A Cross-Sectional Study of Obstetrical and Gynecological Parameters in Twins – A Potential Increase in Premature Rupture of Membranes and Pre-eclampsia in Twin Women

A Cross-Sectional Study of Obstetrical and Gynecological Parameters in Twins – A Potential Increase in Premature Rupture of Membranes and Pre-eclampsia in Twin Women | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Research article A Cross-Sectional Study of Obstetrical and Gynecological Parameters in Twins – A Potential Increase in Premature Rupture of Membranes and Pre-eclampsia in Twin Women Nathan Keller, Kevin C. Kiley This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-74105/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background This cross-sectional study of 192 twins across a wide geographical area compared obstetrical and gynecological parameters between twins and the general population. Methods The study is a cross-sectional study. Gynecological variables included age of menarche, abnormal pap smears, birth control usage, endometriosis, fibroids, infertility, gynecological cancer, and osteoporosis. Obstetrical variables studied included pregnancy, ectopic pregnancies, hypertension, pre-eclampsia, gestational diabetes, and premature rupture of membranes (PROM). Chi Square and Fisher’s Exact tests were utilized to compare these binary variables between identical and fraternal twins. Finally, odds ratios were used to compare the rates of PROM, pre-eclampsia, hypertension, ectopic pregnancy, and gestational diabetes among twins compared to the general population using reputable literature sources. Results Identical twins reported the same age of menarche more frequently than their fraternal counterparts (p = 0.0021) with an odds ratio of 4.56 (95% CI = 1.62,12.83). There was also an increase in the odds of PROM 1.37 to 5.42 (95% CI = 0.95,1.96 and 4.21,6.98) and pre-eclampsia 1.17 to 3.16 (95% CI = 0.66,2.09 and 2.16,4.62) in our twin sample verse the general population. Finally, only 9.9% (18/184) reported knowledge of amnionicity and chorionicity. Conclusions Our findings suggest that further large scale research concerning PROM and pre-eclampsia in twin women may be warranted. Obstetrics & Gynecology Premature Rupture of Membranes Pre-eclampsia Amnion Chorion Twins Figures Figure 1 Figure 2 Background Twin pregnancies have long been a topic of study and investigation. One has little difficulty finding an abundance of information on the diagnosis, management, complications and delivery recommendations for twin gestations. There have been tremendous advances in monochorionic twin pregnancy management and therapy up to and including the role of fetoscopic laser coagulation of placental anastomoses for Twin-Twin Transfusion Syndrome management. What happens when these very twins become of childbearing age however? Are they more likely to develop pre-eclampsia themselves or experience premature rupture of membranes? Would they be more likely to develop gestational diabetes than those born of singleton pregnancies? If twins would be more likely to develop pre-eclampsia or gestational diabetes should they routinely be offered aspirin for pre-eclampsia prophylaxis or early glucose tolerance testing when they become pregnant? The questions remain unanswered. Interestingly, data to answer such questions is nonexistent. Given the increased incidence of premature rupture of membranes, pre-eclampsia, and gestational diabetes in twin gestations it seems feasible that these twin women could be at increased risk of these conditions when they themselves become pregnant. The gynecological questions surrounding twins are equally unknown. Are identical or fraternal twins more likely to both have the same age of menarche, abnormal pap smears, use birth control, have endometriosis, have fibroids, experience infertility, develop gynecological cancer, or be diagnosed with osteoporosis? The goals of this study were to investigate some of these questions. More specifically, social, obstetrical, and gynecological relationships between female identical and fraternal twins were investigated. Additionally, obstetrical frequencies among twins were compared to those in the general population. Methods This study was fully approved by the Institutional Review Board of Albany Medical Center/Albany Medical College before its commencement. The study was a cross sectional study involving the distribution of surveys to female twins. The surveys were developed specifically for this study. In order to be eligible to participate in the study twins needed to be female, be an identical or fraternal twin, and be at least 18 years of age. Surveys were given in registration packets to all twins who attended the Twins Days Festival in Twinsburg, Ohio, in August of 2014. Additionally, surveys were electronically mailed to all twins on the Twins Days Festival mailing list which included twins from the festival’s inception in 1976. Of note, the Twins Days Festival is the largest annual gathering of twins and multiples in the world. Twins were instructed to complete the surveys independently of their twin counterpart and not to collaborate with their twin in any way. Participation in this survey was completely optional and twins could readily opt out of participating. Once a survey was completed it was mailed back to the Department of Obstetrics and Gynecology at Albany Medical Center in Albany, New York. Each survey couplet had a unique tracking number on it so the surveys could be matched back together upon receival. The contents of the individual surveys contained demographic, social, gynecological, and obstetrical questions. Questions were constructed in a binary manner to elicit a yes/no response. Results were tabulated and coded as binary variables either yes (1) or no (0). SAS University Edition