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

Abstract

BackgroundCurrently 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.ObjectiveTo 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.MethodsThis 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.ResultsThe 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.ConclusionDecreased 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.

Human Placental Transcriptome Reveals Critical Alterations in Inflammation and Energy Metabolism with Fetal Sex Differences in Spontaneous Preterm Birth

“…Both TGF-β and TOB play critical roles in maintaining a normal pregnancy, and low levels of TGF-β are associated with an increased risk of preterm birth [ 24 , 25 , 26 ]. Both TGF-β and TOB signaling were predicted to be inhibited in male SPTB placentas (z-score = −0.82 and −2.00, respectively).…”

Regulatory B Cells Are Decreased and Impaired in Their Function in Peripheral Maternal Blood in Pre-term Birth

“…TD, term delivery; PTB, preterm birth; *p < 0.05; **p < 0.005; ***p < 0.001. was previously reported that PTB was associated with IL-10 gene polymorphisms and decreased IL-10 mRNA (20). Independent of the presence of a bacterial vaginosis, decreased IL-10 levels at mid-pregnancy were suggested to be useful as an early predictor of PTB (21). Moreover, stimulation of maternal PBMCs from women with recurrent PTB, PPROM, preeclampsia, or IUGR resulted in lower levels of IL-10 compared to gestational age-matched, healthy pregnant women (22,23).…”

Circulating MicroRNAs in the Second Trimester From Pregnant Women Who Subsequently Developed Preeclampsia: Potential Candidates as Predictive Biomarkers and Pathway Analysis for Target Genes of miR-204-5p

“…The study was approved by the Institutional Review Board of the University of São Paulo at Ribeirão Preto (reference 4116/2008), according to the declaration of Helsinki, and all participants provided written informed consent. This case-control study is based in a prospective cohort, Brazilian Ribeirão Preto and São Luís prenatal cohort (BRISA) (da Silva et al, 2014 ; Pereira et al, 2016 ; Caldeira-Dias et al, 2019 ). The schematic diagram of the study workflow is shown in Figure 1 .…”