Regulatory Cytokine Expression and Preterm Birth: Case-Control Study Nested in a Cohort

Thaís Basso de Brito Pereira; Erika Barbara Abreu Fonseca Thomaz; Flávia Raquel Fernandes do Nascimento; Ana Paula Silva de Azevedo Dos Santos; Rosângela Lucena Fernandes Batista; Heloisa Bettiol; Ricardo de Carvalho Cavalli; Marco Antônio Barbieri; Antônio Augusto Moura da Silva

doi:10.1371/journal.pone.0158380

Regulatory Cytokine Expression and Preterm Birth: Case-Control Study Nested in a Cohort

PLoS One. 2016 Aug 3;11(8):e0158380. doi: 10.1371/journal.pone.0158380. eCollection 2016.

Authors

Thaís Basso de Brito Pereira¹, Erika Barbara Abreu Fonseca Thomaz², Flávia Raquel Fernandes do Nascimento³, Ana Paula Silva de Azevedo Dos Santos³, Rosângela Lucena Fernandes Batista², Heloisa Bettiol⁴, Ricardo de Carvalho Cavalli⁵, Marco Antônio Barbieri⁴, Antônio Augusto Moura da Silva²

Affiliations

¹ Graduate Program in Public Health, Federal University of Maranhão, São Luís, Maranhão, Brazil.
² Department of Public Health, Graduate Program in Public Health, Federal University of Maranhão, São Luís, Maranhão, Brazil.
³ Department of Pathology, Graduate Program in Health Sciences, Federal University of Maranhão, São Luís, Maranhão, Brazil.
⁴ Department of Puericulture and Pediatrics, Graduate Program in Child and Adolescent Health, São Paulo University, Ribeirão Preto, São Paulo, Brazil.
⁵ Department of Gynecology and Obstetrics, São Paulo University, Ribeirão Preto, São Paulo, Brazil.

Abstract

Background: Currently known risk factors explain only a small fraction of preterm birth (PTB). Previous PTB is one of the most important predictors. However, this information is not available in primiparous women. Few studies have looked at associations between regulatory cytokine expression (RCE) and PTB and the results are conflicting.

Objective: To investigate the association of RCE-Interleukin 10 (IL-10) and Transforming Growth Factor β (TGF-β)-with PTB, and to assess whether bacterial vaginosis (BV) is involved in this relationship.

Methods: This was a case-control study nested in a prospective cohort-called BRISA. Women with singleton pregnancies were interviewed from 22 to 25 weeks of gestational age (GA). Women were recruited from health services in São Luís, Brazil. A blood sample was collected and gynecological examination was performed. Serum IL-10 and TGF-β were determined using cytometric bead array. Nugent score >7 and/or the presence of clue cells were used for BV diagnosis. All PTB estimated by ultrasound dating performed before 20 weeks of gestational age were considered cases. Controls were selected by simple random sampling from the rest of the cohort, at a 2:1 ratio. Different models were tested, according to the main independent variable. Odds ratios (OR) and 95% confidence intervals (95%CI) were estimated by regression analyses.

Results: The study included 327 pregnant women, 109 cases and 218 controls. No associations were found between BV and PTB (P = 1.44; 95%CI: 0.51-3.77). Low levels of IL-10 (OR = 2.92 95%CI: 1.38-6.16) or TGF-β (OR = 16.90 95%CI: 6.42-44.51) or both simultaneously (OR = 77.16 95%CI: 7.99-744.88) were associated with increasing odds of PTB, even after adjustment for confounding.

Conclusion: Decreased RCE is a risk factor for PTB. This relationship, however, is not triggered by the presence of BV. Low IL-10/TGF-β levels from 22 to 25 weeks of GA could be used as early predictors of PTB. We suggest monitoring of these RCE, especially among primiparous women, for whom history of previous PTB is not available.

MeSH terms

Adult
Brazil / epidemiology
Case-Control Studies
Female
Humans
Interleukin-10 / metabolism*
Odds Ratio
Pregnancy
Pregnancy Complications, Infectious / epidemiology*
Pregnancy Trimester, Second
Premature Birth / epidemiology*
Premature Birth / immunology
Prospective Studies
Risk Factors
Transforming Growth Factor beta / metabolism*
Vaginosis, Bacterial / epidemiology*
Young Adult

Substances

IL10 protein, human
Transforming Growth Factor beta
Interleukin-10

Grants and funding

This work was supported by the Foundation for Research and Scientific Development of Maranhão (FAPEMA, PRONEX number 001/2007; Productivity grant BEPP-03728/15; and Support for publishing articles, grant number 003/2016) and National Counsel of Technological and Scientific Development (CNPq), by productivity grant. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.