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

Abstract

Objective To investigate the potential value of uterine artery pulsatility index (UtA‐PI) and serum levels of the angiogenic placental growth factor (PlGF) and the 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 at 35–37 weeks' gestation. Methods This was a prospective observational study of 19 209 singleton pregnancies attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation. This visit included recording of maternal demographic characteristics and medical history, sonographic estimation of fetal weight, color Doppler ultrasound for measurement of mean UtA‐PI, and measurement of serum concentrations of PlGF and sFlt‐1. 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 delivery for suspected fetal compromise in labor; third, neonatal death or hypoxic ischemic encephalopathy Grade 2 or 3; and, fourth, admission to the neonatal unit (NNU) for ≥ 48 h. Predicted probabilities from logistic regression analysis were used to construct receiver–operating characteristics curves to assess the 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 h occurred in pregnancies with a non‐SGA neonate. Second, UtA‐PI > 95th percentile, sFlt‐1 > 95th percentile and PlGF < 5th percentile were associated with increased risk of Cesarean delivery for suspected fetal compromise in labor and NNU admission for ≥ 48 h; 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 logistic regression analysis demonstrated that, in the prediction of Cesarean delivery for suspected fetal compromise in labor, there was no significant contribution from biomarkers; the prediction of NNU admission for ≥ 48 h by maternal demographic characteristics and medical history was only marginally improved by the addition of sFlt‐1 or PlGF. Fourth, for each biomarker, the detection rate of adverse outcome was higher in SGA than in non‐SGA neonates, but this 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. Copyright © 20...

The physiology of intrapartum fetal compromise at term

“…24,26 Although low maternal PlGF levels in the third trimester have been shown to be associated with IFC and adverse neonatal outcomes, 148,149 the evidence is conflicting with another recent study, suggesting that it did not predict cesarean birth for fetal compromise. 150 Identification of intrapartum fetal compromise Despite concerted efforts to develop accurate techniques for the identification of intrapartum fetal hypoxia, to date all techniques currently in clinical practice have poor positive predictive values. 151 Reviews of conventional antepartum cardiotocography (CTG), computerized FHR analysis, or intermittent auscultation have concluded that they do not result in improved perinatal outcomes.…”

Stillbirth at term: Does size really matter?

“…In this sense, it seems reasonable that multiple parameters should be assessed for better prediction of fetuses at risk of stillbirth 43,45,46 . Although the use of biomarkers such as placental growth factor and sFlt1 has proved useful in the prediction and timely diagnosis of pre‐eclampsia, 47,48 in pregnancies at 35–37 weeks of gestation, the routine assessment of these markers provided poor prediction of perinatal outcomes in both SGA and non‐SGA fetuses 49 . Maybe the incorporation of these markers to more comprehensive algorithms should be the key to a better predictive performance regarding SGA and term stillbirth.…”

Fetal Growth Restriction Prediction: How to Move beyond

“…Indeed, growth restriction can account for up to half of the fetal deaths of unknown causes [54], being about 6-fold higher than the chance of stillbirth at term (relative risk, RR, 6.0; 95% CI, 3.1–11.5) [11], or when the birthweight is <5 th percentile (compared to the 10–90 th centiles) [17]. Besides perinatal death [6, 11, 12, 15–18, 55], preterm birth [6, 11, 14], and other short-term adverse events are described for SGA infants (Table 1); the adjusted odds ratio (aOR) for composite neonatal morbidity can be as high as 3.22 (95% CI, 3.07–3.39) [12]. Interestingly, SGA suspicion in pregnancy is associated with better neonatal outcomes [18, 57], which turns SGA screening a cornerstone strategy for reducing antepartum fetal loss [13, 58] and meliorating neonatal morbidity ratios.…”