Diploid fetus with partially triploid placenta: case presentation and management strategy

Diploid fetus with partially triploid placenta: case presentation and management strategy | 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 Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Diploid fetus with partially triploid placenta: case presentation and management strategy Behrokh Sahebdel, Zahra Moghimi, Ehsan Sobhanian, Elham Shirali, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4289716/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 02 Dec, 2024 Read the published version in Maternal Health, Neonatology and Perinatology → Version 1 posted 4 You are reading this latest preprint version Abstract Multiple placental cysts are a common finding in obstetric ultrasound imaging. Although it has benign differential diagnoses such as hydropic degeneration of the placenta or placental mesenchymal dysplasia, its important pathologies such as benign gestational trophoblastic disease or hydatiform mole should always be considered. A challenging issue in obstetrics is pregnancies with a placenta that has a bipartite texture. This means that one side of the placenta is normal, but the other side is full of cystic formation and just one fetus is visualized. The main critical concern is the presence of molar pregnancy because of its catastrophic consequences. Here we report a rare case in which the gravid uterus had a normal diploid fetus but had a bipartite placenta which was triploid in the hydropic part, revealing a unique genetic pattern. placental cyst bipartite placenta hydropic placenta twin molar pregnancy Figures Figure 1 Figure 2 Figure 3 Introduction Multiple placental cysts are a common finding in obstetric ultrasound imaging. Although it has benign differential diagnoses such as hydropic degeneration of the placenta or placental mesenchymal dysplasia, its important pathologies such as benign gestational trophoblastic disease or hydatiform mole should always be considered ( 1 , 2 ). A challenging issue in obstetrics is pregnancies with a placenta with a bipartite texture. This means that one side of the placenta is normal, but the other side is full of cystic formation and just one fetus is visualized (Fig. 1 ). A possible explanation could be twin pregnancies, with one normal pregnancy in one sac and a complete molar co-twin in another. These pregnancies are at increased risk of serious complications. Although ultrasound imaging features such as identifying a lambda sign can help in recognizing this kind of pregnancy, they can be inconclusive in some cases. On the other hand, in any pregnancy with a bipartite placenta and only one fetus, placental mesenchymal dysplasia and also partial molar pregnancies should always be considered. Placental mesenchymal dysplasia is a rare, benign placental malformation that is identified with placentomegaly and grape-like vesicles, mimicking molar pregnancy on ultrasound imaging. Prenatal recognition of placental mesenchymal dysplasia during early and late gestation could affect the future of pregnancy and avoid unnecessary pregnancy termination ( 16 , 17 ). Moreover, visualization of anomalous fetus can lead to partial molar pregnancy diagnosis, but it can still be challenging in some cases. Here we report a rare case in which the gravid uterus had a normal diploid fetus, but had a bipartite placenta which was triploid in the hydropic part, revealing a unique genetic pattern. Our management approach for this case can suggest a possible strategy that can be used as guidance in managing similar cases. Case presentation A 36-year-old primigravid woman with no abnormal medical, surgical, and drug history was referred to our clinic for performing her first trimester screening ultrasound imaging in the 12th week of gestation. During this examination (Fig. 1 ) the placenta had a biphasic appearance. There was a hypoechoic cystic appearance in the upper part of the placenta, but the lower part had a homogenous normal view. Due to fetus' normal anatomical survey and nuchal translucency in the ultrasound imaging assessment, the first trimester biochemistry screening test (β-hCG and PAPP-A) suggested a low-risk pregnancy. β-hCG titer was 152000 Miu/MI. At this stage the differential diagnoses were: 1- Twin dichorionic pregnancy with a complete molar in one sac and one normal placenta and fetus in another. However, since lambda sign was not apparent in the ultrasound imaging we could not reach a definite diagnosis. 2- Partial molar pregnancy . Since the fetus had a normal anatomical survey, partial molar pregnancy was less likely as most of the fetuses in partial molar pregnancies are triploid and malformed. 3- Normal pregnancy with mesenchymal dysplasia of the placenta. In the 16th week of pregnancy, she did another ultrasound imaging. The placenta still had the mentioned distinct pattern and the fetus was obviously normal (Fig. 2 ). After counseling and discussing differential diagnosis, the patient decided to undergo a genetic study to confirm the normal fetal karyotype for reaching a definite diagnosis. Chorionic villus sampling (CVS) from the hydropic part of the placenta and also amniocentesis were performed simultaneously. We did QF-PCR and standard GTG-banding karyotype on both samples. The result was normal diploid fetus and the hydropic part of the placenta was triploid. Considering the live fetus with normal condition, the pregnancy continued under close observation. All of her routine laboratory tests were normal during the course of pregnancy. β-hCG titer was 130000–150000 MIU/ML in three consecutive