Comparison of competing‐risks model with angiogenic factors in midgestation screening for preterm growth‐related neonatal morbidity

ABSTRACT Objectives First, to evaluate the predictive performance for preterm growth‐related neonatal morbidity of high soluble fms‐like tyrosine kinase‐1 (sFLT‐1) / placental growth factor (PlGF) ratio or low PlGF at mid‐gestation, and second, to compare the performance of the high sFLT‐1/PlGF ratio or low PlGF with that of the competing risks model for small for gestational age (SGA), utilizing a combination of maternal risk factors, sonographic estimated fetal weight (EFW) and uterine artery pulsatility index (UtA‐PI). Methods This was a prospective observational study in women attending for a routine hospital visit at 19 to 24 weeks’ gestation in two maternity hospitals in England. The visit included recording of maternal demographic characteristics and medical history, carrying out an ultrasound scan and measuring serum PlGF and sFLT‐1. The primary outcome was delivery <32 and <37 weeks’ gestation of SGA neonate with birth weight <10 th or <3 rd percentile for gestational age, combined with neonatal unit (NNU) admission for ≥48 hours or a composite of major neonatal morbidity. The detection rates in screening by either PlGF <10 th percentile, sFLT‐1/PlGF ratio >90 th percentile and the competing risks model for SGA were estimated and they were compared using McNemar's test. Results In the study population of 40241 women prediction of preterm growth‐related neonatal morbidity provided by the competing risks model for SGA was superior to that of screening by low PlGF concentration or high sFlt‐1/PlGF concentration ratio. For example, at screen positive rate (SPR) of 10.0%, as defined by the sFLT‐1/ PlGF ratio >90 th percentile, the competing risks model predicted 70.1% (95% CI 61.0 ‐ 79.2) of SGA <10 th percentile and 76.9% (67.6‐86.3) of SGA <3 rd percentile with NNU admission for ≥48 hours delivered <32 weeks gestation and these were significantly higher than the respective values of 35.0% (25.6‐44.6) and 35.9% (25.3 ‐ 46.5), achieved by the application of the sFLT‐1/ PlGF ratio >90 th percentile (p<0.0001 for both). The respective values for SGA with major neonatal morbidity were 73.8% (64.4‐83.2), 77.9% (68.0‐87.8), 38.1% (27.7‐48.5) and 39.7% (28.1‐51.3) (Both p<0.0001). Conclusion At mid‐gestation, the prediction of growth‐related neonatal morbidity by the competing risks model for SGA is superior to that of high sFlt‐1/PlGF ratio or low PlGF. This article is protected by copyright. All rights reserved.