Cervical cytomegalovirus reactivation, cytokines and spontaneous preterm birth in Kenyan women

• Published in: Clinical and experimental immunology 2021-03, Vol.203 (3), p.472-479
• Main Authors: Begnel, E. R., Drake, A. L., Kinuthia, J., Matemo, D., Huang, M.‐L., Ásbjörnsdóttir, K. H., Chohan, V., Beima‐Sofie, K., John‐Stewart, G., Lehman, D., Slyker, J.
• Format: Article
• Language: English
• Subjects: Adult; Birth; Case-Control Studies; Cervix; Cervix Uteri - metabolism; Cervix Uteri - virology; Cytokines; Cytokines - metabolism; Cytomegalovirus; Cytomegalovirus - physiology; Female; Gestational Age; Humans; Infant, Newborn; Inflammation; Kenya; Logistic Models; Original; Pregnancy; Pregnancy Trimester, Third; Premature birth; Premature Birth - physiopathology; preterm birth; Prospective Studies; sub‐Saharan Africa; Tumor necrosis factor; Tumor necrosis factor-TNF; Virus Activation - physiology; Virus Shedding - physiology; Young Adult
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/cei.13558

Cervical CMV shedding may increase risk of spontaneous preterm birth (sPTB) through the release of inflammatory cytokines in the cervix. Among 86 women who had a sPTB and 86 matched controls from western Kenya, cervical CMV levels were not significantly associated with sPTB but were significantly associated with higher levels of cervical levels of inflammatory cytokine interleukin‐6. Summary Genital cytomegalovirus (CMV) reactivation is common during the third trimester of pregnancy. We hypothesized that cervical CMV shedding may increase risk of spontaneous preterm birth (sPTB) through the release of inflammatory cytokines in the cervix. We conducted a nested case–control analysis to determine the relationship between CMV shedding and sPTB using data and samples from a prospective cohort study in western Kenya. Women who delivered between 28 + 0 and 33 + 6 weeks gestation were matched by gestational age at sample collection to controls who delivered ≥ 37 + 0 weeks. Levels of CMV DNA and interleukin (IL)‐1 beta (β), IL‐6, IL‐8 and tumor necrosis factor (TNF)‐α were measured in cervical swabs. We used conditional logistic regression to assess relationships between CMV shedding, cervical cytokine levels and sPTB. Among 86 cases and 86 matched controls, cervical CMV levels were not significantly associated with sPTB [odds ratio (OR) = 1·23, 95% confidence interval (CI) = 0·59–2·56], but were significantly associated with higher levels of cervical IL‐6 (β = 0·15, 95% CI = 0·02–0·29) and TNF‐α (β = 0·14, 95% CI = 0·01–0·27). In univariate analysis, higher odds of sPTB was associated with higher cervical IL‐6 levels (OR = 1·54, 95% CI = 1·00–2·38), but not with other cervical cytokines. In this cohort of Kenyan women, we did not find a significant association between cervical CMV shedding and sPTB before 34 weeks.