assessments. The fetus followed the normal growth curvature and gained appropriate weight during pregnancy. The pregnancy was terminated in the 38th week due to increased maternal blood pressure (160/90 mmHg). She underwent cesarean section because of fetal breech presentation. Lab tests including liver function tests, platelets count, hemoglobin level, and creatinine level showed normal results. She had 2 + proteinuria in random urine analysis. Apgar scores of the newborn were 9 and 10 in the 1st and 5th minutes. The umbilical artery pH was 7.28 and the birth weight was 2750 grams. Macroscopically, the placenta had two distinct parts, discoid creamy-gray friable soft tissue measuring 60 \(*\) 50 \(*\) 20 mm which was fused to the normal appearing placenta. The patient refused to undergo placental pathological examination. In the postpartum period, she received anti-hypertensive drugs for controlling her blood pressure for two days and also received intravenous MgSO4, as seizure prophylaxis. She was discharged after three days with a normal health condition. Her β-hCG levels in the three-month follow-up was also normal. Discussion Cystic formation in the confined area of the placenta along with a normal appearing texture in the other parts, should raise concern whether it is a twin pregnancy with one normal fetus and complete molar pregnancy in co-twin, partial molar pregnancy or placental mesenchymal dysplasia. Although in most of these pregnancies, the diagnosis can be straight forward according to ultrasound imaging features, in some borderline cases reaching definite diagnosis can be challenging, especially in early stages of pregnancy. The observation of bipartite placenta with cystic areas beside a normal fetus may raise critical concerns regarding the pregnancy outcome. The main differential diagnoses are: 1) dichorionic twin with a normal fetus in one sac and complete mole in another, 2) dichorionic twin with a normal fetus accompanied by partial mole of the missed fetus, 3) mesenchymal dysplasia, and 4) very rare event of a normal fetus and confined placental partial hydatidiform mole. The main critical diagnosis is the presence of complete molar pregnancy because of catastrophic consequences. The karyotype in complete hydatidiform mole is 46,XX, but all the chromosomes are from the paternal origin. In the clinical setting, instead of a genetic study, the diagnosis is established by observing the pathognomonic appearance in ultrasound imaging and also pathological examination and gross visualization of the molar tissue. However, in cases such as pregnancies with normal fetus and a cystic pattern of placenta, a way to reach definite diagnosis should be granted. The prevalence of complete hydatidiform mole is 1%- 6% which is higher than partial mole ( 8 ). On the other hand, partial hydatidiform moles come from dispermic fertilization of a normal haploid oocyte that generally generates a triploid set of chromosomes. In cases with partial hydatidiform moles, the triploid fetus can develop but it is anomalous and is non-viable. In our case we had a normal diploid fetus with triploid hydropic placenta in one side and normal appearing placenta in the other side. There are some case reports with partial hydatidiform molar pregnancy with diploid fetus ( 6 , 12 ). There are three types of molar pregnancies with a normal live fetus ( 9 ). Molar hydatidiform should be considered in pregnancies with high level of serum β-hCG serially ( 10 ). In partial molar pregnancies usually ultrasound imaging shows honeycomb-like echo in the placenta; the borders between the normal placental tissue and the honeycomb echo are not clear, and most fetuses are dead or malformed ( 11 ). In a case report by Hossain et al, the fetus could not continue to live on for more than 21 weeks and the pregnancy ended up with intra-uterine fetal death ( 12 ). Still, there have been cases, e.g. Zeng et al, in which a live baby was delivered ( 13 ). In pregnancies with partial hydatidiform moles, only a few villous vesicular changes occur; the cellular proliferation is bolded, 90% of the fetal chromosome karyotypes are triploid, and most pregnancies end with an abortion and fetal death. To understand the unique genetic pattern in our case and the underlying reason for diploid fetus accompanied by triploid hydropic placenta, we should consider that the characteristic of triploidy is existence of three (3n) instead of two (2n) haploid chromosome sets on the cellular level. There are two types of triploidy depending on the parental origin; "diandric triploidy" or "diandry" where the extra chromosome set comes from the paternal origin, and "digynic triploidy" or "digyny" where the extra chromosome set comes from the mother ( 19 , 20 ). Mosaic triploidy happens less frequently than complete triploidy. The mechanisms suggested for mosaic triploidy include fusion of one normal zygote with one triploid that results in a chimeric fetus; delayed fertilization of a zygote with a second sperm; and reincorporation of the second polar body into the fertilized egg ( 21 ). All the molecular markers used in the QF-PCR assay on both amniotic fluid and chorionic villus samples showed similar size indicating that fetus and molar placenta had originated from the same zygote and the extra chromosome set may come from incorporation of the second polar body into the fertilized egg in very early stages of postzygotic mitotic cell divisions (Fig. 3 ). Conclusion Based on our experience, genetic study of the hydropic part of the placenta and fetus simultaneously can help to clarify the diagnosis confidentially in similar