Pregnancy-induced changes in immune protection of the genital tract: defining normal

Abstract

Objective: Both the state of pregnancy as well as disruption of vaginal flora and immune mediators may increase the risk of human immunodeficiency virus-1 acquisition. The objective of this study was to define immune changes in lower genital and systemic immunity associated with normal pregnancy.

Study design: This prospective cohort enrolled low-risk pregnant and nonpregnant women ages 18-35 years. Pregnant women at <14 weeks and nonpregnant women in follicular phase of the menstrual cycle were included. Cervical and vaginal fluid was collected. Concentrations of immune mediators were measured using enzyme-linked immunosorbent assay-based methods or multiplex immunoassay. Samples were inoculated onto various culture media allowing for growth of Lactobacillus species, Gardnerella vaginalis, Escherichia coli, Enterococcus species, anaerobic gram-negative rods, Candida, Staphylococcus aureus, Ureaplasma species, and Mycoplasma hominis. Concentrations of immune mediators and vaginal colonization frequencies were compared between the pregnant and nonpregnant groups.

Results: Genital tract concentration of interleukin-1β was higher during pregnancy compared to nonpregnant participants. Serum C-reactive protein concentrations were higher in all trimesters of pregnancy. Concentrations of secretory leukocyte protease inhibitor did not differ between groups. Lactobacillus was more commonly isolated from vaginal cultures of nonpregnant participants (100% vs 70.2%, P = .02). Identification of Candida, G vaginalis, M hominis, and S aureus was common and not different between groups. Ureaplasma species was isolated from >60% pregnant participants.

Conclusion: The proinflammatory cytokine, interleukin-1β, as well as the systemic marker of inflammation, C-reactive protein, are increased during pregnancy. The impact of these proinflammatory changes during pregnancy deserves further study.

Figure 1. Scatterplot of vaginal concentration of IL-1β and serum CRP in pregnant and non-pregnant women

a. Levels of IL-1β reported in pg/nl. The Y-axis has been transformed to logarithmic scale in order to allow better comparison among groups. A statistically significant difference was noted between groups during the first trimester and the postpartum period (p = 0.008 and p = 0.04, respectively). b. Serum CRP levels reported in ng/L. A statistically significant difference was noted between groups during the first, second and third trimester (p = 0.005, p < 0.0001 and p = 0.03, respectively).