Angiogenic factors at diagnosis of late-onset small-for-gestational age and histological placental underperfusion

Placenta. 2014 Jun;35(6):398-403. doi: 10.1016/j.placenta.2014.03.021. Epub 2014 Apr 5.

Abstract

Objective: This study was designed to explore the association between angiogenic factors levels at diagnosis of small-for-gestational age (SGA) and placental underperfusion (PUP).

Methods: In a cohort of SGA singleton pregnancies, each delivered at >34 weeks, uterine (UtA), umbilical (UA), and middle cerebral (MCA) arteries were evaluated by Doppler upon diagnosis of SGA status. In addition, maternal circulating concentrations of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were assayed by ELISA, and each placenta was evaluated for histologic signs of PUP using a hierarchical and standardized classification system. Logistic regression was applied to analyze independent relationships (at diagnosis) between angiogenic factors and Doppler parameters.

Results: A total of 122 suspected SGA pregnancies were studied, 70 (57.4%) of which ultimately met PUP criteria. In this group, 85 placental findings qualified as PUP. Both mean UtA pulsatility index z-values (1.26 vs. 0.84; p = 0.038) and PlGF multiples of normal median (0.21 vs. 0.55; p = 0.002) differed significantly in pregnancies with and without PUP, respectively. By logistic regression, PlGF alone was independently predictive of PUP (OR = 0.11 [95% CI 0.025-0.57]; p = 0.008).

Discussion: Histologic placental abnormalities in term SGA neonates reflect latent insufficiency in uteroplacental blood supply. The heightened risk of adverse perinatal outcomes in this context underscores a need for new Doppler or biochemical prenatal markers of placental disease. Angiogenic factors may be pivotal identifying SGA neonates.

Conclusions: Diminished circulating levels of placental growth factor, determined upon discovery of SGA status, are associated with histologic evidence of PUP.

Keywords: Doppler; Fetal growth restriction; Placental growth factor; Placental lesions; Placental underperfusion; Soluble fms-like tyrosine kinase-1.

MeSH terms

  • Adult
  • Biomarkers / blood
  • Female
  • Gestational Age
  • Humans
  • Infant, Newborn
  • Infant, Small for Gestational Age*
  • Male
  • Middle Cerebral Artery / diagnostic imaging
  • Middle Cerebral Artery / pathology
  • Middle Cerebral Artery / physiopathology
  • Placenta / blood supply*
  • Placenta / pathology
  • Placenta Diseases / diagnosis*
  • Placenta Growth Factor
  • Pregnancy
  • Pregnancy Proteins / blood*
  • Pulsatile Flow
  • Ultrasonography, Prenatal
  • Umbilical Arteries / diagnostic imaging
  • Umbilical Arteries / pathology
  • Umbilical Arteries / physiopathology
  • Uterine Artery / diagnostic imaging
  • Uterine Artery / pathology
  • Uterine Artery / physiopathology
  • Vascular Endothelial Growth Factor Receptor-1 / blood

Substances

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