Maternal choline supplementation mitigates alcohol exposure effects on neonatal brain volumes

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.

Keywords: Fagan Test of Infant Intelligence; brain volumes; magnetic resonance imaging; maternal choline supplementation; neonates; prenatal alcohol exposure.

Figure 1.

Flow diagram showing participant numbers at different stages of the choline supplementation trial and number of infants recruited into the neuroimaging sub-study.

Figure 2.

Mean ± 95% confidence intervals of volumes (or areas), normalised to TIV, for regions showing a difference (p ≤ 0.05) between choline- and placebo-treated infants (choline: n = 24; placebo: n = 22). p: from t test; p’: from ANCOVA after adjustment for confounders. Scatterplots show the distribution of sex in the treatment groups.

Figure 3.

Mediation by region size of the effect of choline treatment on Fagan Test of Infant Intelligence (FTII) score (18 choline treated; 19 placebo). Infants were included if maternal treatment adherence ≥ 20%.