Histopathological Changes in the Placenta in Late Intrauterine Fetal Deaths at a Tertiary Hospital in Bangladesh | 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 Research Article Histopathological Changes in the Placenta in Late Intrauterine Fetal Deaths at a Tertiary Hospital in Bangladesh Dr. Sayedatus saba, Dr. Shahnaj Begum, Dr. Jesmin Naz Ferdous, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5042102/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 Introduction: Meticulous gross andmicroscopic studiesof the singleton placenta alone may provide valuable information regarding the cause of unexplained intrauterine fetal deaths(IUFDs) and can offer potential treatment options for its prevention in future pregnancies. Objective: To determine the histopathological changes in the placenta associated with late intrauterine fetal death. Method: A cross-sectional study was carried out in the Department of Pathology, Sir Salimullah Medical College Mitford Hospital, Dhaka, fromMarch 2021 to January 2023. A total of 80 patients aged between 19 and 44 years with late IUFDs were included in this study. Theplacentas of the dead newbornswere histopathologically analyzed. Results: All of the patients presentedsignificant gross andhistopathological changes in the placental specimens. A total of 71.3% of them were <30 years of age. Fifty percent of the patients were multipara, and 45% were primi. The gestational ages of 61.3% of the patients were within 37–40 weeks, 20% were within 28–32 weeks, and 18.8% were within 33–36 weeks. The mean placental weight was 407 gm, and 46.3% of the patients had placental weights within 410–450 gm. A total of 33.8% of the patients had placental diameters within 9–12 cm, and 48.8% had placental diameters within 13–16 cm. Cord insertion was eccentric in 41.3%, central in 45.0% and marginal in 12.5% of the patients. A total of 18.8% of patients had hypocoil, and 10% had hypercoiled cords. Twenty percent ofpatients had retroplacental hemorrhage. The membrane was greenish yellow in 3.8% of the samples and pale bluish in 2.4% of the samples. The significantmicroscopic findings were vascular ectasia with congestion in 26.3% of the patients, disorders of villous maturation in 35%, perivillous fibrin deposition in 15.0%, intervillous hemorrhage in 23.8%, subamniotic hemorrhagein 2.5%, microcalcification in 18.8%, infarct with avascular ghost villi in 17.5%, villous edema in 15%, deciduitis in 6.25%, thrombus in 5%, perivillous fibrin deposition in 15%, chorangiosis in 2.5%, villitis of unknown origin in 25% and chronic intervillositis in 17.5% of the patients. Maternal and fetal inflammatory responses were present in 26 patients, of whom46.2% had stage 1 and 38.5% had stage 2 maternal inflammatory responses. A total of 7.7% had stage 1 inflammatory response, and 23.1% had stage 2 fetalinflammatory response. Discussion: This study revealed that late IUFD is associated withsignificant placental histopathological abnormalities. Identification of these abnormalities can provide information about the etiopathogenesis of late intrauterine fetal deaths, can play a very important role in medicolegal situations and can guide physicians in the management of patients to prevent further pregnancy losses. Pathology Placenta Late IUFD Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 Introduction Fetal death is a matter of great distress to both the family and the obstetrician. Regardless of how much advancement has been achieved in the field of medical science, pregnancy loss still occurs at an alarming rate worldwide. The International Classification for Diseases 11th revision (ICD-11) classifies fetal death as late fetal death (greater than 1000 g or after 28 weeks) or early fetal death (500–1000 g or 22–28 weeks). Worldwide, approximately 60% of stillborn cases are unexplained in otherwise normal pregnancies according to Lancet Global Health, 2018. According to the World Health Organization, in 2022, the stillbirth rate in Bangladesh was 25 per 1000 births. According to the Emergency Obstetric & Newborn Care Services: Yearly DHIS-2 report by the Ministry of Health & Family Welfare, Bangladesh, from February 2021 to February 2022, a total of 10,777 pregnant mothers were admitted to the Department of Gynecology & Obstetrics, Sir Salimullah Medical College Mitford Hospital, Dhaka, for delivery or obstetric complications; among them, the total number of intrauterine fetal deaths was 275. The human placenta is a discoid, choriodeciduate organ that acts as a portal connecting the fetus with the uterine wall of the mother via the umbilical cord. The maternal supply of oxygen and nutrients occurs through the placenta via the umbilical circulation in response to fetal demand, whereas its protective function is derived from the ability to mount an inflammatory response to an external stimulus. Despite its undeniable role in human fetal development, the study of the placenta has lagged behind that of the fetus. The placenta can provide a record of both fetal and maternal intrauterine events, acting as the ‘‘black box’’ of pregnancy. Intrauterine fetal deaths may be caused by maternal, fetal and placental factors, but these factors are usually multiple and overlapping. Conditions resulting in placental dysfunction may be recurrent and can manifest in different ways in different pregnancies. The placental factors include umbilical cord and placental disc abnormalities such as retroplacental hemorrhage, circumvallation, marginal cord, true knot, calcification, inflammatory reactions, circulatory compromise (maternal or fetal), abnormalities in villous maturation, hemorrhage, necrosis, villous edema, perivillous fibrin deposition and other conditions. 1 , 2 , 3 , 4 , 5 As per the Bangladesh Demographic and Health Survey (BDHS), in 2017–18, only 47% of pregnant women in Bangladesh attended at least four WHO-recommended ANC activities 16 . Therefore, evaluation of gross and histopathological findings in the placentas of unexplained late IUFD cases may help physicians understand their accurate etiopathogenesis to prevent recurrence, to take precautionary measures during further management in future pregnancies and to address accountability issues. Moreover, when medicolegal problems arise, a study of placental histopathology can reveal the exact cause of fetal loss and can act as a legal shield to the doctor from the concerned patient. At the national and regional decision-making levels, identifying causes is important for adopting strategic management strategies for prioritizing medical services according to the person and area needed, thus ensuring proper health care services to the general population of the country. Although accurate placental examination is necessary in the evaluation of IUFDs and could play an important role in reducing the unexplained IUFD rate, placental examination is not routinely practiced in our country. Surprisingly, no previous studies have identified gross and histopathological changes in the placentas of unexplained late IUFDs in China. Methods This was a cross-sectional, descriptive and observational study. A total of 80 mothers aged 18 years or above with a diagnosis of late IUFD at a gestational age of 28 weeks or above were included in this study. Any late IUFD with known preexisting maternal conditions such as preeclampsia, diabetes, chronic hypertension, smoking, infections, and antiphospholipid syndrome were excluded from the study, as our sole goal was to identify the factors responsible for unexplained late IUFDs. The study was conducted at the Department of Pathology, Sir Salimullah Medical College, Dhaka, Bangladesh, from March 2021 to January 2023. The placentas were collected from the Department of Obstetrics and Gynecology, Sir Salimullah Medical College Mitford Hospital, Dhaka, immediately after delivery and fixed with 10% neutral buffered formalin for 24 hours. The specimens were subsequently processed and examined at the Department