Endometriosis, is a gynecological disease, where uterine (eutopic) endometrial glands and tissues are present outside the intra-uterine locations, ectopic regions (pelvic peritoneum, fallopian tubes or ovaries). About 5-10% reproductive and 20-50% infertile women have endometriosis. Several factors like hormonal, environmental, genetic and immune system are involved in the pathogenesis of endometriosis both directly or indirectly altering the estrogen level and thus affecting the reproductive health of women. Current study was done with an aim to identify novel and potential biomarker for endometriosis using mRNA seq analysis. From raw gene expression profiles differentially expressed genes (DEGs) were identified and further their functional analysis was conducted. A total of 552 (312 up and 240 downregulated) DEGs were identified in samples from endometriosis suffering women when compared with control subjects. Major DEGs forming hubnodes like C3, PSAP, APP, GNG12 were found to be involved in various functions such as, epithelia cell differentiation and development, proteolysis, gland development, muscle fiber development, response to hormone stimulus. The identified DEGs can be directly or indirectly involved in the pathway of pathogenesis of endometriosis and can act as a potential biomarker for ectopic endometrium. Current study will provide a preliminary insight into the mechanism of endometriosis disease; however, it will require further detailed studies for its complete path of action.
{"title":"Bioinformatical enrichment analysis of genes involved in the pathway of endometriosis disease","authors":"Kushum Kusum, Ashish Ashish, Ravi Bhushan, Radha Chaube, Sangeeta Rai, Royana Singh","doi":"10.1101/2024.02.09.24302561","DOIUrl":"https://doi.org/10.1101/2024.02.09.24302561","url":null,"abstract":"Endometriosis, is a gynecological disease, where uterine (eutopic) endometrial glands and tissues are present outside the intra-uterine locations, ectopic regions (pelvic peritoneum, fallopian tubes or ovaries). About 5-10% reproductive and 20-50% infertile women have endometriosis. Several factors like hormonal, environmental, genetic and immune system are involved in the pathogenesis of endometriosis both directly or indirectly altering the estrogen level and thus affecting the reproductive health of women. Current study was done with an aim to identify novel and potential biomarker for endometriosis using mRNA seq analysis. From raw gene expression profiles differentially expressed genes (DEGs) were identified and further their functional analysis was conducted. A total of 552 (312 up and 240 downregulated) DEGs were identified in samples from endometriosis suffering women when compared with control subjects. Major DEGs forming hubnodes like C3, PSAP, APP, GNG12 were found to be involved in various functions such as, epithelia cell differentiation and development, proteolysis, gland development, muscle fiber development, response to hormone stimulus. The identified DEGs can be directly or indirectly involved in the pathway of pathogenesis of endometriosis and can act as a potential biomarker for ectopic endometrium. Current study will provide a preliminary insight into the mechanism of endometriosis disease; however, it will require further detailed studies for its complete path of action.","PeriodicalId":501409,"journal":{"name":"medRxiv - Obstetrics and Gynecology","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139751718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Genomic information from pregnant women and their husbands may provide effective biomarkers for preeclampsia. This study investigated how parental polygenic risk scores (PRSs) for blood pressure (BP) and preeclampsia are associated with preeclampsia onset and evaluated predictive performances of PRSs with clinical predictive variables. Methods: In the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study, participants were genotyped using either Affymetrix Axiom Japonica Array v2 (further divided into two cohorts?the PRS training cohort and the internal-validation cohort?at a ratio of 1:2) or Japonica Array NEO (external-validation cohort). PRSs were calculated for systolic BP (SBP), diastolic BP (DBP), and preeclampsia. Associations between PRSs and preeclampsia, including preeclampsia superimposed on chronic hypertension, were examined using logistic regression analysis; prediction models were developed using a competing-risks approach with clinical predictive variables and PRSs. Results: In total, 19,836 participants were included. Hyperparameters for PRS calculation were optimized for 3,384 participants in the training cohort. In internal- and external-validation cohorts, 357 of 6,768 (5.3%) and 269 of 9,684 (2.8%) participants developed preeclampsia, respectively. Preeclampsia onset was significantly associated with maternal PRSs for SBP and DBP in internal- and external-validation cohorts and with paternal PRSs for SBP and DBP only in the external-validation cohort. Maternal PRSs for DBP calculated using ?LDpred2? most improved prediction models. Maternal PRSs for DBP provided additional predictive information on clinical predictive variables. Paternal PRSs for DBP improved prediction models in the internal-validation cohort. Conclusions: Parental PRS, along with clinical predictive variables, is potentially useful for predicting preeclampsia.
