Interaction Between Preeclampsia and Previous Preterm Birth Increases the Risk of Subsequent Preterm Delivery: A Prospective Cohort Study

Background:This study aimed to investigate whether a positive additive interaction exists between previous preterm birth (PTB) and preeclampsia, which could increase the risk of subsequent PTB. PTBs can be classified into two categories: iatrogenic preterm births (iPTBs) and spontaneous preterm births (sPTBs).Methods:We conducted a prospective cohort study across 15 hospitals in China in 2018. The case group included parturients who delivered live-born singleton preterm infants. The control group consisted of parturients who delivered live-born singleton term infants of the same sex, paired with the corresponding preterm case within a two-day interval. Exclusion criteria included women with a history of preeclampsia in previous pregnancies or with chronic or gestational hypertension. Logistic regression was used to compare the PTB group with the term birth group. The interaction between the two risk factors was assessed using the synergy index (S) and the relative excess risk due to interaction (RERI).Results:A total of 2533 mothers with PTB and 2533 mothers with term live birth were included. After adjusting for confounding variables through logistic regression, the presence of both exposures—preeclampsia and a history of previous PTB—was significantly associated with all PTBs (adjusted odds ratio [aOR11] = 25.577; 95% confidence interval [CI] 3.445–189.919). The interaction between these two factors was positive (S = 2.072), contributing to a 12.707-fold increase in the risk of all PTBs (RERI = 12.707). Similar patterns were observed for iPTBs (aOR11 = 80.273; 95% CI 10.712–601.512; S = 2.402; RERI = 46.205).Conclusions:Our multicenter study provides novel evidence of a positive additive interaction effect between preeclampsia and a history of previous PTB, which significantly heightens the overall risk of PTBs, particularly in cases of iPTBs. For pregnant women with a history of PTB, the prevention of preeclampsia should be prioritized to reduce the incidence of premature birth.Clinical Trial Registration:This study is registered on the https://clinicaltrials.gov/ (registration number: NCT03602625; registration link: https://clinicaltrials.gov/study/NCT03602625; registration time: July 2018).