of Pathology, SSMC, for histopathological examination. Placentas were weighed after the cord and membrane were removed. After meticulous gross examination, 6 blocks were submitted: 1 block to include a roll of the extraplacental membranes from the rupture edge to the placental margin, 2 cross sections of the umbilical cord (one from the fetal end and another 5 cm from the placental insertion end), and 3 blocks each containing a full thickness or upper 3rd or lower 3rd section of placenta parenchyma. The slides were stained with H&E. Microscopic evaluation of the placenta included evaluation of the maternal and fetal inflammatory response, disorder of villous maturation, vascular ectasia with congestion, villitis of unknown origin, chronic intervillositis, perivillous fibrin deposition, calcification, and villous edema. The presence of findings in 30% or more of the villi was considered significant. Vasculo-syncytial membranes (VSMs) were counted in ten terminal villi in each of ten consecutive high-power fields on 3 slides. Staging of both maternal and fetal inflammatory responses was performed following the criteria described by Khong et al . (2016) 6 . Both the central and peripheral parts of the placenta were examined, keeping in mind which lesions are considered pathological in which locations. Table I: Staging of maternal and fetal inflammatory responses according to the Amsterdam Placental Workshop Group Consensus Statement 6 Maternal inflammatory response Fetal inflammatory response Stage 1: Acute subchorionitis or chorionitis Stage 1: Chorionic vasculitis or umbilical phlebitis Stage 2: Acute chorioamnionitis Stage 2: Involvement of the umbilical vein and one or more umbilical arteries Stage 3: Necrotizing chorioamnionitis Stage 3: Necrotizing funisitis The data of all the variables were put into the checklists, and statistical analysis was carried out by using the Statistical Package for Social ‘IBM SPSS Statistics for Windows, version XXII (IBM Corp., Armonk, N.Y., USA)’. Results Distribution of patients according to age and gestational age Among the 80 patients, 57 (71.3%) were in the < 30 years age group, and 23 (28.7%) were in the ≥ 30 years age group. The mean age of the patients was 25.7 (± 5.9) years. The gestational age of the majority of the patients (49, 61.3%) was between 37–40 weeks, 16 (20.0%) had a gestational age of 28–32 weeks, and 15 (18.8%) had a gestational age between 33–36 weeks. Distribution of patients according to gravida Among the 80 patients, half (40 cases, 50%) had multiple mothers, 36 (45%) were primi, and 4 (5%) were grand multipara mothers. Distribution of patients according to placental weight Table II: Distribution of patients by placental weight (n = 80) Placental weight Frequency (n) Percentage (%) 200–250 11 13.8 260–300 2 2.5 310–350 1 1.3 360–400 16 20.0 410–450 37 46.3 460–500 2 2.5 510–550 11 13.8 Range (in gm) (min–max) 200–550 Distribution of patients according to placental diameter One-third of the patients (27 patients, 33.8%) had a placental diameter ranging from 9–12 cm, 39 (48.8%) had a diameter ranging from 13–16 cm, 12 (15%) had a diameter ranging from 17–20 cm, and 2 (2.5%) had a diameter > 20 cm. The mean placental diameter of the patients was 13.7 (± 2.9) cm. Distribution of patients according to cord insertion and cord coiling Eccentric cord insertion was present in 33 (41.3%) patients, central cord insertion was present in 36 (45.0%) patients, and marginal cord insertion was present in 10 (12.5%) patients. Only one patient underwent velamentous cord insertion. Cord coiling was normal in 57 (71.3%) patients, while 15 (18.8%) had hypocoiled cords, and 8 (10.0%) had hypercoiled cords. Distribution of patients according to the color of the membrane Table III: Distribution of patients by color of the membrane (n = 80) Color of membrane Frequency (n) Percentage (%) Normal 75 93.8 Greenish yellow 3 3.8 Pale Bluish 2 2.4 Distribution of patients with Retroplacental hemorrhage Distribution of patients according to microscopic findings Table IV: Distribution of patients by microscopic findings (n = 80) Microscopic findings Frequency (n) Percentage (%) Maternal & fetal inflammatory response Disorder of villous maturation 26 28 32.5 35 Vascular ectasia with congestion 21 26.3 Villitis of unknown origin 20 25.0 Intervillous Hemorrhage 19 23.8 Microcalcification 15 18.8 Infarct with ghost villi 14 17.5 Chronic intervillositis 14 17.5 Villous edema 12 15.0 Perivillous fibrin deposition 12 15.0 Deciduitis 5 6.25 Thrombus 4 5.0 Subamnionic hemorrhage 2 2.5 Chorangiosis 2 2.5 Increased syncytial knot 2 2.5 Simple cyst 1 1.3 Squamous metaplasia 1 1.3 Placenta increta No changes 1 2 1.3 2.5 Distribution of patients with maternal and fetal inflammatory responses according to stage Table V: Distribution of patients by maternal and fetal inflammatory response (n = 26) Inflammatory response Frequency (n) Percentage (%) Stage 1 Maternal 12 46.2 Stage 2 Maternal 10 38.5 Stage 3 Maternal 1 3.9 Stage 1 Fetal 2 7.7 Stage 2 Fetal 6 23.1 Stage 3 Fetal 0 0.0 Discussion Placental pathology in fetal death is now considered a research priority to gain insights into the causes and mechanism of fetal death, as approximately 60% of total fetal loss cannot be connected to any identifiable antepartum etiology 7 and cannot be readily accessed by doctors or midwives. The aim of the current study was to categorize fetal deaths by different gross and histopathological findings to analyze the underlying mechanisms and to determine how many unexplained fetal deaths remain unexplained after examination of the placenta. In this study, the mean age of the mothers was 25.7 ± 5.9 years, with ages ranging from 19–45 years. Among the 80 patients, the majority (57 patients, 71.3%) were in the < 30 years age group. Both Aminu et al . (2014) 8 and Lema et al . (2020) 9 revealed that advanced maternal age was a factor for stillbirth, which contradicts the findings of the current study. However, Borade et al . (2018) 5 reported that IUFD was more common in mothers aged 21–25 years. This was in accordance with the studies of Patel et al . (2016) 10 and Dave et al . (2016) 11 , all of which are similar to the current study. In the present study, half of the 80 patients (40 cases, 50.0%) had multiple pregnancies, 36 (45.0%) were primi, and only 4 (5.0%) were grand multipara patients; these findings are similar to those of the study of Gunyeli (2011) 7 , where the mean gravidity was 2.60 ± 1.90. In the present study, the gestational age of the majority of the patients (49 patients, 61.3%) ranged from 37–40 weeks, 16 patients (20.0%) had a gestational age of 28–32 weeks, and 15 (18.8%) had a gestational age ranging from 33–36 weeks. However, Borade et al . (2018) 5 , Prasanna et al . (2015) 12 and Dave et al . (2016) 11 reported an increased prevalence of IUFD in preterm fetuses. In the present study, the mean placental weight was 407 gm (mean ± SD = 407 ± 93.8), whereas the majority of the patients (37 cases, 46.3%) had placental weights ranging from 410–450 gm, and 16 patients (20%) had placental weights ranging from 360–400 gm. Twenty-seven patients (33.8%) had placental diameters ranging from 9–12 cm, while the majority (39 patients, 48.8%) had placental diameters ranging from 13–16 cm (Table II). Kamarkar et al . (2018) 13 reported that the average placental weight of IUFDs was 510.1 g, and the average diameter was 15.44 cm. This interpretation supports the current study. In the present study, central cord insertion was present in 36 (45.0%) patients, eccentric cord insertion in 33 (41.3%) patients, and marginal cord insertion in 10 (12.5%) patients. Only one patient underwent velamentous cord insertion. Cord coiling was normal in 57 (71.3%) patients, while 15 (18.8%) had hypocoil, and 8 (10.0%) had hypercoiled cords. Owino et al . (2014) 14 reported that the majority (86.3%) of patients underwent central cord insertion for stillbirth. Among the 80 patients, the color of the membrane was normal in 75 (93.8%) patients, while it was greenish yellow in 3 (3.8%) patients and pale bluish in 2 (2.4%) patients (Table III). Sixteen (20.0%) patients had retroplacental hemorrhage (Fig. 1 ). Similarly, Borade et al . (2018) 5 reported retroplacental hematoma in 28.28% of cases. In the present study, 28 (35%) patients presented with disorders of villous maturation, vascular ectasia with congestion was present in 21 (26.3%) patients, villitis of unknown origin was present in 20 (25.0%) patients, chronic intervillositis was present in 14 (17.5%) patients, and perivillous fibrin deposition was present in 12 (15.0%) patients. Moreover, findings such as intervillous hemorrhage 19 (23.8%), subamniotic hemorrhage 2 (2.5%), microcalcification 15 (18.8%), infarct with avascular ghost villi 14 (17.5%), villous edema 12 (15%), deciduitis 5 (6.25%), thrombus 4 (5%) and chorangiosis 2 (2.5%) are worth mentioning (Table IV). These findings correspond with other similar studies. 