Subpopulation Of Women Research Articles

Evaluation of a polygenic risk score as a predictor of early onset triple-negative breast cancer in Black women.

10501 Background: Black women in the U.S. often develop early, biologically aggressive breast cancer (BC). Triple-negative breast cancer (TNBC) is a particularly aggressive type that occurs more frequently in Black than white women and often develops before recommended regular screening. More accurate risk prediction methods are urgently needed to identify young Black women with elevated risk of TNBC. Incorporating polygenic risk scores (PRS) into clinical models can substantially improve risk assessment, but most PRS have demonstrated poor performance among non-European ancestries. We previously described a multiple-ancestry PRS (MA-PRS), based on 56 ancestry-informative and 329 BC-associated single-nucleotide polymorphisms (SNPs), that predicts overall BC risk for diverse populations by characterizing genetic ancestry at each BC SNP and applying ancestry-specific SNP risks and frequencies. Here, we evaluated the extent to which MA-PRS improves upon clinical factors for the prediction of TNBC and early onset ( < 50 years) TNBC in a large, independent cohort of self-reported Black women. Methods: We examined clinical and genetic records from self-reported Black women referred for hereditary cancer testing from 8/22 - 9/23 and negative for pathogenic variants in BC-associated genes. The association of MA-PRS with TNBC was analyzed using multivariable logistic regression adjusted for personal and family cancer history, age and genetic ancestry. Analyses were conducted within the full cohort and the subpopulation of patients < 50 years old. Odds ratios (OR) are reported per standard deviation (SD) with 95% confidence intervals (CI). Results: We identified 14728 Black women who met study eligibility criteria. Nearly 70% (9895/14728) of patients were under the age of 50. In the full cohort, 629 (4.3%) patients were diagnosed with TNBC, and 173 (1.7%) were younger than 50 years old. MA-PRS significantly improved TNBC risk prediction over clinical factors in the full cohort and in the subpopulation of women under 50 (Table). The effect of MA-PRS on risk stratification was comparable to the 1.4 OR per SD reported in current literature for mammographic density, which is widely recognized as an important risk factor. Women in the top 5% of the MA-PRS distribution were at roughly 2-fold increased risk of TNBC (Table). Conclusions: MA-PRS substantially improved upon clinical factors for the prediction of TNBC and early-onset TNBC in a large cohort of Black women. MA-PRS appears to be equally as important for managing risk of early-onset TNBC as mammographic density for overall BC. Incorporation of MA-PRS into BC risk assessment has the potential to improve TNBC survival through more accurate identification of women at high risk. [Table: see text]

Perception of Risk of Harm from Cannabis Use Among Women of Reproductive Age with Disabilities.

Objectives: To examine perceived risk of harm from weekly cannabis use among reproductive-aged women with disabilities. Methods: Using data from the 2021 National Survey on Drug Use and Health, we assessed perceived risk of harm associated with weekly cannabis use among women of reproductive age by disability status. Disabilities included sensory, cognitive, and those related to daily activities. Logistic regression was employed to examine correlates of risk perception associated with weekly cannabis in this subpopulation of women. Results: A significantly higher percentage of women with any disability perceived no risk associated with weekly cannabis use (37.9%) compared to those with no disabilities (26.1%). Approximately, 60.0% of women with disabilities who used cannabis in the past 12 months perceived no risk of harm from weekly cannabis use. Overall, women with disabilities and cannabis use in the past 12 months had higher adjusted odds (AOR=2.90, 95% CI=2.10-4.10) of perceiving no risk associated with weekly use of cannabis compared to women without any disability and no cannabis use. Other significant factors associated with an increased likelihood of perceiving no risk of harm from weekly use of cannabis included younger women, having higher income, being in good health, and using alcohol or tobacco. Conclusions: Perceived risk of harm associated with weekly cannabis use is particularly low among women with disabilities who use cannabis. Given current attitudes toward cannabis as a harmless drug, and the potential adverse health outcomes, it is imperative to monitor and understand women's perceptions of risk of harm from cannabis use for clinical guidance, provider and patient education, and public health programs to support evidence-based approaches in addressing its use among vulnerable populations such as those of reproductive age with disabilities.

