Randomized Controlled Trial

. 2024 Oct 15;150(16):1223-1235.

doi: 10.1161/CIRCULATIONAHA.124.069907. Epub 2024 Jun 26.

Implementation of First-Trimester Screening and Prevention of Preeclampsia: A Stepped Wedge Cluster-Randomized Trial in Asia

Long Nguyen-Hoang^#¹, Linh Thuy Dinh^#², Angela S T Tai¹, Duy-Anh Nguyen², Ritsuko K Pooh³, Arihiro Shiozaki⁴, Mingming Zheng⁵, Yali Hu⁵, Bin Li⁶, Aditya Kusuma⁷, Piengbulan Yapan⁸, Arundhati Gosavi⁹, Mayumi Kaneko¹⁰, Suchaya Luewan¹¹, Tung-Yao Chang¹², Noppadol Chaiyasit¹³, Tongta Nanthakomon¹⁴, Huishu Liu¹⁵, Steven W Shaw¹⁶, Wing Cheong Leung¹⁷, Zaleha Abdullah Mahdy¹⁸, Angela Aguilar¹⁹, Hillary H Y Leung¹, Nikki M W Lee¹, So Ling Lau¹, Isabella Y M Wah¹, Xiaohong Lu¹, Daljit S Sahota¹, Marc K C Chong²⁰, Liona C Poon¹; FORECAST Collaborators

Collaborators, Affiliations

Collaborators

FORECAST Collaborators:
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

Affiliations

¹ Department of Obstetrics and Gynaecology, Prince of Wales Hospital (L.N.-H., A.S.T.T., H.H.Y.L., N.M.W.L., S.L.L., I.Y.M.W., X.L., D.S.S., L.C.P.), Chinese University of Hong Kong.
² Center for Prenatal and Neonatal Screening and Diagnosis, Hanoi Obstetrics and Gynecology Hospital, Vietnam (L.T.D., D.-A.N.).
³ Clinical Research Institute of Fetal Medicine Prenatal Medical Clinic, Osaka, Japan (R.K.P.).
⁴ Department of Obstetrics and Gynecology, Toyama University Hospital, Toyama, Japan (A.S.).
⁵ Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School, China (M.Z., Y.H.).
⁶ Department of Obstetrics and Gynecology, Kunming Angel Women and Children's Hospital, Teaching Hospital of Kunming University of Science and Technology, China (B.L.).
⁷ Department of Obstetrics and Gynecology, Harapan Kita Women and Children Hospital, Jakarta, Indonesia (A.K.).
⁸ Department of Obstetrics and Gynecology, Faculty of Medicine, Siriraj Hospital, Bangkok, Thailand (P.Y.).
⁹ Department of Obstetrics and Gynecology, Yong Loo Lin School of Medicine, National University of Singapore (A.G.).
¹⁰ Department of Obstetrics and Gynecology, Showa University Hospital, Tokyo, Japan (M.K.).
¹¹ Department of Obstetrics and Gynecology, Faculty of Medicine, Chiang Mai University, Thailand (S.L.).
¹² Department of Fetal Medicine, Taiji Clinic, Taipei, Taiwan (T.-Y.C.).
¹³ Department of Obstetrics and Gynecology, King Chulalongkorn Memorial Hospital, Bangkok, Thailand (N.C.).
¹⁴ Department of Obstetrics and Gynecology, Faculty of Medicine, Thammasat University, Pathumthani, Thailand (T.N.).
¹⁵ Department of Obstetrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, China (H.L.).
¹⁶ Department of Obstetrics and Gynecology, Taipei Chang Gung Memorial Hospital, Taiwan (S.W.S.).
¹⁷ Department of Obstetrics and Gynaecology, Kwong Wah Hospital, Hong Kong SAR, China (W.C.L.).
¹⁸ Department of Obstetrics and Gynaecology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Malaysia (Z.A.M.).
¹⁹ Department of Obstetrics and Gynecology, University of the Philippines College of Medicine, Philippine General Hospital, Manila (A.A.).
²⁰ Jockey Club School of Public Health and Primary Care, Faculty of Medicine (M.K.C.C.), Chinese University of Hong Kong.

^# Contributed equally.

PMID: 38923439
PMCID: PMC11472904
DOI: 10.1161/CIRCULATIONAHA.124.069907

Randomized Controlled Trial

Implementation of First-Trimester Screening and Prevention of Preeclampsia: A Stepped Wedge Cluster-Randomized Trial in Asia

Long Nguyen-Hoang et al. Circulation. 2024.

. 2024 Oct 15;150(16):1223-1235.

doi: 10.1161/CIRCULATIONAHA.124.069907. Epub 2024 Jun 26.

