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

J Rodríguez-Calvo, C Villalaín, P I Gómez-Arriaga, M S Quezada, I Herraiz, A Galindo, J Rodríguez-Calvo, C Villalaín, P I Gómez-Arriaga, M S Quezada, I Herraiz, A Galindo

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.

Keywords: FGR; PlGF; early-onset; fetal growth restriction; perinatal survival.

© 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Figures

Figure 1
Figure 1
Mean area under the receiver‐operating‐characteristics curve of different proposed models for prediction of perinatal survival (a) and severe neonatal morbidity (b) after bootstrapping (1000 replications) in cases with early‐onset fetal growth restriction. Altered Doppler was defined as absent or reversed umbilical artery flow and impaired middle cerebral artery flow. *Evaluated at cut‐offs obtained by Youden's index (for perinatal survival: estimated fetal weight (EFW)

Figure 2

Perinatal survival rates (a), time…

Figure 2

Perinatal survival rates (a), time from diagnosis to delivery (b) and estimated weight…

Figure 2
Perinatal survival rates (a), time from diagnosis to delivery (b) and estimated weight gain from diagnosis to delivery (c) in cases with early‐onset fetal growth restriction, according to estimated fetal weight (EFW) and placental growth factor at diagnosis (PlGF) (, PlGF < 37 pg/mL; , PlGF ≥ 37 pg/mL). In boxplots, boxes with internal lines are median and interquartile range, whiskers are values 1.5‐times the interquartile range and individual datapoints are outliers. *P < 0.05.
Figure 2
Figure 2
Perinatal survival rates (a), time from diagnosis to delivery (b) and estimated weight gain from diagnosis to delivery (c) in cases with early‐onset fetal growth restriction, according to estimated fetal weight (EFW) and placental growth factor at diagnosis (PlGF) (, PlGF < 37 pg/mL; , PlGF ≥ 37 pg/mL). In boxplots, boxes with internal lines are median and interquartile range, whiskers are values 1.5‐times the interquartile range and individual datapoints are outliers. *P < 0.05.

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