was then utilized to perform all statistical analyses. Specifically, Chi Square and Fisher’s Exact Tests were used to compare all binary variables. To compare obstetrical ratios in our twin sample to the general population a literature review was performed and odds ratios were calculated. The incidence of premature rupture of membranes in the general population was estimated to be 10% of all pregnancies [ 1 ], the incidence of pre-eclampsia was estimated to be 4% of all pregnancies [ 2 ], the incidence of hypertension was estimated to be 10% of all pregnancies [ 3 ], the incidence of ectopic pregnancies was estimated to be 2% of all pregnancies [ 4 ], and the incidence of gestational diabetes was estimated to be 6% of all pregnancies [ 5 ]. Using these population estimates, it was determined that an adequate sample size was obtained for all the above variables in this survey to have a confidence level of 95% that the real value is within ± 5% of the surveyed value with each individual population proportion. (Needed sample size of 139 for PROM, 60 for Pre-eclampsia, 139 for hypertension, 31 for ectopic, 87 for gestational diabetes: all of which were obtained). Finally, in order to calculate odds ratios to the general population the number of pregnancies and births in the United States both had to be estimated. Recent CDC data was utilized to estimate the annual number of births in the United States as 3,791,712 [ 6 ] and the annual number of pregnancies as 6,155,000 [ 7 ]. Results In total 192 surveys were received representing 96 sets of twins. Using the attendance at the festival alone, in which there is estimated to be 2,000 female twins annually, the response rate was estimated to be 9.6%. When factoring in the large number of surveys that were sent electronically, the response rate was likely much smaller than this. In total, surveys were received from 23 states, Canada, and Great Britain. 41.7% were from Eastern States, 40.6% were from the Midwest, 9.4% were from Southern States, 6.3% were from Western States, and 1% were from Canada and Great Britain respectively (Figure I). 172 of the twins identified as identical twins and 20 identified as fraternal twins. The average age of respondents was 43.3 years with a standard deviation of 17.0 years (Figure II). Of the respondents, 87.5% identified as White/Hispanic, 8.3% identified as Black, 2.1% identified as Asian, and 2.1% identified as other. This racial breakdown is similar to the United States general population in which it is estimated that 78% are White/Hispanic, 12% are Black, 6% are Asian, and 4% identify as other [ 8 ]. Social factor results are identified in Table I. Gynecological factors are identified in Table II and obstetrical factors in Table III. There was a total of 258 reported pregnancies. A statistically significant greater number of identical twins reported having the same age of menarche than did fraternal twins (69.51% verse 33.33%, p-value: 0.0021). Other gynecological parameters did not have a statistically significant difference between identical and fraternal twins (Table II). There were no statistically significant differences detected among the obstetrical parameters tested between identical and fraternal twins (Table III). Only 9.8% of respondents reported knowing the number of amnions and chorions in their pregnancy. 11% (18/164) of identical twins reported knowing amnions and chorions in their pregnancy compared to 0% (0/18) of fraternal twins (p-value: 0.22). The percentage of women reporting given obstetrical outcomes verse the known total pregnancy percentages are represented in Table IV. Since pregnant women reported their total number of pregnancies and if they ever had a given obstetrical complication but did not report in how many of their pregnancies a complication occurred, two separate odds ratios were calculated. The first odds ratio was calculated assuming that only one of their pregnancies was affected (Minimum Odds Ratio) and the second odds ratio was calculated assuming all of their pregnancies were affected (Maximum Odds Ratio). The true odds ratio undoubtedly lies between these two calculations. The minimum and maximum odds ratios are shown in Table V. Using these calculations, there was an increase between 37% and 442% in the odds of PROM and 17–216% in the odds of pre-eclampsia in our twin sample verse the general population Discussion The increased incidence of PROM and pre-eclampsia in our twin sample verse the general population was of great interest. A literature review identified the incidence of PROM in the general population to be approximately 10% [ 1 ], whereas 24.3% of our pregnant women reported undergoing PROM in at least one of their pregnancies. Likewise, the incidence of pre-eclampsia in the general population is estimated to be about 4% [ 2 ], whereas 8.4% of our pregnant women reported having pre-eclampsia in at least one of their pregnancies. Since the number of pregnancies effected for each twin who had the condition was not known however, minimum and maximum odds ratios were calculated. Using this technique, the minimum odds ratio for PROM was 1.37 (95% CI = 0.95,1.96) and the maximum odds ratio was 5.42 (95% CI = 4.21,6.98). The actual odds ratio undoubtedly lies between these two numbers and is most likely significant. Using the same technique the minimum odds ratio for pre-eclampsia was 1.17 (95% CI = 0.66,2.09) and the maximum odds ratio was 3.16 (95% CI = 2.16,4.62) in our twin sample verse the general population. Since both PROM and pre-eclampsia are more likely in subsequent pregnancies when one pregnancy has been affected, it is likely that at least some of the women in our sample were affected in more than one pregnancy. Interestingly, twin gestations themselves are associated with an increased risk of both PROM