Pub Date : 2023-10-01DOI: 10.1097/ogx.0000000000001191
Avan Shirwani, Jeffrey A. Kuller, Sarah K. Dotters-Katz, Kateena Addae-Konadu
ABSTRACT The use of tobacco and nicotine products during pregnancy is known to increase the risk of adverse effects on the fetus. Increased education and research have resulted in greater rates of smoking cessation during pregnancy, with a decline from 13.2% of pregnant individuals smoking in 2006 to 7.2% in 2016. However, smoking while pregnant still proves to be a prevalent issue that is associated with numerous adverse outcomes, including low birth weight, preterm birth, and developmental delays. Smoking cessation before or during pregnancy can help mitigate these effects, but the appropriate treatment can be challenging to ascertain. Accordingly, clinicians should look to provide individualized care composed of behavioral counseling in conjunction with pharmacotherapies when indicated, combined with ongoing support and education. Target Audience Obstetricians and gynecologists, family physicians. Learning Objectives After completing this activity, the learner should be better able to identify the pathophysiologic effects of smoking during pregnancy and the different forms of nicotine use; describe the maternal risk of smoking, along with its neonatal and childhood effects; and explain the potential screening and treatment strategies for smoking cessation during pregnancy.
{"title":"Nicotine Use During Pregnancy: Cessation and Treatment Strategies","authors":"Avan Shirwani, Jeffrey A. Kuller, Sarah K. Dotters-Katz, Kateena Addae-Konadu","doi":"10.1097/ogx.0000000000001191","DOIUrl":"https://doi.org/10.1097/ogx.0000000000001191","url":null,"abstract":"ABSTRACT The use of tobacco and nicotine products during pregnancy is known to increase the risk of adverse effects on the fetus. Increased education and research have resulted in greater rates of smoking cessation during pregnancy, with a decline from 13.2% of pregnant individuals smoking in 2006 to 7.2% in 2016. However, smoking while pregnant still proves to be a prevalent issue that is associated with numerous adverse outcomes, including low birth weight, preterm birth, and developmental delays. Smoking cessation before or during pregnancy can help mitigate these effects, but the appropriate treatment can be challenging to ascertain. Accordingly, clinicians should look to provide individualized care composed of behavioral counseling in conjunction with pharmacotherapies when indicated, combined with ongoing support and education. Target Audience Obstetricians and gynecologists, family physicians. Learning Objectives After completing this activity, the learner should be better able to identify the pathophysiologic effects of smoking during pregnancy and the different forms of nicotine use; describe the maternal risk of smoking, along with its neonatal and childhood effects; and explain the potential screening and treatment strategies for smoking cessation during pregnancy.","PeriodicalId":19409,"journal":{"name":"Obstetrical & Gynecological Survey","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136009875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-01DOI: 10.1097/ogx.0000000000001212
F. D'Antonio, D. Marinceu, S. Prasad, A. Khalil
ABSTRACT One of the most common causes of infection-related fetal malformations is congenital cytomegalovirus (CMV), which affects approximately 0.5% to 2% of newborns. Several approaches have been investigated for screening, prevention, and treatment; one drug that shows activity against CMV is valacyclovir, and prenatal administration of this drug has been investigated in the context of preventing fetal disorders due to CMV. Although studies and clinical trials have been done regarding the safety and effectiveness of valacyclovir, clinical attitudes regarding universal CMV screening and prenatal valacyclovir treatment have yet to change. This article is a systematic review and meta-analysis of the safety and effectiveness of prenatal valacyclovir in CMV-infected pregnancies. Inclusion criteria included pregnancies with CMV infection diagnosed through serology, with a primary outcome of incidence of congenital CMV confirmed by polymerase chain reaction from amniocentesis. Secondary outcomes included symptomatic infection (rash, jaundice, microcephaly, seizures, hepatosplenomegaly, hearing loss, visual loss, retinitis, and central nervous system anomalies), asymptomatic infection, perinatal death, pregnancy termination, fetal anomaly, or severe symptoms. Adverse events related to the administration of valacyclovir were also recorded. Because relatively few studies were available for inclusion, the authors were unable to assess publication bias, but other risk of bias was assessed using standard tools. Final analysis included 8 studies and 620 pregnant women with CMV in 2 randomized controlled trials and 6 observational studies. One randomized controlled trial focused on valacyclovir treatment for CMV infection acquired in early pregnancy, and the other assessed valacyclovir treatment between 34 and 38 weeks' gestation to reduce risk of CMV within 1 year of delivery. The latter of the 2 studies was not included in pooled data synthesis because of inclusion criteria differences. Three studies focused on valacyclovir treatment for confirmed maternal CMV infection; pooled data analysis showed that valacyclovir-treated pregnancies had lower risk of congenital CMV (odds ratio [OR], 0.37; 95% confidence interval [CI], 0.21–0.64; P < 0.001). When contracted in the first trimester, risk of vertical transmission was lower in those who were treated with valacyclovir (OR, 0.34; 95% CI, 0.15–0.74; P = 0.001); however, there was no effect observed in those with CMV in the periconceptual period. Analysis additionally showed that prenatal valacyclovir treatment was more likely to result in asymptomatic children (OR, 2.98; 95% CI, 1.18–7.55; P = 0.021), but no other significant perinatal differences were observed. These results show that treatment of CMV with prenatal valacyclovir reduces the risk of congenital CMV and its associated complications. Limitations of this analysis include the heterogeneity of inclusion and measurement criteria, as well as small sampl
{"title":"Effectiveness and Safety of Prenatal Valacyclovir for Congenital Cytomegalovirus Infection: Systematic Review and Meta-analysis","authors":"F. D'Antonio, D. Marinceu, S. Prasad, A. Khalil","doi":"10.1097/ogx.0000000000001212","DOIUrl":"https://doi.org/10.1097/ogx.0000000000001212","url":null,"abstract":"ABSTRACT One of the most common causes of infection-related fetal malformations is congenital cytomegalovirus (CMV), which affects approximately 0.5% to 2% of newborns. Several approaches have been investigated for screening, prevention, and treatment; one drug that shows activity against CMV is valacyclovir, and prenatal administration of this drug has been investigated in the context of preventing fetal disorders due to CMV. Although studies and clinical trials have been done regarding the safety and effectiveness of valacyclovir, clinical attitudes regarding universal CMV screening and prenatal valacyclovir treatment have yet to change. This article is a systematic review and meta-analysis of the safety and effectiveness of prenatal valacyclovir in CMV-infected pregnancies. Inclusion criteria included pregnancies with CMV infection diagnosed through serology, with a primary outcome of incidence of congenital CMV confirmed by polymerase chain reaction from amniocentesis. Secondary outcomes included symptomatic infection (rash, jaundice, microcephaly, seizures, hepatosplenomegaly, hearing loss, visual loss, retinitis, and central nervous system anomalies), asymptomatic infection, perinatal death, pregnancy termination, fetal anomaly, or severe symptoms. Adverse events related to the administration of valacyclovir were also recorded. Because relatively few studies were