Insulin-sensitizing agents for infertility treatment in woman with polycystic ovary syndrome: a narrative review of current clinical practice.

Polycystic ovary syndrome (PCOS) is an endocrine, metabolic, and reproductive disorder which, according to the Rotterdam criteria, affects up to 24% of women of childbearing age. Although the prevalence of infertility in this subpopulation of women is high, the optimal treatment has not been fully established yet. Insulin resistance is considered to be an important mechanism involved in the development of PCOS; hence, the aim of this narrative review is to present an overview of the current pharmacological insulin-sensitizing treatment modalities for infertile women with PCOS. A MEDLINE and PubMed search for the years 1990-2023 was performed using a combination of keywords. Clinical trials with insulin sensitizers used for infertility treatment as well as analyses of systematic reviews and meta-analyses were evaluated. When deemed necessary, additional articles referenced in the retrieved papers were included in this narrative review. Several insulin-sensitizing compounds and various therapeutical protocols are available for infertility treatment of women with PCOS. Metformin is the most common adjuvant medication to induce ovulation in infertile women with PCOS and is more frequently administered in combination with clomiphene citrate than on its own. Recently, inositol and glucagon-like peptide-1 (GLP-1) receptor agonists have emerged as possible options for infertility treatment in PCOS. The future of medical treatment of PCOS women with infertility lies in a personalized pharmacological approach, which involves various compounds with different mechanisms of action that could modify ovarian function and endometrial receptivity, ultimately leading to better overall reproductive outcomes in these women.

Economic evaluations of maternal health interventions: a scoping review.

Background Evidence on the affordability and cost-effectiveness of interventions is critical to decision-making for clinical practice guidelines and development of national health policies. This study aimed to develop a repository of primary economic evaluations to support global maternal health guideline development and provide insights into the body of research conducted in this field. Methods A scoping review was conducted to identify and map available economic evaluations of maternal health interventions. We searched six databases (NHS Economic Evaluation Database, EconLit, PubMed, Embase, CINAHL and PsycInfo) on 20 November 2020 with no date, setting or language restrictions. Two authors assessed eligibility and extracted data independently. Included studies were categorised by subpopulation of women, level of care, intervention type, mechanism, and period, economic evaluation type and perspective, and whether the intervention is currently recommended by the World Health Organization. Frequency analysis was used to determine prevalence of parameters. Results In total 923 studies conducted in 72 countries were included. Most studies were conducted in high-income country settings (71.8%). Over half pertained to a general population of pregnant women, with the remainder focused on specific subgroups, such as women with preterm birth (6.2%) or those undergoing caesarean section (5.5%). The most common interventions of interest related to non-obstetric infections (23.9%), labour and childbirth care (17.0%), and obstetric complications (15.7%). Few studies addressed the major causes of maternal deaths globally. Over a third (36.5%) of studies were cost-utility analyses, 1.4% were cost-benefit analyses and the remainder were cost-effectiveness analyses. Conclusions This review provides a navigable, consolidated resource of economic evaluations in maternal health. We identified a clear evidence gap regarding economic evaluations of maternal health interventions in low- and middle-income countries. Future economic research should focus on interventions to address major drivers of maternal morbidity and mortality in these settings.

Better scan personalities than bodies? Prenatal care to enforce a pregnancy self-commitment

ABSTRACT The purpose of this work was to measure the effect of the proper prenatal medical care on the health of newborns. This study was based on a survey conducted in France in 2010 by the National Institute for Health and Medical Research and the Ministry of Health. Three different definitions of newborn health were used, and the definition of proper prenatal care was set based on the recommendations of the Haute Autorité de Santé (HAS). The analysis was conducted based on propensity score methods to adjust for potential confounders. The results showed that proper prenatal may reduce some newborn health problems. But, if allowance is made for women’s behaviour or for mothers’ perceptions of their pregnancy, prenatal care could have no effect on newborn health. Moreover, it seems that a subpopulation of women would use prenatal care visits to enforce a self-commitment, to adhere to personal good conduct rather than for only medical reasons. Better information, prevention and customization of prenatal care according to pregnant women’s profiles might be more effective in terms of health and perhaps cost-saving.

Uptake and continuation of HIV pre-exposure prophylaxis among women of reproductive age in two health facilities in Kisumu County, Kenya.

