A subset of patients destined to develop spontaneous preterm labor has an abnormal angiogenic/anti-angiogenic profile in maternal plasma: Evidence in support of pathophysiologic heterogeneity of preterm labor derived from a longitudinal study
- 16 November 2009
- journal article
- research article
- Published by Informa UK Limited in The Journal of Maternal-Fetal & Neonatal Medicine
- Vol. 22 (12), 1122-1139
- https://doi.org/10.3109/14767050902994838
Abstract
Objective. An imbalance between angiogenic and anti-angiogenic factors in maternal blood has been observed in several obstetrical syndromes including preeclampsia, pregnancies with fetal growth restriction and fetal death. Vascular lesions have been identified in a subset of patients with spontaneous preterm labor (PTL). It is possible that PTL may be one of the manifestations of an anti-angiogenic state. The aim of this study was to determine if patients prior to the clinical diagnosis of PTL leading to preterm delivery had plasma concentrations of angiogenic and anti-angiogenic factors different from normal pregnant women. Study Design. This longitudinal nested case–control study included normal pregnant women (n = 208) and patients with PTL leading to preterm delivery (n = 52). Maternal blood samples were collected at 6 gestational age intervals from 6 to36.9 weeks of gestation. The end point (time of diagnosis) of the study, ‘True PTL’, was defined as patients presenting with PTL and delivered within 1 day. Plasma concentrations of sVEGFR-1, sVEGFR-2, sEng and PlGF were determined by ELISA. Analysis was performed with both cross-sectional and longitudinal (mixed effects model) approaches. Results. (1) Plasma sEng concentration in patients destined to develop PTL was higher than that in normal pregnant women from 15–20 weeks of gestation. The difference became statistical significant at 28 weeks of gestation, or approximately 5–10 weeks prior to the diagnosis of ‘true PTL’. (2) Backward analysis suggests that plasma concentrations of PlGF and sVEGFR-2 were lower, and those of sVEGFR-1 were higher in patients with PTL than in normal pregnant women less than 5 weeks prior to the diagnosis of ‘true PTL’; and (3) Plasma concentrations of sEng and sVEGFR-1 were higher and those of PlGF and sVEGFR-2 were lower in patients diagnosed with PTL and delivery within 1 day than in normal pregnant women who delivered at term. Conclusion. The changes in sEng are demonstrable several weeks prior to the onset of preterm parturition. In contrast, the changes in the other angiogenic proteins are present close to the onset of PTL and delivery. This observation supports the view that an imbalance of angiogenic factors participates in the pathophysiology of spontaneous preterm parturition.Keywords
This publication has 125 references indexed in Scilit:
- Twin-to-twin transfusion syndrome: an antiangiogenic state?American Journal of Obstetrics and Gynecology, 2008
- The change in concentrations of angiogenic and anti-angiogenic factors in maternal plasma between the first and second trimesters in risk assessment for the subsequent development of preeclampsia and small-for-gestational ageThe Journal of Maternal-Fetal & Neonatal Medicine, 2008
- A longitudinal study of angiogenic (placental growth factor) and anti-angiogenic (soluble endoglin and soluble vascular endothelial growth factor receptor-1) factors in normal pregnancy and patients destined to develop preeclampsia and deliver a small for gestational age neonateThe Journal of Maternal-Fetal & Neonatal Medicine, 2008
- Epidemiology and causes of preterm birthThe Lancet, 2008
- Signature pathways identified from gene expression profiles in the human uterine cervix before and after spontaneous term parturitionAmerican Journal of Obstetrics and Gynecology, 2007
- Human spontaneous labor without histologic chorioamnionitis is characterized by an acute inflammation gene expression signatureAmerican Journal of Obstetrics and Gynecology, 2006
- Labor-Associated Gene Expression in the Human Uterine Fundus, Lower Segment, and CervixPLoS Medicine, 2006
- The biology of VEGF and its receptorsNature Medicine, 2003
- Inhibition of TGF-β3 restores the invasive capability of extravillous trophoblasts in preeclamptic pregnanciesJCI Insight, 1999
- Abnormal blood vessel development and lethality in embryos lacking a single VEGF alleleNature, 1996