{"title":"Preeclampsia prediction with maternal and paternal polygenic risk scores: the TMM BirThree Cohort Study","authors":"Hisashi Ohseto, Mami Ishikuro, Taku Obara, Akira Narita, Ippei Takahashi, Genki Shinoda, Aoi Noda, Keiko Murakami, Masatsugu Orui, Noriyuki Iwama, Masahiro Kikuya, Hirohito Metoki, Junichi Sugawara, Gen Tamiya, Shinichi Kuriyama","doi":"10.1101/2024.02.07.24302476","DOIUrl":"https://doi.org/10.1101/2024.02.07.24302476","url":null,"abstract":"Background: Genomic information from pregnant women and their husbands may provide effective biomarkers for preeclampsia. This study investigated how parental polygenic risk scores (PRSs) for blood pressure (BP) and preeclampsia are associated with preeclampsia onset and evaluated predictive performances of PRSs with clinical predictive variables.\u0000Methods: In the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study, participants were genotyped using either Affymetrix Axiom Japonica Array v2 (further divided into two cohorts?the PRS training cohort and the internal-validation cohort?at a ratio of 1:2) or Japonica Array NEO (external-validation cohort). PRSs were calculated for systolic BP (SBP), diastolic BP (DBP), and preeclampsia. Associations between PRSs and preeclampsia, including preeclampsia superimposed on chronic hypertension, were examined using logistic regression analysis; prediction models were developed using a competing-risks approach with clinical predictive variables and PRSs.\u0000Results: In total, 19,836 participants were included. Hyperparameters for PRS calculation were optimized for 3,384 participants in the training cohort. In internal- and external-validation cohorts, 357 of 6,768 (5.3%) and 269 of 9,684 (2.8%) participants developed preeclampsia, respectively. Preeclampsia onset was significantly associated with maternal PRSs for SBP and DBP in internal- and external-validation cohorts and with paternal PRSs for SBP and DBP only in the external-validation cohort. Maternal PRSs for DBP calculated using ?LDpred2? most improved prediction models. Maternal PRSs for DBP provided additional predictive information on clinical predictive variables. Paternal PRSs for DBP improved prediction models in the internal-validation cohort.\u0000Conclusions: Parental PRS, along with clinical predictive variables, is potentially useful for predicting preeclampsia.","PeriodicalId":501409,"journal":{"name":"medRxiv - Obstetrics and Gynecology","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139751715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background Cervical cancer continues to be a major health issue in low- and middle-income countries (LMICs). Despite increasing access to screening, access to precancer treatment remains a significant challenge in LMICs, highlighting a need for innovative, accessible, and resource-appropriate treatment approaches, including self-administered therapies.
{"title":"Men’s perceptions and perceived acceptability of their female partner’s use of self-administered intravaginal therapies for treatment of cervical precancer in Kenya","authors":"Chemtai Mungo, Konyin Adewumi, Grace Ellis, Mercy Rop, Everlyn Adoyo, Yating Zou, Lisa Rahangdale","doi":"10.1101/2024.02.06.24302397","DOIUrl":"https://doi.org/10.1101/2024.02.06.24302397","url":null,"abstract":"<strong>Background</strong> Cervical cancer continues to be a major health issue in low- and middle-income countries (LMICs). Despite increasing access to screening, access to precancer treatment remains a significant challenge in LMICs, highlighting a need for innovative, accessible, and resource-appropriate treatment approaches, including self-administered therapies.","PeriodicalId":501409,"journal":{"name":"medRxiv - Obstetrics and Gynecology","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139751905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-03DOI: 10.1101/2024.02.02.24302191
DMCS Jayasundara, IA Jayawardane, SDS Weliange, TDKM Jayasingha, TMSSB Madugalle