1 , 4 , 5 Table VI: Comparison of microscopic findings of IUFD placentas between similar studies 1 , 4 , 5 Study Uteroplacental vascular malformation/DVM Edema Perivillous fibrin Calcification Hemorrhage Necrosis Villitis Inflammatory responses Thrombus Borade et al. ,2018 9.09% 62.62% 51.51% 46.46% 19.19% 7.07% Uzwala et al. ,2013 11.11% 11.1% 11.1% 3.7% 25.9% 3.7% Ananthan et al. ,2019 38.82% 3.53% 55.29% 18.82% 24.7% 30.59% 14.11% 30.58% Lema et al . (2020) 9 agreed with Ptacek et al . (2014) 15 , who reported fetal thrombotic vasculopathy, endovasculitis, cord abnormalities, choriomanionitis, villitis, and endovasculitis and delayed villous maturation as significant lesions in IUFDs, similar to the findings of the present study. In the present study, a maternal and fetal inflammatory response was present in 26 patients; 12 (46.2%) patients had a stage 1 maternal inflammatory response, and 10 (38.5%) had a stage 2 maternal inflammatory response. On the other hand, 2 (7.7%) patients had stage 1 inflammatory response, and 6 (23.1%) had stage 2 fetal inflammatory response (Table V). This aligns with the results of Ananthan et al . (2019) 4 . Conclusion This study was undertaken to determine the gross and histopathological changes in the placentas of late intrauterine fetal deaths. In this study, various patterns of gross and histopathological changes in the placenta were clearly associated with almost all cases of late intrauterine fetal death. Currently, no such study is available in our country. With respect to this issue, this study will yield highly gainful assistance and help both histopathologists and obstetricians unriddle the facts regarding unexplained pregnancy losses. Abbreviations CD Cluster of Differentiation DHIS District Health Information Software DVH Distal villous hypoplasia DVM Delayed villous maturation H & E Hematoxylin and eosin ICD-11 International Classification of Disease IUFD Intrauterine Fetal Death SD Standard deviation SPSS Statistical Package for Social Sciences VUO Villitis of Unknown Origin WHO World Health Organization Declarations Acknowledgments . We thank Biostatistician Dr. Farzana Azam Tuli ( [email protected] ) for assisting in the data analysis. Author contributions . Saba S prepared the research protocol and was responsible for data collection, arranging the data analysis and preparing the manuscript. Begum S, Ferdous J N and Billah M were responsible for conceptualizing the study and assisted in protocol development, manuscript preparation and proofreading. Funding . This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Conflicts of interest . None. References Ujwala, Ch., Shyamala, G., Sudha, S B., Lavanya, R. and Sugandhi, R. Evaluation of placenta in fetal demise & fetal growth restriction. Journal of clinical & diagnostic research, 2013 ;7(11):2530-2533. Kulkarni, A D., Nithiya, P. and Margaret, J E. Placental pathology & still birth:a review of literature & guideline for the least experienced. Journal of fetal medicine, 2017;4:177-185. Malusi, Z., Schubert P T., Theron, G B. and Wright C A. The value of histopathology of placenta in a tertiary level hospital in South-Africa. South African journal of obstetrics & gynecology, 2019;25(2):64-67. Ananthan, A., Nanavati, R., Sathe, P. and Balasubramanian, H. Placental Findings in Singleton Stillbirths: A Case‒control Study. Journal of Tropical Pediatrics , 2019;65(1):21-28. Borade, P D., Kanetkar, R., Kale, P P., Dhirajkumar, B A B. and Vohra N V. Study of Placental Pathology in Cases of Intrauterine Fetal Deaths. APALM, 2018 ;eISSN: 2349-6983: pISSN: 2394-6466. Khong, T Y., Mooney, E E., Iliana, A., Nathalie, C M Balmus., Theonia, K B., Marie-Anne, B et al . Sampling and Definitions of Placental Lesions: Amsterdam Placental Workshop Group Consensus Statement. Archieves of Pathology and Laboratory Medicine, 2016;140(7):698-713. Gunyeli, I. Histological analysis of the placental lesions in pregnancies complicated with IUGR & stillbirths in comparison with non complicated pregnancies. Journal of Turkish-German Gynecological Association, 2011;12:75-79. Aminu, M., Unkels, R., Mdegela, M., Utz, B., Adaji, S. and Van den Broek, N. Causes of and factors associated with stillbirth in low- and middle-income countries: a systematic literature review. BJOG, 2014;121:141-53. Lema, G., Mremi, A., Amsi, P., Pyuza, J.J., Alloyce, J.P., Mchome, B. and Mlay, P. Placental pathology and maternal factors associated with stillbirth: An institutional based case‒control study in Northern Tanzania. PLoS One, 2020;15(12):1-14. Patel, P G., Patel, S V., Patel, S M., Badal, M J. Morphological study of placenta in pregnancy induced hypertension with its clinical relevance in Sir T Hospital Bhavnagar. International Journal of Anatomy and Research, 2016;4(3):659-64. Dave, A., Patidar, R., Goyal, S. and Dave, A. Intrauterine fetal demise-a tragic event: a study of its epidemiology, causes and methods of induction. International Journal of Reproductive and Contraceptive Obstetrics and Gynecology, 2016;5:1316-21. Prasanna, N., Mahadevappa, K., Antaratani, R C. and Lokare, L. Cause of death and associated conditions of stillbirths. International Journal of Reproductive and Contraceptive Obstetrics and Gynecology, 2015;4:1970-1974. Karmakar MK et al . A study of histological changes of human placenta in rural population of eastern India. International Journal of Reproduction, Contraception, Obstetrics and Gynecology, 2018;7(8):3280-3287. Owino, A., Gachuno, O., Tamooh, H. and Rogena, E.A. Gross presentation and histomorphological changes of placentae in patients presenting with intrauterine fetal death at Kenyatta national hospital. East African Medical Journal, 2014;91(7):219-226. Ptacek, I., Sebire, N J., Man, J A., Brownbill, P. and Heazell, A E. Systematic review of placental pathology reported in association with stillbirth. Journal of Placenta, 2014;35:552-562. National Institute of Population Research and Training (NIPORT), and ICF. 2020. Bangladesh Demographic and Health Survey 2017–18. Dhaka, Bangladesh, and Rockville, Maryland, USA: NIPORT and ICF. Additional Declarations The authors declare no competing interests. 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. 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00:51:40","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":239667,"visible":true,"origin":"","legend":"\u003cp\u003eOn the right, photograph showing greenish discolouration of the membrane (Case no: 39).