TY - JOUR
T1 - Heparin for women with recurrent miscarriage and inherited thrombophilia (ALIFE2)
T2 - an international open-label, randomised controlled trial
AU - Quenby, Siobhan
AU - Booth, Katie
AU - Hiller, Louise
AU - Coomarasamy, Arri
AU - de Jong, Paulien G.
AU - Hamulyák, Eva N.
AU - Scheres, Luuk J.
AU - van Haaps, Thijs F.
AU - Ewington, Lauren
AU - Tewary, Shreeya
AU - ALIFE2 Block Writing Committee
AU - ALIFE2 Investigators
AU - Goddijn, Mariëtte
AU - Middeldorp, Saskia
N1 - Funding Information: The study was endorsed by INVENT-VTE and funded by the Netherlands Organization for Health Research and Development (NWO, VIDI innovative research grant 016.126.364 awarded to SM) and by the National Institute for Health and Care Research (NIHR) under its Research for Patient Benefit Programme (grant reference number PB-PG-1013-32011). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. We thank the funders. We thank all the women who participated in the trial, the staff members of the participating hospitals, and the office members and research nurses of the Dutch Consortium for Women's Health Research and NIHR clinical research network research nurses and midwives. Publisher Copyright: © 2023 Elsevier Ltd
PY - 2023/7/1
Y1 - 2023/7/1
N2 - Background: Anticoagulant therapy might reduce the number of miscarriages and adverse pregnancy outcomes in women with recurrent pregnancy loss and inherited thrombophilia. We aimed to assess use of low-molecular-weight heparin (LMWH) versus standard care in this population. Methods: The ALIFE2 trial was an international open-label, randomised controlled trial undertaken in hospitals in the UK (n=26), the Netherlands (n=10), the USA (n=2), Belgium (n=1), and Slovenia (n=1). Women aged 18–42 years who had two or more pregnancy losses and confirmed inherited thrombophilia, and who were trying to conceive or were already pregnant (≤7 weeks' gestation), were eligible for inclusion. Women were randomly assigned (1:1) to use low-dose LMWH or not (alongside standard care in both groups) once they had a positive urine pregnancy test. LMWH was started at or before 7 weeks' gestation and continued until the end of pregnancy. The primary outcome measure was livebirth rate, assessed in all women with available data. Safety outcomes included bleeding episodes, thrombocytopenia, and skin reactions, and were assessed in all randomly assigned women who reported a safety event. The trial was registered within the Dutch Trial Register (NTR3361) and EudraCT (UK: 2015-002357-35). Findings: Between Aug 1, 2012, and Jan 30, 2021, 10 625 women were assessed for eligibility, 428 were registered, and 326 conceived and were randomly assigned (164 to LMWH and 162 to standard care). 116 (72%) of 162 women with primary outcome data in the LMWH group and 112 (71%) of 158 in the standard care group had livebirths (adjusted odds ratio 1·08, 95% CI 0·65 to 1·78; absolute risk difference, 0·7%, 95% CI –9·2% to 10·6%). 39 (24%) of 164 women in the LMWH group and 37 (23%) of 162 women in the standard care group reported adverse events. Interpretation: LMWH did not result in higher livebirth rates in women who had two or more pregnancy losses and confirmed inherited thrombophilia. We do not advise use of LMWH in women with recurrent pregnancy loss and inherited thrombophilia, and we advise against screening for inherited thrombophilia in women with recurrent pregnancy loss. Funding: National Institute for Health and Care Research and the Netherlands Organization for Health Research and Development.
AB - Background: Anticoagulant therapy might reduce the number of miscarriages and adverse pregnancy outcomes in women with recurrent pregnancy loss and inherited thrombophilia. We aimed to assess use of low-molecular-weight heparin (LMWH) versus standard care in this population. Methods: The ALIFE2 trial was an international open-label, randomised controlled trial undertaken in hospitals in the UK (n=26), the Netherlands (n=10), the USA (n=2), Belgium (n=1), and Slovenia (n=1). Women aged 18–42 years who had two or more pregnancy losses and confirmed inherited thrombophilia, and who were trying to conceive or were already pregnant (≤7 weeks' gestation), were eligible for inclusion. Women were randomly assigned (1:1) to use low-dose LMWH or not (alongside standard care in both groups) once they had a positive urine pregnancy test. LMWH was started at or before 7 weeks' gestation and continued until the end of pregnancy. The primary outcome measure was livebirth rate, assessed in all women with available data. Safety outcomes included bleeding episodes, thrombocytopenia, and skin reactions, and were assessed in all randomly assigned women who reported a safety event. The trial was registered within the Dutch Trial Register (NTR3361) and EudraCT (UK: 2015-002357-35). Findings: Between Aug 1, 2012, and Jan 30, 2021, 10 625 women were assessed for eligibility, 428 were registered, and 326 conceived and were randomly assigned (164 to LMWH and 162 to standard care). 116 (72%) of 162 women with primary outcome data in the LMWH group and 112 (71%) of 158 in the standard care group had livebirths (adjusted odds ratio 1·08, 95% CI 0·65 to 1·78; absolute risk difference, 0·7%, 95% CI –9·2% to 10·6%). 39 (24%) of 164 women in the LMWH group and 37 (23%) of 162 women in the standard care group reported adverse events. Interpretation: LMWH did not result in higher livebirth rates in women who had two or more pregnancy losses and confirmed inherited thrombophilia. We do not advise use of LMWH in women with recurrent pregnancy loss and inherited thrombophilia, and we advise against screening for inherited thrombophilia in women with recurrent pregnancy loss. Funding: National Institute for Health and Care Research and the Netherlands Organization for Health Research and Development.
UR - http://www.scopus.com/inward/record.url?scp=85163411733&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/S0140-6736(23)00693-1
DO - https://doi.org/10.1016/S0140-6736(23)00693-1
M3 - Article
C2 - 37271152
SN - 0140-6736
VL - 402
SP - 54
EP - 61
JO - The Lancet
JF - The Lancet
IS - 10395
ER -