Background:
Placental growth factor (PlGF)-based testing has high diagnostic accuracy for predicting pre-eclampsia needing delivery, significantly reducing time to diagnosis and severe maternal adverse outcomes. The clinical benefit of repeat PlGF-based testing is unclear. The aim of this trial was to determine whether repeat PlGF-based testing (using a clinical management algorithm and nationally recommended thresholds) reduces adverse perinatal outcomes, in pregnant individuals with suspected preterm pre-eclampsia.
Methods:
In this superiority, parallel group, non-masked, multicentre, randomised controlled trial in 22 maternity units across England, Scotland, and Wales, we compared repeat revealed PlGF-based testing with repeat concealed testing, alongside usual care, in women with suspected pre-eclampsia between 22+0- and 35+6-weeks’ gestation. The primary outcome was a perinatal composite of stillbirth, early neonatal death, or neonatal unit admission. Analyses were by intention to treat, with a per-protocol analysis. The trial was prospectively registered with the ISRCTN registry, ISRCTN 85912420.
Findings
Between Dec 17, 2019, and Sept 30, 2022, 1253 women were recruited. 626 were allocated to repeat revealed PlGF-based testing and 627 were allocated to usual care with repeat concealed PlGF-based testing. There was no evidence of a significant difference in the primary perinatal composite outcome between the revealed testing group (31.2%) compared to the concealed testing group (27·8%, relative risk 1·21; 95% CI 0·95-1·33; p=0·18). In the repeat revealed testing group (compared to the concealed testing group), there was a significant reduction in the gestational age at delivery (36·7 vs 37·1 weeks’ gestation, -0·40; -0·68 to -0·12; p=0·005); an increase in the number of participants giving birth before 34 weeks’ gestation (14·4% vs 8·8%; 1·63; 1·19-2·24; p=0·002) and an increase in the rate of caesarean birth (68·3% vs 59·9%; aRR 1·14; 1·05-1·23; p=0·002). There was no significant difference in a composite of severe maternal adverse outcomes. The results from the per-protocol analysis were similar. There were four serious adverse events in the revealed repeat testing group and six in the concealed repeat testing group.
Interpretation:
Repeat PlGF-based testing in women with suspected pre-eclampsia was not associated with improved perinatal outcomes. In this population in a high income setting and a low prevalence of adverse outcomes, universal, routine repeat PlGF-based testing of all individuals with suspected pre-eclampsia is not recommended.
Funding
Tommy’s Charity and Jon Moulton Charitable Trust. Funding for PlGF-based tests was also received from the NIHR Biomedical Research Centre (BRC) and Roche.