available for inclusion, the authors were unable to assess publication bias, but other risk of bias was assessed using standard tools. Final analysis included 8 studies and 620 pregnant women with CMV in 2 randomized controlled trials and 6 observational studies. One randomized controlled trial focused on valacyclovir treatment for CMV infection acquired in early pregnancy, and the other assessed valacyclovir treatment between 34 and 38 weeks' gestation to reduce risk of CMV within 1 year of delivery. The latter of the 2 studies was not included in pooled data synthesis because of inclusion criteria differences. Three studies focused on valacyclovir treatment for confirmed maternal CMV infection; pooled data analysis showed that valacyclovir-treated pregnancies had lower risk of congenital CMV (odds ratio [OR], 0.37; 95% confidence interval [CI], 0.21–0.64; P < 0.001). When contracted in the first trimester, risk of vertical transmission was lower in those who were treated with valacyclovir (OR, 0.34; 95% CI, 0.15–0.74; P = 0.001); however, there was no effect observed in those with CMV in the periconceptual period. Analysis additionally showed that prenatal valacyclovir treatment was more likely to result in asymptomatic children (OR, 2.98; 95% CI, 1.18–7.55; P = 0.021), but no other significant perinatal differences were observed. These results show that treatment of CMV with prenatal valacyclovir reduces the risk of congenital CMV and its associated complications. Limitations of this analysis include the heterogeneity of inclusion and measurement criteria, as well as small sampl","PeriodicalId":19409,"journal":{"name":"Obstetrical & Gynecological Survey","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135963374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-01DOI: 10.1097/01.ogx.0000993668.06748.a3
Jasper Linthorst, Moezammin M. M. Baksi, Matthijs R. A. Welkers, Erik A. Sistermans
ABSTRACT Pregnancy increases the body's vulnerability to infectious disease, and current guidelines during pregnancy include minimizing possible exposure to viral infection. In cases where viral infection does occur, these can cause mild to severe complications in both mother and fetus; many viruses that result in such complications are DNA viruses. Current diagnosis technology for DNA viruses relies largely on polymerase chain reaction (PCR), which is very sensitive but generally targeted at a specific virus and so tends to not be very comprehensive. In addition, this testing is normally performed only on those who are at high risk or expressing symptoms. To more fully understand the effect and prevalence of DNA viruses in pregnancy, this study used noninvasive prenatal testing (NIPT) that captures cell-free DNA (cfDNA) to examine the DNA virome in pregnant women between 2017 and 2020. Data included deidentified NIPT results for 108,349 individuals, and DNA sequences were used to screen for 224 DNA viruses. Viruses that were genetically similar were differentiated based on taxonomy through a meticulous decision tree to avoid generalized errors in categorizing them. The most commonly detected virus was parvovirus B19, occurring in approximately 1 in 3000 cfDNA reads. High viral loads were also observed for hepatitis B, Bocaparvovirus , papillomavirus, adenovirus, adeno-associated virus, Epstein-Barr virus (EBV)/herpesvirus 4, cytomegalovirus (CMV), herpesvirus 6, and torque teno virus. A cross-examination of demographic and pregnancy factors revealed many associations, most of which remained significant after adjustments for multiple comparisons. Available characteristics included maternal age, body mass index (BMI), gestational age, fetal fraction, and the number of sequenced reads with the presence of viral DNA in the samples. Detection of viral DNA was associated with lower BMI, along with a lower concentration of cfDNA and a higher fetal fraction. When individual viruses were analyzed, CMV had the most significant relationship with gestational age and maternal age. Results additionally showed that low fetal fraction was associated with lower detection of viral DNA for specific viruses. These results show that it is feasible to detect viral DNA in NIPT samples. If viral DNA can be detected, there is potential to diagnose infection and to possibly prevent complications due to the virus. Current clinical practice does not use NIPT as a diagnostic tool for viral infection, but there is potential for this in the future. Further research should focus on clinical utility, sensitivity, specificity, and accuracy, as well as the relationship of viral DNA with low fetal fraction.
{"title":"The Cell-Free DNA Virome of 108,349 Dutch Pregnant Women","authors":"Jasper Linthorst, Moezammin M. M. Baksi, Matthijs R. A. Welkers, Erik A. Sistermans","doi":"10.1097/01.ogx.0000993668.06748.a3","DOIUrl":"https://doi.org/10.1097/01.ogx.0000993668.06748.a3","url":null,"abstract":"ABSTRACT Pregnancy increases the body's vulnerability to infectious disease, and current guidelines during pregnancy include minimizing possible exposure to viral infection. In cases where viral infection does occur, these can cause mild to severe complications in both mother and fetus; many viruses that result in such complications are DNA viruses. Current diagnosis technology for DNA viruses relies largely on polymerase chain reaction (PCR), which is very sensitive but generally targeted at a specific virus and so tends to not be very comprehensive. In addition, this testing is normally performed only on those who are at high risk or expressing symptoms. To more fully understand the effect and prevalence of DNA viruses in pregnancy, this study used noninvasive prenatal testing (NIPT) that captures cell-free DNA (cfDNA) to examine the DNA virome in pregnant women between 2017 and 2020. Data included deidentified NIPT results for 108,349 individuals, and DNA sequences were used to screen for 224 DNA viruses. Viruses that were genetically similar were differentiated based on taxonomy through a meticulous decision tree to avoid generalized errors in categorizing them. The most commonly detected virus was parvovirus B19, occurring in approximately 1 in 3000 cfDNA reads. High viral loads were also observed for hepatitis B, Bocaparvovirus , papillomavirus, adenovirus, adeno-associated virus, Epstein-Barr virus (EBV)/herpesvirus 4, cytomegalovirus (CMV), herpesvirus 6, and torque teno virus. A cross-examination of demographic and pregnancy factors revealed many associations, most of which remained significant after adjustments for multiple comparisons. Available characteristics included maternal age, body mass index (BMI), gestational age, fetal fraction, and the number of sequenced reads with the presence of viral DNA in the samples. Detection of viral DNA was associated with lower BMI, along with a lower concentration of cfDNA and a higher fetal fraction. When individual viruses were analyzed, CMV had the most significant relationship with gestational age and maternal age. Results additionally showed that low fetal fraction was associated with lower detection of viral DNA for specific viruses. These results show that it is feasible to detect viral DNA in NIPT samples. If viral DNA can be detected, there is potential to diagnose infection and to possibly prevent complications due to the virus. Current clinical practice does not use NIPT as a diagnostic tool for viral infection, but there is potential for this in the future. Further research should focus on clinical utility, sensitivity, specificity, and accuracy, as well as the relationship of viral DNA with low fetal fraction.","PeriodicalId":19409,"journal":{"name":"Obstetrical & Gynecological Survey","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135963383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-01DOI: 10.1097/01.ogx.0000993672.66513.1f
