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The non-canonical NF-κB signaling may be a central integrator of a placental clock that governs the length of human pregnancy. We sought to identify fetal signals that could activate this NF-κB pathway in the placenta, and in turn, contribute to the onset of labor. Proteomics analysis of exosomes purified from fetal cord arterial blood revealed a total of 328 proteins, among which 48 were more significantly abundant (p < 0.01) in samples from women who delivered following elective Cesarean-section at term (39 to 40 weeks of estimated gestational age, EGA) compared to those who had elective Cesarean deliveries near term (35 to 36 weeks of EGA). Computational, crystal structural, and gene functional analyses showed that one of these 48 proteins, C4BPA, binds to CD40 of placental villous trophoblast to activate p100 processing to p52, and in turn, pro-labor genes. These results suggest that fetal C4BPA-induced activation of non-canonical NF-κB in human placenta may play a critical role in processes of term or preterm labor.

Women exposed to phthalates during pregnancy are at increased risk for delivering preterm, but the mechanism behind this relationship is unknown. Placental corticotropin-releasing hormone (CRH) and cyclooxygenase-2 (COX-2) are key mediators of parturition and are regulated by the non-canonical NF-kB (RelB/p52) signaling pathway. In this study, we demonstrate that one of the major phthalate metabolites, mono-(2-ethylhexyl)-phthalate (MEHP), increased CRH and COX-2 mRNA and protein abundance in a dose-dependent manner in primary cultures of cytotrophoblast. This was coupled with an increase in nuclear import of RelB/p52 and its association with the CRH and COX-2 promoters. Silencing of NF-kB inducing kinase, a central signaling component of the non-canonical NF-kB pathway, blocked MEHP-induced upregulation of CRH and COX-2. These results suggest a potential mechanism mediated by RelB/p52 by which phthalates could prematurely induce pro-labor gene activity and lead to preterm birth.

Pregnant women with mild chronic hypertension were randomly assigned to receive medication targeting a normal blood pressure (<140/90 mm Hg) or to receive no treatment unless severe hypertension (>160/105 mm Hg) developed. The incidence of adverse maternal and neonatal outcomes was significantly lower in the active-treatment group, without an increase in low birth weight.

Citation analysis is a bibliometric method that uses citation rates to evaluate research performance. This type of analysis can identify the articles that have shaped the modern history of obstetrics and gynecology (OBGYN). To identify and characterize top-cited OBGYN articles in the Institute for Scientific Information Web of Science's Science Citation Index Expanded and to compare top-cited OBGYN articles published in specialty OBGYN journals with those published in nonspecialty journals. Cross-sectional bibliometric analysis of top-cited articles that were indexed in the Science Citation Index Expanded from 1980 to 2018. The Science Citation Index Expanded was queried using search terms from the American Board of Obstetrics and Gynecology's 2018 certifying examination topics list. The top 100 articles from all journals and the top 100 articles from OBGYN journals were evaluated for specific characteristics. Data were analyzed in March 2019. The articles were characterized by citation number, publication year, topic, study design, and authorship. After excluding articles that featured on both lists, top-cited articles were compared. The query identified 3 767 874 articles, of which 278 846 (7.4%) were published in OBGYN journals. The top-cited article was published by Rossouw and colleagues in JAMA (2002). Top-cited articles published in nonspecialty journals were more frequently cited than those in OBGYN journals (median [interquartile range], 1738 [1490-2077] citations vs 666 [580-843] citations, respectively; P < .001) and were more likely to be randomized trials (25.0% vs 2.2%, respectively; difference, 22.8%; 95% CI, 13.5%-32.2%; P < .001). Whereas articles from nonspecialty journals focused on broad topics like osteoporosis, articles from OBGYN journal focused on topics like preeclampsia and endometriosis. This study found substantial differences between top-cited OBGYN articles published in nonspecialty vs OBGYN journals. These differences may reflect the different goals of the journals, which work together to ensure optimal dissemination of impactful articles.