In 2020, Kenya had 19,000 new HIV infections among women aged 15+ years. Studies have shown sub-optimal oral pre-exposure prophylaxis (PrEP) use among sub-populations of women. We assessed the uptake and continuation of oral PrEP among women 15-49 years in two health facilities in Kisumu County, Kenya. A retrospective cohort of 262 women aged 15-49 years, initiated into oral PrEP between 12 November 2019 and 31 March 2021, was identified from two health facilities in the urban setting of Kisumu County, Kenya. Data on baseline characteristics and oral PrEP continuation at months 1, 3 and 6 were abstracted from patient records and summarized using descriptive statistics. Missing data in the predictor variables were imputed within the joint modelling multiple imputation framework. Using logistic regression, we evaluated factors associated with the discontinuation of oral PrEP at month 1. Of the 66,054 women screened, 320 (0.5%) were eligible and 262 (82%) were initiated on oral PrEP. Uptake was higher among women 25-29 years as compared to those 15-24 years (77% vs. 33%). Oral PrEP continuation declined significantly with increasing duration of follow-up; 37% at month 1, 21% at month 3 and 12% at month 6 (p<0.05). In the adjusted analysis, women 15-24 years had lower adjusted odds of continuing at month 1 than women ≥25 years (adjusted odds ratio [aOR]: 0.41, 95% CI: 0.21-0.82). There was no association between being sero-discordant and continuation of oral PrEP at month 1 (aOR; 1.21, 95% CI 0.59-2.50). Women from the sub-county hospital were more likely to continue at month 1 of follow-up compared to women enrolled in the county referral hospital (aOR 5.11; 95% CI 2.24-11.70). The low eligibility for oral PrEP observed among women 15-49 years in an urban setting with high HIV prevalence calls for a review of the screening process to validate the sensitivity of the screening tool and its proper application. The low uptake and continuation among adolescent girls and young women underscores the need to identify and address specific patient- and facility-level barriers affecting different sub-populations at risk for HIV acquisition.

Preimplantation genetic testing for aneuploidy in patients with low embryo numbers: benefit or harm?

We sought to explore the utility of preimplantation genetic testing for aneuploidy (PGT-A)in a poor prognosis group of womenwith few embryos available for transfer. This was a retrospective matched cohort study examining records for first or second-cycle IVF patients with 1 to 3 blastocysts. The study group comprised 130 patients who underwent PGT-A on all embryos. The control group included 130 patients matched by age, BMI, and blastocyst number and quality who did not undergo PGT-A during the same time period. The live birth rate (LBR) per embryo transfer (ET)were similar in the PGT-A and control groups, and the spontaneous abortion (SAB) rate was the same (23%). However, we found a significantly higher LBR per oocyte retrieval in the control group vs the PGT-A group (43% vs 20%, respectively) likely due to the many no-euploid cyclesin the PGT-A group. In a subgroup analysis for age, the similar LBR per ET persisted in women < 38. However, in older women, there was a trend to a higher LBR per ET in the PGT-A group (43%) vs the control group (22%) but a higher LBR per oocyte retrieval in the control group (31%) vs the PGT-A group (13%). Overall, we observed a significant increase in LBR per oocyte retrieval in women in the control group compared to women undergoing PGT-A, and no difference in SAB rate. Our data suggests that PGT-A has no benefit in a subpopulation of women with few embryos and may cause harm.

Neonatal stress and loss of ovarian hormones: a novel multidisciplinary approach to understand the coincidence of cardiorespiratory and metabolic disorders in females