L. D. Pacheco, R. G. Clifton, G. R. Saade, S. J. Weiner, S. Parry, J. M. Thorp, M. Longo, A. Salazar, W. Dalton, A. T. N. Tita, C. Gyamfi-Bannerman, S. P. Chauhan, T. D. Metz, K. Rood, D. J. Rouse, J. L. Bailit, W. A. Grobman, H. N. Simhan, G. A. Macones
ABSTRACT Previous research has presented convincing evidence that the administration of tranexamic acid (TXA) after cesarean delivery can reduce the incidence of postpartum hemorrhage (PPH) and the associated mortality and morbidity. Although there have been several significant studies on this topic, they are limited by small sample sizes, which make the studies difficult to generalize and limit their statistical power. This study aimed to address that gap and assess clinical outcomes related to the administration of TXA in a large sample. This was a multicenter, double-blind, randomized controlled trial including 31 hospitals participating in the Maternal-Fetal Medicine Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Eligibility criteria included scheduled or unscheduled cesarean delivery of a singleton or twin gestation. Exclusion criteria included maternal age younger than 18 years, blood transfusion before randomization, plan for transfusion after randomization, contraindications to TXA, patient decision not to use blood products, or administration of antifibrolytic agents or uterotonic agents other than oxytocin. The primary outcome was maternal death or blood transfusion before hospital discharge or 7 days after delivery, whichever came first. Secondary outcomes included intraoperative blood loss of more than 1 L and treatments or interventions in response to bleeding or related complications within 7 days of delivery, as well as infectious complications within 6 weeks of delivery. Final analyses included 11,000 patients, with 5529 in the TXA group and 5471 in the placebo group. Baseline characteristics were not significantly different between groups, and no center-dependent differences were observed. The primary outcome was observed in 3.6% of patients in the TXA group and 4.3% of patients in the placebo group (adjusted relative risk, 0.89; P = 0.19). Intraoperative blood loss of more than 1 L was recorded in 7.3% and 8.0% in the tranexamic and placebo groups, respectively (relative risk, 0.90; 95% CI, 0.79–1.05). Treatments and interventions in response to bleeding occurred in 16.1% of individuals in the TXA group and 18.0% of those in the placebo group (relative risk, 0.90; 95% CI, 0.82–0.97). Infectious complications were reported in 3.2% and 2.5% in the TXA and placebo groups, respectively (relative risk, 1.28; 95% CI, 1.02–1.61). Sensitivity analysis showed similar results to initial analysis, and no significant differences were seen between groups in major safety outcomes. This analysis indicates that the administration of TXA during cesarean delivery did not lower the risk of maternal death or blood transfusion. These results are in direct contradiction to previous research showing that TXA is effective at reducing these outcomes. This trial was stronger than any previous studies in sample size and careful randomization ensuring equal representation of scheduled and unscheduled c
{"title":"Tranexamic Acid to Prevent Obstetrical Hemorrhage After Cesarean Delivery","authors":"L. D. Pacheco, R. G. Clifton, G. R. Saade, S. J. Weiner, S. Parry, J. M. Thorp, M. Longo, A. Salazar, W. Dalton, A. T. N. Tita, C. Gyamfi-Bannerman, S. P. Chauhan, T. D. Metz, K. Rood, D. J. Rouse, J. L. Bailit, W. A. Grobman, H. N. Simhan, G. A. Macones","doi":"10.1097/01.ogx.0000993672.66513.1f","DOIUrl":"https://doi.org/10.1097/01.ogx.0000993672.66513.1f","url":null,"abstract":"ABSTRACT Previous research has presented convincing evidence that the administration of tranexamic acid (TXA) after cesarean delivery can reduce the incidence of postpartum hemorrhage (PPH) and the associated mortality and morbidity. Although there have been several significant studies on this topic, they are limited by small sample sizes, which make the studies difficult to generalize and limit their statistical power. This study aimed to address that gap and assess clinical outcomes related to the administration of TXA in a large sample. This was a multicenter, double-blind, randomized controlled trial including 31 hospitals participating in the Maternal-Fetal Medicine Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Eligibility criteria included scheduled or unscheduled cesarean delivery of a singleton or twin gestation. Exclusion criteria included maternal age younger than 18 years, blood transfusion before randomization, plan for transfusion after randomization, contraindications to TXA, patient decision not to use blood products, or administration of antifibrolytic agents or uterotonic agents other than oxytocin. The primary outcome was maternal death or blood transfusion before hospital discharge or 7 days after delivery, whichever came first. Secondary outcomes included intraoperative blood loss of more than 1 L and treatments or interventions in response to bleeding or related complications within 7 days of delivery, as well as infectious complications within 6 weeks of delivery. Final analyses included 11,000 patients, with 5529 in the TXA group and 5471 in the placebo group. Baseline characteristics were not significantly different between groups, and no center-dependent differences were observed. The primary outcome was observed in 3.6% of patients in the TXA group and 4.3% of patients in the placebo group (adjusted relative risk, 0.89; P = 0.19). Intraoperative blood loss of more than 1 L was recorded in 7.3% and 8.0% in the tranexamic and placebo groups, respectively (relative risk, 0.90; 95% CI, 0.79–1.05). Treatments and interventions in response to bleeding occurred in 16.1% of individuals in the TXA group and 18.0% of those in the placebo group (relative risk, 0.90; 95% CI, 0.82–0.97). Infectious complications were reported in 3.2% and 2.5% in the TXA and placebo groups, respectively (relative risk, 1.28; 95% CI, 1.02–1.61). Sensitivity analysis showed similar results to initial analysis, and no significant differences were seen between groups in major safety outcomes. This analysis indicates that the administration of TXA during cesarean delivery did not lower the risk of maternal death or blood transfusion. These results are in direct contradiction to previous research showing that TXA is effective at reducing these outcomes. This trial was stronger than any previous studies in sample size and careful randomization ensuring equal representation of scheduled and unscheduled c","PeriodicalId":19409,"journal":{"name":"Obstetrical & Gynecological Survey","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135963380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-01DOI: 10.1097/01.ogx.0000993680.79685.68
Tami H. Skoff, Li Deng, Catherine H. Bozio, Susan Hariri
