4.2 Article

Maternal choline supplementation mitigates alcohol exposure effects on neonatal brain volumes

Journal

ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
Volume 45, Issue 9, Pages 1762-1774

Publisher

WILEY
DOI: 10.1111/acer.14672

Keywords

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

Funding

  1. National Institutes of Health (NIH) [R01-AA016781, R21-AA020332, R21-AA020037, R01-HD085813]
  2. Lycaki-Young Fund from the State of Michigan
  3. National Research Foundation of South Africa [48337]
  4. South African National Research Foundation (NRF) Innovative Scholarship
  5. University of Cape Town
  6. [R00--HD061485]
  7. [R01-HD065762]
  8. [1S10RR023401]
  9. [1S10RR019307]
  10. [1S10RR023043]

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High-dose choline supplementation during pregnancy mitigated PAE-related regional volume reductions, with larger volumes associated with improved 12-month recognition memory. This study provides 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 (beta >= 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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