IntroductionIn women, the prevalence of sleep apnea (SA) rises 3‐fold at menopause and most patients also present hypertension and obesity. While the “protective effects” of ovarian hormones are well documented, we do not know why the loss of ovarian hormones leads to SA and related cardiovascular and metabolic disorders only in a subpopulation of women. Because neonatal stress is a major cause of adult diseases, we tested the hypothesis that loss of ovarian function reveals the latent effects of stress on cardiorespiratory and metabolic control. To do so, we subjected female rats to neonatal maternal separation (NMS), a translational model of early life stress.MethodologyRat pups subjected to NMS were placed in a temperature‐controlled incubator 3h/day from postnatal day 3 to 12; controls (CTRL) were undisturbed. The effects of loss of ovarian function were tested using a surgical approach (ovariectomy; OVX, animals with 8 weeks old) and aging (40 weeks old). Measurements of ventilation (by whole body plethysmography), blood pressure (by tail cuff plethysmography), and body composition (by nuclear magnetic resonance) were made. We also harvested brains from 8 weeks old females (SHAM versus OVX). Then, we compared the expression of FosB, a transcription factor that indicates neuronal activity. The number of FosB expressing neurons was counted in the paraventricular nucleus of the hypothalamus (PVH), the main structure regulating the hypothalamic pituitary adrenal (HPA) axis.ResultsNMS does not affect the incidence of apneic events in all groups. At 8 weeks, mean arterial pressure (MAP) of NMS females was 5% lower than CTRL. In addition, NMS females had 10% more body mass compared to CTRL. At 40 weeks, the MAP of NMS females was 15% higher than CTRL. In both ages, NMS presented 4% more fat, and 4% less lean tissue. OVX did not affect cardiorespiratory function but augmented the number of neurons expressing FosB in the PVH by 55% in NMS, not in CTRL females.DiscussionThe hypotension observed in young (8 weeks) NMS females was unexpected but is consistent with the fact that hypotension is a common comorbidity of depression. PVH dysfunction contributes to the increase of sympathetic vasomotor activity, characteristic of multiple forms of hypertension. Additionally, the chronic activation of the HPA axis can leads to obesity. The increased expression of FosB in OVX NMS animals indicate that ovarian hormones prevents the stress‐related rise of activity of the HPA axis. At 40 weeks old, the fact that NMS animals were obese and hypertensive indicates that those effects are age dependent. The emergence of dysregulation on the stress neuroaxis is a plausible mechanism to explain those results. Together, these data indicate that neonatal stress may explain why a subpopulation of women are at risk of developing cardiorespiratory and metabolic disturbance at menopause. Ongoing experiments will evaluate the incidence of SA in older animals (60 weeks old) and exploring the underlying mechanisms.

Economic evaluations of maternal health interventions: a scoping review

Background Evidence on the affordability and cost-effectiveness of interventions is critical to decision-making for clinical practice guidelines and development of national health policies. This study aimed to develop a repository of primary economic evaluations to support global maternal health guideline development and provide insights into the body of research conducted in this field. Methods A scoping review was conducted to identify and map available economic evaluations of maternal health interventions. We searched six databases (NHS Economic Evaluation Database, EconLit, PubMed, Embase, CINAHL and PsycInfo) on 20 November 2020 with no date, setting or language restrictions. Two authors assessed eligibility and extracted data independently. Included studies were categorised by subpopulation of women, level of care, intervention type, mechanism, and period, economic evaluation type and perspective, and whether the intervention is currently recommended by the World Health Organization. Frequency analysis was used to determine prevalence of parameters. Results In total 923 studies conducted in 72 countries were included. Most studies were conducted in high-income country settings (71.8%). Over half pertained to a general population of pregnant women, with the remainder focused on specific subgroups, such as women with preterm birth (6.2%) or those undergoing caesarean section (5.5%). The most common interventions of interest related to non-obstetric infections (23.9%), labour and childbirth care (17.0%), and obstetric complications (15.7%). Few studies addressed the major causes of maternal deaths globally. Over a third (36.5%) of studies were cost-utility analyses, 1.4% were cost-benefit analyses and the remainder were cost-effectiveness analyses. Conclusions This review provides a navigable, consolidated resource of economic evaluations in maternal health. We identified a clear evidence gap regarding economic evaluations of maternal health interventions in low- and middle-income countries. Future economic research should focus on interventions to address major drivers of maternal morbidity and mortality in these settings.

