Fleur L Warton1,2,3, Christopher D Molteno4, Christopher M R Warton1, Pia Wintermark5, Nadine M Lindinger1,6, Neil C Dodge7, Lilla Zöllei8, Andre J W van der Kouwe1,8, R Colin Carter9, Joseph L Jacobson1,4,7, Sandra W Jacobson1,4,7, Ernesta M Meintjes1,2,3,10. 1. Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa. 2. Biomedical Engineering Research Centre, Division of Biomedical Engineering, University of Cape Town, Cape Town, South Africa. 3. Neuroscience Institute, University of Cape Town, Cape Town, South Africa. 4. Department of Psychiatry and Mental Health, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa. 5. Department of Pediatrics, Montreal Children's Hospital, McGill University, Montreal, Canada. 6. ACSENT Laboratory, Department of Psychology, University of Cape Town, Cape Town, South Africa. 7. Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan, USA. 8. Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts, USA. 9. Division of Pediatric Emergency Medicine, Columbia University Medical Center, New York, New York, USA. 10. Cape Universities Body Imaging Centre, University of Cape Town, Cape Town, South Africa.
Abstract
BACKGROUND: Prenatal alcohol exposure (PAE) is associated with smaller regional and global brain volumes. In rats, gestational choline supplementation mitigates adverse developmental effects of ethanol exposure. Our recent randomized, double-blind, placebo-controlled maternal choline supplementation trial showed improved somatic and functional outcomes in infants at 6.5 and 12 months postpartum. Here, we examined whether maternal choline supplementation protected the newborn brain from PAE-related volume reductions and, if so, whether these volume changes were associated with improved infant recognition memory. METHODS: Fifty-two infants born to heavy-drinking women who had participated in a choline supplementation trial during pregnancy underwent structural magnetic resonance imaging with a multi-echo FLASH protocol on a 3T Siemens Allegra MRI (median age = 2.8 weeks postpartum). Subcortical regions were manually segmented. Recognition memory was assessed at 12 months on the Fagan Test of Infant Intelligence (FTII). We examined the effects of choline on regional brain volumes, whether choline-related volume increases were associated with higher FTII scores, and the degree to which the regional volume increases mediated the effects of choline on the FTII. RESULTS: Usable MRI data were acquired in 50 infants (choline: n = 27; placebo: n = 23). Normalized volumes were larger in six of 12 regions in the choline than placebo arm (t ≥ 2.05, p ≤ 0.05) and were correlated with the degree of maternal choline adherence (β ≥ 0.28, p ≤ 0.04). Larger right putamen and corpus callosum were related to higher FTII scores (r = 0.36, p = 0.02) with a trend toward partial mediation of the choline effect on recognition memory. CONCLUSIONS: High-dose choline supplementation during pregnancy mitigated PAE-related regional volume reductions, with larger volumes associated with improved 12-month recognition memory. These results provide the first evidence that choline may be neuroprotective against PAE-related brain structural deficits in humans.
BACKGROUND: Prenatal alcohol exposure (PAE) is associated with smaller regional and global brain volumes. In rats, gestational choline supplementation mitigates adverse developmental effects of ethanol exposure. Our recent randomized, double-blind, placebo-controlled maternal choline supplementation trial showed improved somatic and functional outcomes in infants at 6.5 and 12 months postpartum. Here, we examined whether maternal choline supplementation protected the newborn brain from PAE-related volume reductions and, if so, whether these volume changes were associated with improved infant recognition memory. METHODS: Fifty-two infants born to heavy-drinking women who had participated in a choline supplementation trial during pregnancy underwent structural magnetic resonance imaging with a multi-echo FLASH protocol on a 3T Siemens Allegra MRI (median age = 2.8 weeks postpartum). Subcortical regions were manually segmented. Recognition memory was assessed at 12 months on the Fagan Test of Infant Intelligence (FTII). We examined the effects of choline on regional brain volumes, whether choline-related volume increases were associated with higher FTII scores, and the degree to which the regional volume increases mediated the effects of choline on the FTII. RESULTS: Usable MRI data were acquired in 50 infants (choline: n = 27; placebo: n = 23). Normalized volumes were larger in six of 12 regions in the choline than placebo arm (t ≥ 2.05, p ≤ 0.05) and were correlated with the degree of maternal choline adherence (β ≥ 0.28, p ≤ 0.04). Larger right putamen and corpus callosum were related to higher FTII scores (r = 0.36, p = 0.02) with a trend toward partial mediation of the choline effect on recognition memory. CONCLUSIONS: High-dose choline supplementation during pregnancy mitigated PAE-related regional volume reductions, with larger volumes associated with improved 12-month recognition memory. These results provide the first evidence that choline may be neuroprotective against PAE-related brain structural deficits in humans.
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