Inflammatory Cells in Control and Prolapsed Uterosacral Ligament Tissue.

Pelvic organ prolapse (POP), a downward descent of the vagina and/or uterus through the vaginal canal, is a prevalent condition affecting up to 40% of women. Several risk factors of POP have been identified, including childbirth, connective tissue defects, and chronic intra-abdominal pressure; however, the underlying etiologies of POP development are not fully understood, leading to a high burden on patients and the healthcare systems. The uterosacral ligaments are key support structures of the uterus and upper vagina. Our previous work describes observed histopathological changes in uterosacral ligament (USL) tissue and demonstrates the presence of neutrophils in a subgroup of POP individuals. This presence of neutrophils prompted an examination for the presence of a broader spectrum of inflammatory cell types in the USL. Immunohistochemical staining was performed to identify neutrophils, lymphocytes, macrophages, and mast cells outside of the vasculature. All 4 inflammatory cell types were increased in the POP-HQ system-defined POP-Inflammatory (POP-I) phenotype USL tissue relative to the USL tissues of control or other POP-HQ phenotypes. Focal T-lymphocyte and macrophage co-accumulations were observed in the arterial walls from some patients of the POP-vascular (POP-V) phenotype suggesting previous arterial injury. In addition, 1 control and 2 POP-V subjects' USLs contained arterial wall foamy macrophages, evidence of atherosclerosis. These findings further support a complex etiology for POP and indicate that personalized approaches to preventing and treating the condition may be warranted.

Estrogen and Androgen Receptor Status in Uterosacral Ligaments of Women with Pelvic Organ Prolapse Stratified by the Pelvic Organ Prolapse Histology Quantification System.

Menopause is a significant risk factor for pelvic organ prolapse (POP), suggesting that ovarian sex steroids play a major role in the etiology of the condition. POP results from failure of the uterine-cervix-vagina support structures, including the uterosacral ligament (USL). We previously identified consistent degenerative USL phenotypes that occur in POP and used their characteristics to develop a standardized POP Histologic Quantification System (POP-HQ). In this study, POP and matched control USL tissue was first segregated into the unique POP-HQ phenotypes, and specimens were then compared for estrogen receptor (ER) alpha (ERα), ERbeta (ERß), the G-protein estrogen receptor (GPER), and androgen receptor (AR) content via immunohistochemical staining. ER and AR expression levels in the control USL tissues were indistinguishable from those observed in the POP-A phenotype, and partially overlapped with those of the POP-I phenotype. However, control-USL steroid receptor expression was statistically distinct from the POP-V phenotype. This difference was driven mainly by the increased expression of GPER and AR in smooth muscle, connective tissue, and endothelial cells, and increased expression of ERα in connective tissue. These findings support a multifactorial etiology for POP involving steroid signaling that contributes to altered smooth muscle, vasculature, and connective tissue content in the USL. Furthermore, these data support the concept that there are consistent and distinct degenerative processes that lead to POP and suggest that personalized approaches are needed that target specific cell and tissues in the pelvic floor to treat or prevent this complex condition.

New Jersey maternal mortality dashboard: an interactive social-determinants-of-health tool.

OBJECTIVES: The United States maternal mortality (MM) rate is the highest amid developed/industrialized nations, and New Jersey's rate is among the highest. Healthcare professionals, public health officials, and policy makers are working to understand drivers of MM. An interactive data visualization tool for MM and health-related information (New Jersey Maternal Mortality Dashboard [NJMMD]) was recently developed. METHODS: NJMMD is an open-source application that uses data from publicly available state/federal government sources to provide a cross-sectional, high-level depiction of potential relationships between MM and demographic, social, and public health factors. RESULTS: MM rates or ratios (maternal deaths/1,000 women aged 15-49 years or 100,000 live births, respectively) are available by year (2005-2017), age (5-year [15-49] periods), and race/ethnicity (non-Hispanic White, Black, or Asian; Hispanic; or other), and by contextual social determinants of health (percent insured; percent covered by Medicaid; difference in nulliparous, term, singleton, vertex Cesarian birth rate from New Jersey goal; number of obstetrician/gynecologists or midwives per capita; and poverty rate). Bar graphs also can be produced with these variables. CONCLUSIONS: NJMMD is the first publicly available, interactive, state-focused MM tool that takes into account the intersection of social and demographic determinants of health, which play important roles in health outcomes. Trends and patterns in variables associated with MM and health can be identified for New Jersey and each of its 11 counties, and inform areas of focus for further analysis. Outputs may enable researchers, policy makers, and others to develop appropriate interventions and be better positioned to set benchmarks, allocate resources, and evaluate outcomes.

Prenatal care and pregnancy outcome among incarcerated pregnant individuals in the United States: a systematic review and meta-analysis.

