Circulating angiogenic factors in early pregnancy and the risk of preeclampsia, intrauterine growth restriction, spontaneous preterm birth, and stillbirth

Obstet Gynecol. 2007 Jun;109(6):1316-24. doi: 10.1097/01.AOG.0000265804.09161.0d.


Objective: To estimate the relationship between maternal serum levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) in early pregnancy with the risk of subsequent adverse outcome.

Methods: A nested, case-control study was performed within a prospective cohort study of Down syndrome screening. Maternal serum levels of sFlt-1 and PlGF at 10-14 weeks of gestation were compared between 939 women with complicated pregnancies and 937 controls. Associations were quantified as the odds ratio for a one decile increase in the corrected level of the analyte.

Results: Higher levels of sFlt-1 were not associated with the risk of preeclampsia but were associated with a reduced risk of delivery of a small for gestational age infant (odds ratio [OR] 0.92, 95% confidence interval [CI] 0.88-0.96), extreme (24-32 weeks) spontaneous preterm birth (OR 0.90, 95% CI 0.83-0.99), moderate (33-36 weeks) spontaneous preterm birth (OR 0.93, 95% CI 0.88-0.98), and stillbirth associated with abruption or growth restriction (OR 0.77, 95% CI 0.61-0.95). Higher levels of PlGF were associated with a reduced risk of preeclampsia (OR 0.95, 95% CI 0.90-0.99) and delivery of a small for gestational age infant (OR 0.95, 95% CI 0.91-0.99). Associations were minimally affected by adjustment for maternal characteristics.

Conclusion: Higher early pregnancy levels of sFlt-1 and PlGF were associated with a decreased risk of adverse perinatal outcome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • Case-Control Studies
  • Cohort Studies
  • Confidence Intervals
  • Female
  • Fetal Growth Retardation / epidemiology*
  • Gestational Age
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Infant, Small for Gestational Age
  • Odds Ratio
  • Placenta Growth Factor
  • Pre-Eclampsia / epidemiology*
  • Pregnancy / blood
  • Pregnancy Outcome
  • Pregnancy Proteins / blood*
  • Pregnancy Trimester, First / blood
  • Premature Birth / epidemiology*
  • Prospective Studies
  • Risk Factors
  • Stillbirth / epidemiology*
  • Vascular Endothelial Growth Factor Receptor-1 / blood*


  • Biomarkers
  • PGF protein, human
  • Pregnancy Proteins
  • Placenta Growth Factor
  • FLT1 protein, human
  • Vascular Endothelial Growth Factor Receptor-1