TY - JOUR
T1 - Preterm Delivery as a Unique Pathophysiologic State Characterized by Maternal Soluble FMS-Like Tyrosine Kinase 1 and Uterine Artery Resistance During Pregnancy
T2 - A Longitudinal Cohort Study
AU - Straughen, Jennifer K.
AU - Misra, Dawn P.
AU - Helmkamp, Laura
AU - Misra, Vinod K.
N1 - Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: VKM was supported by a Doris Duke Clinical Scientist Development Award (Grant 2007092) and a National Institutes of Health Mentored Scientist Award (K08-HD045609). The Michigan Clinical Research Unit which was supported by a Clinical and Translational Science Award grant number UL1RR024986 from the National Institutes of Health. JKS was supported by a postdoctoral award from Wayne State University.
Publisher Copyright:
© 2017, © The Author(s) 2017.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
KW - Doppler ultrasound
KW - Flt1 protein
KW - angiogenic factors
KW - longitudinal analysis
KW - placental development
KW - pregnancy
KW - preterm birth
UR - http://www.scopus.com/inward/record.url?scp=85033376212&partnerID=8YFLogxK
U2 - 10.1177/1933719117698574
DO - 10.1177/1933719117698574
M3 - Article
C2 - 28335685
AN - SCOPUS:85033376212
SN - 1933-7191
VL - 24
SP - 1583
EP - 1589
JO - Reproductive Sciences
JF - Reproductive Sciences
IS - 12
ER -