From the Department of Neonatology (Zhang, Jiang), Affiliated Hospital of Qingdao University, Qingdao; from the Department of Neonatology (Chen), Children's Hospital of Fudan University; from the Division of Neonatology (Lu), Gynecology and Obstetrics Hospital of Fudan University, Shanghai; from the Department of Neonatology (Sun), The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou; from the Department of Neonatology (Cui), First Affiliated Hospital Nanjing Medical University, Nanjing, Chin.
Saudi Med J. 2023 Mar;44(3):260-267. doi: 10.15537/smj.2023.44.3.20220695.
To explore if there is a positive additive interaction between no folic acid (FA) supplementation in early period of pregnancy and preeclampsia which increases the risk of preterm birth (PTB).
We matched 1471 women who had live-birth singleton preterm infants with 1471 women who had live-birth singleton term infants at 15 Chinese hospitals in 2018. We excluded women who took folic acid less than 0.4 mg/d or less than 12 weeks in early stage, women with gestational hypertension, chronic hypertension, or preeclampsia during previous pregnancy. We calculate odds ratios for PTB by performing conditional logistic regression comparing preterm group with term group.We quantified the interaction between 2 exposures by synergy (S) and relative excess risk due to interaction (RERI).
Approximately 40% of preterm cases did not take FA in early pregnancy. After adjusting confounding factors by logistic regression, when the 2 exposures (no early FA supplementation and preeclampsia) co-existed, the risk of all PTB increased significantly (aOR11=12.138; 95% CI 5.726-25.73), the interaction between 2 exposures was positive (S=1.27) and increased 2.385-fold risk of all PTB (RERI=2.385); and there were similar results on iatrogenic PTB (aOR11=23.412; 95% CI 8.882-60.71, S=1.18, RERI=3.347).
Our multicenter study showed, for the first time, that there was a positive additive interaction between no FA supplementation in early pregnancy and preeclampsia which increased the risk of all PTB, especially iatrogenic PTB.
探讨妊娠早期是否补充叶酸（FA）与子痫前期之间是否存在正相加交互作用，从而增加早产（PTB）的风险。
我们匹配了 2018 年在中国 15 家医院的 1471 名活产单胎早产儿和 1471 名活产单胎足月儿。我们排除了叶酸摄入量少于 0.4mg/d 或少于妊娠早期 12 周、有妊娠期高血压、慢性高血压或既往妊娠子痫前期的妇女。我们通过比较早产组和足月组进行条件逻辑回归计算 PTB 的比值比。我们通过协同作用（S）和交互归因超额风险（RERI）量化 2 种暴露因素之间的相互作用。
大约 40%的早产病例在妊娠早期没有补充 FA。通过 logistic 回归调整混杂因素后，当 2 种暴露因素（无早期 FA 补充和子痫前期）共存时，所有 PTB 的风险显著增加（aOR11=12.138；95%CI 5.726-25.73），2 种暴露因素之间的相互作用为阳性（S=1.27），增加了所有 PTB 的 2.385 倍风险（RERI=2.385）；在医源性 PTB 中也有类似的结果（aOR11=23.412；95%CI 8.882-60.71，S=1.18，RERI=3.347）。
我们的多中心研究首次表明，妊娠早期不补充 FA 与子痫前期之间存在正相加交互作用，增加了所有 PTB 的风险，尤其是医源性 PTB。
