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Cervicovaginal Cytokines to Predict the Onset of Normal and Preterm Labor: a Pseudo-longitudinal Study

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Abstract

Inflammatory processes associated with human parturition are still not completely understood, not only because the gap between inflammation and the onset of labor has been difficult to study but also because of the limited knowledge about the role of cervicovaginal fluid (CVF) cytokines during the sequence of labor. We aimed to determine whether CVF cytokines could predict the onset of normal and preterm labor. Chemokines and proinflammatory and anti-inflammatory cytokines in CVF were measured in a pseudo-longitudinal manner in healthy women between 12 and 41 weeks gestation with intact fetal membranes before and during the first stage of labor. Women were grouped into five stages, from the absence of uterine activity and cervical changes to regular uterine contractions with cervix dilation > 3 cm (active phase of labor). Of 144 women with spontaneous labor, 96 gave birth at term, 48 gave birth preterm, and both groups displayed similar cytokine concentrations. We found positive correlations between proinflammatory cytokines and the initial sequence of labor, using individual cytokines and score-based data by principal component analysis (IFN-γ, TNF-α, IL-1β, IL-6) as dependent variables. The risk of labor onset increased as the concentrations of IL-6 increased (hazard ratio = 202.09, 95% confidence interval = 24.57–1662.49, P < 0.001). The IL-6 concentration predicted the onset of labor within 12 days of sampling (area under the time-dependent ROC curve = 0.785, 95% confidence interval = 0.693–0.877). Here, we showed that regardless of gestational age, the onset of labor could be predicted by the IL-6 concentration in the CVF, since the initial sequence of spontaneous labor displayed an inflammatory response expressed by the increase in proinflammatory cytokines.

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Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

Funding for this project was provided by Fundación Gonzalo Río Arronte (S.633), SECTEI/253/2019 and Fundación Mexicana para la Salud (Proyecto Interinstitucional). DESC received fellowship (1046662) from the Mexican Council of Science and Technology (CONACyT).

Author information

Authors and Affiliations

  1. MD/PhD Program (PECEM), Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico

    Daniel Eduardo Sandoval-Colin

  2. Unidad de Vinculación de la Facultad de Medicina, UNAM at Instituto Nacional de Medicina Genómica, 14610, Mexico City, Mexico

    Daniel Eduardo Sandoval-Colin, Denisse Alejandra Picazo-Mendoza, Noemí Meraz-Cruz, Erika Chavira-Suárez & Felipe Vadillo-Ortega

  3. Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Mexico City, Mexico

    Myrna Souraye Godines-Enriquez, Aurora Espejel-Núñez & Jesús Jorge Beltrán-Montoya

  4. Secretaría de Salud del Gobierno de la Ciudad de México, Mexico City, Mexico

    Juan Carlos de la Cerda-Ángeles

  5. Instituto Nacional de Geriatría, Mexico City, Mexico

    Omar Yaxmehen Bello-Chavolla

  6. Biochemistry Department, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico

    Erika Chavira-Suárez & Felipe Vadillo-Ortega

  7. Department of Environmental Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA

    Felipe Vadillo-Ortega

Authors
  1. Daniel Eduardo Sandoval-Colin
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  2. Myrna Souraye Godines-Enriquez
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  8. Noemí Meraz-Cruz
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  9. Erika Chavira-Suárez
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  10. Felipe Vadillo-Ortega
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Corresponding author

Correspondence to Felipe Vadillo-Ortega.

Ethics declarations

Ethics Approval and Consent to Participate

This study was approved by the Health Ministry institutional IRB (Register 2010/010/3117, 9 August 2017) and by the INMEGEN IRB (12/2018/I) in accordance with the Declaration of Helsinki and the Guideline for Good Clinical Practices. All participants signed informed consent.

Consent for Publication

All authors agree to participate in this publication. This study does not include images or other personal or clinical details of participants that compromise anonymity. With their consent to participate, all patients have also signed a written consent to publish their data anonymously.

Competing Interests

The authors declare no competing interests.

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Sandoval-Colin, D.E., Godines-Enriquez, M.S., Espejel-Núñez, A. et al. Cervicovaginal Cytokines to Predict the Onset of Normal and Preterm Labor: a Pseudo-longitudinal Study. Reprod. Sci. 30, 221–232 (2023). https://doi.org/10.1007/s43032-022-01007-9

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  • DOI: https://doi.org/10.1007/s43032-022-01007-9

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