Prediction of stillbirth from placental growth factor at 19-24 weeks

Ultrasound Obstet Gynecol. 2016 Nov;48(5):631-635. doi: 10.1002/uog.17229.


Objectives: To investigate whether the addition of maternal serum placental growth factor (PlGF) measured at 19-24 weeks' gestation improves the performance of screening for stillbirth that is achieved by a combination of maternal factors, fetal biometry and uterine artery pulsatility index (UtA-PI) and to evaluate the performance of screening with this model for all stillbirths and those due to impaired placentation and unexplained or other causes.

Methods: This was a prospective screening study of 70 003 singleton pregnancies including 268 stillbirths, carried out in two phases. The first phase included prospective measurement of UtA-PI and fetal biometry, which were available in all cases. The second phase included prospective measurement of maternal serum PlGF, which was available for 9870 live births and 86 antepartum stillbirths. The values of PlGF obtained from this screening study were simulated in the remaining cases based on bivariate Gaussian distributions, defined by the mean and standard deviations. Multivariable logistic regression analysis was used to determine whether the addition of maternal serum PlGF improved the performance of screening that was achieved by a combination of maternal factors, fetal biometry and UtA-PI.

Results: Significant contribution to the prediction of stillbirth was provided by maternal factor-derived a-priori risk, multiples of the median values of PlGF, UtA-PI and fetal biometry Z-scores. A model combining these variables predicted 58% of all stillbirths and 84% of those due to impaired placentation, at a false-positive rate of 10%. Within the impaired-placentation group, the detection rate of stillbirth < 32 weeks' gestation was higher than that of stillbirth ≥ 37 weeks (97% vs 61%; P < 0.01).

Conclusions: A high proportion of stillbirths due to impaired placentation can be identified effectively in the second trimester of pregnancy using a combination of maternal factors, fetal biometry, uterine artery Doppler and maternal serum PlGF. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Keywords: placental growth factor; pyramid of care; stillbirth; uterine artery Doppler.

MeSH terms

  • Adult
  • Biomarkers / blood
  • Biometry
  • Female
  • Humans
  • Logistic Models
  • Placenta Growth Factor / blood*
  • Pregnancy
  • Pregnancy Trimester, Second / blood*
  • Prospective Studies
  • Stillbirth / epidemiology*
  • Uterine Artery / diagnostic imaging*


  • Biomarkers
  • PGF protein, human
  • Placenta Growth Factor