ABSTRACT Many illnesses can become especially serious when contracted within the first year of life; pertussis remains quite deadly despite recent medical advances in disease prevention. Current guidance on vaccination in the United States includes 3 doses of the DTaP (diphtheria, tetanus toxoid, and acellular pertussis) vaccine beginning at 2 months of age, but this regimen leaves infants younger than that very vulnerable to illness. Research has shown both that vaccinating mothers with tetanus toxoid reduces tetanus, diphtheria, and pertussis (Tdap) between 27 and 36 weeks of gestation significantly reduces instances of pertussis in infants younger than 2 months, and that maternal vaccination rates have risen in the last few years. However, research is lacking in analyzing the relationship between vaccination rates in pregnant mothers and the burden of pertussis in infants in the United States. This study was designed to assess data from 2000 to 2019 and examine the association of Tdap vaccination during pregnancy with trends in infant pertussis. This analysis included data obtained from the National Notifiable Diseases Surveillance System between 2000 and 2019. This included a total of 57,460 cases of pertussis in infants younger than 1 year and a total of 19,322 cases in infants younger than 2 months. The rate of pertussis incidence for infants younger than 2 months in the time period before the implementation of prenatal Tdap was calculated to be 165.3 per 100,000 individuals, with no significant trend observed annually ( P = 0.28). After the implementation of routine maternal Tdap, incidence decreased to 80.9 per 100,000 infants between 2017 and 2019. Accounting for both time periods, the mean annual incidence was calculated as 121.8 per 100,000 infants younger than 2 months. Annual incidence also showed a significant decreasing trend in the period after implementation of maternal Tdap vaccination (slope: −14.53 per 100,000 infants per year; P = 0.001). The change in trends before and after this implementation was also significant ( P = 0.01). In a slightly older age group of 6 to 12 months of age, mean annual incidence of pertussis was 19.7 per 100,000 infants. In the time period before implementation of maternal Tdap, incidence among infants aged 6 to 12 months was consistently 4 to 12 times less than infants younger than 2 months and did not significantly change after the implementation of the maternal vaccine. Comparing the 2 age groups, there was no significant change in the difference in incidence between infants younger than 2 months and those between 6 and 12 months in the period before the maternal vaccine, and after its implementation, there was a significant decrease in the incidence difference between the 2 groups ( P < 0.001). These results suggest an association between the maternal Tdap vaccination and trends of pertussis incidence in infants younger than 2 months. This also indicates a possible reduction in disease burden at
{"title":"US Infant Pertussis Incidence Trends Before and After Implementation of the Maternal Tetanus, Diphtheria, and Pertussis Vaccine","authors":"Tami H. Skoff, Li Deng, Catherine H. Bozio, Susan Hariri","doi":"10.1097/01.ogx.0000993680.79685.68","DOIUrl":"https://doi.org/10.1097/01.ogx.0000993680.79685.68","url":null,"abstract":"ABSTRACT Many illnesses can become especially serious when contracted within the first year of life; pertussis remains quite deadly despite recent medical advances in disease prevention. Current guidance on vaccination in the United States includes 3 doses of the DTaP (diphtheria, tetanus toxoid, and acellular pertussis) vaccine beginning at 2 months of age, but this regimen leaves infants younger than that very vulnerable to illness. Research has shown both that vaccinating mothers with tetanus toxoid reduces tetanus, diphtheria, and pertussis (Tdap) between 27 and 36 weeks of gestation significantly reduces instances of pertussis in infants younger than 2 months, and that maternal vaccination rates have risen in the last few years. However, research is lacking in analyzing the relationship between vaccination rates in pregnant mothers and the burden of pertussis in infants in the United States. This study was designed to assess data from 2000 to 2019 and examine the association of Tdap vaccination during pregnancy with trends in infant pertussis. This analysis included data obtained from the National Notifiable Diseases Surveillance System between 2000 and 2019. This included a total of 57,460 cases of pertussis in infants younger than 1 year and a total of 19,322 cases in infants younger than 2 months. The rate of pertussis incidence for infants younger than 2 months in the time period before the implementation of prenatal Tdap was calculated to be 165.3 per 100,000 individuals, with no significant trend observed annually ( P = 0.28). After the implementation of routine maternal Tdap, incidence decreased to 80.9 per 100,000 infants between 2017 and 2019. Accounting for both time periods, the mean annual incidence was calculated as 121.8 per 100,000 infants younger than 2 months. Annual incidence also showed a significant decreasing trend in the period after implementation of maternal Tdap vaccination (slope: −14.53 per 100,000 infants per year; P = 0.001). The change in trends before and after this implementation was also significant ( P = 0.01). In a slightly older age group of 6 to 12 months of age, mean annual incidence of pertussis was 19.7 per 100,000 infants. In the time period before implementation of maternal Tdap, incidence among infants aged 6 to 12 months was consistently 4 to 12 times less than infants younger than 2 months and did not significantly change after the implementation of the maternal vaccine. Comparing the 2 age groups, there was no significant change in the difference in incidence between infants younger than 2 months and those between 6 and 12 months in the period before the maternal vaccine, and after its implementation, there was a significant decrease in the incidence difference between the 2 groups ( P < 0.001). These results suggest an association between the maternal Tdap vaccination and trends of pertussis incidence in infants younger than 2 months. This also indicates a possible reduction in disease burden at","PeriodicalId":19409,"journal":{"name":"Obstetrical & Gynecological Survey","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136009752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-01DOI: 10.1097/ogx.0000000000001202
Jay Idler, Onur Turkoglu, Kara Patek, Sean Stuart, Birce Taskin, Lalitha Sivaswamy, Amy Whitten
Importance Neurocutaneous disorders have significant implications for care of the pregnant patient. As neurocutaneous disorders are uncommon, obstetricians may be unfamiliar with these disorders and with recommendations for appropriate care of this population. Objective This review aims to summarize existing literature on the interaction between neurocutaneous disorders and pregnancy and to provide a guide for physicians caring for an affected patient. Evidence Acquisition A PubMed, MEDLINE, and Google Scholar search was carried out with a broad range of combinations of the medical subject headings (MeSH) terms “pregnancy,” “Sturge -Weber,” “Neurofibromatosis Type 1,” “neurofibromatosis type 2,” “von Hippel Lindau,” “Tuberous Sclerosis,” “neurocutaneous disorder,” “treatment,” “congenital malformations,” “neurodevelopmental defects,” “miscarriage,” “breastfeeding,” “autoimmune,” “pathophysiology,” and “management.” References of included articles were searched to identify any articles that may have been missed after the above method was used. Results Neurocutaneous disorders are associated with increased pregnancy-associated maternal and fetal/neonatal morbidity, largely surrounding hypertensive disorders, epilepsy, and medication exposure. Some features of neurocutaneous disorders may be worsened or accelerated by pregnancy. Neurocutaneous disorders can often be diagnosed prenatally. Therefore, directed assessment should be offered to affected individuals with a personal or family history of a neurocutaneous disorder. Conclusion and Relevance Patients affected by neurocutaneous disorders who are pregnant or planning for future pregnancy should be carefully followed by a multidisciplinary team, which could include maternal-fetal medicine, neurology, and anesthesia, as well as other relevant subspecialists. Additional research is required regarding optimal counseling and management of these patients. Target Audience Obstetricians and gynecologists, family physician. Learning objectives After completing this activity, the learner will be better able to identify the most common neurocutaneous disorders seen in reproductive women and their implications in pregnancy; propose recommendations for genetic evaluation, diagnosis, management, and a differential diagnosis; describe treatment options including labor and delivery management, emphasizing multidisciplinary approach; and discuss potential maternal and fetal adverse outcomes related to neurocutaneous disorders.