cases, allowing the pregnancy to be continued or helping the family to decide to terminate it. Whenever we do not have a diploid genotype with entirely paternal origin in the hydropic part, we can say that the pregnancy is not a complete molar. So a differential diagnosis which is twin pregnancy with complete molar pregnancy accompanied by normal co-twin can be considered. In our case because of the triploid genotype of the hydropic part of the placenta, simultaneous amnion assay of the fetus revealed a normal diploid pattern, saving the pregnancy. However, in our experience and some other cases, sampling of chorionic villous in the hydropic placenta may fail due to the small amount of villous. Further study and more cases are needed to have a decisive conclusion. In our experience after managing this interesting case, genetic assessment of the hydropic part of the placenta and amniotic fluid simultaneously, plus monitoring pregnancy with continuous follow-up of the patient’s β-hCG titers and ultrasound imaging can help in determining the pregnancy’s destiny. Declarations Acknowledgements The authors thank Muhammed Hussein Mousavinasab for editing this text. We appreciate this family for their valuable participation in this report. Funding Declaration This study was supported by a grant to B.S. (Grant no.IR.TUMS.MEDICINE.REC.1402.217) Conflict of Interest The authors declare there is no conflict of interest. Data availability declaration All data about this case is now available in the Tehran university of medical center - Maternal, Fetal and Neonatal Research Center data base Ethics declaration The information of this case has been collected for publication with the full consent of the patient, and there is no mention of the patient's personal information in the text of the article, and all the patient's personal information is kept confidential with the treatment team. Author Contribution the case managed by Dr.behrokh sahebdelDr.Zahra moghimi and Dr.Ehsan sobhanian wrote the main manuscript textDr.Ali Rashidi nejhad analized the genetics dataall other authors had a consulted during management of case References Soper JT, Mutch DG, Schink JC: Diagnosis and treatment of gestational trophoblastic disease: ACOG Practice Bulletin No. 53. Gynecol Oncol. 2004, 93:575-85. 10.1016/j.ygyno.2004.05.013 Genest DR: Partial hydatidiform mole: clinicopathological features, differential diagnosis, ploidy and molecular studies, and gold standards for diagnosis. Int J Gynecol Pathol. 2001, 20:315-22. Candelier J.J., The hydatidiform mole, Cell Adh Migr, 2016, 10, 226-235; doi 10.1080/19336918.2015.1093275 Rohilla M., Singh P., Kaur J., Jain V., Gupta N., Prasad G.R., Individualistic approach to the management of complete hydatidiform mole with coexisting live fetus, Eur J Obstet Gynecol Reprod Biol, 2015, 191, 39-42; doi 10.1016/j. ejogrb.2015.05.017 Jacobs PA, Hunt PA, Matsuura JS, Wilson CC, Szulman AE. Complete and partial hydatidiform mole in Hawaii: cytogenetics, morphology and epidemiology. Br J Obstet Gynaecol. 1982 Apr; 89(4):258-66 Singh S, Swain S, Das L, Das PC. Partial molar pregnancy associated with a normal appearing fetus: a case report and review of the literature. Int J Reprod Contracept Obstet Gynecol. 2017; 6: 2681-2683. Ara R, Begum J, Kasem SB, Hoque S, Nargis SF. Partial Hydatidiform Mole with Alive Term IUGR Fetus. J Bangladesh Coll Phys Surg. 2016; 34(3): 164-167. Bristow RE, Shumway JB, Khouzami AN, Witter FR: Complete hydatidiform mole and surviving coexistent twin. Obstet Gynecol Surv. 1996, 51:705-9. Kawasaki K., Kondoh E., Minamiguchi S., Matsuda F., Higasa K., Fujita K., et al., Live-born diploid fetus complicated with partial molar pregnancy presenting with pre-eclampsia, maternal anemia, and seemingly huge placenta: A rare case of confined placental mosaicism and literature review, J Obstet Gynaecol Res, 2016, 42, 911-917; doi 10.1111/ jog.13025 Stevens FT, Katzorke N, Tempfer C, Kreimer U, Bizjak GI, Fleisch MC, Fehm TN: Gestational trophoblastic disorders: an update in 2015. Geburtshilfe Frauenheilkd. 2015, 75:1043-50. Muminhodzic L., Bogdanovic G., Ultrasonographic signs of partial hydatidiform mole, Med Arch, 2013, 67, 205-208 Al Ghadeer HA, Al Kishi N, Algurini KH, Albesher AB, AlGhadeer MR, Alsalman AA, Bubshait AA, Alkishi BM. Partial Molar Pregnancy With Normal Karyotype. Cureus. 2022 Oct 31;14(10):e30934. Doi: 10.7759/cureus.30934. PMID: 36465796; PMCID: PMC9711909. Zeng, Chengying, Chen, Yanbi, Zhao, Lijuan and Wan, Bo. “Partial hydatidiform mole and coexistent live fetus: a case report and review of the literature” Open Medicine , vol. 14, no. 1, 2019, pp. 843-846. Sebire N.J., Prenatal diagnosis and management of twin pregnancies complicated by a co-existing molar pregnancy, Prenat Diagn, 2006, 26, 373; doi 10.1002/pd.1380 Frederick L., Greene, Carolyn C., Gestational tropho-blastic tumors, Ajcc Cancer Staging Handbook, 2002, 8, 323-328 Mittal D, Anand R, Sisodia N, Singh S, Biswas R. Placental mesenchymal dysplasia: What every radiologist needs to know. Indian J Radiol Imaging. 2017 Jan-Mar;27(1):62-64. Doi: 10.4103/0971-3026.202949. PMID: 28515588; PMCID: PMC5385779. Parveen Z, Tongson-Ignacio JE, Fraser CR, Killeen JL, Thompson KS. Placental mesenchymal dysplasia. Arch Pathol Lab Med. 2007 Jan;131(1):131-7. Doi: 10.5858/2007-131-131-PMD. PMID: 17227114. Maria Chiara Sudano,1 Laura D’Emidio,2 Lucia Mangiafico,2 Luisa Mobili,2 and Claudio Giorlandino2. Placental mesenchymal dysplasia, a case of intrauterine sudden death in a normal-sized fetus. J Prenat Med. 2013 Jan-Mar; 7(1): 9–11. PMCID: PMC3671814-PMID: 23741541 Juan J. Tarín, Alan O. Trounson B and Henry Sathananthan. Origin and ploidy of multipronuclear zygotes. Reprod. Fertil. Dev. , 1999, 11, 273–279. 