• Yi-Jie Zhang, Hong Jiang, Chengqiu Lu, Yi Sun, Shudong Cui, and Chao Chen.
• 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 1; 44 (3): 260267260-267.

ObjectivesTo 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).MethodsWe 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).ResultsApproximately 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).ConclusionOur 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.Copyright: © Saudi Medical Journal.

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