Placental growth factor testing to assess women with suspected pre-eclampsia: a multicentre, pragmatic, stepped-wedge cluster-randomised controlled trial

被引:242
作者
Duhig, Kate E. [1 ]
Myers, Jenny [2 ]
Seed, Paul T. [1 ]
Sparkes, Jenie [1 ]
Lowe, Jessica [1 ]
Hunter, Rachael M. [3 ]
Shennan, Andrew H. [1 ]
Chappell, Lucy C. [1 ]
Bahl, Rachna
Bambridge, Gabrielle
Barnfield, Sonia
Ficquet, Jo
Gill, Carolyn
Girling, Joanna
Harding, Kate
Khalil, Asma
Sharp, Andrew
Simpson, Nigel A. B.
Tuffnell, Derek
机构
[1] Kings Coll London, Dept Women & Childrens Hlth, Sch Life Course Sci, London SE1 7EH, England
[2] Univ Manchester, Div Dev Biol & Med, Manchester, Lancs, England
[3] UCL, Res Dept Primary Care & Populat Hlth, London, England
基金
美国国家卫生研究院;
关键词
PROPOSED CLINICAL MANAGEMENT; PREGNANCIES; OUTCOMES; INFANTS; RATIO;
D O I
10.1016/S0140-6736(18)33212-4
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Previous prospective cohort studies have shown that angiogenic factors have a high diagnostic accuracy in women with suspected pre-eclampsia, but we remain uncertain of the effectiveness of these tests in a real-world setting. We therefore aimed to determine whether knowledge of the circulating concentration of placental growth factor (PlGF), an angiogenic factor, integrated with a clinical management algorithm, decreased the time for clinicians to make a diagnosis in women with suspected pre-eclampsia, and whether this approach reduced subsequent maternal or perinatal adverse outcomes. Methods We did a multicentre, pragmatic, stepped-wedge cluster-randomised controlled trial in 11 maternity units in the UK, which were each responsible for 3000-9000 deliveries per year. Women aged 18 years and older who presented with suspected pre-eclampsia between 20 weeks and 0 days of gestation and 36 weeks and 6 days of gestation, with a live, singleton fetus were invited to participate by the clinical research team. Suspected pre-eclampsia was defined as new-onset or worsening of existing hypertension, dipstick proteinuria, epigastric or right upper-quadrant pain, headache with visual disturbances, fetal growth restriction, or abnormal maternal blood tests that were suggestive of disease (such as thrombocytopenia or hepatic or renal dysfunction). Women were approached individually, they consented for study inclusion, and they were asked to give blood samples. We randomly allocated the maternity units, representing the clusters, to blocks. Blocks represented an intervention initiation time, which occurred at equally spaced 6-week intervals throughout the trial. At the start of the trial, all units had usual care (in which PlGF measurements were also taken but were concealed from clinicians and women). At the initiation time of each successive block, a site began to use the intervention (in which the circulating PlGF measurement was revealed and a clinical management algorithm was used). Enrolment of women continued for the duration of the blocks either to concealed PlGF testing, or after implementation, to revealed PlGF testing. The primary outcome was the time from presentation with suspected pre-eclampsia to documented pre-eclampsia in women enrolled in the trial who received a diagnosis of pre-eclampsia by their treating clinicians. This trial is registered with ISRCTN, number 16842031. Findings Between June 13, 2016, and Oct 27, 2017, we enrolled and assessed 1035 women with suspected pre-eclampsia. 