Abstract Background: Continuous labour support is widely acknowledged for potentially enhancing maternal and neonatal outcomes and smoothing the labour process. However, existing literature lacks a comprehensive analysis of the optimal characteristics of labour companions, particularly in comparing the effects of trained versus untrained and familiar versus unfamiliar labour companions across diverse geographical regions and pre and post-millennial. This meta-analysis addresses these research gaps by providing insights into the most influential aspects of continuous labour support. Methodology: A thorough search of PubMed, Google Scholar, Science Direct, International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov, Research4Life, and Cochrane Library was conducted. Study selection utilised the semi-automated tool Rayyan. The Cochrane risk-of-bias (RoB2) tool and funnel plots gauged the risk of bias. Statistical analysis employed RevMan 5.4, using Mantel-Haenszel statistics and random effects models to calculate risk ratios with 95% confidence intervals. Subgroup analyses were performed for different characteristics, including familiarity, training, temporal associations, and geographical locations. The study was registered in INPLASY. (Registration number: INPLASY202410003) Results: Thirty-five randomised controlled trials (RCTs) were identified from 5,346 studies. The meta-analysis highlighted significant positive effects of continuous labour support across various outcomes. There was a substantial improvement in the 5-minute APGAR score < 7, with an effect size of 1.52 (95% CI 1.05, 2.20). Familiar labour companions showed a higher effect size in reducing tocophobia, 1.73 (95% CI 1.49, 2.42), compared to unfamiliar companions, 1.34 (95% CI 1.14, 1.58). Differences were noted between trained and untrained companions, favouring untrained companions in reducing tocophobia and the cesarean section rate. Studies conducted after 2000 had a more significant impact on decreasing labour duration. Geographical variations indicated more pronounced effects in Asia and Africa than in Europe. Discussion and Conclusion: The meta-analysis underscores the benefits of labour companionship, particularly in facilitating the parturient experience of spontaneous labour. The impact is more pronounced in specific subgroups, such as familiar companions, untrained companions, recent studies, and studies conducted in Asia and Africa. The study recommends integrating labour companionship into obstetric care pending further research, standardisation, and awareness initiatives to enhance maternal and neonatal outcomes. Challenges such as study heterogeneity, insufficient data on companion training, and temporal outcome variations are acknowledged.
{"title":"Impact of continuous labour companion- who is the best: A comprehensive meta-analysis on familiarity, training, temporal association, and geographical location","authors":"DMCS Jayasundara, IA Jayawardane, SDS Weliange, TDKM Jayasingha, TMSSB Madugalle","doi":"10.1101/2024.02.02.24302191","DOIUrl":"https://doi.org/10.1101/2024.02.02.24302191","url":null,"abstract":"Abstract\u0000Background: Continuous labour support is widely acknowledged for potentially enhancing maternal and neonatal outcomes and smoothing the labour process. However, existing literature lacks a comprehensive analysis of the optimal characteristics of labour companions, particularly in comparing the effects of trained versus untrained and familiar versus unfamiliar labour companions across diverse geographical regions and pre and post-millennial. This meta-analysis addresses these research gaps by providing insights into the most influential aspects of continuous labour support.\u0000Methodology: A thorough search of PubMed, Google Scholar, Science Direct, International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov, Research4Life, and Cochrane Library was conducted. Study selection utilised the semi-automated tool Rayyan. The Cochrane risk-of-bias (RoB2) tool and funnel plots gauged the risk of bias. Statistical analysis employed RevMan 5.4, using Mantel-Haenszel statistics and random effects models to calculate risk ratios with 95% confidence intervals. Subgroup analyses were performed for different characteristics, including familiarity, training, temporal associations, and geographical locations. The study was registered in INPLASY. (Registration number: INPLASY202410003)\u0000Results: Thirty-five randomised controlled trials (RCTs) were identified from 5,346 studies. The meta-analysis highlighted significant positive effects of continuous labour support across various outcomes. There was a substantial improvement in the 5-minute APGAR score < 7, with an effect size of 1.52 (95% CI 1.05, 2.20). Familiar labour companions showed a higher effect size in reducing tocophobia, 1.73 (95% CI 1.49, 2.42), compared to unfamiliar companions, 1.34 (95% CI 1.14, 1.58). Differences were noted between trained and untrained companions, favouring untrained companions in reducing tocophobia and the cesarean section rate. Studies conducted after 2000 had a more significant impact on decreasing labour duration. Geographical variations indicated more pronounced effects in Asia and Africa than in Europe.