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

Journal article


Ciobanou, A., Jabak, S., De Castro, H., Frei, L., Akolekar, R. and Nicolaides, K. H. 2019. Biomarkers of impaired placentation at 35-37 weeks' gestation in the prediction of adverse perinatal outcome. Ultrasound in Obstetrics and Gynecology. 54 (1), pp. 79-86.
AuthorsCiobanou, A., Jabak, S., De Castro, H., Frei, L., Akolekar, R. and Nicolaides, K. H.
Abstract

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 <5th percentile were associated with increased risk of cesarean section for presumed fetal compromise in labor and NNU admission for ≥48 hours; the number of stillbirths and cases of neonatal death or hypoxic ischemic encephalopathy was too small to demonstrate significance in the observed differences from cases without these adverse outcomes. Third, multivariable regression analysis demonstrated that in prediction of cesarean section for presumed fetal compromise in labor there was no significant contribution from biomarkers; the prediction of NNU admission for ≥48 hours by maternal demographic characteristics and medical history was only marginally improved by the addition of UtA-PI, sFLT-1 or PlGF. Fourth, for each biomarker the detection rate of adverse outcomes was higher in SGA than in non-SGA neonates, but such increase was accompanied by an increase in false positive rate. Fifth, the relative risk of UtA-PI >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.

KeywordsThird trimester screening; Small for gestational age; Uterine artery Doppler; Placental growth factor; Soluble fms-like tyrosine kinase-1; Cesarean section; Perinatal hypoxia; Stillbirth; Perinatal death; Hypoxic ischemic encephalopathy; Neonatal unit admission
Year2019
JournalUltrasound in Obstetrics and Gynecology
Journal citation54 (1), pp. 79-86
PublisherWiley
ISSN0960-7692
Digital Object Identifier (DOI)doi:10.1002/uog.20346
Official URLhttps://doi.org/10.1002/uog.20346
Publication dates
Online10 Jun 2019
Publication process dates
Accepted13 May 2019
Deposited21 May 2020
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