Choline Intake During Pregnancy and Child Cognition at Age 7 Years

Caroline E. Boeke; Matthew W. Gillman; Michael D. Hughes; Sheryl L. Rifas-Shiman; Eduardo Villamor; Emily Oken


Am J Epidemiol. 2013;177(12):1338-1347. 

In This Article

Abstract and Introduction


Animal models indicate that exposure to choline in utero improves visual memory through cholinergic transmission and/or epigenetic mechanisms. Among 895 mothers in Project Viva (eastern Massachusetts, 1999–2002 to 2008–2011), we estimated the associations between intakes of choline, vitamin B12, betaine, and folate during the first and second trimesters of pregnancy and offspring visual memory (measured by the Wide Range Assessment of Memory and Learning, Second Edition (WRAML2), Design and Picture Memory subtests) and intelligence (measured using the Kaufman Brief Intelligence Test, Second Edition (KBIT-2)) at age 7 years. Mean second-trimester intakes were 328 (standard deviation (SD), 63) mg/day for choline, 10.5 (SD, 5.1) µg/day for vitamin B12, 240 (SD, 104) mg/day for betaine, and 1,268 (SD, 381) µg/day for folate. Mean age 7 test scores were 17.2 (SD, 4.4) points on the WRAML 2 Design and Picture Memory subtests, 114.3 (SD, 13.9) points on the verbal KBIT-2, and 107.8 (SD, 16.5) points on the nonverbal KBIT-2. In a model adjusting for maternal characteristics, the other nutrients, and child's age and sex, the top quartile of second-trimester choline intake was associated with a child WRAML2 score 1.4 points higher (95% confidence interval: 0.5, 2.4) than the bottom quartile (P-trend = 0.003). Results for first-trimester intake were in the same direction but weaker. Intake of the other nutrients was not associated with the cognitive tests administered. Higher gestational choline intake was associated with modestly better child visual memory at age 7 years.


Methyl donor nutrients like choline, vitamin B12, betaine, and folate may affect brain development through involvement in methylation processes,[1] and choline may be particularly important because of its role in cholinergic transmission.[2] Animal studies demonstrate that higher choline exposure in utero improves memory.[3] Offspring of rat dams given choline supplementation during mid- to late gestation displayed better visuospatial memory than those of unsupplemented dams.[4–6] In rodents, choline supplementation in utero changed gene-specific methylation and protein expression, increased cell proliferation, and decreased apoptosis in the fetal hippocampus, the region of the brain associated with memory.[7–9]

Few studies in humans have examined the association of maternal gestational choline intake with child cognition. Among US mother-child pairs, serum choline concentrations in maternal and umbilical cord blood were not associated with child intelligence quotient (IQ) at age 5 years (e.g., 0.61 IQ points per unit difference in cord serum choline level (P = 0.36)).[10] In Project Viva, gestational choline intake was not associated with score on the Peabody Picture Vocabulary Test, Third Edition (PPVT-III), a test of receptive language (per 450-mg/day increase in second-trimester choline intake, adjusted difference = 0.8, 95% confidence interval (CI): −7.4, 9.0), or the Wide Range Assessment of Visual Motor Abilities (WRAVMA) (adjusted difference = −0.4, 95% CI: −7.6, 6.8) at age 3 years.[11] However, the IQ, PPVT-III, and WRAVMA tests do not specifically measure visuospatial memory, which is the cognitive domain that is consistently affected by choline intake in animal models. In the Framingham Offspring Cohort, choline intake during adulthood was associated with better performance on visual and verbal memory tests.[12]

In contrast to choline, more studies have examined maternal intakes of folate and vitamin B12 in relation to child cognition in humans. In the Pune[13] and Mysore Parthenon[14] studies in India, higher maternal plasma B12 and folate levels at approximately 28–30 weeks of pregnancy were associated with improved offspring cognition, including attention and short-term memory at ages 9–10 years. In a cohort study in Mexico, maternal dietary vitamin B12 deficiency was associated with a reduced neurodevelopmental index in offspring within the first year of life.[15] However, these previous studies did not carefully assess total diet to control for confounding and examined only a few methyl donor nutrients.

We sought to examine maternal first- and second-trimester dietary intake of methyl donor nutrients during pregnancy in relation to child visual memory in a generally well-nourished US population. We hypothesized that high maternal intake of choline and other methyl donor nutrients would be associated with higher memory test scores in children at age 7 years.