Introduction After the 2022 Supreme Court decision Dobbs v. Jackson Women’s Health Organization to revoke federal abortion rights, many restrictive state abortion laws took effect.1 2 Most legislation limits abortion under almost all circumstances, with exceptions for ‘life-threatening emergency’ –an ill-defined term. CSEPs occur when an embryo implants within a caesarean hysterotomy site, making progression to a viable gestational age high risk for placenta accreta, hysterectomy and haemorrhage.4 Due to this morbidity, the Society for Maternal–Fetal Medicine (SMFM) recommends CSEP termination, which could be criminalised depending on state law.5 Legislation review We evaluated 22 state abortion bans (table 1) identified via the Guttmacher Institute in January 2023.1 Legislative texts were obtained from state government websites and read to examine requirements for medical exceptions. Table 2 Proposed state abortion bans ‘exceptions’ as of January 2023 Exception requirements States n (%) States ‘Affirmative defence’ to ‘prevent death’ 3 (14) Idaho, North Dakota, Tennessee (*all three have since been amended to remove this language) ‘Life-threatening’, ‘death’ or ‘medical emergency’ 18 (82) Alabama, Arkansas, Arizona, Florida, Georgia, Indiana, Kentucky, Louisiana, Mississippi, Missouri, Ohio, Oklahoma, South Dakota, Texas, Utah, West Virginia, Wisconsin, Wyoming ‘Serious injury’ or ‘impairment’ of a ‘major bodily function’ 14 (64) Alabama, Arizona, Florida, Georgia, Indiana, Kentucky, Louisiana, Mississippi, Missouri, Ohio, Texas, Utah, West Virginia, Wyoming Ectopic pregnancy 7 (32)* Alabama, Arizona, Arkansas, Louisiana, Utah, Texas, West Virginia *Ohio specifies that the ban only applies to ‘intrauterine pregnancies’ but does not explicitly state ‘ectopic pregnancy’. Though medicine has historically failed to defy state authority, if healthcare providers, hospital systems and institutions, and professional medical associations united in refusal to obey restrictions, with strong legal, financial and social support and protections, possibilities begin to unfold.

The non-canonical NF-κB signaling (RelB/p52) pathway drives pro-labor genes in the human placenta, including corticotropin-releasing hormone (CRH) and cyclooxygenase-2 (COX-2), making this a potential therapeutic target to delay onset of labor. Here we sought to identify small molecule compounds from a pre-existing chemical library of orally active drugs that can inhibit this NF-κB signaling, and in turn, human placental CRH and COX-2 production. We used a cell-based assay coupled with a dual-luciferase reporter system to perform an in vitro screening of a small molecule library of 1,120 compounds for inhibition of the non-canonical NF-κB pathway. Cell toxicity studies and drug efflux transport MRP1 assays were used to further characterize the lead compounds. We have found that 14 drugs have selective inhibitory activity against lymphotoxin beta complex-induced activation of RelB/p52 in HEK293T cells, several of which also inhibited expression of CRH and COX-2 in human term trophoblast. We identified sulfapyridine and propranolol with activity against CRH and COX-2 that deserve further study. These drugs could serve as the basis for development of orally active drugs to affect length of gestation, first in an animal model, and then in clinical trials to prevent preterm birth during human pregnancy.

Introduction and Hypothesis The objective was to evaluate the safety and effectiveness of an intrapartum electromechanical pelvic floor dilator designed to reduce the risk of levator ani muscle (LAM) avulsion during vaginal delivery. Methods A multicenter, randomized controlled trial enrolled nulliparous participants planning vaginal delivery. During the first stage of labor, participants were randomized to receive the intravaginal device or standard-of-care labor management. The primary effectiveness endpoint was the presence of full LAM avulsion on transperineal pelvic-floor ultrasound at 3 months. Three urogynecologists performed blinded interpretation of ultrasound images. The primary safety endpoint was adverse events (AEs) through 3 months. Results A total of 214 women were randomized to Device ( n  = 113) or Control ( n  = 101) arms. Of 113 Device assignees, 82 had a device placed, of whom 68 delivered vaginally. Of 101 Control participants, 85 delivered vaginally. At 3 months, 110 participants, 46 Device subjects who received full device treatment, and 64 Controls underwent ultrasound for the per-protocol analysis. No full LAM avulsions (0.0%) occurred in the Device group versus 7 out of 64 (10.9%) in the Control group ( p  = 0.040; two-tailed Fisher’s test). A single maternal serious AE (laceration) was device related; no neonate serious AEs were device related. Conclusions The pelvic floor dilator device significantly reduced the incidence of complete LAM avulsion in nulliparous individuals undergoing first vaginal childbirth. The dilator demonstrated an acceptable safety profile and was well received by recipients. Use of the intrapartum electromechanical pelvic floor dilator in laboring nulliparous individuals may reduce the rate of LAM avulsion, an injury associated with serious sequelae including pelvic organ prolapse.