\u0000Discussion and Conclusion: The meta-analysis underscores the benefits of labour companionship, particularly in facilitating the parturient experience of spontaneous labour. The impact is more pronounced in specific subgroups, such as familiar companions, untrained companions, recent studies, and studies conducted in Asia and Africa. The study recommends integrating labour companionship into obstetric care pending further research, standardisation, and awareness initiatives to enhance maternal and neonatal outcomes. Challenges such as study heterogeneity, insufficient data on companion training, and temporal outcome variations are acknowledged.","PeriodicalId":501409,"journal":{"name":"medRxiv - Obstetrics and Gynecology","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139678916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-30DOI: 10.1101/2024.01.29.24301773
Amruta D.S. Pathare, Natàlia Pujol-Gualdo, Valentina Rukins, Jelisaveta Džigurski, Maire Peters, Estonian Biobank Research Team, Reedik Mägi, Andres Salumets, Merli Saare, Triin Laisk
STUDY QUESTION Can a large-scale genome-wide association study (GWAS) meta-analysis identify the genomic risk loci and associated candidate genes for female genital tract (FGT) polyps, provide insights into the mechanism underlying their development, and inform potential overlap with other traits, including endometrial cancer? SUMMARY ANSWER GWAS meta-analysis of FGT polyps highlighted the potentially shared mechanisms between polyp development and cancerous processes. WHAT IS KNOWN ALREADY Small-scale candidate gene studies have focused on biological processes such as estrogen stimulation and inflammation to clarify the biology behind FGT polyps. However, the exact mechanism for the development of polyps is still elusive. At the same time, a genome-wide approach, which has become the gold standard in complex disease genetics, has never been used to uncover the genetics of the FGT polyps. STUDY DESIGN, SIZE, DURATION We performed a genome wide association study (GWAS) meta-analysis including a total of 25,100 women with FGT polyps (International Classification of Disease, ICD-10 diagnosis code N84) and 207,193 female controls (without N84 code) of European ancestry from the FinnGen study (11,092 cases and 94,394 controls) and the Estonian Biobank (EstBB, 14,008 cases and 112,799 controls). PARTICIPANTS/MATERIALS, SETTING, METHODS A meta-analysis and functional annotation of GWAS signals were performed to identify and prioritise genes in associated loci. To determine associations with other phenotypes, we performed a look-up of associated variants across multiple traits and health conditions, a genetic correlation analysis, and a phenome-wide association study (PheWAS) with ICD10 diagnosis codes. MAIN RESULTS AND THE ROLE OF CHANCE Our GWAS meta-analysis revealed ten significant (P < 5 x 10-8) genomic risk loci. Two signals, rs2277339 (P = 7.6 x 10-10) and rs1265005 (P = 1.1 x 10-9) (in linkage disequilibrium (LD) with rs805698 r2 = 0.75), are exonic missense variants in PRIM1, and COL17A1 genes, respectively. Based on the literature, these genes may play a role in cellular proliferation. Several of the identified genomic loci had previously been linked to endometrial cancer and/or uterine fibroids. Thus, highlighting the potentially shared mechanisms underlying tissue overgrowth and cancerous processes, which may be relevant to the development of polyps. Genetic correlation analysis revealed a negative correlation between sex hormone-binding globulin (SHBG) and the risk of FGT polyps (rg = -0,21, se = 0.04, P = 2.9 x 10-6), and on the phenotypic level (PheWAS), the strongest associations were observed with endometriosis, leiomyoma of the uterus and excessive, frequent and irregular menstruation. LARGE SCALE DATA The complete GWAS summary statistics will be made available after publication through the GWAS Catalogue (https://www.ebi.ac.uk/gwas/). LIMITATIONS, REASONS FOR CAUTION In this study, we focused broadly on polyps of FGT and did not dif
