Mid-pregnancy levels of angiogenic markers as indicators of pathways to preterm delivery

Abstract

Objective: To determine whether mid-pregnancy levels of angiogenic markers were associated with increased risk of preterm delivery (PTD). Methods: We studied a subcohort from the Pregnancy Outcomes and Community Health Study for whom mid-pregnancy angiogenic markers (soluble fms-like tyrosine kinase-1 [sFlt-1], soluble endoglin [sEng] and placental growth factor [PlGF]) and covariate data were available (N = 1301). Angiogenic marker levels were grouped as high/not high (sFlt-1 and sEng), low/not low (PlGF) and high/intermediate/low (sFlt-1). Associations between levels of angiogenic markers and PTD/PTD subtype were determined for women who were nonsmokers during pregnancy (N = 933). Results: Low PlGF and high sEng were associated with medically-indicated PTD and PTD <35 weeks, largely due to preeclampsia (PE). Excluding PE and small-for-gestational-age infants, low sFlt-1 was positively associated with medically-indicated PTD. Conclusions: Among nonsmokers, mid-pregnancy levels of angiogenic markers may mark multiple pathways leading to PTD, only one attributable to PE.

Keywords::

• Endoglin
• placental growth factor
• preeclampsia
• small-for-gestational age
• soluble fms-like tyrosine kinase-1

Acknowledgement

C.B.H is supported by grants from The March of Dimes Foundation (20FY01-38 and 20-FY04-37), National Institute of Child Health and Human Development and the National Institute of Nursing Research (R01 HD34543), Thrasher Research Foundation (Grant 02816-7), Diabetes UK (Grant RD 05-0003099) and The Centers for Disease Control and Prevention (Grant U01 DP000143-01). R.S.M. was supported by an Institutional T32 grant (T32 HD046377) in Perinatal Epidemiology awarded by Michigan State University. S.R. is supported by a Harvard Diversity and Community Partnership Faculty Fellowship Award. S.A.K is an investigator of the Howard Hughes Medical Institute.

Declaration of Interest: S.A.K would like to disclose the following: He is a co-inventor on multiple patents related to angiogenic markers for use in preeclampsia. He also reports serving as a consultant to Beckman Coulter and Roche Diagnostics and having financial interest in Aggamin LLC. None of the other co-authors have any declarations of interest.