Ded into case (n = 109) and TAK-385 site control (n = 218) groups. S Lu , MA, Brasil. 2010?012. AZD1722MedChemExpress Tenapanor Variables Age (years) <20 20?4 35 Race/Skin colour White Not whitea Schooling (years) 9 Up to 8 Economic class A-B C D-E Marital status With a partner Without a partner Number of pregnancies Primigesta Multigesta Missing Previous preterm delivery No Yes (1 or more) Missing Hypertension during pregnancy No Yes Missing Elective cesarian section No Yes Missing Bacterial vaginosis during pregnancyc No Yes Missing Smoking during pregnancy No Only passive Active Missing Alcohol consumption during pregnancy No Yes Use of illicit drugs during pregnancy No 320 66.5 32.5 0.017e (Continued) 298 29 66.8 65.5 33.2 34.5 0.891d 274 43 8 2 66.8 65.1 75.0 33.2 34.9 25.0 232 40 55 0.924e 67.7 62.5 32.3 37.5 226 100 1 0.521d 74.8 49.0 25.2 51.0 252 73 2 <0.001d 71.8 50.7 28.2 49.3 259 65 3 0.001d 80.7 10.8 19.3 89.2 1 <0.001d 145 181 66.2 67.4 33.8 32.6 266 61 67.3 63.9 32.7 36.1 0.820dbn 38 264 25 58 268 46 281 63 220Control ( ) 68.4 68.9 40.0 65.5 67.2 58.7 68.0 58.7 66.4 79.Case ( ) 31.6 31.1 60.P-value 0.013d0.809d 34.5 32.8 0.216d 41.3 32.0 0.079d 41.3 33.6 20.5 0.7616dPLOS ONE | DOI:10.1371/journal.pone.0158380 August 3,6 /Regulatory Cytokine and Preterm BirthTable 1. (Continued) Variables Yes Missing DOI: 10.6084/m9.figshare.a b cn 6Control ( ) 16.Case ( ) 83.P-valueIncludes black, brown/mulatto, yellow/oriental. Economic class according to ABEP (Brazilian acronym for the Brazilian Association of Research Enterprises) 2009 criteria. Chi-square test. Fisher exact test.Using the Nugent criterion.d edoi:10.1371/journal.pone.0158380.tpresent study both for non-adjusted (OR = 13.16) and adjusted (OR = 18.35) analysis. When values above the median were attributed to all missing values, the non-adjusted (OR = 5.54) and adjusted (OR = 5.58) odds ratios continued to be significant.Discussion Principal findingsLow IL-10 and TGF- levels were risk factors for PTB. These changes, however, were not influenced by BV. This is the first report of associations between RCE in the plasma of healthy pregnant women in a nested case-control study conducted in Brazil, in which GA was estimated by US and cytokines were determined before PTB. This is also the first study to assess the joint associations of both regulatory cytokines with the occurrence of PTB. A few studies have related PTB with IL-10 and TGF- levels [1,3,4,10?2,17?9]. Some of these studies assessed spontaneous abortion in an animal [18] or human [19] model, and others determined the cytokines in the umbilical cord [10,11] or amniotic fluid [3], thus differing from the methodology employed in the present investigation, in which these regulatory cytokines were measured in the serum. Some involved a small sample size [1,17] and others investigated factors associated with PTB<35 weeks of GA [4,20] or included only pregnant women with a previous history of PTB [20]. Another difference was the time of cytokine determination, which ranged from 9?3 weeks of GA [1,4,12,17,20] or even occurred at birth [10,11]. Two studies have also identified an association between low serum IL-10 levels and increased odds of PTB in humans [12,20]. Recurrent PTB at less than 35 weeks of GA was associated with a lower production of IL-10 in the second trimester of pregnancy [20], suggesting that high IL-10 levels play a protective role against PTB. In contrast, some authors did not detect an association between serum IL-10 and PTB [4], while others [.Ded into case (n = 109) and control (n = 218) groups. S Lu , MA, Brasil. 2010?012. Variables Age (years) <20 20?4 35 Race/Skin colour White Not whitea Schooling (years) 9 Up to 8 Economic class A-B C D-E Marital status With a partner Without a partner Number of pregnancies Primigesta Multigesta Missing Previous preterm delivery No Yes (1 or more) Missing Hypertension during pregnancy No Yes Missing Elective cesarian section No Yes Missing Bacterial vaginosis during pregnancyc No Yes Missing Smoking during pregnancy No Only passive Active Missing Alcohol consumption during pregnancy No Yes Use of illicit drugs during pregnancy No 320 66.5 32.5 0.017e (Continued) 298 29 66.8 65.5 33.2 34.5 0.891d 274 43 8 2 66.8 65.1 75.0 33.2 34.9 25.0 232 40 55 0.924e 67.7 62.5 32.3 37.5 226 100 1 0.521d 74.8 49.0 25.2 51.0 252 73 2 <0.001d 71.8 50.7 28.2 49.3 259 65 3 0.001d 80.7 10.8 19.3 89.2 1 <0.001d 145 181 66.2 67.4 33.8 32.6 266 61 67.3 63.9 32.7 36.1 0.820dbn 38 264 25 58 268 46 281 63 220Control ( ) 68.4 68.9 40.0 65.5 67.2 58.7 68.0 58.7 66.4 79.Case ( ) 31.6 31.1 60.P-value 0.013d0.809d 34.5 32.8 0.216d 41.3 32.0 0.079d 41.3 33.6 20.5 0.7616dPLOS ONE | DOI:10.1371/journal.pone.0158380 August 3,6 /Regulatory Cytokine and Preterm BirthTable 1. (Continued) Variables Yes Missing DOI: 10.6084/m9.figshare.a b cn 6Control ( ) 16.Case ( ) 83.P-valueIncludes black, brown/mulatto, yellow/oriental. Economic class according to ABEP (Brazilian acronym for the Brazilian Association of Research Enterprises) 2009 criteria. Chi-square test. Fisher exact test.Using the Nugent criterion.d edoi:10.1371/journal.pone.0158380.tpresent study both for non-adjusted (OR = 13.16) and adjusted (OR = 18.35) analysis. When values above the median were attributed to all missing values, the non-adjusted (OR = 5.54) and adjusted (OR = 5.58) odds ratios continued to be significant.Discussion Principal findingsLow IL-10 and TGF- levels were risk factors for PTB. These changes, however, were not influenced by BV. This is the first report of associations between RCE in the plasma of healthy pregnant women in a nested case-control study conducted in Brazil, in which GA was estimated by US and cytokines were determined before PTB. This is also the first study to assess the joint associations of both regulatory cytokines with the occurrence of PTB. A few studies have related PTB with IL-10 and TGF- levels [1,3,4,10?2,17?9]. Some of these studies assessed spontaneous abortion in an animal [18] or human [19] model, and others determined the cytokines in the umbilical cord [10,11] or amniotic fluid [3], thus differing from the methodology employed in the present investigation, in which these regulatory cytokines were measured in the serum. Some involved a small sample size [1,17] and others investigated factors associated with PTB<35 weeks of GA [4,20] or included only pregnant women with a previous history of PTB [20]. Another difference was the time of cytokine determination, which ranged from 9?3 weeks of GA [1,4,12,17,20] or even occurred at birth [10,11]. Two studies have also identified an association between low serum IL-10 levels and increased odds of PTB in humans [12,20]. Recurrent PTB at less than 35 weeks of GA was associated with a lower production of IL-10 in the second trimester of pregnancy [20], suggesting that high IL-10 levels play a protective role against PTB. In contrast, some authors did not detect an association between serum IL-10 and PTB [4], while others [.