This systematic review and meta-analysis assessed the risk of inadequate prenatal care and pregnancy outcome among incarcerated pregnant individuals in the United States. PubMed/MedLine, Embase, ClinicalTrials.gov and Web of Science were searched from inception up to March 30th, 2022. Studies were included if they reported the risk of inadequate prenatal care and/or pregnancy outcomes among incarcerated pregnant individuals in the United States jails or prisons. Adequacy of prenatal care was quantified by Kessner index. The random-effects model was used to pool the mean differences or odds ratios (OR) and the corresponding 95% confidence intervals (CIs) using RevMan software. Nine studies were included in the final review. A total of 11,534 pregnant individuals, of whom 2,544 were incarcerated while pregnant, and 8,990 who were matched non-incarcerated pregnant individuals serving as control group, were utilized. Compared to non-incarcerated pregnancies, incarcerated pregnant individuals were at higher risk of inadequate prenatal care (OR 2.99 [95% CI: 1.60, 5.61], p<0.001) and were more likely to have newborns with low birthweight (OR 1.66 [95% CI: 1.19, 2.32], p=0.003). There was no significant difference between incarcerated and matched control pregnancies in the rates of preterm birth and stillbirth. The findings of the current systematic review and meta-analysis suggest that incarcerated pregnant individuals have an increased risk of inadequate prenatal care. Considering the limited number of current studies, further research is indicated to both assess whether the risk of inadequate prenatal care has negative impact on prenatal outcomes for this population and to determine the steps that can be taken to enhance prenatal care for all pregnant individuals incarcerated in the United States prisons.

Using the novel pelvic organ prolapse histologic quantification system to identify phenotypes in uterosacral ligaments in women with pelvic organ prolapse.

BACKGROUND: Pelvic organ prolapse is common, but the underlying etiologies are poorly understood, which limits our current prevention and treatment options. OBJECTIVE: Our primary objective was to compare the uterosacral ligament histologic features in women with and without prolapse using the novel pelvic organ prolapse histologic quantification system. Our secondary aim was to determine whether composite histologic findings in uterosacral ligaments are associated with prolapse risk factors. STUDY DESIGN: This was a prospective cohort study in which paracervical uterosacral ligament biopsies were performed at the time of hysterectomy for primary prolapse or other benign gynecologic indications and processed for histologic evaluation. The pelvic organ prolapse quantification system was used to determine the prolapse stage. In this study, 9 prominent histologic features were semiquantitatively scored using the pelvic organ prolapse histologic quantification system in a blinded fashion and compared between prolapse and control groups. Unbiased principal component analysis of these scores was independently performed to identify potential relationships between histologic measures and prolapse risk factors. RESULTS: The histologic scores of 81 prolapse and 33 control ligaments were analyzed. Compared with the control group, women in the prolapse group were significantly older and more likely to be in the menopausal phase. There was no difference in the number of vaginal deliveries, body mass index, hormone use, or smoking status between the groups. To control for baseline differences, patients were also stratified by age over 40 years and menopausal status. Compared with the control group, the prolapse ligaments in the premenopausal group had significantly more loss of smooth muscle fibers within the fascicles (P<.001), increased inflammatory infiltrates of neutrophils within the tissue and perineural inflammatory cells (P<.01 and P=.04, respectively), and reduced neointimal hyperplasia (P=.02). Prolapse ligaments in the postmenopausal group exhibited elevated adipose content compared with that of the control group (P=.05). Amount of fibrillar collagen, total nonvascular smooth muscle, and muscle fiber vesicles of prolapse ligaments did not differ in either the premenopausal or postmenopausal group compared with that of the control group. Unbiased principal component analysis of the histologic scores separated the prolapse ligaments into 3 phenotypes: (1) increased adipose accumulation, (2) increased inflammation, and (3) abnormal vasculature, with variable overlap with controls. Posthoc analysis of these subgroups demonstrated a positive correlation between increasing number of vaginal deliveries and body mass index with increasing adipose content in the adipocyte accumulation and inflammatory phenotype and increasing neointimal hyperplasia in the vascular phenotype. However, only the relationship between vaginal delivery and adipocytes was significant in the adipose phenotype (R2=0.13; P=.04). CONCLUSION: Histologic phenotypes exist in pelvic support ligaments that can be distinguished using the pelvic organ prolapse histologic quantification system and principle component analysis. Vaginal delivery is associated with aberrant adipose accumulation in uterosacral ligaments. Our findings support a multifactorial etiology for pelvic organ prolapse contributing to altered smooth muscle, vasculature, and connective tissue content in crucial pelvic support structures. To confirm these associations and evaluate the biomechanical properties of histologic phenotypes of prolapse, larger studies are warranted. Closing this gap in knowledge will help optimize personalized medicine and help identify targets for prevention and treatment of this complex condition.