Fetal DHA inadequacy and the impact on child neurodevelopment: a follow-up of a randomised trial of maternal DHA supplementation in pregnancy.

DHA is an important component of neural lipids accumulating in neural tissue during development. Inadequate DHA in gestation may compromise infant development, but it is unknown whether there are lasting effects. We sought to determine whether the observed effects of fetal DHA inadequacy on infant development persist into early childhood. This follow-up study assessed children (5-6 years) whose mothers received 400 mg/d DHA or a placebo during pregnancy. Child neurodevelopment was assessed with several age-appropriate tests including the Kaufman Assessment Battery for Children. A risk-reduction model was used whereby the odds that a child from the maternal placebo group would fail to achieve a test score in the top quartile was calculated. The association of maternal DHA intake and status in gestation with child test scores, as well as with child DHA intake and status, was also determined. No differences were detected in children (n 98) from the maternal placebo and DHA groups achieving a high neurodevelopment test score (P>0·05). However, maternal DHA status was positively related to child performance on some tests including language and short-term memory. Furthermore, child DHA intake and status were related to the mother's intake and status in gestation. The neurodevelopment effects of fetal DHA inadequacy may have been lost or masked by other variables in the children. Although we provide evidence that maternal DHA status is related to child cognitive performance, the association of maternal and child DHA intake and status limits the interpretation of whether DHA before or after birth is important.

Omega-3 fatty acid deficiency in infants before birth identified using a randomized trial of maternal DHA supplementation in pregnancy.

BACKGROUND: DHA is accumulated in the central nervous system (CNS) before birth and is involved in early developmental processes, such as neurite outgrowth and gene expression. OBJECTIVE: To determine whether fetal DHA insufficiency occurs and constrains CNS development in term gestation infants. DESIGN: A risk reduction model using a randomized prospective study of term gestation single birth healthy infants born to women (n = 270) given a placebo or 400 mg/day DHA from 16 wk gestation to delivery. Fetal DHA deficiency sufficient to constrain CNS development was assessed based on increased risk that infants in the placebo group would not achieve neurodevelopment scores in the top quartile of all infants in the study. RESULTS: Infants in the placebo group were at increased risk of lower language development assessed as words understood (OR 3.22, CL 1.49-6.94, P = 0.002) and produced (OR 2.61, CL 1.22-5.58, P = 0.01) at 14 mo, and words understood (OR 2.77, CL 1.23-6.28, P = 0.03) and sentences produced (OR 2.60, CL 1.15-5.89, P = 0.02) at 18 mo using the McArthur Communicative Developmental Inventory; receptive (OR 2.23, CL 1.08-4.60, P = 0.02) and expressive language (OR 1.89, CL 0.94-3.83, P = 0.05) at 18 mo using the Bayley Scales of Infant Development III; and visual acuity (OR 2.69, CL 1.10-6.54, P = 0.03) at 2 mo. TRIAL REGISTRATION: ClinicalTrials.gov NCT00620672.

Low plasma vitamin B-12 is associated with a lower pregnancy-associated rise in plasma free choline in Canadian pregnant women and lower postnatal growth rates in their male infants.

BACKGROUND: Choline needs are increased in pregnancy. Choline can be used as a source of methyl for homocysteine remethylation to methionine, but choline synthesis requires methyls from methionine. Vitamin B-12 deficiency increases choline use for homocysteine methylation. OBJECTIVES: We investigated whether poor vitamin B-12 status occurs and contributes to low plasma choline and altered biomarkers of choline synthesis in pregnant women. With the use of a post hoc analysis, we addressed the association of maternal plasma vitamin B-12 status with postnatal growth rates in term infants. DESIGN: Blood was analyzed for a prospective study of 264 and 220 pregnant women at 16 and 36 wk of gestation, respectively, and 88 nonpregnant women as a reference. RESULTS: The proportion of women with a plasma total vitamin B-12 concentration <148 pmol/L (deficient) or 148-220 pmol/L (marginal) increased with pregnancy and pregnancy duration, which affected 3% and 9% of nonpregnant women, 10% and 21% of women at 16 wk of gestation, and 23% and 35% of women at 36 wk of gestation, respectively. Plasma free choline, betaine, and dimethylglycine were lower in women at 36 wk of gestation with a deficient or marginal compared with sufficient plasma total vitamin B-12 concentration (>220 pmol/L). Plasma total vitamin B-12 was positively associated with the increase in plasma free choline from midgestation to late gestation (P < 0.001). The postnatal growth rate to 9 mo was lower in infant boys of women classified as total vitamin B-12 deficient compared with sufficient. CONCLUSION: 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.