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

Abstract

Summary 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 co...

The maternal and perinatal implications of hypertensive disorders of pregnancy in a multiple pregnancy cohort

“…With a larger placenta comes higher levels of these circulating angiogenic factors, and studies have shown increased risk of preeclampsia with each for each 2‐fold elevation in sFlt‐1 . Prediction of preeclampsia using these angiogenic factors is topical at present; however, their utility in aiding diagnoses of preeclampsia in multiple pregnancy warrants further research …”

“…24 Prediction of preeclampsia using these angiogenic factors is topical at present; however, their utility in aiding diagnoses of preeclampsia in multiple pregnancy warrants further research. 25,26 Maternal age >40 years, nulliparity and conception through use of a donor oocyte are all well-established risk factors for HDP in both singleton and multiple pregnancies. 27 Over the last number of decades, use of ART has increased and pregnancy through use of a donor oocyte is now common.…”

Diagnostic accuracy of repeat placental growth factor measurements in women with suspected preeclampsia: A case series study

“…When compared with standard practice, there was a reduction seen in the median time to diagnosis of preeclampsia from 4.1 to 1.9 days (time ratio 0.36, 95% CI 0.15-0.87) with a concurrent reduction in severe maternal adverse outcomes (5.4-3.8%, adjusted odds ratio 0.32, 95% CI 0.11-0.96). 12 Of women who tested "normal" for PlGF (>100 pg/mL) in the PARROT trial, 10.9% went on to receive a diagnosis of preeclampsia in the pregnancy. In 2016, there was one small study of 100 women published which looked at repeated PlGF measurements in women presenting with suspected preeclampsia.…”

Placental growth factor testing for suspected pre‐eclampsia: a cost‐effectiveness analysis

“…In prospective observational cohort studies, placental growth factor (PlGF) <5th centile has good test performance in assessing women with suspected pre‐eclampsia for determining need for delivery for pre‐eclampsia within 14 days of testing . We recently reported in the Placental growth factor for the Assessment of hypeRtensive pRegnant wOmen: a stepped wedge Trial (PARROT) that PlGF testing used alongside a clinical management algorithm reduced the time to diagnosis of pre‐eclampsia from 4.1 days (usual care) to 1.9 days (intervention) . Where PlGF was implemented, severe maternal adverse outcomes were reduced from 5.4% (24/447; usual care group) to 3.8% (22/573; intervention group), with no evidence of a difference in gestation at delivery (36.6 versus 36.8 weeks).…”