Authors

Collaborators

FORECAST Collaborators:
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

Affiliations

¹ Department of Obstetrics and Gynaecology, Prince of Wales Hospital (L.N.-H., A.S.T.T., H.H.Y.L., N.M.W.L., S.L.L., I.Y.M.W., X.L., D.S.S., L.C.P.), Chinese University of Hong Kong.
² Center for Prenatal and Neonatal Screening and Diagnosis, Hanoi Obstetrics and Gynecology Hospital, Vietnam (L.T.D., D.-A.N.).
³ Clinical Research Institute of Fetal Medicine Prenatal Medical Clinic, Osaka, Japan (R.K.P.).
⁴ Department of Obstetrics and Gynecology, Toyama University Hospital, Toyama, Japan (A.S.).
⁵ Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School, China (M.Z., Y.H.).
⁶ Department of Obstetrics and Gynecology, Kunming Angel Women and Children's Hospital, Teaching Hospital of Kunming University of Science and Technology, China (B.L.).
⁷ Department of Obstetrics and Gynecology, Harapan Kita Women and Children Hospital, Jakarta, Indonesia (A.K.).
⁸ Department of Obstetrics and Gynecology, Faculty of Medicine, Siriraj Hospital, Bangkok, Thailand (P.Y.).
⁹ Department of Obstetrics and Gynecology, Yong Loo Lin School of Medicine, National University of Singapore (A.G.).
¹⁰ Department of Obstetrics and Gynecology, Showa University Hospital, Tokyo, Japan (M.K.).
¹¹ Department of Obstetrics and Gynecology, Faculty of Medicine, Chiang Mai University, Thailand (S.L.).
¹² Department of Fetal Medicine, Taiji Clinic, Taipei, Taiwan (T.-Y.C.).
¹³ Department of Obstetrics and Gynecology, King Chulalongkorn Memorial Hospital, Bangkok, Thailand (N.C.).
¹⁴ Department of Obstetrics and Gynecology, Faculty of Medicine, Thammasat University, Pathumthani, Thailand (T.N.).
¹⁵ Department of Obstetrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, China (H.L.).
¹⁶ Department of Obstetrics and Gynecology, Taipei Chang Gung Memorial Hospital, Taiwan (S.W.S.).
¹⁷ Department of Obstetrics and Gynaecology, Kwong Wah Hospital, Hong Kong SAR, China (W.C.L.).
¹⁸ Department of Obstetrics and Gynaecology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Malaysia (Z.A.M.).
¹⁹ Department of Obstetrics and Gynecology, University of the Philippines College of Medicine, Philippine General Hospital, Manila (A.A.).
²⁰ Jockey Club School of Public Health and Primary Care, Faculty of Medicine (M.K.C.C.), Chinese University of Hong Kong.

^# Contributed equally.

PMID: 38923439
PMCID: PMC11472904
DOI: 10.1161/CIRCULATIONAHA.124.069907

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.

Keywords: Asia; Fetal Medicine Foundation; aspirin; first-trimester; preeclampsia; screen-and-prevent; screening; stepped wedge cluster randomized trial.

PubMed Disclaimer

Conflict of interest statement

L.C.P. has received speaker fees and consultancy payments from Roche Diagnostics and Ferring Pharmaceuticals. In addition, she has received in-kind contributions from Roche Diagnostics, Revvity Inc (formerly PerkinElmer Life and Analytical Sciences), Thermo Fisher Scientific, Ningbo Aucheer Biological Technology Co, Ltd, and GE HealthCare. D.S.S. has received in-kind contributions from Revvity Inc, Thermo Fisher Scientific, Roche Diagnostics, Diabetomics, and Ningbo Aucheer Biological Technology Co, Ltd. R.K.P. is chief executive officer of Ritz Medical Co Ltd, a genetic testing company, and holds shares in and receives executive compensation from it. The other authors report no conflicts.

Figures

**Figure 1.**
Adjusted step-wedge caused by COVID-19.

**Figure 3.**
Acceptability of preeclampsia screening and aspirin prophylaxis for high-risk women in the intervention phase.

**Figure 4.**
Percentage of different groups of aspirin compliance.

See this image and copyright information in PMC

References

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Implementation of First-Trimester Screening and Prevention of Preeclampsia: A Stepped Wedge Cluster-Randomized Trial in Asia

Collaborators

Affiliations

Implementation of First-Trimester Screening and Prevention of Preeclampsia: A Stepped Wedge Cluster-Randomized Trial in Asia

Authors

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Abstract

Conflict of interest statement

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