Implementation of First-Trimester Screening and Prevention of Preeclampsia: A Stepped Wedge Cluster-Randomized Trial in Asia
Long Nguyen‐Hoang, Linh Thuy Dinh, Angela S.T. Tai, Anh Duy Nguyen, Ritsuko K. Pooh, Arihiro Shiozaki, Mingming Zheng, Yali Hu, Bin Li, Raden Aditya Kusuma, Piengbulan Yapan, Arundhati Gosavi, Mayumi Kaneko, Suchaya Luewan, Tung‐Yao Chang, Noppadol Chaiyasit, Tongta Nanthakomon, Huishu Liu, Steven W. Shaw, Wing Cheong Leung, Zaleha Abdullah Mahdy, Angela Aguilar, Hillary H.Y. Leung, Nikki Lee, So Ling Lau, Isabella Yi Man Wah, Xiaohong Lu, Daljit Singh Sahota, Ka Chun Chong, Liona C. Poon, Iok Seng Wong, Yunyu Chen, Jiao Liu, Jing Lin, Ada W. T. Tse, Lo Wong, Fangzi Liu, Runmei Ma, Jiang Yan Min, Mahesh A. Choolani, Tuangsit Wataganara, Osamu Shimokawa
Abstract
BACKGROUND: This trial aimed to assess the efficacy, acceptability, and safety of a first-trimester screen-and-prevent strategy for preterm preeclampsia in Asia. METHODS: Between August 1, 2019, and February 28, 2022, this multicenter stepped wedge cluster randomized trial included maternity/diagnostic units from 10 regions in Asia. The trial started with a period where all recruiting centers provided routine antenatal care without study-related intervention. At regular 6-week intervals, one cluster was randomized to transit from nonintervention phase to intervention phase. In the intervention phase, women underwent first-trimester screening for preterm preeclampsia using a Bayes theorem-based triple-test. High-risk women, with adjusted risk for preterm preeclampsia ≥1 in 100, received low-dose aspirin from <16 weeks until 36 weeks. RESULTS: Overall, 88.04% (42 897 of 48 725) of women agreed to undergo first-trimester screening for preterm preeclampsia. Among those identified as high-risk in the intervention phase, 82.39% (2919 of 3543) received aspirin prophylaxis. There was no significant difference in the incidence of preterm preeclampsia between the intervention and non-intervention phases (adjusted odds ratio [aOR], 1.59 [95% CI, 0.91-2.77]). However, among high-risk women in the intervention phase, aspirin prophylaxis was significantly associated with a 41% reduction in the incidence of preterm preeclampsia (aOR, 0.59 [95% CI, 0.37-0.92]). In addition, it correlated with 54%, 55%, and 64% reduction in the incidence of preeclampsia with delivery at <34 weeks (aOR, 0.46 [95% CI, 0.23-0.93]), spontaneous preterm birth <34 weeks (aOR, 0.45 [95% CI, 0.22-0.92]), and perinatal death (aOR, 0.34 [95% CI, 0.12-0.91]), respectively. There was no significant between-group difference in the incidence of aspirin-related severe adverse events. CONCLUSIONS: The implementation of the screen-and-prevent strategy for preterm preeclampsia is not associated with a significant reduction in the incidence of preterm preeclampsia. However, low-dose aspirin effectively reduces the incidence of preterm preeclampsia by 41% among high-risk women. The screen-and-prevent strategy for preterm preeclampsia is highly accepted by a diverse group of women from various ethnic backgrounds beyond the original population where the strategy was developed. These findings underpin the importance of the widespread implementation of the screen-and-prevent strategy for preterm preeclampsia on a global scale. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03941886.