\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-5042102/v1/3082f5e8d9524959e7acb748.png"},{"id":64569661,"identity":"54923087-0bb3-4181-8dda-fbde26c53987","added_by":"auto","created_at":"2024-09-16 00:51:39","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":201626,"visible":true,"origin":"","legend":"\u003cp\u003eOn the left, photograph showing the velamentous insertion of the cord (patient 78)\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-5042102/v1/30c3585b905633d6394c190a.png"},{"id":64569662,"identity":"0024c45f-0e18-419f-9c9b-eccafdcda0c0","added_by":"auto","created_at":"2024-09-16 00:51:39","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":184674,"visible":true,"origin":"","legend":"\u003cp\u003eOn the right, photograph showing the hypercoiled cord (Case no: 18)\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-5042102/v1/dbac601cafc46b46ba21722f.png"},{"id":64570016,"identity":"fda5da50-41f8-4238-9a20-f73113c25e60","added_by":"auto","created_at":"2024-09-16 00:59:40","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":218617,"visible":true,"origin":"","legend":"\u003cp\u003eOn the left, photograph showing a histological section of a thrombus in the Umbilical artery (Case no: 51, H\u0026amp;E, 40X).\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-5042102/v1/a72e7d22ea8f1641bc5d3ccf.png"},{"id":64570014,"identity":"96959bb6-7fc3-4ede-b221-c61aa5fa8214","added_by":"auto","created_at":"2024-09-16 00:59:40","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":237422,"visible":true,"origin":"","legend":"\u003cp\u003eOn the right, photograph showing a histological section of a patient with chorionitis (patient no: 56, H\u0026amp;E, 40X)\u003c/p\u003e","description":"","filename":"7.png","url":"https://assets-eu.researchsquare.com/files/rs-5042102/v1/15366bd124a30d3d5f77a3aa.png"},{"id":64569672,"identity":"95cf2488-2573-4a25-9a9b-eb9126b5b82c","added_by":"auto","created_at":"2024-09-16 00:51:40","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":340717,"visible":true,"origin":"","legend":"\u003cp\u003eOn the left, photograph showing a histological section of villitis and intervillositis (patient no: 53, H\u0026amp;E, 40×)\u003c/p\u003e","description":"","filename":"8.png","url":"https://assets-eu.researchsquare.com/files/rs-5042102/v1/6aa95e5cb27c88b2c2eddf34.png"},{"id":64569668,"identity":"8c06871f-4168-4174-aa8c-ff320952ed8d","added_by":"auto","created_at":"2024-09-16 00:51:40","extension":"png","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":295131,"visible":true,"origin":"","legend":"\u003cp\u003eOn the right, photograph showing a histological section of the infection (patient no: 54, H\u0026amp;E, 40X).\u003c/p\u003e","description":"","filename":"9.png","url":"https://assets-eu.researchsquare.com/files/rs-5042102/v1/2e718bc7ca7cf18875273d14.png"},{"id":64569665,"identity":"f7fb7747-5b57-4288-867c-24f551bb4a17","added_by":"auto","created_at":"2024-09-16 00:51:40","extension":"png","order_by":10,"title":"Figure 10","display":"","copyAsset":false,"role":"figure","size":220754,"visible":true,"origin":"","legend":"\u003cp\u003eOn the left, photograph showing a histological section of perivillous fibrin deposition (Case no: 38, H\u0026amp;E, 10X)\u003c/p\u003e","description":"","filename":"10.png","url":"https://assets-eu.researchsquare.com/files/rs-5042102/v1/499ecc4e6edb517bf45e72a1.png"},{"id":64569663,"identity":"2fe7bc47-56a9-45ea-bb92-64c03dfafc4a","added_by":"auto","created_at":"2024-09-16 00:51:40","extension":"png","order_by":11,"title":"Figure 11","display":"","copyAsset":false,"role":"figure","size":214628,"visible":true,"origin":"","legend":"\u003cp\u003eOn the right, photograph showing a histological section of a patient with chorangiosis (patient no: 27, H\u0026amp;E, 10X).\u003c/p\u003e","description":"","filename":"11.png","url":"https://assets-eu.researchsquare.com/files/rs-5042102/v1/486fe3fd7336fcdafd87b90e.png"},{"id":64570015,"identity":"9247e39b-9cdd-4591-b224-0321f66a72b1","added_by":"auto","created_at":"2024-09-16 00:59:40","extension":"png","order_by":12,"title":"Figure 12","display":"","copyAsset":false,"role":"figure","size":227684,"visible":true,"origin":"","legend":"\u003cp\u003eOn the left, photograph showing a histological section of a severe case of delayedvillous maturation (Case no: 53, H\u0026amp;E, 40X).\u003c/p\u003e","description":"","filename":"12.png","url":"https://assets-eu.researchsquare.com/files/rs-5042102/v1/67a6c65da987a5d782871a7d.png"},{"id":64569670,"identity":"354760ad-cfbe-4bbd-8cdf-77e05ee97038","added_by":"auto","created_at":"2024-09-16 00:51:40","extension":"png","order_by":13,"title":"Figure 13","display":"","copyAsset":false,"role":"figure","size":223045,"visible":true,"origin":"","legend":"\u003cp\u003eOn the right, photograph showing a histological section of villous edema (Case no: 37, H\u0026amp;E, 40X).\u003c/p\u003e","description":"","filename":"13.png","url":"https://assets-eu.researchsquare.com/files/rs-5042102/v1/a73f563c84184ff4aa5771fd.png"},{"id":64569675,"identity":"e3fb377b-6ab9-4570-8657-2270a68e391f","added_by":"auto","created_at":"2024-09-16 00:51:40","extension":"png","order_by":14,"title":"Figure 14","display":"","copyAsset":false,"role":"figure","size":206731,"visible":true,"origin":"","legend":"\u003cp\u003eOn the left, photograph showing a histological section of an intervillous hemorrhage and calcification (Case no: 45, H\u0026amp;E, 40X)\u003c/p\u003e","description":"","filename":"14.png","url":"https://assets-eu.researchsquare.com/files/rs-5042102/v1/472a4166a74c351f21ac02d3.png"},{"id":64569673,"identity":"baec0417-d891-48b1-9bf2-e50ebc9596bf","added_by":"auto","created_at":"2024-09-16 00:51:40","extension":"png","order_by":15,"title":"Figure 15","display":"","copyAsset":false,"role":"figure","size":225273,"visible":true,"origin":"","legend":"\u003cp\u003eOn the right, photograph showing a histological section ofintravenous hemorrhage and calcification (Case no: 30, H\u0026amp;E, 40X).\u003c/p\u003e","description":"","filename":"15.png","url":"https://assets-eu.researchsquare.com/files/rs-5042102/v1/756829b3cc332cd6e6f8137c.png"},{"id":64570052,"identity":"c27035ad-4c31-45d6-86b4-477606d0958f","added_by":"auto","created_at":"2024-09-16 00:59:46","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4025629,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5042102/v1/7239bb12-37a3-41dd-8006-388effff9439.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eHistopathological Changes in the Placenta in Late Intrauterine Fetal Deaths at a Tertiary Hospital in Bangladesh\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eFetal death is a matter of great distress to both the family and the obstetrician. Regardless of how much advancement has been achieved in the field of medical science, pregnancy loss still occurs at an alarming rate worldwide. The International Classification for Diseases 11th revision (ICD-11) classifies fetal death as late fetal death (greater than 1000 g or after 28 weeks) or early fetal death (500\u0026ndash;1000 g or 22\u0026ndash;28 weeks). Worldwide, approximately 60% of stillborn cases are unexplained in otherwise normal pregnancies according to Lancet Global Health, 2018. According to the World Health Organization, in 2022, the stillbirth rate in Bangladesh was 25 per 1000 births. According to the Emergency Obstetric \u0026amp; Newborn Care Services: Yearly DHIS-2 report by the Ministry of Health \u0026amp; Family Welfare, Bangladesh, from February 2021 to February 2022, a total of 10,777 pregnant mothers were admitted to the Department of Gynecology \u0026amp; Obstetrics, Sir Salimullah Medical College Mitford Hospital, Dhaka, for delivery or obstetric complications; among them, the total number of intrauterine fetal deaths was 275.\u003c/p\u003e \u003cp\u003eThe human placenta is a discoid, choriodeciduate organ that acts as a portal connecting the fetus with the uterine wall of the mother via the umbilical cord. The maternal supply of oxygen and nutrients occurs through the placenta via the umbilical circulation in response to fetal demand, whereas its protective function is derived from the ability to mount an inflammatory response to an external stimulus. Despite its undeniable role in human fetal development, the study of the placenta has lagged behind that of the fetus. The placenta can provide a record of both fetal and maternal intrauterine events, acting as the \u0026lsquo;\u0026lsquo;black box\u0026rsquo;\u0026rsquo; of pregnancy.