Progesterone effects on vaginal cytokines in women with a history of preterm birth

Abstract

ObjectiveTo determine the effect of intramuscular progesterone on the vaginal immune response of pregnant women with a history of prior preterm birth.MethodsA prospective, cohort study of women at 11–16 weeks gestation, ≥18 years of age, and carrying a singleton pregnancy was conducted from June 2016 to August 2017 after IRB approval. Women in the progesterone arm had a history of preterm birth and received weekly intramuscular 17-hydroxyprogesterone caproate. Controls comprised of women with healthy, uncomplicated pregnancies. Excluded were women with vaginitis, diabetes mellitus, hypertension, or other chronic diseases affecting the immune response. A vaginal wash was performed at enrollment, at 26–28 weeks, and at 35–36 weeks gestation. Samples underwent semi-quantitative detection of human inflammatory markers. Immunofluorescence pixel density data was analyzed and a P value <0.05 was considered significant.ResultsThere 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 to 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 progesterone arm and controls, respectively.ConclusionThere is an increased cytokine presence in vaginal washings of women at risk for preterm birth which appears to be modified following the administration of 17- hydroxyprogesterone caproate to levels similar to healthy controls.

Pregnant Mexican American Biopsychosocial/Cultural risks for adverse infant outcomes

“…Multiple known biological factors are predictive of the risk of PTB. Based on earlier results related to the role of inflammation and PTB, progesterone is important as it counter regulates inflammation in pregnancy (Garry et al., 2018; Ruiz et al., 2008). This reproductive hormone is essential for pregnancy maintenance and is currently extensively used to prevent PTB (Navathe & Berghella, 2016; Ruiz et al., 2008).…”

The Feasibility of Cervical Elastography in Predicting Preterm Delivery in Singleton Pregnancy with Short Cervix Following Progesterone Treatment

“…Progesterone prevents cervical softening by modifying cytokines, regulating the presence of macrophages in the stroma and altering the extracellular matrix in the cervix [ 20 , 21 ]. Therefore, it is widely used in clinical practice to prevent PTD in pregnant women with prior PTD or a short cervix at the mid-trimester [ 2 , 19 , 22 , 28 , 29 , 30 ]. However, predicting PTD by differentiating women who have a good response to progesterone from those who do not respond well, eventually leading to PTD, is difficult.…”

Cervical cerclage for Pregnant Women at High-risk of Recurrent Preterm Birth can act beyond its Mechanical Action

“…Similarly, Ashford et al [23] documented that the levels of IL-1α, IL-6, TNF-α can be used as predicative biomarkers for PTB. Also, Park et al [29] reported that plasma and AF IL-6 levels had an overall diagnostic performance to predict imminent PTB and Garry et al [30] reported increased presence of IL-1α, IL-1β, IL-2 and IL-13 in vaginal washings of women at risk for PTB. Moreover, Liu et al [31] found high AF TNF-α and IL-8 levels before CC affect pregnancy outcome in women with CI and levels higher than 3.58 ng/ml and 0.105 ng/ ml of IL-8 and TNF-α, respectively could predict perinatal death of the infants.…”