Prediction of adverse maternal and perinatal outcomes associated with pre-eclampsia and hypertensive disorders of pregnancy: a systematic review and meta-analysis

Abstract

Background: Hypertensive disorders of pregnancy are a leading cause of maternal and perinatal morbidity and mortality. If women at high risk for developing complications could be identified early, level of care could be triaged, limited resources could be correctly allocated and targeted interventions to prevent complications could be implemented.

Methods: We updated a systematic review and meta-analysis and added single outcomes. Women with hypertensive disorders of pregnancy were included. Exposures were tests predicting adverse maternal and/or perinatal outcomes. We searched Medline, Embase, CINAHL, and Cochrane library from January 2016-February 2024. We included studies identified from the previous review. We calculated effect measures. For similar predictive tests and outcomes, area under the receiver-operating-characteristic curve (AUROC) were pooled. This study was registered by PROSPERO: CRD42022336368.

Findings: Of the 2898 studies identified, 80 were included. Thirty were added from the previous review resulting in 110 included studies with 506,178 women. Despite more than 1500 tests being performed, most outcomes could not be pooled due to heterogeneity in populations, tests, and outcome definitions. For maternal outcomes, only studies reporting on the Pre-eclampsia Integrated Estimate of RiSk (fullPIERS) model could be pooled. For the composite outcome within 48-h the AUROC was 0.78 (95% CI 0.71-0.86, N = 8). There was significant heterogeneity (I ² = 95.7%). For perinatal outcomes, data were pooled for pulsatility index in the umbilical artery and soluble FMS-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio. Biomarkers like the sFlt-1/PlGF ratio showed promising predictive performance for some outcomes but were not externally validated.

Interpretation: Despite including over 100 studies with more than 1500 predictors, we were unable to pool any single maternal outcomes and only a few individual perinatal outcomes. The fullPIERS model was externally validated, showing moderate accuracy which varied across studies and should be validated in each new population. Angiogenic biomarkers showed promise but need validation. Future studies should use standardized outcome measures and validate promising tests.

Funding: VB is supported by the Swedish Research Council, Grant number 2020-01481. University of Gothenburg.

Keywords: Adverse outcomes; Hypertensive disorders; Pre-eclampsia; Prediction; Pregnancy.

Fig. 1

Preferred reporting items for systematic reviews and meta-analyses (PRISMA) flow chart.

Fig. 2

Study distribution map showing the number of studies by county, created with Datawrapper

Fig. 3

Risk of bias summary showing the authors’ judgements on each domain for the included studies using the modified Quality in Prognostic Studies (QUIPS) tool. Studies were sorted according to the number of high risk of bias in the 6 domains from top to bottom starting with lowest number of high risk of bias. Risk of bias assessment of studies retrieved from Ukah et al., 2018 can be found in Supplementary Table S5 of the corresponding publication. D1: Bias due to participation. D2: Bias due to attrition. D3: Bias due to prognostic factor measurement. D4: Bias due to outcome measurement. D5: Bias due to confounding. D6: Bias due to statistical analysis. UK–United Kingdom; US-United States.