46 Prediction of preeclampsia using the sFlt-1:PLGF ratio: A prospective cohort study of unselected nulliparous women

Abstract

Background Preeclampsia remains a significant cause of maternal and perinatal morbidity. A recent study has suggested that the ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) in maternal serum provides clinically useful prediction of risk in women with suspected preeclampsia. Methods We sought to assess a blinded sFlt-1:PlGF ratio as a screening test for preeclampsia in a prospective cohort of unselected nulliparous women, using pre-defined thresholds for screen positive. We studied blood samples from 4512 women recruited to the Pregnancy Outcome Prediction study (see Lancet 2015; 386:2089–2097). Maternal serum levels of sFlt-1 and PlGF were measured using Roche Elecsys assays on the electro-chemiluminescence immunoassay platform, Cobas e411 (Roche Diagnostics). Preeclampsia was defined using the 2013 ACOG system, blind to the results of the biochemical assays. High risk of preeclampsia was defined as either maternal characteristics (using the UK’s National Institute for Health and Care Excellence Guideline) or elevated 20 uterine artery Doppler (mean pulsatility index >90th percentile) at around 20 weeks of gestational age. The primary outcomes were preeclampsia resulting in preterm birth (28 weeks of gestational age [wkGA] measurement, n = 3989) or preeclampsia with severe features (36wkGA measurement, n = 3776). Results Women with an sFlt-1:PlGF ratio >38 at 28wkGA had an incidence of preeclampsia leading to preterm delivery of 32%. The positive predictive value was similar in low and high risk women (33% vs 31%, respectively, P = 0.91). Women with an sFlt-1:PlGF ratio>38 at 36wkGA had an incidence of preeclampsia with severe features of 10%. The positive predictive value was 20% in high risk women and 6.4% in low risk women. Among women with no prior risk factors, an sFlt-1:PlGF ratio 99%). At 36wkGA, 70 women had an sFlt1:PlGF ratio >110 and 21 (30%) developed preeclampsia with severe features. We then analysed a composite definition of screen positive at 36wkGA, namely, an sFlt-1:PlGF ratio of >110 or an sFlt-1:PlGF ratio >38 plus maternal risk factors. A total of 195 (5.2%) women screened positive by this definition: 41 (21%) of them developed pre-eclampsia with severe features and a further 43 (23%) developed preeclampsia without severe features. Conclusions The sFlt-1:PlGF ratio provided clinically useful prediction of the risk of the most important manifestations of preeclampsia in a cohort of nulliparous women. Screening women at 36wkGA could be used to target monitoring and induction of labour prior to development of disease, or its most severe manifestations.