and pre-eclampsia. Whether there is a causative role behind the increased risk of PROM and pre-eclampsia during the antecedent twin gestation and subsequent pregnancies of these twin women remains unclear but is a potential area of further research. For instance, if twin women are more likely to develop pre-eclampsia than singleton women, aspirin prophylaxis for twin women may be routinely offered. Although there is wide variation on the usage of aspirin for pre-eclampsia prophylaxis, The American College of Obstetricians and Gynecologists (ACOG) does not currently list being a twin as an indication for prescribing aspirin for pre-eclampsia prophylaxis. Further, since the incidence of PROM and pre-eclampsia is known to vary across race, the racial breakdown in our sample needed to be similar to the general United States population for meaningful comparisons to be made. Overall, the socio-economic factors that make up this twin cohort are similar to the general United States population. The racial distribution of our twin sample was similar to the general population with 87.5% verse 78% identifying as White/Hispanic, 8.3% verse 12% identifying as Black, 2.1% verse 6% identifying as Asian, and 2.1% verse 4% identifying as other in our sample verse the general population respectively [ 8 ]. Another important consideration was the impact of smoking and PROM in our sample. Since smoking is a known cause of PROM it was very important to consider the potential role of tobacco use in our twin sample verse the general population. It has been estimated that in 2005, 13.8% of women reported smoking during pregnancy [ 9 ]. In our twin sample 9.1% of pregnant women reported smoking at some point during their life. Whether the tobacco use in the twin women occurred during pregnancy or not was not specified so the actual percentage using tobacco during pregnancy was likely lower than 9.1%. Certainly, while smoking is often under-reported the smaller percentage in our twin sample verse the general population makes it unlikely that tobacco use played a significant role in our PROM findings. The scant knowledge of amnionicity and chorionicity among twins was also striking. Although this is one of the most critical factors in the management and prognosis of twin gestations, less than 1 in 10 (9.9%) of twins sampled had this knowledge about their pregnancy. Interestingly, no fraternal twins (0/18) reported having this knowledge. However, every single twin who responded to this survey identified as either an identical or fraternal twin. Since 80 percent of all twins are dichorionic [ 2 ], and could thus be either identical or fraternal, the fact that 100% of the sample reportedly knew they were either identical or fraternal was curious. At any rate, there appears to be a general lack of knowledge about the embryology of twin pregnancies among twins themselves. There were both strengths and limitations to this study. Strengths included a diverse group of female twins in terms of both age and demographics and completely voluntary participation in the study. The cross sectional study design allowed multiple obstetrical and gynecological parameters to be analyzed at the same time. Finally, the medical literature was useful in providing comparisons to our study sample. A significant limitation of the study was that there was no way to definitively corroborate that the twins took the surveys independently despite instructions to not collaborate. Unfortunately, this resulted in the possibility of twin collaboration and respondent bias. There was also a significant possibility of recall bias especially among older twins recounting obstetrical issues. The response rate was also lower than desired. Additionally, there were many non-statistically significant results and more identical twins than fraternal twins responded to the survey. Conclusions This study suggests a potential increase in PROM and pre-eclampsia in twin women, although further large scale research is necessary to further investigate if such a relationship exists. Further areas of research could include large scale analysis of PROM and pre-eclampsia in twin women and potential alterations in counseling and management of these pregnancies. Abbreviations Premature Rupture of Membranes: PROM Declarations Ethics Approval and Consent to Participate : This study was fully Institutional Review Board approved at Albany Medical College and written consent was obtained. Consent for Publication : Not applicable Availability of Data and Materials : All data generated and analyzed during this study are included in this published article and its supplementary information files. Competing Interests : The authors declare that they have no competing interests Funding : No funding was obtained for this study Author Contributions: NAK: Project development, Data collection, Data analysis, Manuscript writing KCK: Project development, Data collection, Data analysis, Manuscript writing All authors read and approved the final manuscript. Acknowledgements We very much appreciate the support and willingness of our twin respondents in this research. Additionally, we would like to acknowledge the Twins Days Festival of Twinsburg, Ohio for their assistance in survey distribution. Authors’ Information Dr. Nathan A. Keller graduated medical school at Penn State Milton S. Hershey Medical Center in 2013 and obstetrics and gynecology residency from Albany Medical Center/Albany Medical College in 2017. He is an identical twin and is currently in private practice in Pennsylvania. Dr. Kevin C. Kiley graduated medical school at Georgetown University School of Medicine in Washington DC. He has served as Surgeon General of the United States Army and most recently as Chairman of the Department of Obstetrics and Gynecology at Albany Medical Center in Albany, New York. Both authors are Fellows of the American College of Obstetrics and Gynecology. References American College of Obstetricians and Gynecologists (ACOG). Practice Bulletin Number 217: Prelabor Rupture of Membranes, 2020. Creasy RK, Resnik R, Iams JD, Lockwood CJ, Moore TR, Greene MF. Creasy & Resnik’s Maternal Fetal Medicine, Principles and Practice. 