Lactobacilluscrispatus dominance in the vaginalmicrobiome reduces the occurrence of spontaneouspreterm birth in women with a short cervical length

Introduction: The majority of pregnant women with a short cervix will deliver at term and, thus, may unnecessarily receive advanced monitoring and treatment. It is still necessary to define more accurately which sub-population of women with a short cervix is at elevated risk for early delivery. Objective: To determine if vaginal microbiome composition influenced the rate of spontaneous preterm birth in women with a short cervical length. Methods: In an exploratory, observational prospective study, vaginal secretions were obtained from 591 women at 21–24 week gestation. Vaginal microbiome composition was determined by analyzing the V1–V3 region of the bacterial 16S ribosomal RNA gene. Results: Lactobacillus crispatus was numerically dominant in the vagina in 41.7% of subjects, followed by L. iners in 32% and Gardnerella vaginalis in 12%. In women whose cervix was ≤25mm, the sensitivity to predict an spontaneous preterm birth was 11.8%. However, when L. crispatus was not the dominant vaginal bacterium, this sensitivity increased to 81.8%. Similarly, in women with a cervical length ≤30mm, the sensitivity to predict an spontaneous preterm birth increased from 21.7 to 78.3% when L. crispatus was not the dominant vaginal bacterium.In women with a prior spontaneous preterm birth and a cervix ≤25 or ≤30mm, L. crispatus dominance was also associated with a reduced rate of spontaneous preterm birth in the current pregnancy (p&lt;0.001). Conclusion: In pregnant women with a cervix ≤25mm or ≤30mm, the risk for an spontaneous preterm birth is increased if L. crispatus is not dominant in the vagina.

Identifying the women most vulnerable to intimate partner violence: A decision tree analysis from 48 low and middle-income countries.

BackgroundPrimary prevention strategies are needed to reduce high rates of intimate partner violence (IPV) in low- and middle-income countries (LMICs). The effectiveness of population-based approaches may be improved by adding initiatives targeted at the most vulnerable groups and tailored to context-specificities.MethodsWe applied a decision-tree approach to identify subgroups of women at higher risk of IPV in 48 LMICs and in all countries combined. Data from the most recent Demographic and Health Survey carried out between 2010 and 2019 with available information on IPV and sociodemographic indicators was used. To create the trees, we selected 15 recognized risk factors for IPV in the literature which had a potential for targeting interventions. Exposure to IPV was defined as having experienced physical and/or sexual IPV in the past 12 months.FindingsIn the pooled decision tree, witnessing IPV during childhood, a low or medium empowerment level and alcohol use by the partner were the strongest markers of IPV vulnerability. IPV prevalence amongst the most vulnerable women was 43% compared to 21% in the overall sample. This high-risk group included women who witnessed IPV during childhood and had lower empowerment levels. These were 12% of the population and 1 in 4 women who experienced IPV in the selected LMICs. Across the individual national trees, subnational regions emerged as the most frequent markers of IPV occurrence.InterpretationStarting with well-known predictors of IPV, the decision-tree approach provides important insights about subpopulations of women where IPV prevalence is high. This information can help designing targeted interventions. For a large proportion of women who experienced IPV, however, no particular risk factors were identified, emphasizing the need for population wide approaches conducted in parallel, including changing social norms, strengthening laws and policies supporting gender equality and women´s rights as well as guaranteeing women´s access to justice systems and comprehensive health services.FundingBill and Melinda Gates Foundation (Grant INV-010051/OPP1199234), 10.13039/100010269Wellcome Trust (Grant Number: 101815/Z/13/Z) and Associação Brasileira de Saúde Coletiva (ABRASCO).

An Examination of Geographic Differences in Social Determinants of Health Among Women with Diagnosed HIV in the United States and Puerto Rico, 2017

Objective: To examine differences, at the census tract level, in the distribution of human immunodeficiency virus (HIV) diagnoses and social determinants of health (SDH) among women with diagnosed HIV in 2017 in the United States and Puerto Rico. Background: In the United States, HIV continues to disproportionately affect women, especially minority women and women in the South. Methods: Data reported in the National HIV Surveillance System (NHSS) of the Centers for Disease Control and Prevention were used to determine census tract-level HIV diagnosis rates and percentages among adult women (aged ≥18 years) in 2017. Data from the American Community Survey were combined with NHSS data to examine regional differences in federal poverty status, education level, income level, employment status, and health insurance coverage among adult women with diagnosed HIV infection in the United States and Puerto Rico. Results: In the United States and Puerto Rico, among 6,054 women who received an HIV diagnosis in 2017, the highest rates of HIV diagnoses generally were among those who lived in census tracts where the median household income was less than $40,000; at least 19% lived below the federal poverty level, at least 18% had less than a high school diploma, and at least 16% were without health insurance. Conclusion: This study is the first of its kind and gives insight into how subpopulations of women are affected differently by the likelihood of an HIV diagnosis. The findings show that rates of HIV diagnosis were highest among women who lived in census tracts having the lowest income and least health coverage.

