The ability of late pregnancy maternal tests to predict adverse pregnancy outcomes associated with placental dysfunction (specifically fetal growth restriction and pre-eclampsia): a protocol for a systematic review and meta-analysis of prognostic accuracy studies

Abstract

Background: Pre-eclampsia and being born small for gestational age are associated with significant maternal and neonatal morbidity and mortality. Placental dysfunction is a key pathological process underpinning these conditions; thus, markers of placental function have the potential to identify pregnancies ending in pre-eclampsia, fetal growth restriction, and the birth of a small for gestational age infant.

Primary objective: To assess the predictive ability of late pregnancy (after 24 weeks' gestation) tests in isolation or in combination for adverse pregnancy outcomes associated with placental dysfunction, including pre-eclampsia, fetal growth restriction, delivery of a SGA infant (more specifically neonatal growth restriction), and stillbirth.

Methods: Studies assessing the ability of biochemical tests of placental function and/or ultrasound parameters in pregnant women beyond 24 weeks' gestation to predict outcomes including pre-eclampsia, stillbirth, delivery of a SGA infant (including neonatal growth restriction), and/or fetal growth restriction will be identified by searching the following databases: EMBASE, MEDLINE, Cochrane CENTRAL, Web of Science, CINAHL, ISRCTN registry, UK Clinical Trials Gateway, and WHO International Clinical Trials Portal. Any study design in which the biomarker and ultrasound scan potential predictors have been assessed after 24 weeks' gestation but before diagnosis of outcomes (pre-eclampsia, fetal growth restriction, SGA (including neonatal growth restriction), and stillbirth) will be eligible (this would include randomized control trials and nested prospective case-control and cohort studies), and there will be no restriction on the background risk of the population. All eligible studies will be assessed for risk of bias using the modified QUADAS-2 tool. Meta-analyses will be undertaken using the ROC models to estimate and compare test discrimination and reclassification indices to test calibration. Validation will be explored by comparing consistency across studies.

Discussion: This review will assess whether current published data reporting either a single or combination of tests in late pregnancy can accurately predict adverse pregnancy outcome(s) associated with placental dysfunction. Accurate prediction could allow targeted management and possible intervention for high-risk pregnancies, ultimately avoiding adverse outcomes associated with placental disease.

Systematic review registration: PROSPERO CRD42018107049.

Keywords: Biomarker; Fetal growth restriction (FGR); Neonatal growth restriction/growth restriction in the newborn (NGR); Placenta; Pre-eclampsia; Small for gestational age (SGA); Stillbirth; Ultrasound.