Yiming Hu, Lei Hou, Miao Yu, Rui Zhang, Xiaomin Wu, Baohua Wang, Jing Wu, Zhu Li
Prenatal folic acid supplementation was modestly associated with lower macrosomia risk and may modify the association between pre-pregnancy BMI and birth weight. Given the small effect sizes, observational design, and historical cohort context, these findings should be interpreted cautiously.
PURPOSE: To evaluate associations of prenatal folic acid supplementation with offspring birth weight and whether supplementation modifies the associations of pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) with birth weight.
METHODS: We conducted a secondary analysis of prospectively collected data from a population-based cohort study in China originally established to evaluate prenatal folic acid supplementation for neural tube defects prevention, including 192,596 mother-infant pairs with complete follow-up and essential variables. Multivariable regression models assessed associations of folic acid supplementation, pre-pregnancy BMI, and GWG with birth weight outcomes, incorporating interaction terms. Restricted cubic splines examined non-linear dose-response relationships. Sensitivity analyses used gestational-age- and sex-specific classifications of small, appropriate, and large for gestational age.
RESULTS: Folic acid supplementation was associated with slightly lower mean birth weight than no supplementation (3,289.64 ± 414.93 g vs. 3,304.50 ± 427.78 g, P < 0.001), although the absolute difference was of limited clinical significance. Spline analyses showed that supplementation modestly attenuated the non-linear positive association between pre-pregnancy BMI and birth weight (Pinteraction < 0.001). Folic acid supplementation was associated with a modestly lower risk of macrosomia (adjusted odds ratio [aOR] = 0.927, 95% CI: 0.889-0.967, P < 0.001), and interacted with pre-pregnancy BMI on macrosomia risk (interaction aOR = 0.977, 95% CI: 0.962-0.993, P = 0.005). Sensitivity analyses supported the findings for excessive fetal growth.
CONCLUSION: Prenatal folic acid supplementation was modestly associated with lower macrosomia risk and may modify the association between pre-pregnancy BMI and birth weight. Given the small effect sizes, observational design, and historical cohort context, these findings should be interpreted cautiously.