7th Edition , 2014. p. 756–781. American College of Obstetricians and Gynecologists (ACOG). Hypertension in Pregnancy. Task Force on Hypertension in Pregnancy, 2013. American College of Obstetricians and Gynecologists (ACOG). Practice Bulletin Number 193: Tubal Ectopic Pregnancy, 2018. American College of Obstetricians and Gynecologists (ACOG). Practice Bulletin Number 190: Gestational Diabetes Mellitus, 2018. CDC National Vital Statistics Report. 2019. Births: Final Data for 2018 . Centers for Disease Control and Prevention. cdc.gov/nchs/data/nvsr/nvsr68/nvsr68_13–508.pdf . Accessed June 10, 2020. CDC National Center for Health Statistics. 2015. 2010 Pregnancy Rates Among US Women . Centers for Disease Control and Prevention. cdc.gov/nchs/data/hestat/pregnancy/2010_pregnancy_rates.pdf . Kaiser Family Foundation. 2020. Population Distribution by Race/Ethnicity. https://www.kff.org/other/state-indicator/distribution-by-raceethnicity/ . Accessed June 20, 2020. CDC Morbidity and Mortality Weekly Report Surveillance Summary. Trends in smoking before, during, and after pregnancy – Pregnancy Risk Assessment Monitoring System (PRAMS), United States, 31 sites, 2000–2005 . May 29, 2009. 58(4): 1–29. Tables Table I – Social parameters in identical and fraternal twins *Fisher’s Exact Test represented by asterisk (*) Table II – Gynecological parameters in identical and fraternal twins Table III – Obstetrical parameters in identical and fraternal twins Table IV – Percentage of women reporting obstetrical outcomes verse known population percentages Table V – Obstetrical odds ratios in twin sample verse general population Supplementary Files Questionnaire.docx TwinsFinalWorksheet.xlsx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-74105","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":2470482,"identity":"7b36c188-5932-40dd-aefc-b421f315b93c","order_by":0,"name":"Nathan Keller","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABA0lEQVRIiWNgGAWjYJACxgYGCxkg1fjgA3EamEFaJHiAjMOGM+BmMDBIEKGFLU2ahxgt5uznDz6cUSHBwy99xkzapsYmmr/9+PMHjDts6nBpsexJZjbccEaCR7Ivx9g651ha7owzOYYNjGfScNpicCCZTfJhmwSPwRkew9u5DYdzNzDkMDYwth3GreX8Y/afD/9J8Nif4TGQtgRp4X/+EKjlP24tN5LZGDc2AG3hYUuSZgRpkUgAOqztAB4tj40lZxyT4JE4AwzkHpBfbrwxnJHYlizZgNNhiQ8/9tTYyPH3AKPyR41Nbn9/+oMPH9vs+HHZggMkkKh+FIyCUTAKRgEqAADYHleD7Gw3xgAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0003-4066-8489","institution":"Womens Health Center of Lebanon","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Nathan","middleName":"","lastName":"Keller","suffix":""},{"id":2470483,"identity":"95327c8a-7bdd-471b-bfb2-d38f47517e54","order_by":1,"name":"Kevin C. Kiley","email":"","orcid":"","institution":"Albany Medical Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Kevin","middleName":"C.","lastName":"Kiley","suffix":""}],"badges":[],"createdAt":"2020-09-08 10:33:01","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-74105/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-74105/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":2518696,"identity":"e559282c-e11f-442e-a539-9a8e168eaf1f","added_by":"auto","created_at":"2020-09-21 18:13:19","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":74950,"visible":true,"origin":"","legend":"Respondent location by geographical area","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-74105/v1/Figure1.png"},{"id":2518697,"identity":"17b14def-fda1-406e-a295-b588314ff15a","added_by":"auto","created_at":"2020-09-21 18:13:19","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":91158,"visible":true,"origin":"","legend":"Age of respondents in sample","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-74105/v1/Figure2.png"},{"id":13594452,"identity":"8a008cec-d576-4110-8eb3-019172633a23","added_by":"auto","created_at":"2021-09-17 05:20:28","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":544889,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-74105/v1/e00bdff3-fb7f-49cb-a87c-87d3188f89d3.pdf"},{"id":2518699,"identity":"1e5aafe8-6fc3-411b-8675-51d70ac91be2","added_by":"auto","created_at":"2020-09-21 18:13:20","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":87490,"visible":true,"origin":"","legend":"","description":"","filename":"Questionnaire.docx","url":"https://assets-eu.researchsquare.com/files/rs-74105/v1/Questionnaire.docx"},{"id":2518700,"identity":"92470305-6d78-4e92-a85b-b014dea6db7f","added_by":"auto","created_at":"2020-09-21 18:13:20","extension":"xlsx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":67968,"visible":true,"origin":"","legend":"","description":"","filename":"TwinsFinalWorksheet.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-74105/v1/TwinsFinalWorksheet.xlsx"}],"financialInterests":"","formattedTitle":"A Cross-Sectional Study of Obstetrical and Gynecological Parameters in Twins – A Potential Increase in Premature Rupture of Membranes and Pre-eclampsia in Twin Women","fulltext":[{"header":"Background","content":" \u003cp\u003eTwin pregnancies have long been a topic of study and investigation. One has little difficulty finding an abundance of information on the diagnosis, management, complications and delivery recommendations for twin gestations. There have been tremendous advances in monochorionic twin pregnancy management and therapy up to and including the role of fetoscopic laser coagulation of placental anastomoses for Twin-Twin Transfusion Syndrome management. What happens when these very twins become of childbearing age however? Are they more likely to develop pre-eclampsia themselves or experience premature rupture of membranes? Would they be more likely to develop gestational diabetes than those born of singleton pregnancies? If twins would be more likely to develop pre-eclampsia or gestational diabetes should they routinely be offered aspirin for pre-eclampsia prophylaxis or early glucose tolerance testing when they become pregnant? The questions remain unanswered. Interestingly, data to answer such questions is nonexistent. Given the increased incidence of premature rupture of membranes, pre-eclampsia, and gestational diabetes in twin gestations it seems feasible that these twin women could be at increased risk of these conditions when they themselves become pregnant.