A clinical evaluation of placental growth factor in routine practice in high-risk women presenting with suspected pre-eclampsia and/or fetal growth restriction

Ormesher, Laura; Johnstone, Edward; Shawkat, Emma; Dempsey, Alice; Chmiel, Catherine; Ingram, Emma; Higgins, Lucy; Myers, Jenny

doi:10.1016/j.preghy.2018.03.007

Cited by 21 publications

(16 citation statements)

References 18 publications

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“…Previous studies11, 20, 26, 27 have used a cohort design to investigate the potential usefulness of angiogenic factors for diagnosis of pre-eclampsia in women presenting with suspected pre-eclampsia, rather than randomised trials. We found similar test performance statistics in our concealed testing group to those seen in other large cohort studies11, 20 and clinical evaluation studies 26, 27. We did not report test performance in the intervention group to avoid the test performance for diagnosis of pre-eclampsia being affected by knowledge of the test result.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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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...

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Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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“…In the recent years, the use of first-trimester screening has been considered as a window of opportunity to predict and prevent APOs [13]. Maternal serum analytes such as pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PlGF), which have already been used in the combined multi-marker screening of preeclampsia and been proven to be associated with APOs, were also available in the first trimester [14][15][16]. However, MS-AFP is routinely tested only in the second trimester and cannot be a candidate marker for the first-trimester screening.…”

Section: Introductionmentioning

confidence: 99%

First-trimester maternal serum alpha-fetoprotein is not a good predictor for adverse pregnancy outcomes: a retrospective study of 3325 cases

Zhang

et al. 2019

Preprint

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Purpose: To investigate the predictive values of first-trimester maternal serum alpha-fetoprotein (MS-AFP) to preterm birth, stillbirth, preeclampsia and small for gestational age (SGA). Methods: We retrospectively reviewed the data on the first-trimester MS-AFP levels and pregnancy outcomes of 3325 singleton pregnant women. The cutoff value of 2.5 multiple of the median (MoM) was used to evaluate the risks of adverse pregnancy outcomes (APOs) regarding MS-AFP. The receiver operating characteristic (ROC) curves were used to evaluate the predictive efficiencies of MS-AFP to these disorders. Results: A total of 181 pregnancies resulted in preterm birth, 32 in stillbirth, 81 in preeclampsia, and 362 in SGA. Compared to women with MS-AFP < 2.5MoM, those with MS-AFP ≥ 2.5MoM had increased risks (odds ratio, 95% confidence interval) of preterm birth (2.53, 1.65~3.88), preeclampsia (3.05, 1.71~5.43) and SGA (1.90, 1.34~2.69), while the risk of stillbirth was not significantly increased (1.33, 0.40~4.41). The areas under ROC curves were 0.572 (P = 0.001), 0.597 (P = 0.060), 0.579 (P = 0.015) and 0.565 (P = 0.000) for preterm birth, stillbirth, preeclampsia and SGA, respectively. Women with MS-AFP ≥ 2.5MoM had an earlier distribution of gestational weeks at delivery (P = 0.004) and a lower distribution of neonatal birth weights (P = 0.000) compared to those with MS-AFP < 2.5MoM, but the actual between-group differences were minuscule. Conclusion: Elevated first-trimester MS-AFP is associated with increased risk of preterm birth, preeclampsia and SGA. However, the predictive efficiencies were low and it is not a good predictor for these APOs.

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“…Another study demonstrated that PlGF outperformed both ultrasound and numerous other biomarkers 37 . A study of PlGF in routine practice in high‐risk women found that PlGF <12 pg/ml was universally associated with an adverse pregnancy outcome, but there were important false‐negatives, including stillbirth 38 . This study found that the PlGF result altered clinical management in over 75% of cases.…”

Section: The Future Of Plgfmentioning

confidence: 84%

Placental growth factor in suspected preterm pre‐eclampsia: a review of the evidence and practicalities of implementation

Hurrell

Beardmore-Gray

Duhig

et al. 2020

BJOG

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Despite extensive research, the pathophysiology and prevention of pre‐eclampsia remain elusive, diagnosis is challenging, and pre‐eclampsia remains associated with adverse maternal and perinatal outcomes. Angiogenic biomarkers, including placental growth factor (PlGF) and soluble fms‐like tyrosine kinase 1 (sFlt‐1), have been identified as valuable biomarkers for preterm pre‐eclampsia, accelerating diagnosis and reducing maternal adverse outcomes by risk stratification, with enhanced surveillance for high‐risk women. PlGF‐based testing is increasingly being implemented in clinical practice in several countries. This review provides healthcare providers with an understanding of the evidence for PlGF‐based testing and describes the practicalities and challenges to implementation. Tweetable abstract Placental growth factor in pre‐eclampsia: evidence and implementation of testing.

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A clinical evaluation of placental growth factor in routine practice in high-risk women presenting with suspected pre-eclampsia and/or fetal growth restriction

Cited by 21 publications

References 18 publications

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

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

First-trimester maternal serum alpha-fetoprotein is not a good predictor for adverse pregnancy outcomes: a retrospective study of 3325 cases

Placental growth factor in suspected preterm pre‐eclampsia: a review of the evidence and practicalities of implementation

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