Physiological Need for Calcium, Iron, and Folic Acid for Women of Various Subpopulations During Pregnancy and Beyond.

Women tend to supplement their diets with multivitamin/mineral (MVM) supplements more often than men, and reports indicate that more than 90% of pregnant women in the United States supplement their diets with prenatal MVMs. Given the widespread use of MVMs among women and given the increasing efforts to unveil the importance of phenotype-specific health determinants, it seems imperative to review what is known about variations in nutrient physiology among women from different ethnic and racial groups and at different reproductive stages of life. In this study, we embark on an assessment of the scientific evidence and knowledge gaps that impact the precise determination of nutrient levels (specifically calcium, iron, and folic acid) that confer benefits to various subpopulations of women in the United States.

1090 Cervicovaginal fluid (CVF) TNFα as a biomarker for preterm birth

The prediction of preterm birth (PTB) is complex due to its multifactorial etiology. The inflammatory response through TNFα activation of the NFκB pathway is a proposed mechanism of preterm birth. TNFα can also be found in cervicovaginal fluid (CVF) in women who deliver preterm. We have demonstrated that cytokine profiles vary by obstetric history. The goal of our study was to examine CVF TNFα as a predictor of PTB in women discriminated by obstetric history. This was a secondary analysis of a longitudinal multicenter study of women with singleton gestations. Maternal CVF specimens were collected in the first (5w0d-13w6d) and second (14w0d-26w6d) trimester and assayed for cytokine concentrations (IL-1a, IL-1b, IL-6, IL-8, IL-10, TNFα, CRP and MMP-8) using a multiplex beadlyte assay on a Luminex IS-100. Women were grouped by obstetric history: nulliparous, multiparous with history of PTB and multiparous without history of PTB. Women were followed throughout pregnancy and outcomes were obtained by medical record review. ROC analysis was used to determine an optimal cutpoint, chosen to maximize the Youden’s distance and minimize the distance to the perfect (0,1), in predicting PTB. Analysis included 217 women: 102 nulliparas (47%), 46 (21%) multiparous with a history of PTB, and 69 (32%) multiparous without history of PTB. Thirteen (28%) of those with a history of PTB had a recurrent PTB. Only TNF-α was found to be a potentially useful predictor of PTB and only in the subpopulation of women with a history of PTB. A ROC curve for women with history of PTB (Figure 1) was constructed and the cutpoint maximizing the Youden’s index was 0.82 pg/ml; yielding a sensitivity of 92% and specificity of 63%. A ROC curve for women without a history of PTB was constructed for comparison (Figure 2). CVF TNFα can be used as a predictor of PTB in women with a history of PTB. A proposed cutpoint for CVF TNFα could be 0.82 pg/ml with a sensitivity of 92% and specificity of 63%. A large validation study is warranted to assess the value of this biomarker in this subpopulation.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Identifying&amp;nbsp;the Women Most Vulnerable to Intimate Partner Violence: A Decision Tree Analysis From 48 Low and Middle-Income Countries

