Diagnosis of fetal alcohol spectrum disorder (FASD) is difficult because information regarding prenatal exposure is often lacking, many affected children do not exhibit the characteristic facial anomalies, and no distinctive behavioral phenotype has been identified. Development of appropriate treatments has been hampered by limited understanding of the pathophysiology of FASD. Since 1999, we have been conducting a prospective, longitudinal study in the Cape Coloured (mixed ancestry) community in Cape Town, South Africa, where there is an exceptionally high incidence of fetal alcohol syndrome (FAS). In a 5-year follow-up of this cohort, we found a remarkably consistent effect of fetal alcohol exposure on eyeblink conditioning, a cerebellar-dependent form of learning whose neural circuitry and alcohol effects have been documented in detail in laboratory animals;not a single child with full FAS met criterion for conditioning, compared with 75% of the non-exposed controls. Thus, we have identified a potential biomarker of alcohol-related CNS impairment. Moreover, because it is well established in early infancy, short-delay EBC may provide an important tool in the early diagnosis of FASD and in the evaluation of the efficacy of intrapartum and early postpartum interventions. In this study we will follow-up our Cape Town cohort of 165 children at 8.5 years and recruit a new prospective cohort of 60 infants (30 heavy exposed, 30 controls) from the same community. The principal aims are to characterize the developmental course of alcohol-related impairment in EBC;to use selected neuroimaging techniques to examine the impact of fetal alcohol exposure on the neural circuitry mediating EBC;and to use neurobehavioral and functional MRI tasks to assess effects on cerebellar- mediated timing, a central element of EBC. Advanced neuroimaging will include high resolution structural MRI to examine the regional pattern of brain hypoplasia and the first whole brain diffusion tensor imaging (DTI) in children with FASD to assess the integrity of white matter tracts. The moderating effects of maternal age, alcohol abuse history, and variants of the ADH1B polymorphism on the child's vulnerability to FASD will also be examined. Public Health Relevance: A better understanding of the effects of fetal alcohol exposure on the EBC cerebellar circuit in childhood and infancy has the potential to advance our understanding of the neuropathology of FASD, to improve the diagnosis and treatment of this disorder, and to enable earlier identification of affected children.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Research Project (R01)
Project #
Application #
Study Section
Child Psychopathology and Developmental Disabilities Study Section (CPDD)
Program Officer
Matochik, John A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Wayne State University
Schools of Medicine
United States
Zip Code
Carter, R Colin; Jacobson, Sandra W; Booley, Sharmilah et al. (2018) Development and validation of a quantitative choline food frequency questionnaire for use with drinking and non-drinking pregnant women in Cape Town, South Africa. Nutr J 17:108
Warton, Fleur L; Meintjes, Ernesta M; Warton, Christopher M R et al. (2018) Prenatal methamphetamine exposure is associated with reduced subcortical volumes in neonates. Neurotoxicol Teratol 65:51-59
Warton, Fleur L; Taylor, Paul A; Warton, Christopher M R et al. (2018) Prenatal methamphetamine exposure is associated with corticostriatal white matter changes in neonates. Metab Brain Dis 33:507-522
Woods, Keri J; Thomas, Kevin G F; Molteno, Christopher D et al. (2018) Prenatal alcohol exposure affects brain function during place learning in a virtual environment differently in boys and girls. Brain Behav 8:e01103
Jacobson, Sandra W; Carter, R Colin; Molteno, Christopher D et al. (2018) Feasibility and Acceptability of Maternal Choline Supplementation in Heavy Drinking Pregnant Women: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Alcohol Clin Exp Res 42:1315-1326
Jacobson, Sandra W; Carter, R Colin; Molteno, Christopher D et al. (2018) Efficacy of Maternal Choline Supplementation During Pregnancy in Mitigating Adverse Effects of Prenatal Alcohol Exposure on Growth and Cognitive Function: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Alcohol Clin Exp Res 42:1327-1341
Jacobson, Sandra W; Jacobson, Joseph L (2017) Cardiac Orienting Response as an Early Indicator of Impairment in Fetal Alcohol Spectrum Disorders. Alcohol Clin Exp Res 41:262-265
Biffen, Stevie C; Warton, Christopher M R; Lindinger, Nadine M et al. (2017) Reductions in Corpus Callosum Volume Partially Mediate Effects of Prenatal Alcohol Exposure on IQ. Front Neuroanat 11:132
Kodali, Vikas N; Jacobson, Joseph L; Lindinger, Nadine M et al. (2017) Differential Recruitment of Brain Regions During Response Inhibition in Children Prenatally Exposed to Alcohol. Alcohol Clin Exp Res 41:334-344
Fan, Jia; Taylor, Paul A; Jacobson, Sandra W et al. (2017) Localized reductions in resting-state functional connectivity in children with prenatal alcohol exposure. Hum Brain Mapp 38:5217-5233

Showing the most recent 10 out of 44 publications