\u003c/p\u003e \u003cp\u003eIntrauterine fetal deaths may be caused by maternal, fetal and placental factors, but these factors are usually multiple and overlapping. Conditions resulting in placental dysfunction may be recurrent and can manifest in different ways in different pregnancies. The placental factors include umbilical cord and placental disc abnormalities such as retroplacental hemorrhage, circumvallation, marginal cord, true knot, calcification, inflammatory reactions, circulatory compromise (maternal or fetal), abnormalities in villous maturation, hemorrhage, necrosis, villous edema, perivillous fibrin deposition and other conditions.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eAs per the Bangladesh Demographic and Health Survey (BDHS), in 2017\u0026ndash;18, only 47% of pregnant women in Bangladesh attended at least four WHO-recommended ANC activities\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. Therefore, evaluation of gross and histopathological findings in the placentas of unexplained late IUFD cases may help physicians understand their accurate etiopathogenesis to prevent recurrence, to take precautionary measures during further management in future pregnancies and to address accountability issues. Moreover, when medicolegal problems arise, a study of placental histopathology can reveal the exact cause of fetal loss and can act as a legal shield to the doctor from the concerned patient. At the national and regional decision-making levels, identifying causes is important for adopting strategic management strategies for prioritizing medical services according to the person and area needed, thus ensuring proper health care services to the general population of the country.\u003c/p\u003e \u003cp\u003eAlthough accurate placental examination is necessary in the evaluation of IUFDs and could play an important role in reducing the unexplained IUFD rate, placental examination is not routinely practiced in our country. Surprisingly, no previous studies have identified gross and histopathological changes in the placentas of unexplained late IUFDs in China.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis was a cross-sectional, descriptive and observational study. A total of 80 mothers aged 18 years or above with a diagnosis of late IUFD at a gestational age of 28 weeks or above were included in this study. Any late IUFD with known preexisting maternal conditions such as preeclampsia, diabetes, chronic hypertension, smoking, infections, and antiphospholipid syndrome were excluded from the study, as our sole goal was to identify the factors responsible for unexplained late IUFDs. The study was conducted at the Department of Pathology, Sir Salimullah Medical College, Dhaka, Bangladesh, from March 2021 to January 2023.\u003c/p\u003e \u003cp\u003eThe placentas were collected from the Department of Obstetrics and Gynecology, Sir Salimullah Medical College Mitford Hospital, Dhaka, immediately after delivery and fixed with 10% neutral buffered formalin for 24 hours. The specimens were subsequently processed and examined at the Department of Pathology, SSMC, for histopathological examination.\u003c/p\u003e \u003cp\u003ePlacentas were weighed after the cord and membrane were removed. After meticulous gross examination, 6 blocks were submitted: 1 block to include a roll of the extraplacental membranes from the rupture edge to the placental margin, 2 cross sections of the umbilical cord (one from the fetal end and another 5 cm from the placental insertion end), and 3 blocks each containing a full thickness or upper 3rd or lower 3rd section of placenta parenchyma. The slides were stained with H\u0026amp;E.\u003c/p\u003e \u003cp\u003eMicroscopic evaluation of the placenta included evaluation of the maternal and fetal inflammatory response, disorder of villous maturation, vascular ectasia with congestion, villitis of unknown origin, chronic intervillositis, perivillous fibrin deposition, calcification, and villous edema. The presence of findings in 30% or more of the villi was considered significant. Vasculo-syncytial membranes (VSMs) were counted in ten terminal villi in each of ten consecutive high-power fields on 3 slides. Staging of both maternal and fetal inflammatory responses was performed following the criteria described by Khong \u003cem\u003eet al\u003c/em\u003e. (2016)\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. Both the central and peripheral parts of the placenta were examined, keeping in mind which lesions are considered pathological in which locations.\u003c/p\u003e \u003cp\u003eTable I: Staging of maternal and fetal inflammatory responses according to the Amsterdam Placental Workshop Group Consensus Statement\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal inflammatory response\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFetal inflammatory response\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage 1: Acute subchorionitis or chorionitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStage 1: Chorionic vasculitis or umbilical phlebitis\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage 2: Acute chorioamnionitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStage 2: Involvement of the umbilical vein and one or more umbilical arteries\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage 3: Necrotizing chorioamnionitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStage 3: Necrotizing funisitis\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe data of all the variables were put into the checklists, and statistical analysis was carried out by using the Statistical Package for Social \u0026lsquo;IBM SPSS Statistics for Windows, version XXII (IBM Corp., Armonk, N.Y., USA)\u0026rsquo;.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eDistribution of patients according to age and gestational age\u003c/h2\u003e \u003cp\u003eAmong the 80 patients, 57 (71.3%) were in the \u0026lt;\u0026thinsp;30 years age group, and 23 (28.7%) were in the \u0026ge;\u0026thinsp;30 years age group. The mean age of the patients was 25.7 (\u0026plusmn;\u0026thinsp;5.9) years. The gestational age of the majority of the patients (49, 61.3%) was between 37\u0026ndash;40 weeks, 16 (20.0%) had a gestational age of 28\u0026ndash;32 weeks, and 15 (18.8%) had a gestational age between 33\u0026ndash;36 weeks.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eDistribution of patients according to gravida\u003c/h2\u003e \u003cp\u003eAmong the 80 patients, half (40 cases, 50%) had multiple mothers, 36 (45%) were primi, and 4 (5%) were grand multipara mothers.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eDistribution of patients according to placental weight\u003c/h2\u003e \u003cp\u003eTable II: Distribution of patients by placental weight (n\u0026thinsp;=\u0026thinsp;80)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabb\" border=\"1\"\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlacental weight\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFrequency (n)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePercentage (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e200\u0026ndash;250\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e260\u0026ndash;300\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e310\u0026ndash;350\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e360\u0026ndash;400\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e410\u0026ndash;450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e460\u0026ndash;500\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e510\u0026ndash;550\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRange (in gm) (min\u0026ndash;max)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e200\u0026ndash;550\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eDistribution of patients according to placental diameter\u003c/h2\u003e \u003cp\u003eOne-third of the patients (27 patients, 33.8%) had a placental diameter ranging from 9\u0026ndash;12 cm, 39 (48.8%) had a diameter ranging from 13\u0026ndash;16 cm, 12 (15%) had a diameter ranging from 17\u0026ndash;20 cm, and 2 (2.5%) had a diameter\u0026thinsp;\u0026gt;\u0026thinsp;20 cm. The mean placental diameter of the patients was 13.7 (\u0026plusmn;\u0026thinsp;2.9) cm.