20- Mechanisms giving rise to triploid zygotes during assisted reproduction. Bernd E. Rosenbusch. Fertil Steril 2008 Jul;90(1):49-55. Doi: 10.1016/j.fertnstert.2007.06.031. (chapter 24: Prenatal Diagnosis of Chromosome Abnormalities) Book name: Fetal Medicine Basic Science and Clinical Practice, Third Edition, 2020. Authors: Author : By Pranav P Pandya, Ronald Wapner, Dick Oepkes and Neil Sebire Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 02 Dec, 2024 Read the published version in Maternal Health, Neonatology and Perinatology → Version 1 posted Editorial decision: Revision requested 21 Jun, 2024 Editor assigned by journal 24 Apr, 2024 Submission checks completed at journal 23 Apr, 2024 First submitted to journal 18 Apr, 2024 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. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board 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-4289716","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":295042940,"identity":"85596b85-e9e6-4c78-95d6-6af0ef20c947","order_by":0,"name":"Behrokh Sahebdel","email":"","orcid":"","institution":"Tehran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Behrokh","middleName":"","lastName":"Sahebdel","suffix":""},{"id":295042943,"identity":"6a39e4ef-5fc6-4db4-917b-643752d30011","order_by":1,"name":"Zahra Moghimi","email":"","orcid":"","institution":"Tehran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Zahra","middleName":"","lastName":"Moghimi","suffix":""},{"id":295042946,"identity":"c19fc7ab-0310-41ca-84a0-9698eeef2b4a","order_by":2,"name":"Ehsan Sobhanian","email":"","orcid":"","institution":"Children ’ s Medical Center, Tehran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Ehsan","middleName":"","lastName":"Sobhanian","suffix":""},{"id":295042949,"identity":"80cac0e4-7882-4345-8bd9-9f56c92931be","order_by":3,"name":"Elham Shirali","email":"","orcid":"","institution":"Tehran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Elham","middleName":"","lastName":"Shirali","suffix":""},{"id":295042952,"identity":"d4ded989-2095-4c83-b015-bcd43f093157","order_by":4,"name":"Fariba Yarandi","email":"","orcid":"","institution":"Tehran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Fariba","middleName":"","lastName":"Yarandi","suffix":""},{"id":295042954,"identity":"432ed0e1-52af-479c-8088-76f7b8efe24e","order_by":5,"name":"Fatemeh Golshahi","email":"","orcid":"","institution":"Tehran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Fatemeh","middleName":"","lastName":"Golshahi","suffix":""},{"id":295042956,"identity":"1e63c56b-4ab1-4a94-95c5-1da24f9e9d70","order_by":6,"name":"Mahboobeh Shirazi","email":"","orcid":"","institution":"Tehran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Mahboobeh","middleName":"","lastName":"Shirazi","suffix":""},{"id":295042959,"identity":"70ef645e-bcca-4168-af9a-030047cdd474","order_by":7,"name":"Nafiseh Saedi","email":"","orcid":"","institution":"Tehran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Nafiseh","middleName":"","lastName":"Saedi","suffix":""},{"id":295042960,"identity":"4a4f2a0b-dc33-4f04-a8b0-0b665c305b5d","order_by":8,"name":"Ali Rashidi-Nezhad","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/0lEQVRIiWNgGAWjYJACZgYDZh4gzQZENnBRHmK1pEkQqQWEIFoOS+BTCQb8sw8//lxQYC1jzt7+7MGPsvN1BteOP2D4UcMgY96AXYvEuTQz6RkG6TyWPQfSDXvO3ZYwuJ1jwNhzjIFH5gAOa84wmDHzGBzmMbiRcEyCtw2shYGBt4GBB5cT5c+wf/4M1nL/YZvk37ZzQC3pDxj/4tFicIbHQBpiCzObNG/bAaCWBANmfLYYnuEpA2pJ5zE4k8YmLXMuWXIm0C+HZY5J4NQid4Z982eeP9b2BsePP5N8U2bHz3c7/eHDNzU29oSDGxkcAAYlSRpGwSgYBaNgFKACAKUKT9iX3xfEAAAAAElFTkSuQmCC","orcid":"","institution":"Tehran University of Medical Sciences","correspondingAuthor":true,"prefix":"","firstName":"Ali","middleName":"","lastName":"Rashidi-Nezhad","suffix":""}],"badges":[],"createdAt":"2024-04-18 20:44:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4289716/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4289716/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s40748-024-00195-3","type":"published","date":"2024-12-02T15:57:57+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":55628079,"identity":"8c18143b-76c0-4bf3-9616-66843bf11415","added_by":"auto","created_at":"2024-04-30 18:55:51","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":149889,"visible":true,"origin":"","legend":"\u003cp\u003eplacental ultrasound imaging in the first trimester revealed bipartite placenta with two distinct zones: N (normal appearance) and H (hydropic appearance)\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4289716/v1/8bc2085df8572e809011ab74.jpg"},{"id":55629141,"identity":"36ad71d9-a313-42f0-9e7e-740215df8fbc","added_by":"auto","created_at":"2024-04-30 19:03:51","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":117437,"visible":true,"origin":"","legend":"\u003cp\u003ePlacental appearance in 16\u003csup\u003eth\u003c/sup\u003e week of pregnancy. Apparently, the normal part (N) was distinct from the hydropic part (H).\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4289716/v1/eff0f60584adbfb0ca0d5f94.jpg"},{"id":55628080,"identity":"e4909e88-82db-4dc1-b99b-4538aba159e3","added_by":"auto","created_at":"2024-04-30 18:55:51","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":186418,"visible":true,"origin":"","legend":"\u003cp\u003eThe QF-PCR result. It shows triploidy pattern in the CVS (A), and normal diploid pattern in the AF (B). All the molecular markers had the same length in both samples, indicating that the extra chromosomal set in the triploid CVS has the same genetic constitution with one of the gametes in this case ovum. Therefore, it can be inferred that the possible explanation of occurrence of mosaic diploid/triploid in this case can be due to incorporation of second polar body into the fertilized egg in the early stages of postzygotic mitotic cell divisions.