Maternal choline supplementation mitigates alcohol exposure effects on neonatal brain volumes.

Abstract

BACKGROUND\nPrenatal 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.\n\n\nMETHODS\n52 infants born to heavy-drinking women, who had participated in our choline supplementation trial during pregnancy, received structural magnetic resonance imaging with a multiecho 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.\n\n\nRESULTS\nUsable MRI data were acquired in 50 infants (choline: n=27; placebo: n=23). Normalised volumes were larger in 6 of 12 regions in the choline than placebo arm (t≥2.05, p≤0.05) and were correlated with 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) and showed a trend towards partial mediation of the choline effect on recognition memory.\n\n\nCONCLUSIONS\nHigh-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.