12 (1%) women were found to be ineligible. Of the 1023 eligible women, 576 (56%) women were assigned to the intervention (revealed testing) group, and 447 (44%) women were assigned to receive usual care with additional concealed testing (concealed testing group). Three (1%) women in the revealed testing group were lost to follow-up, so 573 (99%) women in this group were included in the analyses. One (<1%) woman in the concealed testing group withdrew consent to follow-up data collection, so 446 (>99%) women in this group were included in the analyses. The median time to pre-eclampsia diagnosis was 4 . 1 days with concealed testing versus 1.9 days with revealed testing (time ratio 0.36, 95% CI 0.15-0.87;p=0.027).Maternal severe adverse outcomes were reported in 24 (5%) of 447 women in the concealed testing group versus 22 (4%) of 573 women in the revealed testing group (adjusted odds ratio 0.32, 95% CI 0.11-0.96; p=0.043), but there was no evidence of a difference in perinatal adverse outcomes (15% vs 14%, 1.45, 0.73-2.90) or gestation at delivery (36.6 weeks vs 36.8 weeks; mean difference -0.52, 95% CI -0.63 to 0.73). Interpretation We found that the availability of PlGF test results substantially reduced the time to clinical confirmation of pre-eclampsia. Where PlGF was implemented, we found a lower incidence of maternal adverse outcomes, consistent with adoption of targeted, enhanced surveillance, as recommended in the clinical management algorithm for clinicians. Adoption of PlGF testing in women with suspected pre-eclampsia is supported by the results of this study. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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收藏
页码:1807 / 1818
页数:12
相关论文
共 31 条
[1]   Predicting complications in pre-eclampsia: external validation of the fullPIERS model using the PETRA trial dataset [J].
Akkermans, Joost ;
Payne, Beth ;
von Dadelszen, Peter ;
Groen, Henk ;
de Vries, Johanna ;
Magee, Laura A. ;
Mol, Ben Willem ;
Ganzevoort, Wessel .
EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY, 2014, 179 :58-62
[2]  
[Anonymous], INV MAN SMALL FOR GE
[3]  
British Association of Perinatal Medicine, 2011, CAT OF CAR
[4]   CONSORT statement: extension to cluster randomised trials [J].
Campbell, MK ;
Elbourne, DR ;
Altman, DG .
BMJ-BRITISH MEDICAL JOURNAL, 2004, 328 (7441) :702-708
[5]   Diagnostic Accuracy of Placental Growth Factor in Women With Suspected Preeclampsia A Prospective Multicenter Study [J].
Chappell, Lucy C. ;
Duckworth, Suzy ;
Seed, Paul T. ;
Griffin, Melanie ;
Myers, Jenny ;
Mackillop, Lucy ;
Simpson, Nigel ;
Waugh, Jason ;
Anumba, Dilly ;
Kenny, Louise C. ;
Redman, Christopher W. G. ;
Shennan, Andrew H. .
CIRCULATION, 2013, 128 (19) :2121-2131
[6]   The Global Impact of Pre-eclampsia and Eclampsia [J].
Duley, Lelia .
SEMINARS IN PERINATOLOGY, 2009, 33 (03) :130-137
[7]   A prospective comparison of total protein/creatinine ratio versus 24-hour urine protein in women with suspected preeclampsia [J].
Durnwald, C ;
Mercer, B .
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY, 2003, 189 (03) :848-852
[8]   Estimating the Cost of Preeclampsia in the Healthcare System Cross-Sectional Study Using Data From SCOPE Study (Screening for Pregnancy End Points) [J].
Fox, Aimee ;
McHugh, Sheena ;
Browne, John ;
Kenny, Louise C. ;
Fitzgerald, Anthony ;
Khashan, Ali S. ;
Dempsey, Eugene ;
Fahy, Ciara ;
O'Neill, Ciaran ;
Kearney, Patricia M. .
HYPERTENSION, 2017, 70 (06) :1243-1249
[9]   The PCORI Perspective on Patient-Centered Outcomes Research [J].
Frank, Lori ;
Basch, Ethan ;
Selby, Joe V. .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2014, 312 (15) :1513-1514
[10]   The stepped wedge cluster randomised trial: rationale, design, analysis, and reporting [J].
Hemming, K. ;
Haines, T. P. ;
Chilton, P. J. ;
Girling, A. J. ;
Lilford, R. J. .
BMJ-BRITISH MEDICAL JOURNAL, 2015, 350