Virtual reality (VR) offers immersive, realistic, three-dimensional experiences that \"transport\" users to novel environments. Because VR is effective for acute pain and anxiety, it may have benefits for hospitalized patients; however, there are few reports using VR in this setting. The aim was to evaluate the acceptability and feasibility of VR in a diverse cohort of hospitalized patients. We assessed the acceptability and feasibility of VR in a cohort of patients admitted to an inpatient hospitalist service over a 4-month period. We excluded patients with motion sickness, stroke, seizure, dementia, nausea, and in isolation. Eligible patients viewed VR experiences (eg, ocean exploration; Cirque du Soleil; tour of Iceland) with Samsung Gear VR goggles. We then conducted semistructured patient interview and performed statistical testing to compare patients willing versus unwilling to use VR. We evaluated 510 patients; 423 were excluded and 57 refused to participate, leaving 30 participants. Patients willing versus unwilling to use VR were younger (mean 49.1, SD 17.4 years vs mean 60.2, SD 17.7 years; P=.01); there were no differences by sex, race, or ethnicity. Among users, most reported a positive experience and indicated that VR could improve pain and anxiety, although many felt the goggles were uncomfortable. Most inpatient users of VR described the experience as pleasant and capable of reducing pain and anxiety. However, few hospitalized patients in this \"real-world\" series were both eligible and willing to use VR. Consistent with the \"digital divide\" for emerging technologies, younger patients were more willing to participate. Future research should evaluate the impact of VR on clinical and resource outcomes. Clinicaltrials.gov NCT02456987; https://clinicaltrials.gov/ct2/show/NCT02456987 (Archived by WebCite at http://www.webcitation.org/6iFIMRNh3).

The New Jersey Kids Study (NJKS) is a transdisciplinary statewide initiative to understand influences on child health, development, and disease. We conducted a mixed-methods study of project planning teams to investigate team effectiveness and relationships between team dynamics and quality of deliverables. Ten theme-based working groups (WGs) (e.g., Neurodevelopment, Nutrition) informed protocol development and submitted final reports. WG members ( = 79, 75%) completed questionnaires including de-identified demographic and professional information and a modified TeamSTEPPS Team Assessment Questionnaire (TAQ). Reviewers independently evaluated final reports using a standardized tool. We analyzed questionnaire results and final report assessments using linear regression and performed constant comparative qualitative analysis to identify central themes. WG-level factors associated with greater team effectiveness included proportion of full professors ( = 31.24, 95% CI 27.65-34.82), team size ( = 0.81, 95% CI 0.70-0.92), and percent dedicated research effort ( = 0.11, 95% CI 0.09-0.13); age distribution ( = -2.67, 95% CI -3.00 to -2.38) and diversity of school affiliations ( = -33.32, 95% CI -36.84 to -29.80) were inversely associated with team effectiveness. No factors were associated with final report assessments. Perceptions of overall initiative leadership were associated with expressed enthusiasm for future NJKS participation. Qualitative analyses of final reports yielded four themes related to team science practices: organization and process, collaboration, task delegation, and decision-making patterns. We identified several correlates of team effectiveness in a team science initiative's early planning phase. Extra effort may be needed to bridge differences in team members' backgrounds to enhance the effectiveness of diverse teams. This work also highlights leadership as an important component in future investigator engagement.

Women exposed to phthalates during pregnancy are at increased risk for delivering preterm, but the mechanism behind this relationship is unknown. Placental corticotropin-releasing hormone (CRH) and cyclooxygenase-2 (COX-2) are key mediators of parturition and are regulated by the non-canonical NF-kB (RelB/p52) signaling pathway. In this study, we demonstrate that one of the major phthalate metabolites, mono-(2-ethylhexyl)-phthalate (MEHP), increased CRH and COX-2 mRNA and protein abundance in a dose-dependent manner in primary cultures of cytotrophoblast. This was coupled with an increase in nuclear import of RelB/p52 and its association with the CRH and COX-2 promoters. Silencing of NF-kB inducing kinase, a central signaling component of the non-canonical NF-kB pathway, blocked MEHP-induced upregulation of CRH and COX-2. These results suggest a potential mechanism mediated by RelB/p52 by which phthalates could prematurely induce pro-labor gene activity and lead to preterm birth.