Prediction of stillbirth from placental growth factor at 11-13 weeks

Ultrasound Obstet Gynecol. 2016 Nov;48(5):618-623. doi: 10.1002/uog.17288.


Objectives: To investigate whether the addition of maternal serum placental growth factor (PlGF) measured at 11-13 weeks' gestation improves the performance of screening for stillbirths that is achieved by a combination of maternal factors and first-trimester biomarkers such as maternal serum pregnancy-associated plasma protein-A (PAPP-A), fetal ductus venosus pulsatility index for veins (DV-PIV) 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 causes.

Methods: This was a prospective screening study of 45 452 singleton pregnancies including 45 225 live births and 227 (0.49%) antepartum stillbirths; 131 (58%) were secondary to impaired placentation and 96 (42%) were due to other or unexplained causes. 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 and PAPP-A, DV-PIV and UtA-PI.

Results: Significant contribution to the prediction of stillbirth was provided by maternal factor-derived a-priori risk and multiples of the median values of PlGF, DV-PIV and UtA-PI but not of serum PAPP-A. A model combining these variables predicted 42% of all stillbirths and 61% 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 (71% vs 46%; P = 0.031).

Conclusions: A high proportion of stillbirths due to impaired placentation can be identified effectively in the first trimester of pregnancy. Addition of PlGF improves the performance of screening achieved by other maternal factors and biomarkers. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Keywords: first‐trimester screening; placental growth factor; pyramid of pregnancy care; stillbirth.

MeSH terms

  • Adult
  • Early Diagnosis
  • Female
  • Humans
  • Membrane Proteins / blood*
  • Models, Theoretical
  • Pregnancy
  • Pregnancy Trimester, First / blood*
  • Pregnancy-Associated Plasma Protein-A / analysis*
  • Prospective Studies
  • Software
  • Stillbirth / epidemiology*
  • Uterine Artery


  • Membrane Proteins
  • PIGF protein, human
  • Pregnancy-Associated Plasma Protein-A