BackgroundThe importance of maternal dietary choline for fetal neural development and later cognitive function has been well-documented in experimental studies. Although choline is an essential dietary nutrient for humans, evidence that low maternal choline in pregnancy impacts neurodevelopment in human infants is lacking. We determined potential associations between maternal plasma free choline and its metabolites betaine and dimethylglycine in pregnancy and infant neurodevelopment at 18 months of age.MethodologyThis was a prospective study of healthy pregnant women and their full-term, single birth infants. Maternal blood was collected at 16 and 36 weeks of gestation and infant neurodevelopment was assessed at 18 months of age for 154 mother-infant pairs. Maternal plasma choline, betaine, dimethylglycine, methionine, homocysteine, cysteine, total B12, holotranscobalamin and folate were quantified. Infant neurodevelopment was evaluated using the Bayley Scales of Infant Development–III. Multivariate regression, adjusting for covariates that impact development, was used to determine the associations between maternal plasma choline, betaine and dimethylglycine and infant neurodevelopment.ResultsThe maternal plasma free choline at 16 and 36 weeks gestation was median (interquartile range) 6.70 (5.78–8.03) and 9.40 (8.10–11.3) µmol/L, respectively. Estimated choline intakes were (mean ±SD) 383±98.6 mg/day, and lower than the recommended 450 mg/day. Betaine intakes were 142±70.2 mg/day. Significant positive associations were found between infant cognitive test scores and maternal plasma free choline (B = 6.054, SE = 2.283, p = 0.009) and betaine (B = 7.350, SE = 1.933, p = 0.0002) at 16 weeks of gestation. Maternal folate, total B12, or holotranscobalamin were not related to infant development.ConclusionWe show that choline status in the first half of pregnancy is associated with cognitive development among healthy term gestation infants. More work is needed on the potential limitation of choline or betaine in the diets of pregnant women.
This study shows that maternal vitamin B-12 status is related to choline status in late gestation in a folate-replete population and may be a determinant of infant growth even in the absence of undernutrition.
In metabolomic analysis of human milk amines, we found a previously unidentified compound. This was tentatively identified as hypaphorine, an indole alkaloid composed of tryptophan and three methyls, and with neurological and glucose-lowering effects in rodents. Hypaphorine identity was confirmed by hypaphorine synthesis, and then a fluorometric method was developed to quantify hypaphorine in milk and foods. Using dietary records, we identified peanut products as probable sources of hypaphorine. Milk from 24 lactating women showed widely varying hypaphorine, with a mean ± SD 0.34 ± 0.33 μM, and the highest concentration of 1.24 μM. Peanuts showed high hypaphorine of 70 μg/g compared to 60 and 100 μg/g in dried chickpeas and lentils. Dietary challenge in lactating women with hypaphorine-rich foods demonstrated transfer of hypaphorine into milk with hypaphorine appearance peaking 5-18 h after consumption and prolonged disappearance indicative of slow excretion or metabolism. The potential functional roles of hypaphorine in human nutrition remain to be addressed.
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