The rate of preterm delivery among African American (AA) women is 1.5 to 2.4 times higher than Caucasian (CS). The 2010 national public health goal is eliminating ethnic disparity in preterm delivery (PTD). Although the mechanism of PTD is unclear, infections are among the main ethnologic factors implicated. We propose here a unifying hypothesis by which infection and host factors may increase the risk of PTD among African Americans (AA). The fetus is a semiallogenic antigen that requires efficient protection from the maternal humoral immune system. Decay accelerating factor (DAF) is a protective host factor DAF is expressed in the feto-maternal interphase and its main function is protection from cytotoxic effect of autologous complement (c)attack. DAF expression is controlled by progesterone (P) and P was implicated in pregnancy losses. Infection upregulates nitric oxide (NO) and in turn NO downregulates DAF expression. Decreased DAF expression alters the protective quality of the feto-maternal interphase and may trigger complement mediated increases in proinflarnmatory tumor necrosis factor (TNF), and prostaglandin production resulting in PTL/PTD. We propose that both infection and biologic/genetic factors may contribute to the disturbances in the endocrine-NO-immune axis. Various factors in concert may act to alter the C/DAF ratio in the feto-maternal interface thereby leading to the activation of proinflammatory/prostaglandin pathway. The C cascade and TNF response occurs upon infection or vaginal colonization. Virulent E. coli is capable to display synergistic signaling via E.coli adhesin-host receptor and elicit aggressive cytokine responses. Although these factors may effect all women, AA are at higher risk due to an increased inherent capacity of rejection or hyperresponsiveness of alloantigens. The inherent differences may result in the observed PTD disparities between AA and CS. We propose to the following: 1. Characterize expression of DAF among AA and CS women undergoing elective pregnancy tennination, term and pretenn labor. 2. Characterize allelic polymorphism in the DAF Tcb, Cr(a-), and TNFA alleles and analyze possible association with infection, PTD and race. 3. Characterize genotypes of vaginal colonization isolates in patients with term and preterm delivery. The long-term goal of our project is to characterize mechanism of infection associated PTL/PTD and the role of the host and pathogen factors interacting at the urogenital interphase in birth outcome.

R01HD041687

2001-09-24

2005-09-30