\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4289716/v1/a8db328ada41c8b1f4c5a0b7.jpg"},{"id":70964841,"identity":"b38af55b-c0e4-4db5-840d-ef332f1527d7","added_by":"auto","created_at":"2024-12-09 16:16:37","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":744039,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4289716/v1/2864cbe5-8262-4084-b847-dbf31f26e799.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Diploid fetus with partially triploid placenta: case presentation and management strategy","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMultiple placental cysts are a common finding in obstetric ultrasound imaging. Although it has benign differential diagnoses such as hydropic degeneration of the placenta or placental mesenchymal dysplasia, its important pathologies such as benign gestational trophoblastic disease or hydatiform mole should always be considered (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eA challenging issue in obstetrics is pregnancies with a placenta with a bipartite texture. This means that one side of the placenta is normal, but the other side is full of cystic formation and just one fetus is visualized (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). A possible explanation could be twin pregnancies, with one normal pregnancy in one sac and a complete molar co-twin in another. These pregnancies are at increased risk of serious complications. Although ultrasound imaging features such as identifying a lambda sign can help in recognizing this kind of pregnancy, they can be inconclusive in some cases. On the other hand, in any pregnancy with a bipartite placenta and only one fetus, placental mesenchymal dysplasia and also partial molar pregnancies should always be considered. Placental mesenchymal dysplasia is a rare, benign placental malformation that is identified with placentomegaly and grape-like vesicles, mimicking molar pregnancy on ultrasound imaging.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ePrenatal recognition of placental mesenchymal dysplasia during early and late gestation could affect the future of pregnancy and avoid unnecessary pregnancy termination (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Moreover, visualization of anomalous fetus can lead to partial molar pregnancy diagnosis, but it can still be challenging in some cases.\u003c/p\u003e \u003cp\u003eHere we report a rare case in which the gravid uterus had a normal diploid fetus, but had a bipartite placenta which was triploid in the hydropic part, revealing a unique genetic pattern. Our management approach for this case can suggest a possible strategy that can be used as guidance in managing similar cases.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 36-year-old primigravid woman with no abnormal medical, surgical, and drug history was referred to our clinic for performing her first trimester screening ultrasound imaging in the 12th week of gestation. During this examination (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) the placenta had a biphasic appearance. There was a hypoechoic cystic appearance in the upper part of the placenta, but the lower part had a homogenous normal view. Due to fetus' normal anatomical survey and nuchal translucency in the ultrasound imaging assessment, the first trimester biochemistry screening test (β-hCG and PAPP-A) suggested a low-risk pregnancy. β-hCG titer was 152000 Miu/MI. At this stage the differential diagnoses were:\u003c/p\u003e \u003cp\u003e1- \u003cb\u003eTwin dichorionic pregnancy\u003c/b\u003e with a complete molar in one sac and one normal placenta and fetus in another. However, since lambda sign was not apparent in the ultrasound imaging we could not reach a definite diagnosis.\u003c/p\u003e \u003cp\u003e2- \u003cb\u003ePartial molar pregnancy\u003c/b\u003e. Since the fetus had a normal anatomical survey, partial molar pregnancy was less likely as most of the fetuses in partial molar pregnancies are triploid and malformed.\u003c/p\u003e \u003cp\u003e3- \u003cb\u003eNormal pregnancy\u003c/b\u003e with mesenchymal dysplasia of the placenta.\u003c/p\u003e \u003cp\u003eIn the 16th week of pregnancy, she did another ultrasound imaging. The placenta still had the mentioned distinct pattern and the fetus was obviously normal (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). After counseling and discussing differential diagnosis, the patient decided to undergo a genetic study to confirm the normal fetal karyotype for reaching a definite diagnosis. Chorionic villus sampling (CVS) from the hydropic part of the placenta and also amniocentesis were performed simultaneously. We did QF-PCR and standard GTG-banding karyotype on both samples. The result was normal diploid fetus and the hydropic part of the placenta was triploid.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eConsidering the live fetus with normal condition, the pregnancy continued under close observation. All of her routine laboratory tests were normal during the course of pregnancy. β-hCG titer was 130000\u0026ndash;150000 MIU/ML in three consecutive assessments. The fetus followed the normal growth curvature and gained appropriate weight during pregnancy. The pregnancy was terminated in the 38th week due to increased maternal blood pressure (160/90 mmHg). She underwent cesarean section because of fetal breech presentation. Lab tests including liver function tests, platelets count, hemoglobin level, and creatinine level showed normal results.