\u003c/p\u003e \u003cp\u003eThe gynecological questions surrounding twins are equally unknown. Are identical or fraternal twins more likely to both have the same age of menarche, abnormal pap smears, use birth control, have endometriosis, have fibroids, experience infertility, develop gynecological cancer, or be diagnosed with osteoporosis? The goals of this study were to investigate some of these questions. More specifically, social, obstetrical, and gynecological relationships between female identical and fraternal twins were investigated. Additionally, obstetrical frequencies among twins were compared to those in the general population.\u003c/p\u003e "},{"header":"Methods","content":" \u003cp\u003eThis study was fully approved by the Institutional Review Board of Albany Medical Center/Albany Medical College before its commencement. The study was a cross sectional study involving the distribution of surveys to female twins. The surveys were developed specifically for this study. In order to be eligible to participate in the study twins needed to be female, be an identical or fraternal twin, and be at least 18\u0026nbsp;years of age. Surveys were given in registration packets to all twins who attended the \u003cem\u003eTwins Days Festival\u003c/em\u003e in Twinsburg, Ohio, in August of 2014. Additionally, surveys were electronically mailed to all twins on the \u003cem\u003eTwins Days Festival\u003c/em\u003e mailing list which included twins from the festival\u0026rsquo;s inception in 1976. Of note, the \u003cem\u003eTwins Days Festival\u003c/em\u003e is the largest annual gathering of twins and multiples in the world. Twins were instructed to complete the surveys independently of their twin counterpart and not to collaborate with their twin in any way. Participation in this survey was completely optional and twins could readily opt out of participating. Once a survey was completed it was mailed back to the Department of Obstetrics and Gynecology at Albany Medical Center in Albany, New York. Each survey couplet had a unique tracking number on it so the surveys could be matched back together upon receival.\u003c/p\u003e \u003cp\u003eThe contents of the individual surveys contained demographic, social, gynecological, and obstetrical questions. Questions were constructed in a binary manner to elicit a yes/no response. Results were tabulated and coded as binary variables either yes (1) or no (0). SAS University Edition was then utilized to perform all statistical analyses. Specifically, Chi Square and Fisher\u0026rsquo;s Exact Tests were used to compare all binary variables. To compare obstetrical ratios in our twin sample to the general population a literature review was performed and odds ratios were calculated. The incidence of premature rupture of membranes in the general population was estimated to be 10% of all pregnancies [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], the incidence of pre-eclampsia was estimated to be 4% of all pregnancies [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], the incidence of hypertension was estimated to be 10% of all pregnancies [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], the incidence of ectopic pregnancies was estimated to be 2% of all pregnancies [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], and the incidence of gestational diabetes was estimated to be 6% of all pregnancies [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Using these population estimates, it was determined that an adequate sample size was obtained for all the above variables in this survey to have a confidence level of 95% that the real value is within \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;5% of the surveyed value with each individual population proportion. (Needed sample size of 139 for PROM, 60 for Pre-eclampsia, 139 for hypertension, 31 for ectopic, 87 for gestational diabetes: all of which were obtained). Finally, in order to calculate odds ratios to the general population the number of pregnancies and births in the United States both had to be estimated. Recent CDC data was utilized to estimate the annual number of births in the United States as 3,791,712 [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] and the annual number of pregnancies as 6,155,000 [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e "},{"header":"Results","content":" \u003cp\u003eIn total 192 surveys were received representing 96 sets of twins. Using the attendance at the festival alone, in which there is estimated to be 2,000 female twins annually, the response rate was estimated to be 9.6%. When factoring in the large number of surveys that were sent electronically, the response rate was likely much smaller than this. In total, surveys were received from 23 states, Canada, and Great Britain. 41.7% were from Eastern States, 40.6% were from the Midwest, 9.4% were from Southern States, 6.3% were from Western States, and 1% were from Canada and Great Britain respectively\u003ca class=\"FNLink\" href=\"#Fn2\" id=\"#FNLinkFn2\"\u003e\u003c/a\u003e (Figure I). 