Maternal methyl-donor nutrient intake and serum one-carbon metabolites in relation to small- and large-for-gestational-age births: a prospective cohort study

Evidence regarding the relationship between maternal methyl donor nutrients (MDNs) status and neonatal birth weight remains limited. This study aims to investigate the associations between maternal intakes of MDNs (vitamins B₂, B₆, folate, B₁₂, choline, betaine, methionine), serum one-carbon metabolism biomarkers (including serum MDNs, S-adenosyl methionine [SAM], S-Adenosyl-L-homocysteine [SAH], and homocysteine), and the risk of small- (SGA) and large-for-gestational-age (LGA) births. A total of 2121 mother-infant pairs from the Tongji Birth Cohort were included. During the second trimester, we conducted dietary assessments using a validated food frequency questionnaire and collected fasting blood samples. Serum biomarkers of one-carbon metabolism were quantified via ultra-performance liquid chromatography-tandem mass spectrometry. Robust Poisson and weighted quantile sum (WQS) regressions were employed for analysis. Among participants, 147 SGA and 288 LGA births were identified. Higher food-derived vitamin B₂ and methionine intakes were associated with reduced SGA risk (RR = 0.61, 0.40-0.95 and RR = 0.46, 0.29-0.72, respectively). Intakes of supplement-derived vitamin B₂, B₆, folate, and B₁₂ were inversely associated with the risk of LGA, showing reductions of 35%, 32%, 33%, and 29% in the highest tertile. MDN-rich dietary patterns and higher MDN scores were inversely associated with SGA and LGA risks, respectively. Elevated serum vitamin B₁₂(0.60, 0.37-0.99), choline(0.58, 0.34-0.98), betaine(0.64, 0.42-0.98), and SAH(0.37, 0.20-0.68) levels were associated with a reduced risk of SGA. Conversely, elevated homocysteine levels were linked to an increased SGA risk(27.52, 9.61-78.82). Higher serum betaine(0.74, 0.56-0.98) and SAM(0.71, 0.51-0.99) levels were inversely associated with LGA risk. WQS regression showed inverse associations between mixed one-carbon metabolites and both SGA and LGA risks. Adequate maternal MDN intakes and a favorable one-carbon metabolism status are associated with reduced risks of SGA and LGA births, highlighting the importance of maternal nutrition during pregnancy.