Objective The aim of the study is to examine clinical and demographic factors associated with trial of labor (TOL) among women with twin gestations eligible for a vaginal delivery. Study Design This was a population-based cohort study of women giving birth to twin gestations in the United States (2012–2014). Inclusion criteria for the analysis included live births greater than 23 weeks' gestation and a cephalic presenting twin. Women with prior cesarean delivery were excluded. Women were categorized by whether they underwent a TOL. Clinical and demographic characteristics associated with TOL status were evaluated using multivariable logistic regression analyses. Secondary analyses with stratification by parity and by second twin presentation were performed. Results Of 90,000 women eligible for inclusion, a minority (39.3%) underwent TOL. Women who had a greater gestational age at delivery were more likely to have a TOL. In contrast, several demographic factors were associated with decreased likelihood of TOL, including maternal age >35 years and identifying as Hispanic or Asian compared with non-Hispanic White. No differences in odds of TOL were observed for women who were identified as non-Hispanic Black versus non-Hispanic White, nor were other demographic factors such as marital status, insurance status, or educational attainment associated with undergoing TOL. Clinical factors associated with decreased odds of TOL included nulliparity, obesity, and hypertensive disorders of pregnancy. Results did not substantively change when stratified by parity or second twin presentation, nor did findings differ in the subgroup who delivered at 32 weeks of gestation or greater. Conclusion In this large population of women with twins who were eligible for a TOL, a minority of individuals attempted a vaginal delivery. Demographic and clinical factors such as older maternal age, Asian or Hispanic racial or ethnic identification, nulliparity, and obesity are associated with decreased odds of undergoing TOL. Key Points
Background: In humans, methane (CH4) is exclusively produced by the intestinal microbiota and has been implicated in several conditions including cardiovascular disease. After microbial production of CH4 in the gut, it steadily crosses into the systemic circulation and reaches the lungs where it can be detected in the exhaled breath, as a surrogate measure for intestinal CH4 production. Recent reports have shown an association between CH4 and vagal dysfunction as well as the inhibition of CH4 activity on ileal contractions with atropine, suggesting its action on the parasympathetic nervous system. Given these findings we hypothesized that CH4 may be affecting resting heart rate based on the potential effect of CH4 on the vagus nerve. Objectives: Given its possible role in the parasympathetic nervous system, we aimed to study the relationship between breath CH4 and resting heart rate (HR) in humans. Additionally, we performed a longitudinal study analyzing the change in HR and its association to breath CH4 over time. Methods: First, we reviewed 1,126 subjects and compared HR in subjects with detectable and undetectable breath CH4. Second, we performed a post-hoc analysis of a randomized control trial to compare the change in HR for those who had an increase in breath CH4 vs those that had a decrease in breath CH4 over 14 weeks. Lastly, we assessed whether a larger decrease in CH4 is associated with a larger increase in HR over time. Results: In the retrospective cohort, subjects with detectable CH4 had a lower HR compared to those with undetectable CH4 (73.0±0.83 vs 76.0±0.44 beats/min; p=0.01). In the post-hoc analysis, a decrease in CH4 over time was associated with an increase in heart rate (median ∆ = 6.5 ± 8.32 beats/min, p=0.0006). Lastly, we demonstrated a biological gradient whereby a larger drop in CH4 is associated with a greater increase in heart rate (R= -0.31, p=0.03). Conclusion: Our findings suggest a potential role for the microbiome (and specifically CH4 from methanogens) to regulate heart rate. Considering these findings, mechanistic studies are warranted to further investigate this potential novel microbiome-neurocardiac axis.
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