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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

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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 I (sFltI), 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 sFltI were determined using solidphase 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). sFltI was stable through 21 3/7 weeks of gestation and then increased rapidly; women who delivered preterm had significantly higher sFltI levels in the third trimester (P =.04). The relationship between uterine artery RI and sFltI from the prior visit was significantly different between the groups (P < .0001). For term deliveries, higher sFltI 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 sFltI 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.

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Authors and Affiliations

  1. Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA

    Jennifer K. Straughen PhD

  2. Department of Family Medicine and Public Health Sciences, The Wayne State University School of Medicine, Detroit, MI, USA

    Dawn P. Misra PhD & Laura Helmkamp MS

  3. Department of Pediatrics, Division of Genetic, Genomic, and Metabolic Disorders, Children’s Hospital of Michigan, The Wayne State University School of Medicine, 3950 Beaubien Blvd, Detroit, MI, 48201, USA

    Vinod K. Misra MD, PhD

Authors
  1. Jennifer K. Straughen PhD
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  2. Dawn P. Misra PhD
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  3. Laura Helmkamp MS
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  4. Vinod K. Misra MD, PhD
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Correspondence to Vinod K. Misra MD, PhD.

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Straughen, J.K., Misra, D.P., Helmkamp, L. et al. 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. Reprod. Sci. 24, 1583–1589 (2017). https://doi.org/10.1177/1933719117698574

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