The association of dietary methionine, natural folate and folic acid supplementation with the risk of preterm birth during pregnancy: a case control study

Abstract

This study aimed to investigate the association of dietary methionine, natural folate and folic acid supplementation with the risk of preterm birth during pregnancy and to assess the interaction between dietary methionine and folic acid. A case-control study conducted at Gansu Provincial Maternal and Child Health Hospital comprised 8,705 subjects, of whom 7,865 underwent normal delivery and 840 preterm birth. Eligible participants completed questionnaires to collect dietary and other baseline characteristic data. Unconditional logistic regression analysis was employed to assess the association between dietary methionine, natural folate and folic acid supplementation intake with preterm birth and its subtypes. We found the risk of preterm birth was increased by 36% in the low dietary methionine intake group compared with the high group in late pregnancy (OR = 1.36, 95%CI: 1.10–1.70), and dietary methionine intake was significantly associated with medically induced preterm birth ( P -trend = 0.0285). The risk of preterm birth was increased by 23% in the low natural folate intake group compared to the high group (OR = 1.23, 95%CI: 1.03–1.48) and natural folate intake was significantly associated with spontaneous preterm birth ( P -trend = 0.0298). Those with low folic acid supplementation had a 105% increased risk of preterm birth (OR = 2.05, 95%CI: 1.15–3.65) and folic acid supplementation intake was significantly associated with spontaneous preterm birth ( P -trend = 0.0195). Interaction analyses showed that the combination of low methionine and low natural folate further increased the risk ( P -interaction < 0.0001). The combination of low methionine and low folate supplementation further increased the risk ( P -interaction = 0.0005), and the risk of preterm birth was increased if intake of all three was low compared with the adequate intake group. Inadequate intake of dietary methionine, natural folate, and folic acid supplementation may elevate the risk of preterm birth. Moreover, low levels of these nutrients during pregnancy—specifically reduced methionine intake, insufficient natural folate intake, and inadequate folic acid supplementation—may act synergistically to further increase this risk. Attention should be paid to ensuring adequate intake of methionine and folic acid during late pregnancy and throughout gestation to reduce the incidence of preterm birth.