\u003c/p\u003e \u003cp\u003eShe had 2\u0026thinsp;+\u0026thinsp;proteinuria in random urine analysis. Apgar scores of the newborn were 9 and 10 in the 1st and 5th minutes. The umbilical artery pH was 7.28 and the birth weight was 2750 grams. Macroscopically, the placenta had two distinct parts, discoid creamy-gray friable soft tissue measuring 60\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(*\\)\u003c/span\u003e\u003c/span\u003e50\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(*\\)\u003c/span\u003e\u003c/span\u003e20 mm which was fused to the normal appearing placenta. The patient refused to undergo placental pathological examination. In the postpartum period, she received anti-hypertensive drugs for controlling her blood pressure for two days and also received intravenous MgSO4, as seizure prophylaxis. She was discharged after three days with a normal health condition. Her β-hCG levels in the three-month follow-up was also normal.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eCystic formation in the confined area of the placenta along with a normal appearing texture in the other parts, should raise concern whether it is a twin pregnancy with one normal fetus and complete molar pregnancy in co-twin, partial molar pregnancy or placental mesenchymal dysplasia. Although in most of these pregnancies, the diagnosis can be straight forward according to ultrasound imaging features, in some borderline cases reaching definite diagnosis can be challenging, especially in early stages of pregnancy.\u003c/p\u003e \u003cp\u003eThe observation of bipartite placenta with cystic areas beside a normal fetus may raise critical concerns regarding the pregnancy outcome. The main differential diagnoses are: 1) dichorionic twin with a normal fetus in one sac and complete mole in another, 2) dichorionic twin with a normal fetus accompanied by partial mole of the missed fetus, 3) mesenchymal dysplasia, and 4) very rare event of a normal fetus and confined placental partial hydatidiform mole.\u003c/p\u003e \u003cp\u003eThe main critical diagnosis is the presence of complete molar pregnancy because of catastrophic consequences. The karyotype in complete hydatidiform mole is 46,XX, but all the chromosomes are from the paternal origin. In the clinical setting, instead of a genetic study, the diagnosis is established by observing the pathognomonic appearance in ultrasound imaging and also pathological examination and gross visualization of the molar tissue. However, in cases such as pregnancies with normal fetus and a cystic pattern of placenta, a way to reach definite diagnosis should be granted.\u003c/p\u003e \u003cp\u003eThe prevalence of complete hydatidiform mole is 1%- 6% which is higher than partial mole (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). On the other hand, partial hydatidiform moles come from dispermic fertilization of a normal haploid oocyte that generally generates a triploid set of chromosomes. In cases with partial hydatidiform moles, the triploid fetus can develop but it is anomalous and is non-viable. In our case we had a normal diploid fetus with triploid hydropic placenta in one side and normal appearing placenta in the other side.\u003c/p\u003e \u003cp\u003eThere are some case reports with partial hydatidiform molar pregnancy with diploid fetus (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). There are three types of molar pregnancies with a normal live fetus (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Molar hydatidiform should be considered in pregnancies with high level of serum β-hCG serially (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). In partial molar pregnancies usually ultrasound imaging shows honeycomb-like echo in the placenta; the borders between the normal placental tissue and the honeycomb echo are not clear, and most fetuses are dead or malformed (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). In a case report by Hossain et al, the fetus could not continue to live on for more than 21 weeks and the pregnancy ended up with intra-uterine fetal death (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Still, there have been cases, e.g. Zeng et al, in which a live baby was delivered (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). In pregnancies with partial hydatidiform moles, only a few villous vesicular changes occur; the cellular proliferation is bolded, 90% of the fetal chromosome karyotypes are triploid, and most pregnancies end with an abortion and fetal death.\u003c/p\u003e \u003cp\u003eTo understand the unique genetic pattern in our case and the underlying reason for diploid fetus accompanied by triploid hydropic placenta, we should consider that the characteristic of triploidy is existence of three (3n) instead of two (2n) haploid chromosome sets on the cellular level. There are two types of triploidy depending on the parental origin; \"diandric triploidy\" or \"diandry\" where the extra chromosome set comes from the paternal origin, and \"digynic triploidy\" or \"digyny\" where the extra chromosome set comes from the mother (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). Mosaic triploidy happens less frequently than complete triploidy. The mechanisms suggested for mosaic triploidy include fusion of one normal zygote with one triploid that results in a chimeric fetus; delayed fertilization of a zygote with a second sperm; and reincorporation of the second polar body