Prediction of perinatal survival in early‐onset fetal growth restriction: role of placental growth factor

Abstract

Objective To analyze the ability to predict perinatal survival and severe neonatal morbidity of cases with early‐onset fetal growth restriction (eoFGR) using maternal variables, ultrasound parameters and angiogenic markers at the time of diagnosis. Methods This was a prospective observational study in a cohort of singleton pregnancies with a diagnosis of eoFGR (< 32 weeks of gestation). At diagnosis of eoFGR, complete assessment was performed, including ultrasound examination (anatomy, biometry and Doppler assessment) and maternal serum measurement of the angiogenic biomarkers, soluble fms‐like tyrosine kinase‐1 (sFlt‐1) and placental growth factor (PlGF). Logistic regression models for the prediction of perinatal survival (in cases diagnosed at < 28 weeks) and severe neonatal morbidity (in all liveborn cases) were calculated. Results In total, 210 eoFGR cases were included, of which 185 (88.1%) survived perinatally. The median gestational age at diagnosis was 27 + 0 weeks. All cases diagnosed at ≥ 28 weeks survived. In cases diagnosed < 28 weeks, survivors (vs non‐survivors) had a higher gestational age (26.1 vs 24.4 weeks), estimated fetal weight (EFW; 626 vs 384 g), cerebroplacental ratio (1.1 vs 0.9), PlGF (41 vs 18 pg/mL) and PlGF multiples of the median (MoM; 0.10 vs 0.06) and lower sFlt‐1/PlGF ratio (129 vs 479) at the time of diagnosis (all P < 0.001). The best combination of two variables for predicting perinatal survival was provided by EFW and PlGF MoM (area under the receiver‐operating‐characteristics curve (AUC), 0.84 (95% CI, 0.75–0.92)). These were also the best variables for predicting severe neonatal morbidity (AUC, 0.73 (95% CI, 0.66–0.80)). Conclusions A model combining EFW and maternal serum PlGF predicts accurately perinatal survival in eoFGR cases diagnosed before 28 weeks of gestation. Prenatal prediction of severe neonatal morbidity in eoFGR cases is modest regardless of the model used. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Prediction of fetal and neonatal outcomes after preterm manifestations of placental insufficiency: systematic review of prediction models

“…All included studies were published as full-text papers. The 14 included studies developed a total of 41 individual prediction models 6,[11][12][13][14][15][16][17][18][19][20][21][22][23] . All the studies were derivation studies, meaning that, within the study project, a new prediction model was developed and none of the included studies validated a pre-existing prediction model.…”

“…Rodríguez-Calvo et al 20 developed 16 prediction models, including eight models for the prediction of perinatal survival and eight for the prediction of a composite outcome of severe neonatal morbidity. A total of 210 pregnancies complicated by preterm FGR were included.…”

Counseling in fetal medicine: pre‐ and periviable fetal growth restriction

“…Additionally, the studies of Sharp et al 41 . and Rodríguez‐Calvo et al 42 . have demonstrated the role of estimated fetal weight at diagnosis and the levels of angiogenic biomarkers, such as soluble fms‐like tyrosine kinase‐1 (sFlt‐1), placental growth factor (PlGF) and their ratio, as independent predictors of perinatal survival in early FGR.…”

“…'Late' changes in Doppler parameters of the umbilical arteries and ductus venosus, including absent or reversed umbilical artery end-diastolic flow and absent or reversed ductus venosus a-wave, have been shown to correlate with adverse outcome in early FGR 39,40 . Additionally, the studies of Sharp et al 41 and Rodríguez-Calvo et al 42 have demonstrated the role of estimated fetal weight at diagnosis and the levels of angiogenic biomarkers, such as soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF) and their ratio, as independent predictors of perinatal survival in early FGR. The sFlt-1/PlGF ratio has also been shown to predict the occurrence of HDP in patients at risk 43 , such as those with primary placental insufficiency leading to early FGR, which further supports the concept that the assessment of circulating angiogenic biomarkers could assist in parental counseling in the context of pre-and periviable FGR.…”