{"title":"Neurocutaneous Disorders in Pregnancy","authors":"Jay Idler, Onur Turkoglu, Kara Patek, Sean Stuart, Birce Taskin, Lalitha Sivaswamy, Amy Whitten","doi":"10.1097/ogx.0000000000001202","DOIUrl":"https://doi.org/10.1097/ogx.0000000000001202","url":null,"abstract":"Importance Neurocutaneous disorders have significant implications for care of the pregnant patient. As neurocutaneous disorders are uncommon, obstetricians may be unfamiliar with these disorders and with recommendations for appropriate care of this population. Objective This review aims to summarize existing literature on the interaction between neurocutaneous disorders and pregnancy and to provide a guide for physicians caring for an affected patient. Evidence Acquisition A PubMed, MEDLINE, and Google Scholar search was carried out with a broad range of combinations of the medical subject headings (MeSH) terms “pregnancy,” “Sturge -Weber,” “Neurofibromatosis Type 1,” “neurofibromatosis type 2,” “von Hippel Lindau,” “Tuberous Sclerosis,” “neurocutaneous disorder,” “treatment,” “congenital malformations,” “neurodevelopmental defects,” “miscarriage,” “breastfeeding,” “autoimmune,” “pathophysiology,” and “management.” References of included articles were searched to identify any articles that may have been missed after the above method was used. Results Neurocutaneous disorders are associated with increased pregnancy-associated maternal and fetal/neonatal morbidity, largely surrounding hypertensive disorders, epilepsy, and medication exposure. Some features of neurocutaneous disorders may be worsened or accelerated by pregnancy. Neurocutaneous disorders can often be diagnosed prenatally. Therefore, directed assessment should be offered to affected individuals with a personal or family history of a neurocutaneous disorder. Conclusion and Relevance Patients affected by neurocutaneous disorders who are pregnant or planning for future pregnancy should be carefully followed by a multidisciplinary team, which could include maternal-fetal medicine, neurology, and anesthesia, as well as other relevant subspecialists. Additional research is required regarding optimal counseling and management of these patients. Target Audience Obstetricians and gynecologists, family physician. Learning objectives After completing this activity, the learner will be better able to identify the most common neurocutaneous disorders seen in reproductive women and their implications in pregnancy; propose recommendations for genetic evaluation, diagnosis, management, and a differential diagnosis; describe treatment options including labor and delivery management, emphasizing multidisciplinary approach; and discuss potential maternal and fetal adverse outcomes related to neurocutaneous disorders.","PeriodicalId":19409,"journal":{"name":"Obstetrical & Gynecological Survey","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136009882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-01DOI: 10.1097/ogx.0000000000001207
Carrie E. Jung, Lie H. Chen, Linda T. Brubaker, Shawn A. Menefee
ABSTRACT Postoperative urinary tract infection (PO-UTI) is seen in 6.4%–32% of stress urinary incontinence (SUI) and/or pelvic organ prolapse (POP) surgeries despite perioperative antibiotic prophylaxis. Postoperative complications associated with PO-UTI include increased mortality and longer hospitalization. Increasing prevalence of resistance to antibiotics and antibiotic stewardship principles necessitate both the improvement of infection prevention strategies and judicious antibiotic prescriptions. Four factors are known to increase PO-UTI risk: (1) recurrent UTI (RUTI) history, (2) preoperative UTI, (3) day-of-surgery UTI, and (4) prolonged postoperative catheterization. This study intended to determine (1) risk factors of PO-UTI and PO-RUTI, (2) preoperative and postoperative UTI temporal distribution, and (3) detected uropathogens in a large database. The study used medical record data of all SUI/POP surgical procedures performed in the Kaiser Southern California Hospital system from January 1, 2008 to December 31, 2016 for women 18 years of age or older. Procedures used Current Procedural Terminology codes for identifying and subcategorizing surgical procedures and their route (SUI or POP; abdominal or vaginal, respectively). The study-wide definition of UTI was as follows: (1) positive standard urine culture of greater than 10 5 CFU/mL of ≤2 uropathogens, or (2) prescription of urinary antibiotics prescribed for the indication of UTI symptoms. The analysis consisted of 21,063 urogynecologic surgical procedures performed on 20,051 women (33,626 POP and/or SUI procedures), with 22,641 UTI events being diagnosed in 10,091 women. Mean age was 56.9 years, and mean BMI was 29.1. The cohort underwent surgery for only SUI (35.4%), only POP (32.7%), or POP/SUI combined (31.9%). In the 13.5 months postoperatively, 11,976 UTIs were diagnosed in 6733 women. The first month experienced a sharp increase compared with the preoperative year, the second month increased further, and the third month showed leveling of PO-UTI incidence. Prescribed antibiotics captured most UTI events (13,337 or 58.3%). Prescribed antibiotics, in order of most-prescribed to least-prescribed, were as follows: ciprofloxacin (33.7%), cephalexin (21.4%), nitrofurantoin (20.4%), and sulfamethoxazole-trimethoprim (17.6%). The study determined that most PO-UTIs occurred within the first 2 months, with many of these being diagnosed within 2 weeks of surgery. For those patients already having a history of RUTI, RUTI significantly increases in postoperative year 1 when compared with the preoperative year. All patients undergoing SUI procedures had increased PO-RUTI risks compared with their POP-only group peers. Escherichia coli was the most common pathogen found. Risk and event timing were affected by surgical indication: although surgery for only SUI had a lower 6-week PO-UTI risk, it was counterintuitively associated with a higher PO-RUTI risk. Multivariate regression revealed pred
