Evaluation of angiogenic factors in prediction of growth related neonatal morbidity at term and comparison with competing risks model

Abstract

ABSTRACTObjectivesFirst, to describe the distribution of biomarkers of impaired placentation in small for gestational age (SGA) pregnancies with neonatal morbidity, second, to examine the predictive performance for growth related neonatal morbidity of high soluble fms‐like tyrosine kinase‐1 (sFLT‐1) / placental growth factor (PlGF) ratio or low PlGF, and third, to compare the performance of the high sFLT‐1/PlGF ratio or low PlGF with that of the competing risks model for SGA.MethodsThis was a prospective observational study in women attending for a routine hospital visit at 36 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 within 4 weeks from assessment and <42 weeks’ gestation of SGA neonate with birth weight <10th or <3rd 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 <10th percentile, sFLT‐1/PlGF ratio >90th percentile, sFLT‐1/PlGF ratio >38 and the competing risks model for SGA, using combinations of maternal risk factors and z scores of EFW with MoM values of uterine artery pulsatility index (UtA‐PI), PlGF and sFLT‐1, were estimated. The detection rates by the different methods of screening were compared using McNemar's test.ResultsIn the study population of 29,035 women prediction of growth related neonatal morbidity at term provided by the competing risks model was superior to that of screening by low PlGF concentration or high sFlt‐1/PlGF concentration ratio. For example, at SPR of 13.1%, as defined by the sFLT‐1/ PlGF ratio >38, the competing risks model using maternal risk factors and EFW predicted 77.5% (95% CI 71.7‐83.3) of SGA <10th percentile and 89.2% (83.7‐94.8) of SGA <3rd percentile with NNU admission for ≥48 hours delivered within 4 weeks after assessment; these were significantly higher than the respective values of 41.0% (34.2‐47.8) and 48.8% (39.9‐57.7), achieved by the application of the sFLT‐1/ PlGF ratio >38 (p<0.0001, p<0.0001). The respective values for SGA with major neonatal morbidity were 71.4% (56.5‐86.4), 90.0% (76.9‐100), 37.1% (21.1‐53.2) and 55.0% (33.2‐76.8) (p=0.003, p=0.035).At a SPR of 10.0%, as defined by the PlGF ratio <10th percentile, the competing risks model using maternal factors and EFW predicted 71.5% (65.2‐77.8) of SGA <10th percentile and 84.3% (77.8‐90.8) of SGA <3rd percentile with NNU admission for ≥48 hours delivered within 4 weeks after assessment; these were significantly higher than the respective values of 36.5% (29.8‐43.2) and 46.3% (37.4‐55.2), achieved by the application of PlGF <10th percentile (p<0.0001, p<0.0001). The respective values for SGA with major neonatal morbidity were 68.5% (53.1‐83.9), 85.0% (69.4‐100), 37.1% (21.1‐53.2) and 55.0% (33.2‐76.80) (p=0.003, p=0.021).ConclusionAt 36 weeks’ gestation, the prediction of growth related neonatal morbidity by the competing risks model for SGA, using maternal risk factors and EFW, is superior to that of high sFlt‐1/PlGF ratio or low PlGF.This article is protected by copyright. All rights reserved.