叶酸水平与妊娠结局相关性研究进展

Advances in Research on the Correlation between Folic Acid Levels and Pregnancy Outcomes

摘要: 叶酸作为一碳代谢核心底物，参与核苷酸合成与DNA甲基化，影响胚胎细胞分裂和胎盘功能。流行病学与政策实践一致证实，围受孕期补充叶酸可显著降低神经管畸形(NTD)发生。除NTD外，较佳叶酸状态与早产、低出生体重/小于胎龄儿及部分先天畸形(如口腔裂、部分心脏畸形)风险下降相关，但对子痫前期与妊娠期糖尿病的证据尚存分歧，可能受剂量、起始时机、合并B12状态、肥胖等因素影响。生物标志物方面，红细胞叶酸能反映中期储备，建议人群目标 ≥ 906 nmol/L。实践上，育龄女性应自受孕前至少1个月起每日补充400 μg并持续至孕早期；既往有NTD患儿、抗癫痫药物使用等高危人群需个体化方案。安全性总体良好，但不宜长期超剂量，以避免潜在未代谢叶酸与U形风险信号。未来研究应聚焦精准营养与因果推断，明确不同人群的最佳剂量–时程窗口，并阐明叶酸对表观遗传及母胎结局的长期影响。

Abstract: Folic acid, a core substrate in one-carbon metabolism, supports nucleotide synthesis and DNA methylation, thereby influencing embryonic cell division and placental function. Epidemiologic evidence and policy experience consistently show that periconceptional folic acid supplementation substantially reduces neural tube defects (NTDs). Beyond NTDs, optimal folic acid status is associated with reduced risks of preterm birth, low birth weight/small for gestational age, and selected congenital anomalies (e.g., orofacial clefts and some congenital heart defects). Evidence regarding preeclampsia and gestational diabetes mellitus (GDM) remains mixed, potentially modified by dose, timing of initiation, vitamin B12 status, and obesity. As a biomarker, red blood cell (RBC) folic acid reflects medium-term stores; a population target of ≥906 nmol/L is recommended. In practice, women of reproductive age should take 400 μg/day starting ≥1 month before conception and continuing through early pregnancy; high-risk groups (e.g., prior NTD-affected pregnancy, antiepileptic drug use) require individualized regimens. Overall safety is favorable, but prolonged high doses are discouraged to avoid potential unmetabolized folic acid and possible U-shaped risk signals. Future research should emphasize precision nutrition and causal inference to define subgroup-specific dose-timing windows and to clarify folic acid’s epigenetic and long-term maternal-fetal outcomes.