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

Objectives First, to evaluate the predictive performance for preterm growth-related neonatal morbidity of a high soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio or low PlGF at midgestation and, second, to compare the performance of a 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 and uterine artery pulsatility index. Methods This was a prospective observational study in women attending for a routine hospital visit at 19-24 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 a SGA neonate with birth weight < 10(th) or < 3(rd) percentile, combined with neonatal unit (NNU) admission for >= 48 h or a composite of major neonatal morbidity. The detection rates in screening by PlGF < 10(th) percentile, sFlt-1/PlGF ratio > 90th percentile and the competing-risks model for SGA were estimated and then compared using McNemar's test. Results In the study population of 40 241 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 ratio. For example, at a screen-positive rate of 10.0%, as defined by the sFlt-1/PlGF ratio > 90th percentile, the competing-risks model predicted 70.1% (95% CI, 61.0-79.2%) of SGA < 10(th) percentile and 76.9% (95% CI, 67.6-86.3%) of SGA < 3(rd) percentile with NNU admission for >= 48 h delivered < 32 weeks' gestation. The respective values for SGA with major neonatal morbidity were 73.8% (95% CI, 64.4-83.2%) and 77.9% (95% CI, 68.0-87.8%). These were significantly higher than the respective values of 35.1% (95% CI, 25.6-44.6%), 35.9% (95% CI, 25.3-46.5%), 38.1% (95% CI, 27.7-48.5%) and 39.7% (95% CI, 28.1-51.3%) achieved by the application of the sFlt-1/PlGF ratio > 90(th) percentile (all P < 0.0001). Conclusion At midgestation, the prediction of growth-related neonatal morbidity by the competing-risks model for SGA is superior to that of a high sFlt-1/PlGF ratio or low PlGF.