Biomarkers of impaired placentation at 35-37 weeks' gestation in the prediction of adverse perinatal outcome

Objective: This screening study at 35-37 weeks’ gestation investigates the potential value of uterine artery pulsatility index (UtA-PI) and serum levels of the angiogenic placental growth factor (PlGF) and antiangiogenic factor soluble fms-like tyrosine kinase-1 (sFLT-1) in the prediction of adverse perinatal outcome in small for gestational age (SGA) and non-SGA neonates. Methods: This was a prospective observational study in 19,209 singleton pregnancies attending for a routine hospital visit at 35+0 - 36+6 weeks’ gestation. This visit included recording of maternal demographic characteristics and medical history, sonographic estimation of fetal weight (EFW), color Doppler ultrasound for measurement of the mean UtA-PI, and measurement of serum concentration of PlGF and sFLT. Multivariable logistic regression analysis was carried out to determine which of the factors from maternal or pregnancy characteristics and measurements of UtA-PI, PlGF and sFLT-1, provided a significant contribution in the prediction of each of four adverse outcome measures: first, stillbirth, second, cesarean section for presumed fetal compromise in labor, third, neonatal death or hypoxic ischemic encephalopathy grades 2 and 3, and fourth, admission to the neonatal unit (NNU) for ≥48 hours. Predicted probabilities from logistic regression analysis were used to construct receiver operating characteristic (ROC) curves to assess performance of screening for these adverse outcomes. Results: First, 83% of stillbirths, 82% of cesarean sections for presumed fetal compromise in labor, 91% of cases of neonatal death or hypoxic ischemic encephalopathy and 86% of NNU admissions for ≥48 hours occurred in pregnancies with non-SGA babies. Second, UtA-PI >95th percentile, sFLT-1 >95th percentile and PLGF 95th, sFLT-1 >95th and PLGF <5th percentiles for most adverse outcomes was <2.5 in both SGA and non-SGA neonates. Conclusions: In pregnancies undergoing routine antenatal assessment at 35-37 weeks’ gestation measurements of UtA-PI, sFLT-1 or PlGF provide poor prediction of adverse perinatal outcome in both SGA and non-SGA fetuses