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eDistribution of patients according to cord insertion and cord coiling\u003c/h2\u003e \u003cp\u003eEccentric cord insertion was present in 33 (41.3%) patients, central cord insertion was present in 36 (45.0%) patients, and marginal cord insertion was present in 10 (12.5%) patients. Only one patient underwent velamentous cord insertion. Cord coiling was normal in 57 (71.3%) patients, while 15 (18.8%) had hypocoiled cords, and 8 (10.0%) had hypercoiled cords.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eDistribution of patients according to the color of the membrane\u003c/h2\u003e \u003cp\u003eTable III: Distribution of patients by color of the membrane (n\u0026thinsp;=\u0026thinsp;80)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabc\" border=\"1\"\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eColor of membrane\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFrequency (n)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePercentage (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e93.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGreenish yellow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePale Bluish\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eDistribution of patients with Retroplacental hemorrhage\u003c/h2\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eDistribution of patients according to microscopic findings\u003c/h2\u003e \u003cp\u003eTable IV: Distribution of patients by microscopic findings (n\u0026thinsp;=\u0026thinsp;80)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabd\" border=\"1\"\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMicroscopic findings\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFrequency (n)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePercentage (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal \u0026amp; fetal inflammatory response\u003c/p\u003e \u003cp\u003eDisorder of villous maturation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26\u003c/p\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32.5\u003c/p\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVascular ectasia with congestion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVillitis of unknown origin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntervillous Hemorrhage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMicrocalcification\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInfarct with ghost villi\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic intervillositis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVillous edema\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePerivillous fibrin deposition\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeciduitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThrombus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSubamnionic hemorrhage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChorangiosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIncreased syncytial knot\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSimple cyst\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSquamous metaplasia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlacenta increta\u003c/p\u003e \u003cp\u003eNo changes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.3\u003c/p\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eDistribution of patients with maternal and fetal inflammatory responses according to stage\u003c/h2\u003e \u003cp\u003eTable V: Distribution of patients by maternal and fetal inflammatory response (n\u0026thinsp;=\u0026thinsp;26)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabe\" border=\"1\"\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInflammatory response\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFrequency (n)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePercentage (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage 1 Maternal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage 2 Maternal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage 3 Maternal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage 1 Fetal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage 2 Fetal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage 3 Fetal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003ePlacental pathology in fetal death is now considered a research priority to gain insights into the causes and mechanism of fetal death, as approximately 60% of total fetal loss cannot be connected to any identifiable antepartum etiology\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e and cannot be readily accessed by doctors or midwives. The aim of the current study was to categorize fetal deaths by different gross and histopathological findings to analyze the underlying mechanisms and to determine how many unexplained fetal deaths remain unexplained after examination of the placenta.\u003c/p\u003e \u003cp\u003eIn this study, the mean age of the mothers was 25.7\u0026thinsp;\u0026plusmn;\u0026thinsp;5.9 years, with ages ranging from 19\u0026ndash;45 years. Among the 80 patients, the majority (57 patients, 71.3%) were in the \u0026lt;\u0026thinsp;30 years age group. Both Aminu \u003cem\u003eet al\u003c/em\u003e. (2014)\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e and Lema \u003cem\u003eet al\u003c/em\u003e. (2020)\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e revealed that advanced maternal age was a factor for stillbirth, which contradicts the findings of the current study. However, Borade \u003cem\u003eet al\u003c/em\u003e. (2018)\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e reported that IUFD was more common in mothers aged 21\u0026ndash;25 years. This was in accordance with the studies of Patel \u003cem\u003eet al\u003c/em\u003e. (2016)\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e and Dave \u003cem\u003eet al\u003c/em\u003e. (2016)\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e, all of which are similar to the current study.\u003c/p\u003e \u003cp\u003eIn the present study, half of the 80 patients (40 cases, 50.0%) had multiple pregnancies, 36 (45.0%) were primi, and only 4 (5.0%) were grand multipara patients; these findings are similar to those of the study of Gunyeli (2011)\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e, where the mean gravidity was 2.60\u0026thinsp;\u0026plusmn;\u0026thinsp;1.90.\u003c/p\u003e \u003cp\u003eIn the present study, the gestational age of the majority of the patients (49 patients, 61.3%) ranged from 37\u0026ndash;40 weeks, 16 patients (20.0%) had a gestational age of 28\u0026ndash;32 weeks, and 15 (18.8%) had a gestational age ranging from 33\u0026ndash;36 weeks. However, Borade \u003cem\u003eet al\u003c/em\u003e. (2018)\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e, Prasanna \u003cem\u003eet al\u003c/em\u003e. (2015)\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e and Dave \u003cem\u003eet al\u003c/em\u003e. (2016)\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e reported an increased prevalence of IUFD in preterm fetuses.\u003c/p\u003e \u003cp\u003eIn the present study, the mean placental weight was 407 gm (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u0026thinsp;=\u0026thinsp;407\u0026thinsp;\u0026plusmn;\u0026thinsp;93.8), whereas the majority of the patients (37 cases, 46.3%) had placental weights ranging from 410\u0026ndash;450 gm, and 16 patients (20%) had placental weights ranging from 360\u0026ndash;400 gm. Twenty-seven patients (33.8%) had placental diameters ranging from 9\u0026ndash;12 cm, while the majority (39 patients, 48.8%) had placental diameters ranging from 13\u0026ndash;16 cm (Table II). Kamarkar \u003cem\u003eet al\u003c/em\u003e. (2018)\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e reported that the average placental weight of IUFDs was 510.1 g, and the average diameter was 15.44 cm. This interpretation supports the current study.