{"title":"Large-scale genome-wide association study to determine the genetic underpinnings of female genital tract polyps","authors":"Amruta D.S. Pathare, Natàlia Pujol-Gualdo, Valentina Rukins, Jelisaveta Džigurski, Maire Peters, Estonian Biobank Research Team, Reedik Mägi, Andres Salumets, Merli Saare, Triin Laisk","doi":"10.1101/2024.01.29.24301773","DOIUrl":"https://doi.org/10.1101/2024.01.29.24301773","url":null,"abstract":"STUDY QUESTION\u0000Can a large-scale genome-wide association study (GWAS) meta-analysis identify the genomic risk loci and associated candidate genes for female genital tract (FGT) polyps, provide insights into the mechanism underlying their development, and inform potential overlap with other traits, including endometrial cancer?\u0000SUMMARY ANSWER\u0000GWAS meta-analysis of FGT polyps highlighted the potentially shared mechanisms between polyp development and cancerous processes. WHAT IS KNOWN ALREADY\u0000Small-scale candidate gene studies have focused on biological processes such as estrogen stimulation and inflammation to clarify the biology behind FGT polyps. However, the exact mechanism for the development of polyps is still elusive. At the same time, a genome-wide approach, which has become the gold standard in complex disease genetics, has never been used to uncover the genetics of the FGT polyps.\u0000STUDY DESIGN, SIZE, DURATION\u0000We performed a genome wide association study (GWAS) meta-analysis including a total of 25,100 women with FGT polyps (International Classification of Disease, ICD-10 diagnosis code N84) and 207,193 female controls (without N84 code) of European ancestry from the FinnGen study (11,092 cases and 94,394 controls) and the Estonian Biobank (EstBB, 14,008 cases and 112,799 controls).\u0000PARTICIPANTS/MATERIALS, SETTING, METHODS\u0000A meta-analysis and functional annotation of GWAS signals were performed to identify and prioritise genes in associated loci. To determine associations with other phenotypes, we performed a look-up of associated variants across multiple traits and health conditions, a genetic correlation analysis, and a phenome-wide association study (PheWAS) with ICD10 diagnosis codes. MAIN RESULTS AND THE ROLE OF CHANCE\u0000Our GWAS meta-analysis revealed ten significant (P < 5 x 10-8) genomic risk loci. Two signals, rs2277339 (P = 7.6 x 10-10) and rs1265005 (P = 1.1 x 10-9) (in linkage disequilibrium (LD) with rs805698 r2 = 0.75), are exonic missense variants in PRIM1, and COL17A1 genes, respectively. Based on the literature, these genes may play a role in cellular proliferation. Several of the identified genomic loci had previously been linked to endometrial cancer and/or uterine fibroids. Thus, highlighting the potentially shared mechanisms underlying tissue overgrowth and cancerous processes, which may be relevant to the development of polyps. Genetic correlation analysis revealed a negative correlation between sex hormone-binding globulin (SHBG) and the risk of FGT polyps (rg = -0,21, se = 0.04, P = 2.9 x 10-6), and on the phenotypic level (PheWAS), the strongest associations were observed with endometriosis, leiomyoma of the uterus and excessive, frequent and irregular menstruation. LARGE SCALE DATA\u0000The complete GWAS summary statistics will be made available after publication through the GWAS Catalogue (https://www.ebi.ac.uk/gwas/).\u0000LIMITATIONS, REASONS FOR CAUTION\u0000In this study, we focused broadly on polyps of FGT and did not dif","PeriodicalId":501409,"journal":{"name":"medRxiv - Obstetrics and Gynecology","volume":"1 1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139584748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: To develop a model based on first trimester maternal serum LC-MS/MS to predict spontaneous preterm birth (sPTB) < 37weeks. Methods: A cohort of 2,053 women were enrolled in a tertiary maternity hospital in China from July 1, 2018 to January 31, 2019. In total, 110 singleton pregnancies (26 cases of sPTB and 84 controls) at 11-136/7 gestational weeks were used for model development and internal validation. A total of 72 pregnancies (25 cases of sPTB and 47 controls) at 20-32 gestational weeks from an additional cohort of 2,167 women were used to evaluate the scalability of the prediction model. Maternal serum samples were collected at enrollment and analyzed by LC-MS/MS, and candidate proteins were used to develop an optimal predictive model by machine learning algorithms. Results: A novel predictive panel with four proteins, including sFlt-1, MMP-8, ceruloplasmin, and SHBG, which was the most discriminative subset, was developed. The optimal model of logistic regression had an AUC of 0.934, with additional prediction of sPTB in second and third trimester (0.868 AUC). Importantly, higher-risk subjects defined by the prediction generally gave birth earlier than lower-risk subjects. Conclusion: First trimester modeling based on maternal serum LC-MS/MS identifies pregnant women at risk of sPTB, which may provide utility in identifying women at risk at an early stage of pregnancy before clinical presentation to allow for earlier intervention.