172 of the twins identified as identical twins and 20 identified as fraternal twins. The average age of respondents was 43.3\u0026nbsp;years with a standard deviation of 17.0\u0026nbsp;years (Figure II). Of the respondents, 87.5% identified as White/Hispanic, 8.3% identified as Black, 2.1% identified as Asian, and 2.1% identified as other. This racial breakdown is similar to the United States general population in which it is estimated that 78% are White/Hispanic, 12% are Black, 6% are Asian, and 4% identify as other [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Social factor results are identified in Table I. Gynecological factors are identified in Table II and obstetrical factors in Table III. There was a total of 258 reported pregnancies. A statistically significant greater number of identical twins reported having the same age of menarche than did fraternal twins (69.51% verse 33.33%, p-value: 0.0021). Other gynecological parameters did not have a statistically significant difference between identical and fraternal twins (Table II). There were no statistically significant differences detected among the obstetrical parameters tested between identical and fraternal twins (Table III). Only 9.8% of respondents reported knowing the number of amnions and chorions in their pregnancy. 11% (18/164) of identical twins reported knowing amnions and chorions in their pregnancy compared to 0% (0/18) of fraternal twins (p-value: 0.22). The percentage of women reporting given obstetrical outcomes verse the known total pregnancy percentages are represented in Table IV. Since pregnant women reported their total number of pregnancies and if they ever had a given obstetrical complication but did not report in how many of their pregnancies a complication occurred, two separate odds ratios were calculated. The first odds ratio was calculated assuming that only one of their pregnancies was affected (Minimum Odds Ratio) and the second odds ratio was calculated assuming all of their pregnancies were affected (Maximum Odds Ratio). The true odds ratio undoubtedly lies between these two calculations. The minimum and maximum odds ratios are shown in Table V. Using these calculations, there was an increase between 37% and 442% in the odds of PROM and 17\u0026ndash;216% in the odds of pre-eclampsia in our twin sample verse the general population\u003c/p\u003e "},{"header":"Discussion","content":" \u003cp\u003eThe increased incidence of PROM and pre-eclampsia in our twin sample verse the general population was of great interest. A literature review identified the incidence of PROM in the general population to be approximately 10% [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], whereas 24.3% of our pregnant women reported undergoing PROM in at least one of their pregnancies. Likewise, the incidence of pre-eclampsia in the general population is estimated to be about 4% [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], whereas 8.4% of our pregnant women reported having pre-eclampsia in at least one of their pregnancies. Since the number of pregnancies effected for each twin who had the condition was not known however, minimum and maximum odds ratios were calculated. Using this technique, the minimum odds ratio for PROM was 1.37 (95% CI\u0026thinsp;=\u0026thinsp;0.95,1.96) and the maximum odds ratio was 5.42 (95% CI\u0026thinsp;=\u0026thinsp;4.21,6.98). The actual odds ratio undoubtedly lies between these two numbers and is most likely significant.\u003c/p\u003e \u003cp\u003eUsing the same technique the minimum odds ratio for pre-eclampsia was 1.17 (95% CI\u0026thinsp;=\u0026thinsp;0.66,2.09) and the maximum odds ratio was 3.16 (95% CI\u0026thinsp;=\u0026thinsp;2.16,4.62) in our twin sample verse the general population. Since both PROM and pre-eclampsia are more likely in subsequent pregnancies when one pregnancy has been affected, it is likely that at least some of the women in our sample were affected in more than one pregnancy. Interestingly, twin gestations themselves are associated with an increased risk of both PROM and pre-eclampsia. Whether there is a causative role behind the increased risk of PROM and pre-eclampsia during the antecedent twin gestation and subsequent pregnancies of these twin women remains unclear but is a potential area of further research. For instance, if twin women are more likely to develop pre-eclampsia than singleton women, aspirin prophylaxis for twin women may be routinely offered. Although there is wide variation on the usage of aspirin for pre-eclampsia prophylaxis, The American College of Obstetricians and Gynecologists (ACOG) does not currently list being a twin as an indication for prescribing aspirin for pre-eclampsia prophylaxis. Further, since the incidence of PROM and pre-eclampsia is known to vary across race, the racial breakdown in our sample needed to be similar to the general United States population for meaningful comparisons to be made. Overall, the socio-economic factors that make up this twin cohort are similar to the general United States population. The racial distribution of our twin sample was similar to the general population with 87.5% verse 78% identifying as White/Hispanic, 8.3% verse 12% identifying as Black, 2.1% verse 6% identifying as Asian, and 2.1% verse 4% identifying as other in our sample verse the general population respectively [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAnother important consideration was the impact of smoking and PROM in our sample. Since smoking is a known cause of PROM it was very important to consider the potential role of tobacco use in our twin sample verse the general population. It has been estimated that in 2005, 13.8% of women reported smoking during pregnancy [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In our twin sample 9.1% of pregnant women reported smoking at some point during their life. Whether the tobacco use in the twin women occurred during pregnancy or not was not specified so the actual percentage using tobacco during pregnancy was likely lower than 9.1%. Certainly, while smoking is often under-reported the smaller percentage in our twin sample verse the general population makes it unlikely that tobacco use played a significant role in our PROM findings.