Implementation of First-Trimester Screening and Prevention of Preeclampsia: A Stepped Wedge Cluster-Randomized Trial in Asia
Authors: Nguyen-Hoang Long , Dinh Linh Thuy , Tai Angela S.T. , Nguyen Duy-Anh , Pooh Ritsuko K. , Shiozaki Arihiro , Zheng Mingming , Hu Yali , Li Bin , Kusuma Aditya , Yapan Piengbulan , Gosavi Arundhati , Kaneko Mayumi , Luewan Suchaya , Chang Tung-Yao , Chaiyasit Noppadol , Nanthakomon Tongta , Liu Huishu , Shaw Steven W. , Leung Wing Cheong , Mahdy Zaleha Abdullah , Aguilar Angela , Leung Hillary H.Y. , Lee Nikki M.W. , Lau So Ling , Wah Isabella Y.M. , Lu Xiaohong , Sahota Daljit S. , Chong Marc K.C. , Poon Liona C. , Wong Iok Seng , Chen Yunyu , Liu Jiao , Lin Jing , Tse Ada W. T. , Wong Lo , Liu Fangzi , Ma Runmei , Min Jiang Yan , Choolani Mahesh A. , Wataganara Tuangsit , Shimokawa Osamu 
Published: June 2024

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.