Progesterone Effects On Vaginal Cytokines In Women With A History Of Preterm Birth

INTRODUCTION: To evaluate the vaginal immune response of intramuscular progesterone supplementation in pregnant women at risk for preterm birth compared to normal healthy pregnant controls. METHODS: A prospective, cohort study from June 2016 to August 2017 included women at a gestational age 11-16 weeks, >18 years of age, and a singleton pregnancy after IRB approval. Women in the progesterone arm had a history of preterm birth and received intramuscular 17-hydroxyprogesterone caproate. Controls were comprised of healthy, uncomplicated pregnancies. Exclusion criteria were vaginitis, diabetes mellitus, hypertension, and other chronic diseases affecting the immune response. A vaginal wash was performed on entry to the study, at 26 to 28 weeks, and at 35-36 weeks. Samples underwent semi-quantitative detection of human inflammatory markers. Immunofluorescence pixel density data was analyzed and P value <0.05 was considered significant. RESULTS: There were 39 women included, 10 with a prior preterm birth and 29 controls. The baseline demographics and pregnancy outcomes for both groups were similar in age, parity, race, BMI, gestational age at delivery, mode of delivery, and birth weight. Enrollment cytokines in women with a prior preterm birth, including IL-1 alpha (39.2+25.1% versus 26.1+13.2%; P=0.04), IL-1 beta (47.9+26.4% versus 24.9+17%; P<0.01), IL-2 (16.7+9.3% versus 11.3+6.3%; P=0.03), and IL-13 (16.9+12.4% versus 8.2+7.4%; P=0.01), were significantly elevated compared with controls. In the third trimester the cytokine densities for IL-1 alpha (26.0+18.2% versus 22.3+12.0%; P=0.49), IL-1 beta (31.8+15.9% versus 33.1+16.8%; P=0.84), IL-2 (10.0+8.4% versus 10.9+5.9%; P=0.71), and IL-13 (9.1+5.9% versus 10.0+6.5%; P=0.71) were all statistically similar between the prior preterm birth group and the healthy controls, respectively. CONCLUSION: There is an increased cytokine presence in vaginal washings of women at risk for preterm birth which appears to be modified following administration of 17- hydroxyprogesterone caproate compared with healthy controls.