59 Gestational age-specific reference ranges for the sFlt-1/PlGF ratio in multiple pregnancies

Abstract

Introduction The Elecsys® immunoassay soluble fms-like tyrosine kinase (sFlt-1)/placental growth factor (PlGF) ratio is a CE-IVD-approved diagnostic and predictive aid for preeclampsia. Reference ranges for Elecsys® sFlt-1, PlGF and the sFlt-1/PlGF ratio were generated for normal singleton pregnancies [1,2]. Ranges in normal multiple pregnancies may be different [3,4]. Objectives To establish reference ranges for the Elecsys® immunoassay sFlt-1/PlGF ratio in normal multiple pregnancies. Methods We analyzed sFlt-1/PlGF ratio, sFlt-1 and PlGF data from three studies in women with normal multiple pregnancies (without preeclampsia/eclampsia/HELLP syndrome/IUGR). The Prediction of Short-Term Outcome in Pregnant Women with Suspected Preeclampsia Study (PROGNOSIS) derived and validated an sFlt-1/PlGF ratio cut-off of 38 to rule out preeclampsia within 1 week in women with suspicion of preeclampsia (24 w + 0 d–36 w + 6 d; 25 normal multiple pregnancies) [5]. The Study of Early Preeclampsia in Spain (STEPS) evaluated the sFlt-1/PlGF ratio as a predictive marker for early-onset preeclampsia (11/20/24/28 w gestation; 729 women [188 normal multiple pregnancies] at risk of the syndrome) [6]. A multicenter case-control study (10 w + 0 d–delivery; 234 women with preeclampsia/915 normal pregnancies including 30 multiple pregnancies) examined the sFlt-1/PlGF ratio as a preeclampsia diagnostic aid [1]. Results Median sFlt-1/PlGF ratio, sFlt-1 and PlGF values in normal multiple pregnancies were generated (6 gestational age windows). Median sFlt-1/PlGF ratios were: 30.6 (10 w + 0 d–14 w+ 6d); 6.39 (15 w + 0 d–19 w + 6 d); 3.84 (20 w + 0d–23 w + 6 d); 3.81 (24 w + 0 d–28 w + 6 d); 22.2 (29 w + 0 d–33 w + 6 d); 47.1 (34 w + 0 d–36 w + 6 d). These values were not different to the median sFlt-1/PlGF ratios in singleton pregnancies up to gestational age 28 w + 6 d; from 29 w + 0 d–36 w + 6 d, the median sFlt-1/PlGF ratios were higher for multiple pregnancies (although the sample size was small here). Compared with singleton pregnancies, median sFlt-1 values were higher for multiple pregnancies, and median PlGF values were higher in multiple pregnancies until 28 w + 6 d, and then lower. Conclusion Reference ranges for the sFlt-1/PlGF ratio, sFlt-1 and PlGF in multiple pregnancies were different to singleton pregnancies; from 29 w + 0 d, the median sFlt-1/PlGF ratio was higher in multiple pregnancies. The Elecsys® immunoassay sFlt-1/PlGF ratio, sFlt-1 and PlGF reference ranges (median [5th–95th percentile]) in normal multiple pregnancies, compared with singleton pregnancies. Download : Download high-res image (671KB) Download : Download full-size image