Inflammation During Pregnancy and its Association with Preterm Birth in Mexico City.

Abstract

Preterm birth (PTB) is a global public health problem with significant short and long term effects. Preterm babies are at increased risk of neonatal mortality and long term morbidity. While the etiology of PTB is poorly understood, inflammation occurs frequently in the pathway between several identified risk factors and PTB. Inflammation is also a normal part of pregnancy. Therefore, longitudinal measures are required to evaluate when and what markers of inflammation are normal and what predict PTB. The objectives of this dissertation were to evaluate the expression of inflammatory biomarkers (specifically cytokines) during pregnancy, and to explore whether patterns of cytokine secretion can identify women at risk of PTB. Using longitudinal data from a pregnancy cohort in Mexico City, this dissertation 1) characterized 20 cervico-vaginal cytokines obtained during gestation and described cytokine patterns among 181 term births; 2) evaluated differences in concurrently measured systemic and reproductive tract cytokines, and evaluated the associations between air pollution exposure and serum and cervico-vaginal cytokines among 104 term births; and 3) compared cytokine expression between women who delivered term (n=78) and preterm (n=12); and evaluated associations between individual and patterns of cervico-vaginal cytokines at points in pregnancy and PTB. Among term births, mean cervico-vaginal cytokine concentrations were stable during gestation within cytokines but varied across cytokines; inflammation severity varied. Cervico-vaginal cytokines were uncorrelated with serum cytokines; air pollution was positively associated with serum but inversely associated with cervico-vaginal cytokines. Finally, cervico-vaginal cytokine concentrations differed between term and PTBs, and the first trimester was most predictive of PTB. This dissertation increases understanding of the role of inflammation and PTB. The range of cytokines in normal pregnancy is wide, such that deviation from ‘mean’ concentrations is an insufficient marker of risk; the effects of air pollution on these levels may be specific to serum or the cervico-vaginal cavity. Finally, early differences in cytokine levels between term and preterm births may be useful for risk identification. Future studies should use other cytokine categories, particularly ratios and inflammatory milieu, to assess for deviations from homeostasis, especially during the first trimester, to evaluate for preterm risk.