{"title":"Urinary Tract Infections After Urogynecologic Surgery: Risk Factors, Timeline, and Uropathogens","authors":"Carrie E. Jung, Lie H. Chen, Linda T. Brubaker, Shawn A. Menefee","doi":"10.1097/ogx.0000000000001207","DOIUrl":"https://doi.org/10.1097/ogx.0000000000001207","url":null,"abstract":"ABSTRACT Postoperative urinary tract infection (PO-UTI) is seen in 6.4%–32% of stress urinary incontinence (SUI) and/or pelvic organ prolapse (POP) surgeries despite perioperative antibiotic prophylaxis. Postoperative complications associated with PO-UTI include increased mortality and longer hospitalization. Increasing prevalence of resistance to antibiotics and antibiotic stewardship principles necessitate both the improvement of infection prevention strategies and judicious antibiotic prescriptions. Four factors are known to increase PO-UTI risk: (1) recurrent UTI (RUTI) history, (2) preoperative UTI, (3) day-of-surgery UTI, and (4) prolonged postoperative catheterization. This study intended to determine (1) risk factors of PO-UTI and PO-RUTI, (2) preoperative and postoperative UTI temporal distribution, and (3) detected uropathogens in a large database. The study used medical record data of all SUI/POP surgical procedures performed in the Kaiser Southern California Hospital system from January 1, 2008 to December 31, 2016 for women 18 years of age or older. Procedures used Current Procedural Terminology codes for identifying and subcategorizing surgical procedures and their route (SUI or POP; abdominal or vaginal, respectively). The study-wide definition of UTI was as follows: (1) positive standard urine culture of greater than 10 5 CFU/mL of ≤2 uropathogens, or (2) prescription of urinary antibiotics prescribed for the indication of UTI symptoms. The analysis consisted of 21,063 urogynecologic surgical procedures performed on 20,051 women (33,626 POP and/or SUI procedures), with 22,641 UTI events being diagnosed in 10,091 women. Mean age was 56.9 years, and mean BMI was 29.1. The cohort underwent surgery for only SUI (35.4%), only POP (32.7%), or POP/SUI combined (31.9%). In the 13.5 months postoperatively, 11,976 UTIs were diagnosed in 6733 women. The first month experienced a sharp increase compared with the preoperative year, the second month increased further, and the third month showed leveling of PO-UTI incidence. Prescribed antibiotics captured most UTI events (13,337 or 58.3%). Prescribed antibiotics, in order of most-prescribed to least-prescribed, were as follows: ciprofloxacin (33.7%), cephalexin (21.4%), nitrofurantoin (20.4%), and sulfamethoxazole-trimethoprim (17.6%). The study determined that most PO-UTIs occurred within the first 2 months, with many of these being diagnosed within 2 weeks of surgery. For those patients already having a history of RUTI, RUTI significantly increases in postoperative year 1 when compared with the preoperative year. All patients undergoing SUI procedures had increased PO-RUTI risks compared with their POP-only group peers. Escherichia coli was the most common pathogen found. Risk and event timing were affected by surgical indication: although surgery for only SUI had a lower 6-week PO-UTI risk, it was counterintuitively associated with a higher PO-RUTI risk. Multivariate regression revealed pred","PeriodicalId":19409,"journal":{"name":"Obstetrical & Gynecological Survey","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136009999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-01DOI: 10.1097/01.ogx.0000993700.13780.f9
Ana Domingo-Muelas, Robin M. Skory, Adam A. Moverley, Goli Ardestani, Oz Pomp, Carmen Rubio, Piotr Tetlak, Blake Hernandez, Eric A. Rhon-Calderon, Luis Navarro-Sanchez, Carmen M. García-Pascual, Stephanie Bissiere, Marisa S. Bartolomei, Denny Sakkas, Carlos Simon, Nicolas Plachta
ABSTRACT The proportion of babies born from in vitro fertilization (IVF) is rising at an exponential rate, highlighting the importance that we have a comprehensive understanding of human preimplantation development and determinants of embryo quality. The early divisions of the embryo after fertilization but before implantation and resulting mitotic errors have been studied primarily in the mouse embryo; however, thus far we have lacked the technology to characterize these critical steps in humans. Establishing an approach that can bypass genetic manipulation and microinjections of DNA or mRNA into human embryos would allow us to better uncover the processes patterning preimplantation human development. This study aimed to evaluate human blastocyst preimplantation development with noninvasive imaging using membrane permeable fluorescent dyes. First, the dyes SPY650-DNA, which labels genomic DNA, and SPY555-actin, which labels F-actin, were validated in the mouse embryo where they produced high contrast labelling with similar results to microinjection of fluorescent mRNAs and produced offspring at a similar rate to nondyed control embryos. Live imaging data using these dyes enabled 3-dimensional scans of the embryo at 5- to 10-minute intervals of the following central events during preimplantation development: the main phases of mitosis, visualizing the major changes in cell shape that characterize embryo compaction at the 8-cell stage, detecting cell polarization at the 8-cell stage, establishing apical F-actin rings at the 16-cell stage, tracking the expansion and zippering of F-actin rings, detecting the first internalized cells within the 16-cell embryo, and visualizing blastocyst expansion and hatching from the zona pellucida. Cleavage-stage human IVF embryos were then studied using the fluorescent dyes to track early cellular and morphogenetic processes. Early cell-cycle dynamics and mitotic stages revealed that the duration of human mitosis is similar to that of mice, but interphase is 27% ± 4% longer in humans (16.1 ± 0.9 vs 12.7 ± 0.4 hours; P < 0.01). Using live imaging, compaction dynamics such as increased cell-cell contact and angle between apical membranes with a decrease in cell sphericity were observed beginning at the 12-cell stage and differed significantly from development in mice. In comparison to mice, human compaction was found to be more asynchronous and did not have clear links to apical polarization or inner-outer segregation. Next, chromosomal segregation was analyzed to determine if this approach allowed detection of segregation errors in the human embryo leading to aneuploidy. Lagging chromosomes detected in human embryos using SPY-DNA appeared morphologically similar to those found in mouse embryos and had similar segregation dynamics. During blastocyst expansion, a subset of trophectoderm cell nuclei forms protruding bud-like that is shed into cytoplasm producing cytoplasmic DNA structures (cytDNA), suggesting an addit
