Elevated Maternal Serum Isoflavones in Early Pregnancy Are Associated with Increased Fetal Growth in the Second Trimester: from a prospective cohort in Guangxi, China.

BACKGROUND: Isoflavones are plant-derived estrogenic compounds that can cross the placenta and influence fetal development, but evidence on fetal ultrasound parameters is limited. OBJECTIVES: To assess associations between individual and combined isoflavones and fetal ultrasound parameters in a prospective birth cohort in Guangxi, China. METHODS: We included 577 mother-infant pairs. Fetal parameters included biparietal diameter, head circumference, femur length, abdominal circumference, and estimated fetal weight. Maternal serum isoflavones in early pregnancy were measured by ultra-high-performance liquid chromatography-mass spectrometry. Associations were analyzed using multiple linear regression and Bayesian kernel machine regression. RESULTS: Higher daidzein, genistein, and glycitein levels (highest vs. lowest tertile) were linked to significantly increased second-trimester biparietal diameter (β = 0.291, 95% CI: 0.091, 0.492; β = 0.256, 95% CI: 0.053, 0.459 and β = 0.296, 95% CI: 0.095, 0.498, respectively) and head circumference z-scores (β = 0.216, 95% CI: 0.004, 0.427, β = 0.240, 95% CI: 0.025, 0.456 and β = 0.264, 95% CI: 0.050, 0.478, respectively). Higher daidzein levels was also also correlated with significantly increased third-trimester head circumference (β = 0.304, 95% CI: 0.086, 0.522). Glycitein exhibited sex-specific effects on abdominal circumference and estimated fetal weight in females, while daidzein affected third-trimester estimated fetal weight in females and head circumference in males (all P<0.05). In BKMR, higher isoflavones combined levels (daidzein, genistein, glycitein, equol) were significantly associated with increased second-trimester biparietal diameter (BPD) z-scores in the total population and female fetuses, as well as increased second-trimester estimated fetal weight (EFW) in female fetuses, with glycitein identified as the major contributor. CONCLUSIONS: Early-pregnancy isoflavone exposure may positively influence fetal growth, with trimester- and sex-specific effects. Further mechanistic studies on placental nutrient transport, gene expression, and long-term offspring outcomes are warranted.