavioral SciencesEmory University School of MedicineAtlantaUSA

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