Background: Primary prevention strategies are needed to reduce high levels of intimate partner violence (IPV) in low- and middle-income countries (LMICs), and their effectiveness may be improved by targeting the most vulnerable populational groups and by focusing on context-specific risk factors. Methods: We selected the most recent Demographic and Health Survey carried out since 2010 and with available information on IPV. Exposure to IPV was defined as having experienced physical and/or sexual IPV in the past 12 months. We selected 15 recognized IPV risk factors (or proxies) which were available in the surveys and had a potential for tailoring and targeting interventions. To identify groups of women most vulnerable to IPV, we applied a decision tree approach, creating individual trees for each country and for all countries combined. Findings: We identified 48 countries with suitable data. In the pooled decision tree, witnessing IPV during childhood, a lower empowerment level (attitude to violence) and partner’s alcohol use were the strongest markers of IPV vulnerability. IPV prevalence among the most vulnerable women was 43% compared to 21% in the overall sample. This high-risk group concentrated 1 in every 4 women who experienced IPV in LMICs. Across the individual national trees, the subnational regions emerged as the most frequent markers of IPV occurrence. Interpretation: This study contributes evidence that can be used to plan and improve policies and programmes aimed at reducing population levels of IPV by reaching high-risk women and families with focused interventions in LMICs. By using a decision-tree approach - a simple-to-use yet powerful statistical tool we provide important insights about subpopulations of women where IPV have very high prevalence and to which interventions could be prioritised and tailored. Funding Information: Grant number: 101815/Z/13/Z and The Bill & Melinda Gates Foundation Health - Grant Number: INV-007594 / OPP1148933 Declaration of Interests: None to declare. Ethics Approval Statement: Ethical approval was obtained by the national agencies responsible for conducting each survey. All analyses relied on publicly available, anonymized databases for which permission to access was received through the DHS Program.

BRCA Methylation Testing Identifies a Subset of Ovarian Carcinomas without Germline Variants That Can Benefit from PARP Inhibitor.

Homologous Recombination Deficiency (HRD) is a frequent feature of high-grade epithelial ovarian carcinoma (EOC), associated with sensitivity to PARP-inhibitors (PARPi). The best characterized causes of HRD in EOCs are germline or somatic mutations in BRCA1 and BRCA2 genes. Although promoter methylation is a well-known mechanism of gene transcriptional repression, few data have been published about BRCA gene methylation in EOCs. In this retrospective study, we quantitatively analyzed by pyrosequencing a selected series of 90 formalin-fixed (FFPE) primary EOCs without BRCA germline mutations. We identified 20/88 (22.7%) EOCs showing BRCA promoter methylation, including 17/88 (19.3%) in BRCA1 and 4/86 (4.6%) in BRCA2 promoters, one of which showing concomitant BRCA1 methylation. Mean methylation levels were 49.6% and 45.8% for BRCA1 and BRCA2, respectively, with methylation levels ≥50% in 10/20 methylated EOCs. Constitutive BRCA methylation was excluded by testing blood-derived DNA. In conclusion, pyrosequencing methylation analysis of BRCA genes is a robust, quantitative and sensitive assay applicable to FFPE samples. Remarkably, a considerable subset of germline BRCA-negative EOCs showed somatic methylation and, likely, HRD. A subpopulation of women with BRCA methylation, even without BRCA mutations, could potentially benefit from PARP-inhibitors; further clinical studies are needed to clarify the predictive role of somatic BRCA methylation of PARP-therapy response.

Tumor immunology from the viewpoint of reproductive immunology

There is a trend towards offering immunotherapy to women with unexplained reproductive failure based on abnormal Natural Killer (NK) cell levels. Previous systematic reviews evaluating immunotherapy usage have not focused on women with abnormal level of NK cells. To address the gap in literature, this systematic review aims to evaluate the efficacy of immunotherapy to improve pregnancy outcome in women with recurrent miscarriage (RM) or implantation failure (RIF) specifically selected based on abnormal levels and/or activity of NK cells. Six databases were searched for peer-reviewed studies following PRISMA guidelines. Risk of bias assessment was conducted using RoB2 for randomized controlled trials (RCT) and ROBINS-I for non-RCT. Of 1025 studies identified, seven studies on intravenous immunoglobulin (IVIG) (four), prednisolone (one), etanercept (one) and intralipid (one) were included. Meta-analysis of the non-RCT IVIG studies (557 participants; 312 intervention, 245 controls) showed livebirth in favour of intervention (RR 2.57; 95 % CI = 1.79–3.69; p < 0.05), however there were significant heterogeneity (I2 = 62 %) and moderate to severe risk of bias in these studies. Individual RCTs reported improved livebirth outcome in etanercept, intralipid and prednisolone and this was significant in the former two (p < 0.05). In conclusion, there may be some benefit of immunotherapy, but paucity of high quality evidence means that it is not possible to support the use of immunotherapy even when selected based on abnormal NK cell level/activity. Further research with application of scientifically validated immunological biomarkers in well-planned large scale RCTs will determine whether immunotherapy is beneficial in this subpopulation of women.