\u003c/p\u003e \u003cp\u003eIn the present study, central cord insertion was present in 36 (45.0%) patients, eccentric cord insertion in 33 (41.3%) patients, and marginal cord insertion in 10 (12.5%) patients. Only one patient underwent velamentous cord insertion. Cord coiling was normal in 57 (71.3%) patients, while 15 (18.8%) had hypocoil, and 8 (10.0%) had hypercoiled cords. Owino \u003cem\u003eet al\u003c/em\u003e. (2014)\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e reported that the majority (86.3%) of patients underwent central cord insertion for stillbirth.\u003c/p\u003e \u003cp\u003eAmong the 80 patients, the color of the membrane was normal in 75 (93.8%) patients, while it was greenish yellow in 3 (3.8%) patients and pale bluish in 2 (2.4%) patients (Table III). Sixteen (20.0%) patients had retroplacental hemorrhage (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Similarly, Borade \u003cem\u003eet al\u003c/em\u003e. (2018)\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e reported retroplacental hematoma in 28.28% of cases.\u003c/p\u003e \u003cp\u003eIn the present study, 28 (35%) patients presented with disorders of villous maturation, vascular ectasia with congestion was present in 21 (26.3%) patients, villitis of unknown origin was present in 20 (25.0%) patients, chronic intervillositis was present in 14 (17.5%) patients, and perivillous fibrin deposition was present in 12 (15.0%) patients. Moreover, findings such as intervillous hemorrhage 19 (23.8%), subamniotic hemorrhage 2 (2.5%), microcalcification 15 (18.8%), infarct with avascular ghost villi 14 (17.5%), villous edema 12 (15%), deciduitis 5 (6.25%), thrombus 4 (5%) and chorangiosis 2 (2.5%) are worth mentioning (Table IV). These findings correspond with other similar studies.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eTable VI: Comparison of microscopic findings of IUFD placentas between similar studies\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabf\" border=\"1\"\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStudy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUteroplacental vascular malformation/DVM\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eEdema\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePerivillous fibrin\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCalcification\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHemorrhage\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNecrosis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eVillitis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eInflammatory responses\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eThrombus\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBorade\u003c/p\u003e \u003cp\u003e\u003cem\u003eet al.\u003c/em\u003e,2018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.09%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e62.62%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e51.51%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e46.46%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e19.19%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e7.07%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUzwala\u003c/p\u003e \u003cp\u003e\u003cem\u003eet al.\u003c/em\u003e,2013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.11%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11.1%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11.1%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.7%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e25.9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e3.7%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnanthan\u003c/p\u003e \u003cp\u003e\u003cem\u003eet al.\u003c/em\u003e,2019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38.82%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.53%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e55.29%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e18.82%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e24.7%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e30.59%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e14.11%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e30.58%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eLema \u003cem\u003eet al\u003c/em\u003e. (2020)\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e agreed with Ptacek \u003cem\u003eet al\u003c/em\u003e. (2014)\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e, who reported fetal thrombotic vasculopathy, endovasculitis, cord abnormalities, choriomanionitis, villitis, and endovasculitis and delayed villous maturation as significant lesions in IUFDs, similar to the findings of the present study.\u003c/p\u003e \u003cp\u003eIn the present study, a maternal and fetal inflammatory response was present in 26 patients; 12 (46.2%) patients had a stage 1 maternal inflammatory response, and 10 (38.5%) had a stage 2 maternal inflammatory response. On the other hand, 2 (7.7%) patients had stage 1 inflammatory response, and 6 (23.1%) had stage 2 fetal inflammatory response (Table V). This aligns with the results of Ananthan \u003cem\u003eet al\u003c/em\u003e. (2019)\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study was undertaken to determine the gross and histopathological changes in the placentas of late intrauterine fetal deaths. In this study, various patterns of gross and histopathological changes in the placenta were clearly associated with almost all cases of late intrauterine fetal death. Currently, no such study is available in our country. With respect to this issue, this study will yield highly gainful assistance and help both histopathologists and obstetricians unriddle the facts regarding unexplained pregnancy losses.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCD \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Cluster of Differentiation\u003c/p\u003e\n\u003cp\u003eDHIS \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; District Health Information Software\u003c/p\u003e\n\u003cp\u003eDVH \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Distal\u0026nbsp;villous hypoplasia\u003c/p\u003e\n\u003cp\u003eDVM \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Delayed\u0026nbsp;villous maturation\u003c/p\u003e\n\u003cp\u003eH \u0026amp; E \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Hematoxylin and\u0026nbsp;eosin\u003c/p\u003e\n\u003cp\u003eICD-11 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;International Classification of Disease\u003c/p\u003e\n\u003cp\u003eIUFD \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Intrauterine Fetal Death\u003c/p\u003e\n\u003cp\u003eSD \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Standard deviation\u003c/p\u003e\n\u003cp\u003eSPSS \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Statistical Package for Social Sciences\u003c/p\u003e\n\u003cp\u003eVUO \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Villitis of Unknown Origin\u003c/p\u003e\n\u003cp\u003eWHO \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; World Health Organization\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e. We thank Biostatistician Dr. Farzana Azam Tuli (
