Timing of Cervico-Vaginal Cytokine Collection during Pregnancy and Preterm Birth: A Comparative Analysis in the PRINCESA Cohort

Abstract

Preterm birth (PTB), defined as birth before 37 completed weeks of gestation, is a major cause of infant morbidity and mortality. Inflammation is an important component in the physiopathologic pathway leading to PTB but results from cross-sectional studies on associations between inflammation, as measured by cytokines, and PTB are inconsistent. Timing of cytokine measurement during pregnancy varies between studies and may contribute to inconsistent findings. We investigated the effects of timing on associations between 16 cervico-vaginal cytokines (Eotaxin, IL-10, IL-12p40, IL-17, IL-1RA, sIL-2rα, IL-1a, IL-1β, IL-2, IL-6, IP-10, MCP-1, MIP-1α, MIP-1β, TNFα, and VEGF) and PTB among 90 women throughout pregnancy. We used logistic regression to compare associations between concentrations of cervico-vaginal cytokines from periods in pregnancy and PTB. Trimester 1 cytokines had the strongest positive associations with PTB; for example, OR = 1.76 (95% confidence interval: 1.28, 2.42) for IL-6. Second and third trimester associations were weaker but largely positive. IL-1α was the only cytokine with a negative association (trimesters 2, 3 and overall pregnancy). Strong first trimester associations between cytokines and PTB suggest that measuring cytokines early in pregnancy may hold promise for early identification of PTB risk. Variations in cytokine measurement during pregnancy may contribute to inconsistencies among studies.

A Novel Predictive Machine Learning Model Integrating Cytokines in Cervical-Vaginal Mucus Increases the Prediction Rate for Preterm Birth

“…In this study, we first focused on the charactering the inflammatory cytokine profiles in cervical-vaginal mucus of pregnant women with high and low risk for PB, as classified according to the CL measured at the second trimester of gestation. In agreement with previous reports, a higher concentration of IL-2, IL-6, and IFN-γ was found in the cervical-vaginal samples of the high-risk group, and also a higher concentration of IL-1ra in the low-risk group [ 25 , 26 , 27 ].…”

A Novel Predictive Machine Learning Model Integrating Cytokines in Cervical-Vaginal Mucus Increases the Prediction Rate for Preterm Birth

“…In this study, we first focused on the charactering the inflammatory cytokine profiles in cervical-vaginal mucus of pregnant women with high and low risk for PB, as classified according to the CL measured at the second trimester of gestation. In agreement with previous reports, a higher concentration of IL-2, IL-6, and IFN-γ was found in the cervicalvaginal samples of the high-risk group, and also a higher concentration of IL-1ra in the low-risk group [25][26][27].…”

Prediction of spontaneous preterm birth using CCL2 and CXCL10 in maternal serum of symptomatic high-risk pregnant women: a prospective cohort study

“…Various studies examined the connection between CXCL10 and preterm birth. Levels of CXCL10 were increased in cases of preterm birth in the amnion fluid [ 50 , 51 ], the cervicovaginal fluid [ 52 ], the fetal membranes as well as the placenta [ 53 ]. The increase of CXCL10 at the maternal fetal interface is not specific for PTB and higher levels were detected in cases of preeclampsia [ 54 ], chorioamnionitis [ 55 ] and villous inflammation [ 56 ].…”