Relationship between one‐carbon metabolism and fetal growth in twins: A cohort study

Abstract We investigated the associations of one‐carbon metabolism (OCM)‐related metabolites, including choline, betaine, dimethylglycine (DMG), and methionine with fetal growth of twins. This hospital‐based cohort study included dichorionic twin gestations. Blood samples were collected at a median of 14.7 weeks of gestation. Blood plasma metabolite levels were measured using high‐performance liquid chromatography–triple quadrupole mass spectrometry. Generalized estimating equations and mixed effects models were used to explore associations between plasma metabolite levels and fetal growth. In total, 115 women with dichorionic diamniotic pregnancies were included. The maternal plasma DMG level was negatively correlated with fetal birth weight (β = −43.5, 95% confidence interval [CI] = −74.1 to −12.8, p < .05) and head circumference (β = −0.23, 95% CI = −0.39 to −0.07, p < .05). Other metabolites were not significantly associated with birth weight, body length, head circumference (HC), or chest circumference. Analysis of the relationships between plasma metabolite levels and fetal biological parameters on ultrasound revealed that the maternal choline level was negatively correlated with fetal abdominal circumference (AC) (β = −0.12, 95% CI = 0.24 to −0.004, p < .05); the maternal DMG level was negatively correlated with fetal AC (β = −0.17, 95% CI = 0.28–0.07, p < .05), femur length (β = 0.02, 95% CI = 0.04–0.003, p < .05), and estimated fetal weight (β = 26.4, 95% CI = −41.6 to −11.2, p < .05), but not with HC. The maternal methionine level was negatively correlated with HC (β = −0.08, 95% CI = −0.14 to −0.02, p < .05). The plasma level of the OCM‐related metabolite DMG during the second trimester was negatively correlated with fetal intrauterine growth and birth weight. However, further studies with larger samples are needed.