into the fertilized egg (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAll the molecular markers used in the QF-PCR assay on both amniotic fluid and chorionic villus samples showed similar size indicating that fetus and molar placenta had originated from the same zygote and the extra chromosome set may come from incorporation of the second polar body into the fertilized egg in very early stages of postzygotic mitotic cell divisions (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eBased on our experience, genetic study of the hydropic part of the placenta and fetus simultaneously can help to clarify the diagnosis confidentially in similar cases, allowing the pregnancy to be continued or helping the family to decide to terminate it. Whenever we do not have a diploid genotype with entirely paternal origin in the hydropic part, we can say that the pregnancy is not a complete molar. So a differential diagnosis which is twin pregnancy with complete molar pregnancy accompanied by normal co-twin can be considered. In our case because of the triploid genotype of the hydropic part of the placenta, simultaneous amnion assay of the fetus revealed a normal diploid pattern, saving the pregnancy. However, in our experience and some other cases, sampling of chorionic villous in the hydropic placenta may fail due to the small amount of villous. Further study and more cases are needed to have a decisive conclusion.\u003c/p\u003e \u003cp\u003eIn our experience after managing this interesting case, genetic assessment of the hydropic part of the placenta and amniotic fluid simultaneously, plus monitoring pregnancy with continuous follow-up of the patient\u0026rsquo;s β-hCG titers and ultrasound imaging can help in determining the pregnancy\u0026rsquo;s destiny.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank Muhammed Hussein Mousavinasab for editing this text. We appreciate this family for their valuable participation in this report.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by a grant to B.S. (Grant no.IR.TUMS.MEDICINE.REC.1402.217)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare there is no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data about this case is now available in the Tehran university of medical center -\u0026nbsp;Maternal, Fetal and Neonatal Research Center data base\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe information of this case has been collected for publication with the full consent of the patient, and there is no mention of the patient's personal information in the text of the article, and all the patient's personal information is kept confidential with the treatment team.\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003ethe case managed by Dr.behrokh sahebdelDr.Zahra moghimi and Dr.Ehsan sobhanian wrote the main manuscript textDr.Ali Rashidi nejhad analized the genetics dataall other authors had a consulted during management of case\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eSoper JT, Mutch DG, Schink JC: Diagnosis and treatment of gestational trophoblastic disease: ACOG Practice Bulletin No. 53. Gynecol Oncol. 2004, 93:575-85. 10.1016/j.ygyno.2004.05.013\u003c/li\u003e\n \u003cli\u003eGenest DR: Partial hydatidiform mole: clinicopathological features, differential diagnosis, ploidy and molecular studies, and gold standards for diagnosis. Int J Gynecol Pathol. 2001, 20:315-22.\u003c/li\u003e\n \u003cli\u003eCandelier J.J., The hydatidiform mole, Cell Adh Migr, 2016, 10, 226-235; doi 10.1080/19336918.2015.1093275\u003c/li\u003e\n \u003cli\u003eRohilla M., Singh P., Kaur J., Jain V., Gupta N., Prasad G.R., Individualistic approach to the management of complete hydatidiform mole with coexisting live fetus, Eur J Obstet Gynecol Reprod Biol, 2015, 191, 39-42; doi 10.1016/j. ejogrb.2015.05.017\u003c/li\u003e\n \u003cli\u003eJacobs PA, Hunt PA, Matsuura JS, Wilson CC, Szulman AE.\u0026nbsp;Complete and partial hydatidiform mole in Hawaii: cytogenetics, morphology and epidemiology.\u0026nbsp;Br J Obstet Gynaecol.\u0026nbsp;1982 Apr;\u0026nbsp;89(4):258-66\u003c/li\u003e\n \u003cli\u003eSingh S, Swain S, Das L, Das PC.\u0026nbsp;Partial molar pregnancy associated with a normal appearing fetus: a case report and review of the literature.\u0026nbsp;Int J Reprod Contracept Obstet Gynecol.\u0026nbsp;2017;\u0026nbsp;6: 2681-2683.\u003c/li\u003e\n \u003cli\u003eAra R, Begum J, Kasem SB, Hoque S, Nargis SF.\u0026nbsp;Partial Hydatidiform Mole with Alive Term IUGR Fetus.\u0026nbsp;J Bangladesh Coll Phys Surg.\u0026nbsp;2016;\u0026nbsp;34(3): 164-167.\u003c/li\u003e\n \u003cli\u003eBristow RE, Shumway JB, Khouzami AN, Witter FR: Complete hydatidiform mole and surviving coexistent twin. Obstet Gynecol Surv. 1996, 51:705-9.\u003c/li\u003e\n \u003cli\u003eKawasaki K., Kondoh E., Minamiguchi S., Matsuda F., Higasa K., Fujita K., et al., Live-born diploid fetus complicated with partial molar pregnancy presenting with pre-eclampsia, maternal anemia, and seemingly huge placenta: A rare case of confined placental mosaicism and literature review, J Obstet Gynaecol Res, 2016, 42, 911-917; doi 10.1111/ jog.13025\u003c/li\u003e\n \u003cli\u003eStevens FT, Katzorke N, Tempfer C, Kreimer U, Bizjak GI, Fleisch MC, Fehm TN: Gestational trophoblastic disorders: an update in 2015. Geburtshilfe Frauenheilkd. 2015, 75:1043-50.\u003c/li\u003e\n \u003cli\u003eMuminhodzic L., Bogdanovic G., Ultrasonographic signs of partial hydatidiform mole, Med Arch, 2013, 67, 205-208\u003c/li\u003e\n \u003cli\u003eAl Ghadeer HA, Al Kishi N, Algurini KH, Albesher AB, AlGhadeer MR, Alsalman AA, Bubshait AA, Alkishi BM. Partial Molar Pregnancy With Normal Karyotype. Cureus. 