Can the PlGF/sVEGFR-1 Ratio be Used to Predict Fetal Death?
BACKGROUND AND PURPOSE:
Abnormal placentation is a cause of unexplained stillbirth
Angiogenic proteins such as placental growth factor (PlGF) and antiangiogenic proteins such as soluble vascular endothelial growth factor receptor 1 (sVEGFR-1) and soluble endoglin (sEng) circulate in the maternal compartment and reflect placental malperfusion
Chaiworapongsa et al. (AJOG, 2017) sought to determine if maternal plasma PlGF/sVEGFR-1 ratio (angiogenic index-1) at 24-28 weeks can predict fetal death
Subjects: 1000 randomly selected women with singleton pregnancies from a cohort of 4006 enrolled in a longitudinal biomarker cohort study
Placentas underwent histological examination for maternal vascular lesions of underperfusion (now known as maternal vascular malperfusion)
Fetal Death: Confirmation by ultrasound >20 weeks
Small for gestation (SGA) neonate: Birthweight <10th centile for gestational age
Preterm: Delivery < 37th weeks
All fetal deaths were examined for placental growth factor, soluble endoglin, and soluble vascular endothelial growth factor receptor-1 concentrations, measured by enzyme-linked immunosorbent assays
A positive test was defined as analyte concentrations (or ratios)
<2.5th and 10th centiles (PlGF, PlGF/sVEGFR-1, and PlGF/sEng or
>90th and 97.5th centiles (sVEGFR-1 and sEng)
11 fetal deaths and 829 controls with samples were available for analysis between 24-28 weeks of gestation
Maternal vascular underperfusion lesion rate was 33.3% among those placentae where there was fetal death <28 weeks and 87.5% when fetal death occurred after ≥28 weeks of gestation
An angiogenic index-1 value <10th centile
Seen in 63.6% of the fetal death group and in 11.1% of the controls
37% of women had preclampsia or SGA
Angiogenic index-1 value <2.5th centile
Seen in 54.5% of the fetal death group and in 3.7% of the controls
61% developed preeclampsia or had an SGA neonate
Associated with the largest positive likelihood ratio (14.6) for predicting fetal death >24 weeks (95% CI, 7.7–27.7) with a relative risk (RR) of 29.1 (95% CI, 8.8–97.1)
sEng >97.5th centile and PlGF/sEng <2.5th both had a positive likelihood ratio of 13.7 (95% CI, 7.3–25.8) and an RR of 27.4 (95% CI, 8.2–91.2)
The maternal plasma angiogenic index-1 value <2.5th centile at 24-28 weeks
Carries a 29-fold risk increase of fetal death
Can identify 55% of fetal deaths with 3.5% false positive rate
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