通过体外受精(IVF)出生的婴儿比例正以指数速度上升，这凸显了我们对人类着床前发育和胚胎质量决定因素有全面了解的重要性。胚胎在受精后着床前的早期分裂以及由此产生的有丝分裂错误主要在小鼠胚胎中进行了研究;然而，到目前为止，我们还缺乏描述人类这些关键步骤的技术。建立一种可以绕过基因操作和向人类胚胎中微量注射DNA或mRNA的方法，将使我们能够更好地揭示胚胎植入前人类发育的过程。本研究旨在利用膜透性荧光染料无创成像技术评价人胚泡着床前发育。首先，标记基因组DNA的染料SPY650-DNA和标记f -肌动蛋白的染料SPY555-actin在小鼠胚胎中得到验证，它们产生的高对比度标记与显微注射荧光mrna的结果相似，并且产生后代的速度与未染色的对照胚胎相似。使用这些染料的实时成像数据可以在胚胎着床前发育期间每隔5到10分钟对以下中心事件进行三维扫描:有丝分裂的主要阶段，在8细胞阶段观察表征胚胎压实的细胞形状的主要变化，在8细胞阶段检测细胞极化，在16细胞阶段建立顶端的f -肌动蛋白环，跟踪f -肌动蛋白环的扩张和收缩，在16细胞胚胎中检测第一个内化细胞，并观察囊胚从透明带扩张和孵化。然后使用荧光染料跟踪早期细胞和形态发生过程研究卵裂期人类体外受精胚胎。早期细胞周期动力学和有丝分裂阶段显示，人类有丝分裂的持续时间与小鼠相似，但间期比小鼠长27%±4%(16.1±0.9 vs 12.7±0.4小时);P & lt;0.01)。通过实时成像，从12个细胞阶段开始观察到细胞接触增加、细胞顶膜之间角度增加、细胞球形度降低等压实动力学，这与小鼠的发育有很大不同。与小鼠相比，人类的压实更不同步，与根尖极化或内外分离没有明确的联系。接下来，对染色体分离进行分析，以确定这种方法是否允许检测人类胚胎中导致非整倍体的分离错误。利用SPY-DNA在人类胚胎中检测到的滞后染色体在形态上与在小鼠胚胎中发现的染色体相似，并且具有相似的分离动力学。在囊胚扩增过程中，滋养外胚层细胞核的一部分形成突出的芽状，并脱落到细胞质中，产生细胞质DNA结构(cytDNA)，这表明有丝分裂过程中存在不同于染色体分离错误的DNA丢失过程。在早期空化阶段形成的核周角蛋白网络似乎可以保护细胞DNA结构的形成，而囊胚膨胀的机械应力似乎会破坏某些细胞中的角蛋白网络，增加DNA脱落。接下来，在小鼠和人类胚胎中进行了滋养外胚层活检，以确定机械应力是否会增加DNA脱落。人囊胚活检导致核出芽显著增加(6.0% vs 0.70%;P = 0.0022)，这表明机械应力和DNA脱落之间存在联系。本研究展示了荧光染料和实时成像在人类胚胎着床前关键细胞和形态发生过程表征中的应用，并描述了机械应激反应中DNA脱落的过程，这值得未来的研究。
{"title":"Human Embryo Live Imaging Reveals Nuclear DNA Shedding During Blastocyst Expansion and Biopsy","authors":"Ana Domingo-Muelas, Robin M. Skory, Adam A. Moverley, Goli Ardestani, Oz Pomp, Carmen Rubio, Piotr Tetlak, Blake Hernandez, Eric A. Rhon-Calderon, Luis Navarro-Sanchez, Carmen M. García-Pascual, Stephanie Bissiere, Marisa S. Bartolomei, Denny Sakkas, Carlos Simon, Nicolas Plachta","doi":"10.1097/01.ogx.0000993700.13780.f9","DOIUrl":"https://doi.org/10.1097/01.ogx.0000993700.13780.f9","url":null,"abstract":"ABSTRACT The proportion of babies born from in vitro fertilization (IVF) is rising at an exponential rate, highlighting the importance that we have a comprehensive understanding of human preimplantation development and determinants of embryo quality. The early divisions of the embryo after fertilization but before implantation and resulting mitotic errors have been studied primarily in the mouse embryo; however, thus far we have lacked the technology to characterize these critical steps in humans. Establishing an approach that can bypass genetic manipulation and microinjections of DNA or mRNA into human embryos would allow us to better uncover the processes patterning preimplantation human development. This study aimed to evaluate human blastocyst preimplantation development with noninvasive imaging using membrane permeable fluorescent dyes. First, the dyes SPY650-DNA, which labels genomic DNA, and SPY555-actin, which labels F-actin, were validated in the mouse embryo where they produced high contrast labelling with similar results to microinjection of fluorescent mRNAs and produced offspring at a similar rate to nondyed control embryos. Live imaging data using these dyes enabled 3-dimensional scans of the embryo at 5- to 10-minute intervals of the following central events during preimplantation development: the main phases of mitosis, visualizing the major changes in cell shape that characterize embryo compaction at the 8-cell stage, detecting cell polarization at the 8-cell stage, establishing apical F-actin rings at the 16-cell stage, tracking the expansion and zippering of F-actin rings, detecting the first internalized cells within the 16-cell embryo, and visualizing blastocyst expansion and hatching from the zona pellucida. Cleavage-stage human IVF embryos were then studied using the fluorescent dyes to track early cellular and morphogenetic processes. Early cell-cycle dynamics and mitotic stages revealed that the duration of human mitosis is similar to that of mice, but interphase is 27% ± 4% longer in humans (16.1 ± 0.9 vs 12.7 ± 0.4 hours; P < 0.01). Using live imaging, compaction dynamics such as increased cell-cell contact and angle between apical membranes with a decrease in cell sphericity were observed beginning at the 12-cell stage and differed significantly from development in mice. In comparison to mice, human compaction was found to be more asynchronous and did not have clear links to apical polarization or inner-outer segregation. Next, chromosomal segregation was analyzed to determine if this approach allowed detection of segregation errors in the human embryo leading to aneuploidy. Lagging chromosomes detected in human embryos using SPY-DNA appeared morphologically similar to those found in mouse embryos and had similar segregation dynamics. During blastocyst expansion, a subset of trophectoderm cell nuclei forms protruding bud-like that is shed into cytoplasm producing cytoplasmic DNA structures (cytDNA), suggesting an addit","PeriodicalId":19409,"journal":{"name":"Obstetrical & Gynecological Survey","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135963382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-01DOI: 10.1097/ogx.0000000000001208
Birgit M. M. Wever, Rianne van den Helder, Annina P. van Splunter, Mignon D. J. M. van Gent, Jenneke C. Kasius, Johannes W. Trum, Harold R. Verhoeve, Wilhelmina M. van Baal, Alicia Hulbert, Lisanne Verhoef, Daniëlle A. M. Heideman, Birgit I. Lissenberg-Witte, Nienke E. van Trommel, Renske D. M. Steenbergen, Maaike C. G. Bleeker