[email protected]) for\u0026nbsp;assisting\u0026nbsp;in\u0026nbsp;the\u0026nbsp;data analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e. Saba S prepared the research protocol and was responsible for data collection, arranging\u0026nbsp;the\u0026nbsp;data analysis and preparing the manuscript. Begum S, Ferdous J N and Billah M were responsible for conceptualizing the study and assisted in protocol development, manuscript preparation and\u0026nbsp;proofreading.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest\u003c/strong\u003e. None.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eUjwala, Ch., Shyamala, G., Sudha, S B., Lavanya, R. and Sugandhi, R. Evaluation of placenta in fetal demise \u0026amp; fetal growth restriction. Journal of clinical \u0026amp; diagnostic research, 2013 ;7(11):2530-2533.\u003c/li\u003e\n \u003cli\u003eKulkarni, A D., Nithiya, P. and Margaret, J E. Placental pathology \u0026amp; still birth:a review \u0026nbsp;of literature \u0026amp; guideline for the least experienced. Journal of fetal medicine, 2017;4:177-185.\u003c/li\u003e\n \u003cli\u003eMalusi, Z., Schubert P T., Theron, G B. and Wright C A. The value of histopathology of placenta in a tertiary level hospital in South-Africa. South African journal of obstetrics \u0026amp; gynecology, 2019;25(2):64-67.\u003c/li\u003e\n \u003cli\u003eAnanthan, A., Nanavati, R., Sathe, P. and Balasubramanian, H. Placental Findings in Singleton Stillbirths: A Case‒control Study. \u003cem\u003eJournal of Tropical Pediatrics\u003c/em\u003e\u003cem\u003e,\u003c/em\u003e 2019;65(1):21-28.\u003c/li\u003e\n \u003cli\u003eBorade, P D., Kanetkar, R., Kale, P P., Dhirajkumar, B A B. and Vohra N V. Study of Placental Pathology in Cases of Intrauterine Fetal Deaths. APALM, 2018 ;eISSN: 2349-6983: pISSN: 2394-6466.\u003c/li\u003e\n \u003cli\u003eKhong, T \u0026nbsp;Y., Mooney, E E., Iliana, A., Nathalie, C M Balmus., Theonia, K B., Marie-Anne, B \u003cem\u003eet al\u003c/em\u003e. Sampling and Definitions of Placental Lesions: Amsterdam Placental Workshop Group Consensus Statement. Archieves of Pathology and Laboratory Medicine, 2016;140(7):698-713.\u003c/li\u003e\n \u003cli\u003eGunyeli, I. Histological analysis of the placental lesions in pregnancies complicated with IUGR \u0026amp; stillbirths in comparison with non complicated pregnancies. Journal of Turkish-German Gynecological Association, 2011;12:75-79.\u003c/li\u003e\n \u003cli\u003eAminu, M., Unkels, R., Mdegela, M., Utz, B., Adaji, S. and Van den Broek, N. Causes of and factors associated with stillbirth in low- and middle-income countries: a systematic literature review. BJOG, 2014;121:141-53.\u003c/li\u003e\n \u003cli\u003eLema, G., Mremi, A., Amsi, P., Pyuza, J.J., Alloyce, J.P., Mchome, B. and Mlay, P. Placental pathology and maternal factors associated with stillbirth: An institutional based case‒control study in Northern Tanzania. PLoS One, 2020;15(12):1-14.\u003c/li\u003e\n \u003cli\u003ePatel, P G., Patel, S V., Patel, S M., Badal, M J. Morphological study of placenta in pregnancy induced hypertension with its clinical relevance in Sir T Hospital Bhavnagar. International Journal of Anatomy and Research, 2016;4(3):659-64.\u003c/li\u003e\n \u003cli\u003eDave, A., Patidar, R., Goyal, S. and Dave, A. Intrauterine fetal demise-a tragic event: a study of its epidemiology, causes and methods of induction. International Journal of \u0026nbsp;Reproductive \u0026nbsp;and Contraceptive Obstetrics and Gynecology, 2016;5:1316-21.\u003c/li\u003e\n \u003cli\u003ePrasanna, N., Mahadevappa, K., Antaratani, R C. and Lokare, L. Cause of death and associated conditions of stillbirths. International Journal of Reproductive and Contraceptive Obstetrics and Gynecology, 2015;4:1970-1974.\u003c/li\u003e\n \u003cli\u003eKarmakar MK \u003cem\u003eet al\u003c/em\u003e. A study of histological changes of human placenta in rural population of eastern India. International Journal of Reproduction, Contraception, Obstetrics and Gynecology, 2018;7(8):3280-3287.\u003c/li\u003e\n \u003cli\u003eOwino, A., Gachuno, O., Tamooh, H. and Rogena, E.A. Gross presentation and histomorphological changes of placentae in patients presenting with intrauterine fetal death at Kenyatta national hospital. East African Medical Journal, 2014;91(7):219-226.\u003c/li\u003e\n \u003cli\u003ePtacek, I., Sebire, N J., Man, J A., Brownbill, P. and Heazell, A E. Systematic review of placental pathology reported in association with stillbirth. Journal of Placenta, 2014;35:552-562.\u003c/li\u003e\n \u003cli\u003eNational Institute of Population Research and Training (NIPORT), and ICF. 2020. Bangladesh Demographic and Health Survey 2017\u0026ndash;18. Dhaka, Bangladesh, and Rockville, Maryland, USA: NIPORT and ICF.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"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":"Placenta, Late IUFD","lastPublishedDoi":"10.21203/rs.3.rs-5042102/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5042102/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction:\u003c/strong\u003eMeticulous gross andmicroscopic studiesof the singleton placenta alone may provide valuable information regarding the cause of unexplained intrauterine fetal deaths(IUFDs) and can offer potential treatment options for its prevention in future pregnancies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjective: \u003c/strong\u003eTo determine the histopathological changes in the placenta associated with late intrauterine fetal death.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethod: \u003c/strong\u003eA cross-sectional study was carried out in the Department of Pathology, Sir Salimullah Medical College Mitford Hospital, Dhaka, fromMarch 2021 to January 2023. A total of 80 patients aged between 19 and 44 years with late IUFDs were included in this study. Theplacentas of the dead newbornswere histopathologically analyzed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eAll of the patients presentedsignificant gross andhistopathological changes in the placental specimens. A total of 71.3% of them were \u0026lt;30 years of age. Fifty percent of the patients were multipara, and 45% were primi. The gestational ages of 61.3% of the patients were within 37–40 weeks, 20% were within 28–32 weeks, and 18.8% were within 33–36 weeks. The mean placental weight was 407 gm, and 46.3% of the patients had placental weights within 410–450 gm. A total of 33.8% of the patients had placental diameters within 9–12 cm, and 48.8% had placental diameters within 13–16 cm. Cord insertion was eccentric in 41.3%, central in 45.0% and marginal in 12.5% of the patients. A total of 18.8% of patients had hypocoil, and 10% had hypercoiled cords. Twenty percent ofpatients had retroplacental hemorrhage. The membrane was greenish yellow in 3.8% of the samples and pale bluish in 2.4% of the samples. The significantmicroscopic findings were vascular ectasia with congestion in 26.3% of the patients, disorders of villous maturation in 35%, perivillous fibrin deposition in 15.0%, intervillous hemorrhage in 23.8%, subamniotic hemorrhagein 2.5%, microcalcification in 18.8%, infarct with avascular ghost villi in 17.5%, villous edema in 15%, deciduitis in 6.25%, thrombus in 5%, perivillous fibrin deposition in 15%, chorangiosis in 2.5%, villitis of unknown origin in 25% and chronic intervillositis in 17.5% of the patients. Maternal and fetal inflammatory responses were present in 26 patients, of whom46.2% had stage 1 and 38.5% had stage 2 maternal inflammatory responses. A total of 7.7% had stage 1 inflammatory response, and 23.1% had stage 2 fetalinflammatory response.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiscussion: \u003c/strong\u003eThis study revealed that late IUFD is associated withsignificant placental histopathological abnormalities. Identification of these abnormalities can provide information about the etiopathogenesis of late intrauterine fetal deaths, can play a very important role in medicolegal situations and can guide physicians in the management of patients to prevent further pregnancy losses.\u003c/p\u003e","manuscriptTitle":"Histopathological Changes in the Placenta in Late Intrauterine Fetal Deaths at a Tertiary Hospital in Bangladesh","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-09-16 00:51:35","doi":"10.21203/rs.3.rs-5042102/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"
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