PRE-EMPT is excited to announce that we have published "Placental growth factor as a marker of fetal growth restriction caused by placental dysfunction" in Placenta. This paper demonstrates the capacity of maternal circulating placental growth factor measurement to discriminate between fetuses who are constitutionally-small (normal) and those who are truly growth-restricted.This project was strongly facilitated by The Global Pregnancy Collaboration (CoLab), who gained access to samples that had been stored at -80°C for 20 years to accelerate discovery.
The highlights of the paper include:
- Low PlGF is associated with significant placental pathology in FGR pregnancies.
- Low PlGF has high sensitivity and moderate specificity in identifying placental FGR.
- Low PlGF is associated with shorter sampling-to-delivery intervals than normal PlGF.
- Low PlGF has a greater post-test probability of stillbirth than normal PlGF.
Discriminating between placentally-mediated fetal growth restriction and constitutionally-small fetuses is a challenge in obstetric practice. Placental growth factor (PlGF), measurable in the maternal circulation, may have this discriminatory capacity.
Plasma PlGF was measured in women presenting with suspected fetal growth restriction (FGR; ultrasound fetal abdominal circumference <10th percentile for gestational age) at sites in Canada, New Zealand and the United Kingdom. When available, placenta tissue underwent histopathological examination for lesions indicating placental dysfunction, blinded to PlGF and clinical outcome. Lesions were evaluated according to pre-specified severity criteria and an overall severity grade was assigned (0–3, absent to severe). Low PlGF (concentration <5th percentile for gestational age) to identify placental FGR (severity grade≥2) was assessed and compared with routine parameters for fetal assessment. For all cases, the relationship between PlGF and the sampling-to-delivery interval was determined.
Low PlGF identified placental FGR with an area under the receiver-operator characteristic curve of 0.96 [95% CI 0.93–0.98], 98.2% [95% CI 90.5–99.9] sensitivity and 75.1% [95% CI 67.6–81.7] specificity. Negative and positive predictive values were 99.2% [95% CI 95.4–99.9] and 58.5% [95% CI 47.9–68.6], respectively. Low PlGF outperformed gestational age, abdominal circumference and umbilical artery resistance index in predicting placental FGR. Very low PlGF (<12 pg/mL) was associated with shorter sampling-to-delivery intervals than normal PlGF (13 vs. 29.5 days, P < 0.0001).
Low PlGF identifies small fetuses with significant underlying placental pathology and is a promising tool for antenatal discrimination of FGR from fetuses who are constitutionally-small.