Serial placental growth factor-based testing in pre-eclampsia

Pre-eclampsia is a hypertensive disorder of pregnancy and a major contributor to maternal and fetal adverse outcomes. 1 Chappell LC Cluver CA Kingdom J Tong S Pre-eclampsia. Lancet. 2021; 398: 341-354 Summary Full Text Full Text PDF PubMed Scopus (303) Google Scholar With its incidence on the rise due to increased prevalence of risk factors, such as obesity and in-vitro fertilisation, 2 van Oostwaard MF The alarming rise in risk factors for hypertensive disorders of pregnancy. BJOG. 2022; 1291061 Crossref PubMed Scopus (2) Google Scholar it is a growing public health concern. Clinical management of patients with suspected pre-eclampsia is challenging due to its non-specific presentation. 1 Chappell LC Cluver CA Kingdom J Tong S Pre-eclampsia. Lancet. 2021; 398: 341-354 Summary Full Text Full Text PDF PubMed Scopus (303) Google Scholar The recognition that the maternal signs and symptoms of pre-eclampsia are heralded by elevated circulating soluble fms-like tyrosine kinase 1 (sFlt-1) and low free concentrations of placental growth factor (PlGF) 3 Levine RJ Maynard SE Qian C et al. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004; 350: 672-683 Crossref PubMed Scopus (2983) Google Scholar has led to recent development of new molecular diagnostics for early detection of this condition referred to as PlGF-based tests (sFlt-1/PlGF ratio or PlGF alone), with UK National Institute for Health and Care Excellence (NICE) approval several years ago 4 National Institute for Health and Care ExcellencePlGF-based testing to help diagnose suspected pre-eclampsia (Triage PlGF test, Elecsys immunoassay sFlt-1/PlGF ratio, DELFIA Xpress PlGF 1–2–3 test, and BRAHMS sFlt-1 Kryptor/BRAHMS PlGF plus Kryptor PE ratio). https://www.nice.org.uk/guidance/DG23Date: 2016 Date accessed: November 10, 2022 Google Scholar and US Food and Drug Administration approval recently in the USA. 5 Tanne JH Pre-eclampsia: FDA approves blood test to identify pregnant women at risk. BMJ. 2023; 3821594 Google Scholar During the third trimester, PlGF-based testing can effectively rule out the development of pre-eclampsia within 1–2 weeks in patients presenting with signs and symptoms. 6 Zeisler H Llurba E Chantraine F et al. Predictive value of the sFlt-1:PlGF ratio in women with suspected preeclampsia. N Engl J Med. 2016; 374: 13-22 Crossref PubMed Scopus (1053) Google Scholar , 7 Chappell LC Duckworth S Seed PT et al. Diagnostic accuracy of placental growth factor in women with suspected preeclampsia: a prospective multicenter study. Circulation. 2013; 128: 2121-2131 Crossref PubMed Scopus (337) Google Scholar An sFlt-1/PlGF ratio of 38 or less or a PlGF concentration alone of more than 100 pg/mL demonstrated negative predictive values (NPVs) exceeding 98%, significantly surpassing standard clinical variables. 6 Zeisler H Llurba E Chantraine F et al. Predictive value of the sFlt-1:PlGF ratio in women with suspected preeclampsia. N Engl J Med. 2016; 374: 13-22 Crossref PubMed Scopus (1053) Google Scholar , 7 Chappell LC Duckworth S Seed PT et al. Diagnostic accuracy of placental growth factor in women with suspected preeclampsia: a prospective multicenter study. Circulation. 2013; 128: 2121-2131 Crossref PubMed Scopus (337) Google Scholar , 8 Cerdeira AS O'Sullivan J Ohuma EO et al. Randomized interventional study on prediction of preeclampsia/eclampsia in women with suspected preeclampsia: INSPIRE. Hypertension. 2019; 74: 983-990 Crossref PubMed Scopus (77) Google Scholar , 9 Duhig KE Myers J Seed PT et al. Placental growth factor testing to assess women with suspected pre-eclampsia: a multicentre, pragmatic, stepped-wedge cluster-randomised controlled trial. Lancet. 2019; 393: 1807-1818 Summary Full Text Full Text PDF PubMed Scopus (186) Google Scholar These tests are also reliable for detecting progression to pre-eclampsia with severe features, with a positive predictive value of 66% and a NPV of 96%. 10 Thadhani R Lemoine E Rana S et al. Circulating angiogenic factor levels in hypertensive disorders of pregnancy. NEJM Evid. 2022; 1: 1-13 Crossref Google Scholar Importantly, two clinical trials (INSPIRE 7 Chappell LC Duckworth S Seed PT et al. Diagnostic accuracy of placental growth factor in women with suspected preeclampsia: a prospective multicenter study. Circulation. 2013; 128: 2121-2131 Crossref PubMed Scopus (337) Google Scholar and PARROT-1 9 Duhig KE Myers J Seed PT et al. Placental growth factor testing to assess women with suspected pre-eclampsia: a multicentre, pragmatic, stepped-wedge cluster-randomised controlled trial. Lancet. 2019; 393: 1807-1818 Summary Full Text Full Text PDF PubMed Scopus (186) Google Scholar ) have asserted the clinical use of a single PlGF-based test in patients presenting with suspected pre-eclampsia, showing an improvement in clinical precision, reduced time to pre-eclampsia diagnosis (from 4·1 days to 1·9 days; time ratio 0·36 [95% CI 0·15–0·87]) and lower incidence of adverse maternal outcomes (adjusted odds ratio 0·32 [95% CI 0·11–0·96]) when compared with standard clinical practice (ie, no PlGF-based testing). Repeat placental growth factor-based testing in women with suspected preterm pre-eclampsia (PARROT-2): a multicentre, parallel-group, superiority, randomised controlled trialRepeat PlGF-based testing in pregnant women with suspected pre-eclampsia was not associated with improved perinatal outcomes. In a high-income setting with a low prevalence of adverse outcomes, universal, routine repeat PlGF-based testing of all individuals with suspected pre-eclampsia is not recommended. Full-Text PDF Open Access