Maternal choline supplementation during the third trimester of pregnancy improves infant information processing speed: a randomized, double-blind, controlled feeding study

Abstract

Rodent studies demonstrate that supplementing the maternal diet with choline during pregnancy produces life-long cognitive benefits for the offspring. In contrast, the two experimental studies examining cognitive effects of maternal choline supplementation in humans produced inconsistent results, perhaps because of poor participant adherence and/or uncontrolled variation in intake of choline or other nutrients. We examined the effects of maternal choline supplementation during pregnancy on infant cognition, with intake of choline and other nutrients tightly controlled. Women entering their third trimester were randomized to consume, until delivery, either 480 mg choline/d ( n = 13) or 930 mg choline/d ( n = 13). Infant information processing speed and visuospatial memory were tested at 4, 7, 10, and 13 mo of age ( n = 24). Mean reaction time averaged across the four ages was significantly faster for infants born to mothers in the 930 ( vs. 480) mg choline/d group. This result indicates that maternal consumption of approximately twice the recommended amount of choline during the last trimester improves infant information processing speed. Furthermore, for the 480-mg choline/d group, there was a significant linear effect of exposure duration (infants exposed longer showed faster reaction times), suggesting that even modest increases in maternal choline intake during pregnancy may produce cognitive benefits for offspring.-Caudill, M. A., Strupp, B. J., Muscalu, L., Nevins, J. E. H., Canfield, R. L. Maternal choline supplementation during the third trimester of pregnancy improves infant information processing speed: a randomized, double-blind, controlled feeding study.

Keywords: longitudinal; reaction time; saccade; visuospatial memory.

Conflict of interest statement

The authors thank the women participants for their extraordinary cooperation and compliance with the controlled feeding trial and for making their infants available for this neurobehavioral follow-up study. This work was funded, in part, by the Egg Nutrition Center, The Beef Checkoff, the U.S. Department of Agriculture (USDA) Cooperative State Research, Education, and Extension Service (special research Grant 00444528), The Institute for the Social Sciences Small Grants Program, a Bronfenbrenner Life Course Center Research Grant, and the U.S. National Institute of Food and Agriculture, and the USDA (Hatch Accession No. 1007195). None of the funding sources had any role in trial design, participant recruitment, data collection, data analysis, data interpretation, manuscript preparation, or any aspect pertinent to the study. The authors declare no conflicts of interest.

Figures

Figure 1.

Trial profile. Flow of participants through the study screening, intervention, and infant follow-up study phases.

Figure 2.

Infant mean saccade reaction time as a function of age and maternal third-trimester choline intake group status. Data points are predicted values from the a priori mixed-effects regression model of maternal choline intake group on mean saccade reaction time, adjusted for the natural logarithm of infant age at testing, gestational age at birth, birth weight, presence of pregnancy or labor complications, maternal age, maternal ethnicity, and maternal education level. Each infant could contribute up to 2 data points for mean reaction time at each age, one for the baseline sequence and one for the postbaseline alternating sequence. The choline intake group effect is significant at P = 0.03. Lines represent least-squares linear-regression estimates and shadings represent 95% confidence limits.

Figure 3.

Infant mean saccade reaction time as a function of the number of days of third-trimester maternal intake of 480 mg choline/d. A) Data points are predicted values of mean saccade reaction time for all ages combined (estimated at the mean age of 8.05 mo) from the a priori mixed-effects regression model, adjusted for days of maternal third-trimester intake of choline at 480 mg/d, the natural logarithm of infant age at testing, gestational age at birth, birth weight, presence of pregnancy or labor complications, maternal age, maternal ethnicity, and maternal education level. Each infant could contribute up to 2 data points for mean reaction time at each age, one for the baseline sequence and one for the postbaseline alternating sequence. The simple slope estimate for the effect of days of third-trimester maternal choline intake at 480 mg choline/d is −2.25 (se = 0.64, P < 0.001) and is represented by the least-squares fitted line. The shading represents the 95% confidence limit for the slope estimate. B) The same relationship estimated separately for each assessment age (4, 7, 10, and 13 mo), illustrating the consistency of the effect of days of choline intake within each assessment age. The reduced range for the abscissa in the plot of 4-mo data is due to missing data, at that age only, for the participant with the longest duration of prenatal exposure.