2022 Oct 31;14(10):e30934. Doi: 10.7759/cureus.30934. PMID: 36465796; PMCID: PMC9711909.\u003c/li\u003e\n \u003cli\u003eZeng, Chengying, Chen, Yanbi, Zhao, Lijuan and Wan, Bo. \u0026ldquo;Partial hydatidiform mole and coexistent live fetus: a case report and review of the literature\u0026rdquo; \u003cem\u003eOpen Medicine\u003c/em\u003e, vol. 14, no. 1, 2019, pp. 843-846.\u003c/li\u003e\n \u003cli\u003eSebire N.J., Prenatal diagnosis and management of twin pregnancies complicated by a co-existing molar pregnancy, Prenat Diagn, 2006, 26, 373; doi 10.1002/pd.1380\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;Frederick L., Greene, Carolyn C., Gestational tropho-blastic tumors, Ajcc Cancer Staging Handbook, 2002, 8, 323-328\u003c/li\u003e\n \u003cli\u003eMittal D, Anand R, Sisodia N, Singh S, Biswas R. Placental mesenchymal dysplasia: What every radiologist needs to know. Indian J Radiol Imaging. 2017 Jan-Mar;27(1):62-64. Doi: 10.4103/0971-3026.202949. PMID: 28515588; PMCID: PMC5385779.\u003c/li\u003e\n \u003cli\u003eParveen Z, Tongson-Ignacio JE, Fraser CR, Killeen JL, Thompson KS. Placental mesenchymal dysplasia. Arch Pathol Lab Med. 2007 Jan;131(1):131-7. Doi: 10.5858/2007-131-131-PMD. PMID: 17227114.\u003c/li\u003e\n \u003cli\u003eMaria Chiara Sudano,1 Laura D\u0026rsquo;Emidio,2 Lucia Mangiafico,2 Luisa Mobili,2 and Claudio Giorlandino2.\u0026nbsp;Placental mesenchymal dysplasia, a case of intrauterine sudden death in a normal-sized fetus.\u0026nbsp;J Prenat Med. 2013 Jan-Mar; 7(1): 9\u0026ndash;11.\u0026nbsp;PMCID: PMC3671814-PMID: 23741541\u003c/li\u003e\n \u003cli\u003eJuan J. Tar\u0026iacute;n, Alan O. Trounson B and Henry Sathananthan. Origin and ploidy of multipronuclear zygotes. \u003cem\u003eReprod. Fertil. Dev.\u003c/em\u003e, 1999, 11, 273\u0026ndash;279.\u003c/li\u003e\n \u003cli\u003e20- Mechanisms giving rise to triploid zygotes during assisted reproduction. Bernd E. Rosenbusch. Fertil Steril 2008 Jul;90(1):49-55. Doi: 10.1016/j.fertnstert.2007.06.031.\u003c/li\u003e\n \u003cli\u003e(chapter 24: Prenatal Diagnosis of Chromosome Abnormalities) Book name: Fetal Medicine Basic Science and Clinical Practice, Third Edition, 2020. Authors: Author : By Pranav P Pandya, Ronald Wapner, Dick Oepkes and Neil Sebire\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"maternal-health-neonatology-and-perinatology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"mhnp","sideBox":"Learn more about [Maternal Health, Neonatology and Perinatology](http://mhnpjournal.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/mhnp/default.aspx","title":"Maternal Health, Neonatology and Perinatology","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"placental cyst, bipartite placenta, hydropic placenta, twin molar pregnancy","lastPublishedDoi":"10.21203/rs.3.rs-4289716/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4289716/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eMultiple placental cysts are a common finding in obstetric ultrasound imaging. Although it has benign differential diagnoses such as hydropic degeneration of the placenta or placental mesenchymal dysplasia, its important pathologies such as benign gestational trophoblastic disease or hydatiform mole should always be considered. A challenging issue in obstetrics is pregnancies with a placenta that has a bipartite texture. This means that one side of the placenta is normal, but the other side is full of cystic formation and just one fetus is visualized. The main critical concern is the presence of molar pregnancy because of its catastrophic consequences. Here we report a rare case in which the gravid uterus had a normal diploid fetus but had a bipartite placenta which was triploid in the hydropic part, revealing a unique genetic pattern.\u003c/p\u003e","manuscriptTitle":"Diploid fetus with partially triploid placenta: case presentation and management strategy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-30 18:55:46","doi":"10.21203/rs.3.rs-4289716/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-06-21T15:20:52+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-04-24T14:10:27+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-04-23T08:05:41+00:00","index":"","fulltext":""},{"type":"submitted","content":"Maternal Health, Neonatology and Perinatology","date":"2024-04-18T20:34:42+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"maternal-health-neonatology-and-perinatology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"mhnp","sideBox":"Learn more about [Maternal Health, Neonatology and Perinatology](http://mhnpjournal.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/mhnp/default.aspx","title":"Maternal Health, Neonatology and Perinatology","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"fab75e7e-ead8-41f4-a793-862b69e56598","owner":[],"postedDate":"April 30th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-12-09T16:05:46+00:00","versionOfRecord":{"articleIdentity":"rs-4289716","link":"https://doi.org/10.1186/s40748-024-00195-3","journal":{"identity":"maternal-health-neonatology-and-perinatology","isVorOnly":false,"title":"Maternal Health, Neonatology and Perinatology"},"publishedOn":"2024-12-02 15:57:57","publishedOnDateReadable":"December 2nd, 2024"},"versionCreatedAt":"2024-04-30 18:55:46","video":"","vorDoi":"10.1186/s40748-024-00195-3","vorDoiUrl":"https://doi.org/10.1186/s40748-024-00195-3","workflowStages":[]},"version":"v1","identity":"rs-4289716","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4289716","identity":"rs-4289716","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}