{"title":"Development of a spontaneous preterm birth predictive model using a panel of serum protein biomarkers for early pregnant women: A nested case-control study","authors":"Shuang Liang, Yuling Chen, Tingting Jia, Ying Chang, Wen Li, Yongjun Piao, Xu Chen","doi":"10.1101/2024.01.29.24301917","DOIUrl":"https://doi.org/10.1101/2024.01.29.24301917","url":null,"abstract":"Objective: To develop a model based on first trimester maternal serum LC-MS/MS to predict spontaneous preterm birth (sPTB) < 37weeks.\u0000Methods: A cohort of 2,053 women were enrolled in a tertiary maternity hospital in China from July 1, 2018 to January 31, 2019. In total, 110 singleton pregnancies (26 cases of sPTB and 84 controls) at 11-136/7 gestational weeks were used for model development and internal validation. A total of 72 pregnancies (25 cases of sPTB and 47 controls) at 20-32 gestational weeks from an additional cohort of 2,167 women were used to evaluate the scalability of the prediction model. Maternal serum samples were collected at enrollment and analyzed by LC-MS/MS, and candidate proteins were used to develop an optimal predictive model by machine learning algorithms.\u0000Results: A novel predictive panel with four proteins, including sFlt-1, MMP-8, ceruloplasmin, and SHBG, which was the most discriminative subset, was developed. The optimal model of logistic regression had an AUC of 0.934, with additional prediction of sPTB in second and third trimester (0.868 AUC). Importantly, higher-risk subjects defined by the prediction generally gave birth earlier than lower-risk subjects.\u0000Conclusion: First trimester modeling based on maternal serum LC-MS/MS identifies pregnant women at risk of sPTB, which may provide utility in identifying women at risk at an early stage of pregnancy before clinical presentation to allow for earlier intervention.","PeriodicalId":501409,"journal":{"name":"medRxiv - Obstetrics and Gynecology","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139584993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-24DOI: 10.1101/2024.01.22.24301562
Mark Allen Clapp, Jessica Cohen, Cynthia Gyamfi-Bannerman, Anjali Kaimal, Scott Lorch, Jason Wright, Alexander Melamed
As the risk of preterm birth is known to vary widely, we aimed to determine if antenatal steroid exposure among LPBs varied based on sociodemographic characteristics. We hypothesized that sociodemographic factors may influence a provider's clinical judgment of a patient's likelihood of preterm birth and, therefore, also be associated with antenatal steroid use. This cross-sectional analysis used the 2021 US natality data and included non-anomalous, liveborn, hospital-based singleton births at >=34 weeks of gestation to mothers without diabetes, a cohort similar to those in the ALPS Trial. The following sociodemographic factors were compared among those who received vs. did not receive steroids using chi-square tests: age, race (as designated and categorized on the birth certificate), ethnicity, primary pay for the delivery, marital status, and education. In 2021, 237,025 late preterm births met eligibility criteria, of which 17.3% were exposed to antenatal steroids. Among the following sociodemographic factors, the odds of antenatal steroid receipt were lower compared to the reference majority population (Table 1): 1) Black (adjusted odds ratio (aOR) 0.88 (95% CI 0.81, 0.96)) and Native Hawaiian or Other Pacific Islander (NHOPI) (aOR 0.58 (95% CI 0.43, 0.79) compared to White race; 2) less than high school education (aOR 0.76 (95% CI 0.72, 0.81)) or high school education (aOR 0.87 (95% CI 0.83, 0.91)) compared to post-secondary education; and 3) public (aOR 0.83 (95% CI 0.78, 0.87)) or no insurance (aOR 0.68 (95% CI 0.61, 0.77)) compared to private insurance. Age and marital status were not associated with steroid receipt. Despite no known differential treatment effects of antenatal steroids by sociodemographic factors, steroid exposure among LBPs varied significantly among races, ethnicities, payers, and education levels in the US.
众所周知，早产的风险差异很大，因此我们旨在确定早产儿产前类固醇暴露是否因社会人口特征而异。我们假设，社会人口学因素可能会影响医疗服务提供者对患者早产可能性的临床判断，因此也与产前类固醇的使用有关。这项横断面分析使用了美国 2021 年的出生人口数据，包括妊娠 34 周的非异常、活产、住院单胎新生儿，这些新生儿的母亲无糖尿病，与 ALPS 试验中的人群相似。使用卡方检验比较了接受与未接受类固醇治疗的产妇的以下社会人口学因素：年龄、种族（出生证明上的指定和分类）、民族、分娩的主要费用、婚姻状况和教育程度。2021 年，有 237 025 名晚期早产儿符合资格标准，其中 17.3% 接受了产前类固醇治疗。在以下社会人口学因素中，与参照多数人群相比，接受产前类固醇治疗的几率较低（表 1）：1）与白种人相比，黑人（调整后的几率比（aOR）为 0.88（95% CI 0.81，0.96））和夏威夷原住民或其他太平洋岛民（NHOPI）（aOR 0.58（95% CI 0.43，0.79））；2）教育程度低于高中（aOR 0.76（95% CI 0.72，0.81））或高中学历（aOR 0.87 (95% CI 0.83，0.91)）与大专学历相比；以及 3）公共保险（aOR 0.83 (95% CI 0.78，0.87)）或无保险（aOR 0.68 (95% CI 0.61，0.77)）与私人保险相比。年龄和婚姻状况与接受类固醇治疗无关。尽管产前类固醇治疗效果因社会人口因素而异，但在美国，不同种族、族裔、付款人和教育水平的枸杞患者接受类固醇治疗的情况差异很大。
