Association of Maternal and Cord Blood Choline and Betaine Concentrations with Birthweight: A Prospective Mother–Infant Cohort Study

Background: Experimental studies indicated that maternal choline and betaine status have the potential to alter fetal growth, but epidemiological data remain sparse. Objective: We aimed to investigate the association of maternal and cord blood choline and betaine concentrations with birthweight outcomes. Methods: This prospective cohort study involved 988 mother–infant dyads from Hebei and Shandong provinces. Plasma concentrations of choline and betaine in maternal late pregnancy and cord blood were quantified using ultra-performance liquid chromatography–mass spectrometry. Multivariable linear or logistic regression was performed to examine their association with continuous or binary birthweight outcomes. Results: Maternal plasma choline and betaine concentrations in late pregnancy (median [interquartile range]; 12.34 [10.13, 14.78] and 14.99 [12.01, 18.36] μmol/L) were significantly lower than those in cord blood (29.98 [24.74, 35.93] and 31.14 [25.56, 37.28] μmol/L). Each 1 μmol/L increase of late-pregnancy and cord blood betaine concentrations were associated with 9.87 g (95% confidence interval [CI]: −16.08, −3.66 g) and 5.29 g (95% CI: −8.52, −2.06 g) lower birthweight, respectively. Compared with the lowest quintile, the highest quintiles of late-pregnancy and cord blood betaine concentrations were associated with lower risks of large-for-gestational-age (adjusted odds ratios [ORs] = 0.47 [95% CI: 0.24, 0.90] and 0.31 [95% CI: 0.17, 0.56]) and macrosomia (adjusted ORs = 0.12 [95% CI: 0.03, 0.43] and 0.15 [95% CI: 0.05, 0.40]). These associations, particularly for cord blood, persisted and appeared more pronounced in pregnancies with maternal overweight/obesity or gestational diabetes mellitus (GDM), but the interaction effect did not reach statistical significance. No significant associations were observed for choline in any periods. Conclusions: Higher plasma concentrations of betaine in maternal late-pregnancy and cord blood were associated with lower birthweight. These findings emphasize the importance of sufficient betaine status during pregnancy, especially among mothers with obesity or GDM.