Association between Maternal Choline, Fetal Brain Development, and Child Neurocognition: Systematic Review and Meta-Analysis of Human Studies

Abstract

We studied associations between prenatal and early postnatal choline intake, brain development, and neurocognitive function of children. We conducted a systematic review followed by a meta-analysis and critical appraisal of human studies published from 1997 to 2021. Thirty publications were identified. The meta-analysis included 5 of 7 case-control studies studying neural tube defects (NTDs) in relation to maternal choline intakes/circulating concentrations. Low maternal choline intake/circulating concentrations were associated with a higher OR for NTDs among 1131 mothers of newborns with NTDs and 4439 control mothers (pooled estimate = 1.36; 95% CI: 1.11, 1.67). The 95% prediction intervals were 0.78, 2.36. Findings and critical evaluation of 10 publications with interventional designs showed that higher maternal choline intakes during the second half of pregnancy and early postnatal period (550 mg up to 1 g/d on top of the diet) or a child intake of 513 to 625 mg/d from supplements were safe and likely to demonstrate favorable effects on several domains of child neurocognition, such as memory, attention, and visuospatial learning versus the comparators. Findings from observational studies (n = 13) partly supported the association between maternal choline intake/serum concentrations and child neurocognition, but there was low confidence in the use of plasma choline concentrations as a choline intake marker. In conclusion, low maternal choline intakes were associated with a higher OR for NTDs. The risk could be up to 2.36-fold in some populations. Despite limitations of available trials and observational studies, higher maternal choline intake was likely to be associated with better child neurocognition/neurodevelopment. The results should be used to guide choline intake recommendations in pregnancy and lactation, especially because most young women are not achieving the reference intake of choline. This meta-analysis is registered at PROSPERO as CRD42021233790.

Keywords: brain; choline; essential nutrient; first trimester; infant; lactation; neural tube defects; neurocognition; pregnancy; prenatal.

FIGURE 1

Study flow chart. RCT, randomized controlled trial; Suppl., Supplemental.

FIGURE 2

(A) Forest plot of the association between low maternal choline intake or serum total choline concentration (vs. high intake/concentration) and the OR and 95% CIs of NTDs. The analysis was run at the study level and the studies were weighted by the inverse variance. (B) The analysis was performed at the sub-study level to evaluate the consistency of the association across the subgroups. Serum total choline in the study of Shaw et al. (36) consisted of the sum of all choline-containing compounds. NTD, neural tube defect.

FIGURE 3

Forest plot showing subgroup analysis of the association between low maternal choline intake (vs. high intake) and the OR and 95% CIs of anencephaly (A) and spina bifida (B). NTD, neural tube defect.