Maternal choline supplementation in a sheep model of first trimester binge alcohol fails to protect against brain volume reductions in peripubertal lambs

Sharla M. Birch, Mark W. Lenox, Joe N. Kornegay, Beatriz Paniagua, Martin A. Styner, Charles R. Goodlett, Tim A. Cudd, Shannon E. Washburn

Research output: Contribution to journalArticle

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Abstract

Fetal alcohol spectrum disorder (FASD) is a leading potentially preventable birth defect. Poor nutrition may contribute to adverse developmental outcomes of prenatal alcohol exposure, and supplementation of essential micronutrients such as choline has shown benefit in rodent models. The sheep model of first-trimester binge alcohol exposure was used in this study to model the dose of maternal choline supplementation used in an ongoing prospective clinical trial involving pregnancies at risk for FASD. Primary outcome measures including volumetrics of the whole brain, cerebellum, and pituitary derived from magnetic resonance imaging (MRI) in 6-month-old lambs, testing the hypothesis that alcohol-exposed lambs would have brain volume reductions that would be ameliorated by maternal choline supplementation. Pregnant sheep were randomly assigned to one of five groups – heavy binge alcohol (HBA; 2.5 g/kg/treatment ethanol), heavy binge alcohol plus choline supplementation (HBC; 2.5 g/kg/treatment ethanol and 10 mg/kg/day choline), saline control (SC), saline control plus choline supplementation (SCC; 10 mg/kg/day choline), and normal control (NC). Ewes were given intravenous alcohol (HBA, HBC; mean peak BACs of ∼280 mg/dL) or saline (SC, SCC) on three consecutive days per week from gestation day (GD) 4–41; choline was administered on GD 4–148. MRI scans of lamb brains were performed postnatally on day 182. Lambs from both alcohol groups (with or without choline) showed significant reductions in total brain volume; cerebellar and pituitary volumes were not significantly affected. This is the first report of MRI-derived volumetric brain reductions in a sheep model of FASD following binge-like alcohol exposure during the first trimester. These results also indicate that maternal choline supplementation comparable to doses in human studies fails to prevent brain volume reductions typically induced by first-trimester binge alcohol exposure. Future analyses will assess behavioral outcomes along with regional brain and neurohistological measures.

LanguageEnglish (US)
Pages1-8
Number of pages8
JournalAlcohol
Volume55
DOIs
StatePublished - Sep 1 2016

Fingerprint

First Pregnancy Trimester
Choline
Brain
Sheep
brain
alcohol
Alcohols
Mothers
Fetal Alcohol Spectrum Disorders
Magnetic resonance
Magnetic Resonance Imaging
Pregnancy
Imaging techniques
Ethanol
Micronutrients
Cerebellum
Nutrition
Rodentia
nutrition
Outcome Assessment (Health Care)

Keywords

  • Choline
  • Diagnosis
  • FASD
  • Magnetic resonance imaging
  • Prenatal alcohol
  • Volumetrics

ASJC Scopus subject areas

  • Health(social science)
  • Biochemistry
  • Toxicology
  • Neurology
  • Behavioral Neuroscience

Cite this

Maternal choline supplementation in a sheep model of first trimester binge alcohol fails to protect against brain volume reductions in peripubertal lambs. / Birch, Sharla M.; Lenox, Mark W.; Kornegay, Joe N.; Paniagua, Beatriz; Styner, Martin A.; Goodlett, Charles R.; Cudd, Tim A.; Washburn, Shannon E.

In: Alcohol, Vol. 55, 01.09.2016, p. 1-8.

Research output: Contribution to journalArticle

Birch, Sharla M. ; Lenox, Mark W. ; Kornegay, Joe N. ; Paniagua, Beatriz ; Styner, Martin A. ; Goodlett, Charles R. ; Cudd, Tim A. ; Washburn, Shannon E./ Maternal choline supplementation in a sheep model of first trimester binge alcohol fails to protect against brain volume reductions in peripubertal lambs. In: Alcohol. 2016 ; Vol. 55. pp. 1-8
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