Early vs delayed amniotomy following transcervical Foley balloon in the induction of labor: a randomized clinical trial.

BACKGROUND: The optimal timing of amniotomy during labor induction is a topic of ongoing debate due to the potential risks associated with both amniotomy and prolonged labor. As such, individuals in the field of obstetrics and gynecology must carefully evaluate the associated benefits and drawbacks of this procedure. While amniotomy can expedite the labor process, it may also lead to complications such as umbilical cord prolapse, fetal distress, and infection. Therefore, a careful and thorough examination of the risks and benefits of amniotomy during labor induction is essential in making an informed decision regarding the optimal timing of this procedure. OBJECTIVE: This study aimed to determine if an amniotomy within 2 hours after Foley balloon removal reduced the duration of active labor and time taken to achieve vaginal delivery when compared with an amniotomy ≥4 hours after balloon removal among term pregnant women who underwent labor induction. STUDY DESIGN: This was an open-label, randomized controlled trial that was conducted at a single academic center from October 2020 to March 2023. Term participants who were eligible for preinduction cervical ripening with a Foley balloon were randomized into 2 groups, namely the early amniotomy (rupture of membranes within 2 hours after Foley balloon removal) and delayed amniotomy (rupture of membranes performed more than 4 hours after Foley balloon removal) groups. Randomization was stratified by parity. The primary outcome was time from Foley balloon insertion to active phase of labor. Secondary outcomes, including time to delivery, cesarean delivery rates, and maternal and neonatal complications, were analyzed using intention-to-treat and per-protocol analyses. RESULTS: Of the 150 participants who consented and were enrolled, 149 were included in the analysis. In the intention-to-treat population, an early amniotomy did not significantly shorten the time between Foley balloon insertion and active labor when compared with a delayed amniotomy (885 vs 975 minutes; P=.08). An early amniotomy was associated with a significantly shorter time from Foley balloon placement to active labor in nulliparous individuals (1211; 584-2340 vs 1585; 683-2760; P=.02). When evaluating the secondary outcomes, an early amniotomy was associated with a significantly shorter time to active labor onset (312.5 vs 442.5 minutes; P=.02) and delivery (484 vs 587 minutes; P=.03) from Foley balloon removal with a higher rate of delivery within 36 hours (96% vs 85%; P=.03). Individuals in the early amniotomy group reached active labor 1.5 times faster after Foley balloon insertion than those in the delayed group (hazard ratio, 1.5; 95% confidence interval, 1.1-2.2; P=.02). Those with an early amniotomy also reached vaginal delivery 1.5 times faster after Foley balloon removal than those in the delayed group (hazard ratio, 1.5; 95% confidence interval, 1-2.2; P=.03). A delayed amniotomy was associated with a higher rate of postpartum hemorrhage (0% vs 9.5%; P=.01). No significant differences were observed in the cesarean delivery rates, length of hospital stay, maternal infection, or neonatal outcomes. CONCLUSION: Although an early amniotomy does not shorten the time from Foley balloon insertion to active labor, it shortens time from Foley balloon removal to active labor and delivery without increasing complications. The increased postpartum hemorrhage rate in the delayed amniotomy group suggests increased risks with delayed amniotomy.

Regulation of NF-kappaB activation and nuclear translocation by exogenous nitric oxide (NO) donors in TNF-alpha activated vascular endothelial cells.

Nitric oxide (NO) is a unique mediator which may promote or suppress inflammation. In this study, we examine the effect of exogenous NO on nuclear translocation of nuclear factor-kappa B (NF-kappaB) in quiescent human umbilical vein endothelial cells (HUVECs) subsequently activated by tumor necrosis factor-alpha (TNF-alpha), and in HUVECs previously activated by TNF-alpha, a model of vascular inflammation. Quiescent and activated HUVECs are exposed to exogenous NO donors of varying half-lives and the degree of NF-kappaB translocation into the nucleus determined by unique application of immunofluorescence image analysis in whole cells and correlative biochemical analysis of activated NF-kappaB proteins in the nucleus. NO donors with shorter half-lives are more effective in blocking the activation and translocation of NF-kappaB, when added to quiescent HUVECs prior to cellular activation by TNF-alpha. However, in previously activated HUVECs where NF-kappaB had relocated into the cytoplasm, addition of short half-life NO donors, but not TNF-alpha, induced re-translocation of NF-kappaB back into the nucleus sustaining the inflamed cell phenotype. These data suggest that NO as an inhibitor or activator of NF-kappaB may depend on the state of activation of vascular endothelial cells in which it contacts. Additionally, in activated cells, NO may modulate expression of NF-kappaB-dependent gene products, when cytokines are ineffective.

Analysis and quantitation of NF-kappaB nuclear translocation in tumor necrosis factor alpha (TNF-alpha) activated vascular endothelial cells.

Nuclear factor-kappa B (NF-kappaB) is a heterodimeric transcription factor typically composed of p50 and p65 subunits and is a pleiotropic regulator of various inflammatory and immune responses. In quiescent cells, p50/p65 dimers are sequestered in the cytoplasm bound to its inhibitors, the I-kappaBs, which prevent entry into the nucleus. Following cellular stimulation, the I-kappaBs are rapidly degraded, activating NF-kappaB. The active form of NF-kappaB rapidly translocates into the nucleus, binding to consensus sequences in the promoter/enhancer region of various genes, promoting their transcription. In human vascular endothelial cells activated with tumor necrosis factor-alpha, the activation and translocation of NF-kappaB is rapid, reaching maximal nuclear localization by 30 min. In this study, the appearance of NF-kappaB (p65 subunit, p65-NF-kappaB) in the nucleus visualized by immunofluorescence and quantified by morphometric image analysis (integrated optical density, IOD) is compared to the appearance of activated p65-NF-kappaB protein in the nucleus determined biochemically. The appearance of p65-NF-kappaB in the nucleus measured by fluorescence image analysis and biochemically express a linear correlation (R2 = 0.9477). These data suggest that localization and relative protein concentrations of NF-kappaB can be reliably determined from IOD measurements of the immunofluorescent labeled protein.