{"title":"Sociodemographic Factors Associated with Antenatal Steroid Exposure among Late Preterm Births","authors":"Mark Allen Clapp, Jessica Cohen, Cynthia Gyamfi-Bannerman, Anjali Kaimal, Scott Lorch, Jason Wright, Alexander Melamed","doi":"10.1101/2024.01.22.24301562","DOIUrl":"https://doi.org/10.1101/2024.01.22.24301562","url":null,"abstract":"As the risk of preterm birth is known to vary widely, we aimed to determine if antenatal steroid exposure among LPBs varied based on sociodemographic characteristics. We hypothesized that sociodemographic factors may influence a provider's clinical judgment of a patient's likelihood of preterm birth and, therefore, also be associated with antenatal steroid use. This cross-sectional analysis used the 2021 US natality data and included non-anomalous, liveborn, hospital-based singleton births at >=34 weeks of gestation to mothers without diabetes, a cohort similar to those in the ALPS Trial. The following sociodemographic factors were compared among those who received vs. did not receive steroids using chi-square tests: age, race (as designated and categorized on the birth certificate), ethnicity, primary pay for the delivery, marital status, and education. In 2021, 237,025 late preterm births met eligibility criteria, of which 17.3% were exposed to antenatal steroids. Among the following sociodemographic factors, the odds of antenatal steroid receipt were lower compared to the reference majority population (Table 1): 1) Black (adjusted odds ratio (aOR) 0.88 (95% CI 0.81, 0.96)) and Native Hawaiian or Other Pacific Islander (NHOPI) (aOR 0.58 (95% CI 0.43, 0.79) compared to White race; 2) less than high school education (aOR 0.76 (95% CI 0.72, 0.81)) or high school education (aOR 0.87 (95% CI 0.83, 0.91)) compared to post-secondary education; and 3) public (aOR 0.83 (95% CI 0.78, 0.87)) or no insurance (aOR 0.68 (95% CI 0.61, 0.77)) compared to private insurance. Age and marital status were not associated with steroid receipt.\u0000Despite no known differential treatment effects of antenatal steroids by sociodemographic factors, steroid exposure among LBPs varied significantly among races, ethnicities, payers, and education levels in the US.","PeriodicalId":501409,"journal":{"name":"medRxiv - Obstetrics and Gynecology","volume":"110 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139552801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-23DOI: 10.1101/2024.01.22.24301627
Katherine Mahoney, Licia Bravo, Arden McAllister, Kacie Bogar, Sean Hennessy, Courtney A Schreiber, Alice Abernathy
Objectives: While it is well documented that abortion access is associated with improved health, pregnancy-related, and socioeconomic outcomes, the association between abortion access and other reproductive health outcomes is less well described. Abortion-providing clinics also offer preventative reproductive health services. We conducted a scoping review to ascertain the extent to which preventive reproductive healthcare services (contraception, sexually transmitted infection testing and treatment, cervical cancer screening) are affected by abortion access in the United States. Methods: Researchers screened articles and extracted data from PubMed, Embase, Scopus and CINAHL. We excluded articles that did not link abortion to contraception, sexually transmitted infection testing and treatment and cervical cancer screening; or took place outside the US. Results: 5,359 papers were screened, 74 were included for full text review. Sixty-five were about contraception, seven on STIs, one on cervical cancer screening, and one on other services. The association between policies that restrict or protect abortion access and preventative health services has not been studied on a national scale. Drivers of variation were: insurance and billing policies; regulatory requirements of abortion-providing facilities, lack of staff training in clinics that did not specialize in abortion care; and limited follow up after abortion. Conclusions: Abortion-providing clinics are a highly utilized access point for reproductive health services. More research is needed to determine the public health impact of constrained abortion access on contraceptive use, STI rates and cervical cancer in regions where many abortion-providing clinics have closed.