ABSTRACT Endometrial cancer is the sixth most common cancer in women globally and has a rising incidence, accounting for 417,000 new diagnoses and more than 97,000 deaths in 2020. Early detection is critical because of a poor advanced-stage prognosis and high relapse risk. Postmenopausal bleeding precedes endometrial cancer in 90% of cases, yet only 5% to 10% of patients with this symptom have an underlying malignancy. Recent cytology research has demonstrated endometrial cancer cells in vaginal samples, suggesting urine and cervicovaginal self-samples may allow convenient and minimally invasive screening. In addition, screening samples for DNA methylation in tumor suppressor genes can increase testing efficacy of triaging patients with postmenopausal bleeding as it does not require intact tumor cells. This study aimed to evaluate the diagnostic performance of endometrial cancer detection using DNA methylation analysis in paired urine, cervicovaginal self-samples, and clinician-taken cervical scrapes. Paired samples from participants of the SOLUTION1 study with endometrial cancer were collected between October 2016 and August 2020. A complete urine void and cervicovaginal self-sample was collected at home, whereas the cervical scrape was taken by a clinician in the operating room before surgery. Each patient had a paired urine, cervicovaginal self-sample, and clinician-taken cervical scrape available for methylation analysis. Controls were collected from the Urine Controls (URIC) biobank and Dutch national cervical cancer screening program. Promoter hypermethylation of the ADCYAP1 , BHLHE22 , CDH13 , CDO1 , GALR1 , GHSR , HAND2 , SST , and ZIC1 genes was tested using quantitative methylation-specific polymerase chain reaction. Optimal 3-marker combinations were determined for each sample type using multivariable logistic regression analysis, and diagnostic performances of each marker and 3-marker panels were assessed by leave-one-out cross validation. A total of 103 endometrial cancer patients were included in this study, with 317 unpaired samples of control women. Methylation levels of all markers were significantly higher in all 3 sample types of endometrial cancer patients compared with healthy control women. In urine, the non–cross-validated area under the curve of the DNA methylation markers ranged between 0.61 and 0.93, in cervicovaginal self-samples between 0.62 and 0.91, and in clinician-taken cervical scrapes between 0.61 and 0.95. Most markers (7/9) showed the highest performance in urine, with the remaining 2 showing best performance in clinician-taken cervical scrapes. The optimal 3-marker combination panels showed area under the curve values of 0.95 (05% confidence interval [CI], 0.92–0.98) for urine, 0.94 (95% CI, 0.90–0.97) for cervicovaginal self-samples, and 0.97 (95% CI, 0.96–0.99) for clinician-taken cervical scrapes. The sensitivity and specificity of the optimal urine testing panel were both 90%, were 89% sensitivity and 92%
{"title":"DNA Methylation Testing for Endometrial Cancer Detection in Urine, Cervicovaginal Self-Samples and Cervical Scrapes","authors":"Birgit M. M. Wever, Rianne van den Helder, Annina P. van Splunter, Mignon D. J. M. van Gent, Jenneke C. Kasius, Johannes W. Trum, Harold R. Verhoeve, Wilhelmina M. van Baal, Alicia Hulbert, Lisanne Verhoef, Daniëlle A. M. Heideman, Birgit I. Lissenberg-Witte, Nienke E. van Trommel, Renske D. M. Steenbergen, Maaike C. G. Bleeker","doi":"10.1097/ogx.0000000000001208","DOIUrl":"https://doi.org/10.1097/ogx.0000000000001208","url":null,"abstract":"ABSTRACT Endometrial cancer is the sixth most common cancer in women globally and has a rising incidence, accounting for 417,000 new diagnoses and more than 97,000 deaths in 2020. Early detection is critical because of a poor advanced-stage prognosis and high relapse risk. Postmenopausal bleeding precedes endometrial cancer in 90% of cases, yet only 5% to 10% of patients with this symptom have an underlying malignancy. Recent cytology research has demonstrated endometrial cancer cells in vaginal samples, suggesting urine and cervicovaginal self-samples may allow convenient and minimally invasive screening. In addition, screening samples for DNA methylation in tumor suppressor genes can increase testing efficacy of triaging patients with postmenopausal bleeding as it does not require intact tumor cells. This study aimed to evaluate the diagnostic performance of endometrial cancer detection using DNA methylation analysis in paired urine, cervicovaginal self-samples, and clinician-taken cervical scrapes. Paired samples from participants of the SOLUTION1 study with endometrial cancer were collected between October 2016 and August 2020. A complete urine void and cervicovaginal self-sample was collected at home, whereas the cervical scrape was taken by a clinician in the operating room before surgery. Each patient had a paired urine, cervicovaginal self-sample, and clinician-taken cervical scrape available for methylation analysis. Controls were collected from the Urine Controls (URIC) biobank and Dutch national cervical cancer screening program. Promoter hypermethylation of the ADCYAP1 , BHLHE22 , CDH13 , CDO1 , GALR1 , GHSR , HAND2 , SST , and ZIC1 genes was tested using quantitative methylation-specific polymerase chain reaction. Optimal 3-marker combinations were determined for each sample type using multivariable logistic regression analysis, and diagnostic performances of each marker and 3-marker panels were assessed by leave-one-out cross validation. A total of 103 endometrial cancer patients were included in this study, with 317 unpaired samples of control women. Methylation levels of all markers were significantly higher in all 3 sample types of endometrial cancer patients compared with healthy control women. In urine, the non–cross-validated area under the curve of the DNA methylation markers ranged between 0.61 and 0.93, in cervicovaginal self-samples between 0.62 and 0.91, and in clinician-taken cervical scrapes between 0.61 and 0.95. Most markers (7/9) showed the highest performance in urine, with the remaining 2 showing best performance in clinician-taken cervical scrapes. The optimal 3-marker combination panels showed area under the curve values of 0.95 (05% confidence interval [CI], 0.92–0.98) for urine, 0.94 (95% CI, 0.90–0.97) for cervicovaginal self-samples, and 0.97 (95% CI, 0.96–0.99) for clinician-taken cervical scrapes. The sensitivity and specificity of the optimal urine testing panel were both 90%, were 89% sensitivity and 92% ","PeriodicalId":19409,"journal":{"name":"Obstetrical & Gynecological Survey","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135963379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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