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

This study aims 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 ultrahigh-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 compared with lowest tertile) were linked to significantly increased second-trimester biparietal diameter [β = 0.291, 95% confidence interval (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 concentrations were 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, whereas daidzein affected third-trimester estimated fetal weight in females and head circumference in males (all P < 0.05). In Bayesian kernel machine regression, higher isoflavone combined levels (daidzein, genistein, glycitein, and equol) were significantly associated with increased second-trimester biparietal diameter) z-scores in the total population and female fetuses, as well as increased second-trimester estimated fetal weight 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.