\u003c/p\u003e \u003cp\u003eThe scant knowledge of amnionicity and chorionicity among twins was also striking. Although this is one of the most critical factors in the management and prognosis of twin gestations, less than 1 in 10 (9.9%) of twins sampled had this knowledge about their pregnancy. Interestingly, no fraternal twins (0/18) reported having this knowledge. However, every single twin who responded to this survey identified as either an identical or fraternal twin. Since 80 percent of all twins are dichorionic [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], and could thus be either identical or fraternal, the fact that 100% of the sample reportedly knew they were either identical or fraternal was curious. At any rate, there appears to be a general lack of knowledge about the embryology of twin pregnancies among twins themselves.\u003c/p\u003e \u003cp\u003eThere were both strengths and limitations to this study. Strengths included a diverse group of female twins in terms of both age and demographics and completely voluntary participation in the study. The cross sectional study design allowed multiple obstetrical and gynecological parameters to be analyzed at the same time. Finally, the medical literature was useful in providing comparisons to our study sample. A significant limitation of the study was that there was no way to definitively corroborate that the twins took the surveys independently despite instructions to not collaborate. Unfortunately, this resulted in the possibility of twin collaboration and respondent bias. There was also a significant possibility of recall bias especially among older twins recounting obstetrical issues. The response rate was also lower than desired. Additionally, there were many non-statistically significant results and more identical twins than fraternal twins responded to the survey.\u003c/p\u003e "},{"header":"Conclusions","content":" \u003cp\u003eThis study suggests a potential increase in PROM and pre-eclampsia in twin women, although further large scale research is necessary to further investigate if such a relationship exists. Further areas of research could include large scale analysis of PROM and pre-eclampsia in twin women and potential alterations in counseling and management of these pregnancies.\u003c/p\u003e "},{"header":"Abbreviations","content":"\u003cp\u003ePremature Rupture of Membranes: PROM\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics Approval and Consent to Participate\u003c/strong\u003e: This study was fully Institutional Review Board approved at Albany Medical College and written consent was obtained.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for Publication\u003c/strong\u003e: Not applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of Data and Materials\u003c/strong\u003e: All data generated and analyzed during this study are included in this published article and its supplementary information files.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e: The authors declare that they have no competing interests\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: No funding was obtained for this study\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNAK: Project development, Data collection, Data analysis, Manuscript writing\u003c/p\u003e\n\u003cp\u003eKCK: Project development, Data collection, Data analysis, Manuscript writing\u003c/p\u003e\n\u003cp\u003eAll authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe very much appreciate the support and willingness of our twin respondents in this research. Additionally, we would like to acknowledge the \u003cem\u003eTwins Days Festival\u003c/em\u003e of Twinsburg, Ohio for their assistance in survey distribution.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; Information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDr. Nathan A. Keller graduated medical school at Penn State Milton S. Hershey Medical Center in 2013 and obstetrics and gynecology residency from Albany Medical Center/Albany Medical College in 2017. He is an identical twin and is currently in private practice in Pennsylvania. Dr. Kevin C. Kiley graduated medical school at Georgetown University School of Medicine in Washington DC. He has served as Surgeon General of the United States Army and most recently as Chairman of the Department of Obstetrics and Gynecology at Albany Medical Center in Albany, New York. Both authors are Fellows of the American College of Obstetrics and Gynecology.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e \u003cspan\u003eAmerican College of Obstetricians and Gynecologists (ACOG). Practice Bulletin Number 217: Prelabor Rupture of Membranes, 2020.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eCreasy RK, Resnik R, Iams JD, Lockwood CJ, Moore TR, Greene MF. \u003cem\u003eCreasy \u0026amp; Resnik\u0026rsquo;s Maternal Fetal Medicine, Principles and Practice. 7th Edition\u003c/em\u003e, 2014. p.\u0026nbsp;756\u0026ndash;781.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eAmerican College of Obstetricians and Gynecologists (ACOG). Hypertension in Pregnancy. Task Force on Hypertension in Pregnancy, 2013.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eAmerican College of Obstetricians and Gynecologists (ACOG). Practice Bulletin Number 193: Tubal Ectopic Pregnancy, 2018.