The interaction between preeclampsia and advanced maternal age on adverse perinatal outcomes: a retrospective cohort study (2013-2022)

Abstract Background: This study aims to explore the risk of pregnancy complications and outcomes among younger women (aged 20-34 years) and older women ( aged 35 years or older) with PE and further investigate the interaction between PE and advanced maternal age (AMA) on the development of these outcomes. Methods: This retrospective cohort study included 75860 single pregnant women aged 20-55 years, logistic regression was perform to find the associations between PE and pregnancy complications and outcomes. Additive interaction analysis between PE and AMA on the development of these outcomes was performed by using odds ratio (OR) due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (SI) with their 95% confidence intervals (95%CIs). Results:Among younger women, PE was associated with higher risk of gestational diabetes mellitus (GDM), caesarean delivery, placental accreta spectrum , placental abruption , intrahepatic cholestasis of pregnancy (ICP) , haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome, abnormal placental location and cord insertion, postpartum haemorrhage, preterm birth, low birth weight, fetal distress, intrauterine growth restriction (IUGR), and birth defects when compared to women without PE. The (OR 95%CI) was (1.34, 1.20-1.50), (3.57, 3.22-3.97), (1.40, 1.03-1.92),(6.39, 4.55-8.99), (1.92, 1.59-2.31), (64.98, 29.86-141.41), (1.43, 1.18-1.74), (1.66, 1.26-2.18), (4.50, 4.02-5.04), (6.55, 5.88-7.04), (1.52, 91.34-1.71), (9.37, 8.10-10.83), (1.37, 1.01-1.88), respectively. Among older women, PE had a higher risk of GDM, caesarean delivery, placental abruption, ICP, HELLP syndrome, preterm birth, low birth weight, fetal distress, and IUGR, the (OR 95%CI) was (1.19, 1.03-1.38), (2.92, 2.45-3.48), (4.20, 2.43-7.27), (2.03, 1.57-2.63), (17.74, 7.79-40.42), (4.59, 3.92-5.34), (7.33, 6.26-8.59), (1.56, 1.29-1.88), (9.44, 7.54-11.81), respectively. PE and AMA had a significant synergistic effect on caesarean delivery, preterm birth, and low birth weight (RERI 1.93, 95%CI 0.64-3.22; AP 0.29, 95%CI 0.14-0.43; SI 1.50, 95%CI 1.19-1.90), (RERI 1.40, 95%CI 0.35-2.45; AP 0.23, 95%CI 0.09-0.37; SI 1.37, 95%CI 1.10-1.70), (RERI 2.45, 95%CI 0.93-3.97; AP 0.27, 95%CI 0.14-0.40; SI  1.42, 95%CI 1.16-1.74). Conclusion: PE was an independent risk factor for a series of pregnancy complications and outcomes, and may play an important role in the interaction with AMA on the development of caesarean delivery, preterm birth and low birth weight.