Preterm Delivery as a Unique Pathophysiologic State Characterized by Maternal Soluble FMS-Like Tyrosine Kinase 1 and Uterine Artery Resistance During Pregnancy: A Longitudinal Cohort Study

Jennifer K. Straughen, Dawn P. Misra, Laura Helmkamp, Vinod K. Misra

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Background: Preterm delivery (PTD) may be characterized by altered interrelationships among angiogenic factors and measures of placental function. We analyzed the longitudinal relationship between maternal serum concentrations of soluble fms-like tyrosine kinase 1 (sFlt1), an important antiangiogenic factor, and uterine artery resistance in pregnancies resulting in preterm and term deliveries. Methods: Data were collected in a longitudinal cohort study involving 278 women monitored at 6 to 10, 10 to 14, 16 to 20, 22 to 26, and 32 to 36 weeks of gestation. Concentrations of maternal serum sFlt1 were determined using solid-phase enzyme-linked immunosorbent assay, and uterine artery resistance indices (RI) were measured by Doppler velocimetry at each interval. Preterm delivery was defined as birth before 37-weeks completed gestation. Data analyses used multivariable repeated measures regression models. Results: Uterine artery RI decreased across gestation. As pregnancy progressed, RI trajectories diverged for term and preterm deliveries; the mean RI was significantly higher in third trimester for pregnancies resulting in PTD (P =.08). sFlt1 was stable through 21 3/7 weeks of gestation and then increased rapidly; women who delivered preterm had significantly higher sFlt1 levels in the third trimester (P =.04). The relationship between uterine artery RI and sFlt1 from the prior visit was significantly different between the groups (P <.0001). For term deliveries, higher sFlt1 concentrations were associated with a smaller RI at the subsequent visit (β = −.08, 95% confidence interval [CI]: −0.14 to −0.02). For PTD, higher sFlt1 concentrations were associated with a larger uterine artery RI (β =.14, 95% CI: 0.06 to 0.22). Conclusion: PTD is characterized by altered relationships between angiogenic factors and placental vascular blood flow starting in early pregnancy.

Original languageEnglish
Pages (from-to)1583-1589
Number of pages7
JournalReproductive Sciences
Volume24
Issue number12
DOIs
StatePublished - Dec 1 2017

Keywords

  • Doppler ultrasound
  • Flt1 protein
  • angiogenic factors
  • longitudinal analysis
  • placental development
  • pregnancy
  • preterm birth

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