Principal investigator: Enrique F. Schisterman, Ph.D.
Spontaneous abortion, defined as loss of clinically recognized pregnancy prior to 20 weeks of gestation, has been identified as the most common complication of pregnancy with estimated incidence among clinically recognized pregnancies of 15 to 25 percent. The possible role of immunologic factors has been considered as a molecular mechanism leading to pregnancy loss.

Cytokines and chemokines are proteins produced by immune cells and have been shown to regulate immune response. Departures from the molecular homeostasis may be affected by polymorphisms in the genes coding for cytokines, excessive generation of radical oxygen species (ROS), and the resultant oxidative stress on the system, as well as other factors. It has been proposed that imbalances in cytokine levels may be associated with loss of pregnancy. Though such an effect is considered to be due to an altered T-helper type 1 (Th1) to Th2 ratio, the association has not been consistently observed.

The complex pleiotropic nature of cytokines has complicated their use in epidemiologic studies. Investigations of targeted individual cytokines in small samples have observed alterations of production in pregnancy, the broader picture of cytokine and chemokine activity on pregnancy and pregnancy loss has not been assessed in a large study sample. Additionally, advancements in laboratory assay technology allow for concurrent assessment of larger numbers of cytokines that provide information regarding individual levels as well as the relative levels of Th1 and Th2 type cytokines.

The goal of this study is to further elucidate the association between circulating levels of cytokines, chemokines, and spontaneous pregnancy loss. Achieving a better understanding of these molecular factors in spontaneous abortion is an important step in the development of screening tools or even interventions.
 
DESPR Collaborators

· Aiyi Liu, Ph.D.
· Mark A. Klebanoff, M.D.,M.P.H.

Selected Publications

Whitcomb BW, Schisterman EF, Klebanoff MA, Flaws JA, Luo X, & Chegini N. (In press). Circulating Cytokine levels in pregnancy; Thrombopoietin is elevated in spontaneous abortion. Fertility and Sterility.

Whitcomb BW, Schisterman EF, Klebanoff MK, Flaws JA, Luo X, & Chegini N. (2007). Circulating chemokine levels and miscarriage. American Journal of Epidemiology, 166:323-331.  [Abstract]