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eAmerican College of Obstetricians and Gynecologists (ACOG). Practice Bulletin Number 190: Gestational Diabetes Mellitus, 2018.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eCDC National Vital Statistics Report. 2019. \u003cem\u003eBirths: Final Data for 2018\u003c/em\u003e. Centers for Disease Control and Prevention. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ecdc.gov/nchs/data/nvsr/nvsr68/nvsr68_13\u0026ndash;508.pdf\u003c/span\u003e\u003c/span\u003e. Accessed June 10, 2020.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eCDC National Center for Health Statistics. 2015. \u003cem\u003e2010 Pregnancy Rates Among US Women\u003c/em\u003e. Centers for Disease Control and Prevention. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ecdc.gov/nchs/data/hestat/pregnancy/2010_pregnancy_rates.pdf\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eKaiser Family Foundation. 2020. Population Distribution by Race/Ethnicity. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.kff.org/other/state-indicator/distribution-by-raceethnicity/\u003c/span\u003e\u003c/span\u003e. Accessed June 20, 2020.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eCDC Morbidity and Mortality Weekly Report Surveillance Summary. \u003cem\u003eTrends in smoking before, during, and after pregnancy \u0026ndash; Pregnancy Risk Assessment Monitoring System (PRAMS), United States, 31 sites, 2000\u0026ndash;2005\u003c/em\u003e. May 29, 2009. 58(4): 1\u0026ndash;29.\u003c/span\u003e \u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable I \u0026ndash; Social parameters in identical and fraternal twins\u003c/p\u003e\n\u003cp\u003e\u003cimg src=\"https://myfiles.space/user_files/58891_537ccc6497188def/58891_custom_files/img1600676108.png\" alt=\"\" /\u003e\u003c/p\u003e\n\u003cp\u003e*Fisher\u0026rsquo;s Exact Test represented by asterisk (*)\u003c/p\u003e\n\u003cp\u003eTable II \u0026ndash; Gynecological parameters in identical and fraternal twins\u003c/p\u003e\n\u003cp\u003e\u003cimg src=\"https://myfiles.space/user_files/58891_537ccc6497188def/58891_custom_files/img1600676132.png\" alt=\"\" /\u003e\u003c/p\u003e\n\u003cp\u003eTable III \u0026ndash; Obstetrical parameters in identical and fraternal twins\u003c/p\u003e\n\u003cp\u003e\u003cimg src=\"https://myfiles.space/user_files/58891_537ccc6497188def/58891_custom_files/img1600676143.png\" alt=\"\" /\u003e\u003c/p\u003e\n\u003cp\u003eTable IV \u0026ndash; Percentage of women reporting obstetrical outcomes verse known population percentages\u003c/p\u003e\n\u003cp\u003e\u003cimg src=\"https://myfiles.space/user_files/58891_537ccc6497188def/58891_custom_files/img1600676154.png\" alt=\"\" /\u003e\u003c/p\u003e\n\u003cp\u003eTable V \u0026ndash; Obstetrical odds ratios in twin sample verse general population\u003c/p\u003e\n\u003cp\u003e\u003cimg src=\"https://myfiles.space/user_files/58891_537ccc6497188def/58891_custom_files/img1600676164.png\" alt=\"\" /\u003e\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Premature Rupture of Membranes, Pre-eclampsia, Amnion, Chorion, Twins","lastPublishedDoi":"10.21203/rs.3.rs-74105/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-74105/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThis cross-sectional study of 192 twins across a wide geographical area compared obstetrical and gynecological parameters between twins and the general population.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThe study is a cross-sectional study. Gynecological variables included age of menarche, abnormal pap smears, birth control usage, endometriosis, fibroids, infertility, gynecological cancer, and osteoporosis. Obstetrical variables studied included pregnancy, ectopic pregnancies, hypertension, pre-eclampsia, gestational diabetes, and premature rupture of membranes (PROM). Chi Square and Fisher\u0026rsquo;s Exact tests were utilized to compare these binary variables between identical and fraternal twins. Finally, odds ratios were used to compare the rates of PROM, pre-eclampsia, hypertension, ectopic pregnancy, and gestational diabetes among twins compared to the general population using reputable literature sources.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eIdentical twins reported the same age of menarche more frequently than their fraternal counterparts (p\u0026thinsp;=\u0026thinsp;0.0021) with an odds ratio of 4.56 (95% CI\u0026thinsp;=\u0026thinsp;1.62,12.83). There was also an increase in the odds of PROM 1.37 to 5.42 (95% CI\u0026thinsp;=\u0026thinsp;0.95,1.96 and 4.21,6.98) and pre-eclampsia 1.17 to 3.16 (95% CI\u0026thinsp;=\u0026thinsp;0.66,2.09 and 2.16,4.62) in our twin sample verse the general population. Finally, only 9.9% (18/184) reported knowledge of amnionicity and chorionicity.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eOur findings suggest that further large scale research concerning PROM and pre-eclampsia in twin women may be warranted.\u003c/p\u003e","manuscriptTitle":"A Cross-Sectional Study of Obstetrical and Gynecological Parameters in Twins – A Potential Increase in Premature Rupture of Membranes and Pre-eclampsia in Twin Women","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-09-21 18:12:50","doi":"10.21203/rs.3.rs-74105/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2f3be584-c7c3-4986-a1ce-1bd6953d3de9","owner":[],"postedDate":"September 21st, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":563621,"name":"Obstetrics \u0026 Gynecology"}],"tags":[],"updatedAt":"2020-09-23T20:02:01+00:00","versionOfRecord":[],"versionCreatedAt":"2020-09-21 18:12:50","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-74105","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-74105","identity":"rs-74105","version":["v1"]},"buildId":"eB-D7MK2yqyqIWuf3Ze0-","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}