Autoantibodies to epidermal growth factor (EGF) in patients with recurrent pregnancy loss and repeated implantation failure

There is a trend towards offering immunotherapy to women with unexplained reproductive failure based on abnormal Natural Killer (NK) cell levels. Previous systematic reviews evaluating immunotherapy usage have not focused on women with abnormal level of NK cells. To address the gap in literature, this systematic review aims to evaluate the efficacy of immunotherapy to improve pregnancy outcome in women with recurrent miscarriage (RM) or implantation failure (RIF) specifically selected based on abnormal levels and/or activity of NK cells. Six databases were searched for peer-reviewed studies following PRISMA guidelines. Risk of bias assessment was conducted using RoB2 for randomized controlled trials (RCT) and ROBINS-I for non-RCT. Of 1025 studies identified, seven studies on intravenous immunoglobulin (IVIG) (four), prednisolone (one), etanercept (one) and intralipid (one) were included. Meta-analysis of the non-RCT IVIG studies (557 participants; 312 intervention, 245 controls) showed livebirth in favour of intervention (RR 2.57; 95 % CI = 1.79–3.69; p < 0.05), however there were significant heterogeneity (I2 = 62 %) and moderate to severe risk of bias in these studies. Individual RCTs reported improved livebirth outcome in etanercept, intralipid and prednisolone and this was significant in the former two (p < 0.05). In conclusion, there may be some benefit of immunotherapy, but paucity of high quality evidence means that it is not possible to support the use of immunotherapy even when selected based on abnormal NK cell level/activity. Further research with application of scientifically validated immunological biomarkers in well-planned large scale RCTs will determine whether immunotherapy is beneficial in this subpopulation of women.

Food Insecurity and Likely Psychological Distress: Isolation of BMI and Income among Women in California

ABSTRACT California’s rate of food insecurity is nearly double the national goal. Women with lower socioeconomic status are disproportionately affected by higher rates of food insecurity, obesity, and poorer mental health. The study purpose was to investigate the adjusted relationship between likely psychological distress and food insecurity among women with low-income and obesity in California. Secondary data analysis study of the 2016 California Health Interview Survey adult (18+) public-use dataset. Weighted analyses of women with low-income and obesity included univariate, bivariate, and a multivariable logistic regression. Women with likely psychological distress had more than 350% higher adjusted odds of food insecurity (AOR 4.63, 95% CI 2.30–9.32). Findings support the growing literature on the positive association between psychological distress and food insecurity among women living in high-income countries. This study makes a novel contribution by focusing on the effects within a subpopulation of women with low-income and obesity.

Determinants favoring weight regain after weight-loss therapy among postmenopausal women

Little is known about the factors affecting body weight-loss maintenance among postmenopausal women. We thus performed an analysis to identify some sociodemographic, physiological, and behavioral predictors of weight regain in a targeted subpopulation of women who had lost weight 1 year earlier. We also measured how eating behaviors and habits as well as physical activity pattern differ among successful and unsuccessful weight-loss maintainers over the trial. Sixty-four postmenopausal women were followed up for a year after dieting, and the successful and unsuccessful maintainers were identified. The regainers had regained an average of 4.9 kg of their lost body weight, while the maintainers had regained only 1.5 kg. Regainers had fewer years of education and lower initial body weight loss than maintainers. They also showed poor dietary adherence during dieting, and had unhealthy patterns of eating involving the avoidance of breakfast and a lower intake of nuts, seeds, and pulses, and a higher intake of sweets, biscuits, cakes, and pastries over time (excluding the dieting period). All the significant sociodemographic, physiological and behavioral variables differentiating regainers and maintainers before and after dieting were then examined as independent variables in a logistic regression model. The model showed that less weight reduction during dieting, higher disinhibition scores after dieting, and avoidance of breakfast before dieting were significant predictors of body weight regain in postmenopausal women. From a practical point of view, early identification of postmenopausal women who are at risk of regaining lost weight can allow health professionals to create behavioral and dietary supports to help prevent this. A regular schedule of follow-ups over at least the first year should be considered for them—including psychological and dietary intervention, if necessary. Since this sample study included only postmenopausal women, our findings are not generalizable to other populations.