{"title":"Health services provided at the time of abortion in the US: a scoping review of the qualitative and quantitative evidence","authors":"Katherine Mahoney, Licia Bravo, Arden McAllister, Kacie Bogar, Sean Hennessy, Courtney A Schreiber, Alice Abernathy","doi":"10.1101/2024.01.22.24301627","DOIUrl":"https://doi.org/10.1101/2024.01.22.24301627","url":null,"abstract":"Objectives: While it is well documented that abortion access is associated with improved health, pregnancy-related, and socioeconomic outcomes, the association between abortion access and other reproductive health outcomes is less well described. Abortion-providing clinics also offer preventative reproductive health services. We conducted a scoping review to ascertain the extent to which preventive reproductive healthcare services (contraception, sexually transmitted infection testing and treatment, cervical cancer screening) are affected by abortion access in the United States. Methods: Researchers screened articles and extracted data from PubMed, Embase, Scopus and CINAHL. We excluded articles that did not link abortion to contraception, sexually transmitted infection testing and treatment and cervical cancer screening; or took place outside the US. Results: 5,359 papers were screened, 74 were included for full text review. Sixty-five were about contraception, seven on STIs, one on cervical cancer screening, and one on other services. The association between policies that restrict or protect abortion access and preventative health services has not been studied on a national scale. Drivers of variation were: insurance and billing policies; regulatory requirements of abortion-providing facilities, lack of staff training in clinics that did not specialize in abortion care; and limited follow up after abortion. Conclusions: Abortion-providing clinics are a highly utilized access point for reproductive health services. More research is needed to determine the public health impact of constrained abortion access on contraceptive use, STI rates and cervical cancer in regions where many abortion-providing clinics have closed.","PeriodicalId":501409,"journal":{"name":"medRxiv - Obstetrics and Gynecology","volume":"72 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139552671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-17DOI: 10.1101/2024.01.16.24301371
Alex C. Soupir, Mary K. Townsend, Cassandra A. Hathaway, Jonathan Nguyen, Carlos Moran Segura, Daryoush Saeed-Vafa, Oscar E. Ospina, Lauren C. Peres, Jose R. Conejo-Garcia, Kathryn L. Terry, Shelley S. Tworoger, Brooke L. Fridley
Background Studies have shown that tumor infiltrating lymphocyte (TILs) abundance is associated with overall survival in patients with high-grade serous ovarian cancer (HGSOC); however, the role of the spatial contexture and organization of TILs is less clear.
{"title":"Impact of spatial clustering of cytotoxic and tumor infiltrating lymphocytes on overall survival in women with high grade serous ovarian cancer","authors":"Alex C. Soupir, Mary K. Townsend, Cassandra A. Hathaway, Jonathan Nguyen, Carlos Moran Segura, Daryoush Saeed-Vafa, Oscar E. Ospina, Lauren C. Peres, Jose R. Conejo-Garcia, Kathryn L. Terry, Shelley S. Tworoger, Brooke L. Fridley","doi":"10.1101/2024.01.16.24301371","DOIUrl":"https://doi.org/10.1101/2024.01.16.24301371","url":null,"abstract":"<strong>Background</strong> Studies have shown that tumor infiltrating lymphocyte (TILs) abundance is associated with overall survival in patients with high-grade serous ovarian cancer (HGSOC); however, the role of the spatial contexture and organization of TILs is less clear.","PeriodicalId":501409,"journal":{"name":"medRxiv - Obstetrics and Gynecology","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139500909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-15DOI: 10.1101/2024.01.14.24301280
Elbert-Jaap I. Schipper, Klaas J. Wardenaar, Annemieke C. Bolte, Rei Monden, Titus W.D.P. van Os, Marieke Wichers, Peter de Jonge
Background Research suggests that besides somatic factors, psychological and social factors are associated with pregnancy outcomes. The objective of this study was to determine the independent effects of psychosocial risk factors on maternal blood pressure, gestational age at birth, birthweight and Apgar score.
{"title":"Psychological and social risk factors and pregnancy outcome: a prospective cohort study","authors":"Elbert-Jaap I. Schipper, Klaas J. Wardenaar, Annemieke C. Bolte, Rei Monden, Titus W.D.P. van Os, Marieke Wichers, Peter de Jonge","doi":"10.1101/2024.01.14.24301280","DOIUrl":"https://doi.org/10.1101/2024.01.14.24301280","url":null,"abstract":"<strong>Background</strong> Research suggests that besides somatic factors, psychological and social factors are associated with pregnancy outcomes. The objective of this study was to determine the independent effects of psychosocial risk factors on maternal blood pressure, gestational age at birth, birthweight and Apgar score.","PeriodicalId":501409,"journal":{"name":"medRxiv - Obstetrics and Gynecology","volume":"698 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139500735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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