Kartik K Venkatesh1, David E Cantonwine2, Kelly Ferguson3, Melanie Arjona2, John D Meeker4, Thomas F McElrath2. 1. Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, MA, USA. kvenkatesh@partners.org. 2. Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, MA, USA. 3. National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. 4. University of Michigan School of Public Health, Ann Arbor, MI, USA.
Abstract
PROBLEM: We assess whether inflammatory and oxidative stress markers early in pregnancy are associated with decreasing cervical length in the second trimester. METHOD OF STUDY: This is a secondary analysis of a nested case-control study of preterm birth conducted at a tertiary care center from 2006 to 2008. Plasma inflammatory markers included the following: interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), and C-reactive protein (CRP); and urine oxidative stress markers included the following: 8-hydroxydeoxyguanosine (8-OHdG) and 8-isoprostane, measured at two study visits (median 10 and 18 weeks of gestation). The primary outcome was cervical length<10th percentile measured between 16 and 24 weeks of gestation. Logistic regression models were used, adjusting for body mass index, age, race, parity, tobacco use, education, and gestational age at cervical length measurement. RESULTS: Among 384 observed women, the 10th percentile cervical length was 3.0 cm. IL-10 levels were significantly higher among women with a cervical length<10th percentile compared to women with a longer cervix (mean IL-10: 95.5 vs 25.8 pg/mL, P<.01). Similarly, IL-6 levels were significantly higher among women with a cervical length<10th percentile (mean IL-6: 25.2 vs 4.3 pg/mL, P<.01). After controlling for potential confounders, an increase in IL-10 was significantly associated with a cervical length<10th percentile at both 10 and 18 weeks (adjusted odd ratio [AOR]: 1.74; 95% CI: 1.18-2.58; P=.005). At 18 weeks, only IL-6 was also significantly associated with a cervical length<10th percentile (AOR: 1.54; 95% CI: 1.11-2.13; P=.009). Other inflammatory biomarkers, including CRP, IL-1β, TNF-α, and oxidative stress biomarkers, 8-OHdG and 8-isoprostane, were not associated with cervical length. CONCLUSION: There was a significant association between the cytokines IL-6 and IL-10 early in pregnancy and decreased cervical length, suggesting an imbalance of immune regulation could impact cervical length.
PROBLEM: We assess whether inflammatory and oxidative stress markers early in pregnancy are associated with decreasing cervical length in the second trimester. METHOD OF STUDY: This is a secondary analysis of a nested case-control study of preterm birth conducted at a tertiary care center from 2006 to 2008. Plasma inflammatory markers included the following: interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), and C-reactive protein (CRP); and urine oxidative stress markers included the following: 8-hydroxydeoxyguanosine (8-OHdG) and 8-isoprostane, measured at two study visits (median 10 and 18 weeks of gestation). The primary outcome was cervical length<10th percentile measured between 16 and 24 weeks of gestation. Logistic regression models were used, adjusting for body mass index, age, race, parity, tobacco use, education, and gestational age at cervical length measurement. RESULTS: Among 384 observed women, the 10th percentile cervical length was 3.0 cm. IL-10 levels were significantly higher among women with a cervical length<10th percentile compared to women with a longer cervix (mean IL-10: 95.5 vs 25.8 pg/mL, P<.01). Similarly, IL-6 levels were significantly higher among women with a cervical length<10th percentile (mean IL-6: 25.2 vs 4.3 pg/mL, P<.01). After controlling for potential confounders, an increase in IL-10 was significantly associated with a cervical length<10th percentile at both 10 and 18 weeks (adjusted odd ratio [AOR]: 1.74; 95% CI: 1.18-2.58; P=.005). At 18 weeks, only IL-6 was also significantly associated with a cervical length<10th percentile (AOR: 1.54; 95% CI: 1.11-2.13; P=.009). Other inflammatory biomarkers, including CRP, IL-1β, TNF-α, and oxidative stress biomarkers, 8-OHdG and 8-isoprostane, were not associated with cervical length. CONCLUSION: There was a significant association between the cytokines IL-6 and IL-10 early in pregnancy and decreased cervical length, suggesting an imbalance of immune regulation could impact cervical length.
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