Maternal Betaine and Methylation Potential during Pregnancy Are Associated with Child Growth at Birth and Early Childhood: Results of the Chilean Maternal & Infant Cohort Study-II.

BACKGROUND

One-carbon metabolism regulates growth through methyl group transfer required for DNA synthesis and epigenetic processes. In folate-replete populations, the contribution of betaine-dependent remethylation and methylation potential to postnatal growth remains unclear.

OBJECTIVES

This study examined if maternal plasma concentrations of betaine, methionine, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), cystathionine, and the SAM:SAH ratio are associated with offspring growth and body composition at birth and during early childhood.

METHODS

This study included 150 mother-child dyads randomly selected from the prospective Chilean Maternal & Infant Cohort Study-II cohort. Maternal fasting plasma concentrations of betaine, methionine, SAM, SAH, and cystathionine were quantified by liquid chromatography-mass spectrometry (LC-MS)/MS) before 30 wk of gestation. Anthropometric outcomes at birth (weight, length, head circumference) and at 2 to 3 y of age (weight, height, BMI-for-age, and weight-for-height), as well as body composition (fat mass and fat-free mass), were assessed in children. Associations were evaluated using multivariable linear regression models adjusted for prepregnancy BMI, child sex, gestational age at birth, and gestational age at blood collection.

RESULTS

Maternal betaine concentrations showed no significant associations with anthropometric measures at birth. In contrast, higher maternal betaine concentrations were associated with greater child weight, weight-for-height z-score, and BMI-for-age z-score at 2 to 3 y. Higher SAM:SAH ratio was associated with lower child weight and weight gain, whereas SAM and SAH concentrations showed opposing associations consistent with their roles in methylation balance. Methionine concentrations were positively associated with multiple growth outcomes. Betaine and methionine concentrations were positively associated with fat mass, whereas SAM concentrations were inversely associated with fat-free mass at 2 to 3 y.

CONCLUSIONS

Maternal plasma concentrations of betaine and methylation potential during pregnancy are differentially associated with early childhood growth and body composition in a folate-replete population. These findings support a role for maternal one-carbon metabolism in shaping postnatal growth trajectories, beyond the neonatal period.