title: Regulatory Cytokine Expression and Preterm Birth: Case-Control Study Nested in a Cohort.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Graduate Program in Public Health, Federal University of Maranhão, São Luís, Maranhão, Brazil.
authors.forename: Thaís Basso de Brito
authors.initials: TB
authors.lastname: Pereira
authors.affiliation: Department of Public Health, Graduate Program in Public Health, Federal University of Maranhão, São Luís, Maranhão, Brazil.
authors.forename: Erika Barbara Abreu Fonseca
authors.initials: EB
authors.lastname: Thomaz
authors.affiliation: Department of Pathology, Graduate Program in Health Sciences, Federal University of Maranhão, São Luís, Maranhão, Brazil.
authors.forename: Flávia Raquel Fernandes do
authors.initials: FR
authors.lastname: Nascimento
authors.affiliation: Department of Pathology, Graduate Program in Health Sciences, Federal University of Maranhão, São Luís, Maranhão, Brazil.
authors.forename: Ana Paula Silva de Azevedo Dos
authors.initials: AP
authors.lastname: Santos
authors.affiliation: Department of Public Health, Graduate Program in Public Health, Federal University of Maranhão, São Luís, Maranhão, Brazil.
authors.forename: Rosângela Lucena Fernandes
authors.initials: RL
authors.lastname: Batista
authors.affiliation: Department of Puericulture and Pediatrics, Graduate Program in Child and Adolescent Health, São Paulo University, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Heloisa
authors.initials: H
authors.lastname: Bettiol
authors.affiliation: Department of Gynecology and Obstetrics, São Paulo University, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Ricardo de Carvalho
authors.initials: Rde C
authors.lastname: Cavalli
authors.affiliation: Department of Puericulture and Pediatrics, Graduate Program in Child and Adolescent Health, São Paulo University, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Marco Antônio
authors.initials: MA
authors.lastname: Barbieri
authors.affiliation: Department of Public Health, Graduate Program in Public Health, Federal University of Maranhão, São Luís, Maranhão, Brazil.
authors.forename: Antônio Augusto Moura da
authors.initials: AA
authors.lastname: Silva
mesh_terms: D000328:Adult; D001938:Brazil / Q000453:epidemiology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism*; D016017:Odds Ratio; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000453:epidemiology*; D011262:Pregnancy Trimester, Second; D047928:Premature Birth / Q000453:epidemiology* / Q000276:immunology; D011446:Prospective Studies; D012307:Risk Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D016585:Vaginosis, Bacterial / Q000453:epidemiology*; D055815:Young Adult
chemical_list: C508609:IL10 protein, human; D016212:Transforming Growth Factor beta; D016753:Interleukin-10