Heterotopic Pregnancy and Amniotic Embolism: a Case Report

Heterotopic Pregnancy and Amniotic Embolism: a Case Report | 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 Heterotopic Pregnancy and Amniotic Embolism: a Case Report Gabriella Soecki, Elisa Carolina Hlatchuk, Caroline Thereza Raymundo, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3777853/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 14 Nov, 2024 Read the published version in BMC Pregnancy and Childbirth → Version 1 posted 11 You are reading this latest preprint version Abstract BACKGROUND Heterotopic pregnancy and amniotic embolism are rare conditions that can be challenging to diagnose. To date, there are no cases of heterotopic pregnancy associated with amniotic embolism described in the literature. Therefore, we report the case of a pancreatic heterotopic pregnancy, which led to amniotic embolism and an unfavorable maternal outcome. CASE PRESENTATION: A 20-year-old pregnant woman presented with nausea and abdominal pain refractory to drug treatment. She had a increased lipase of 205 U/L (reference 8 to 78 U/L) and a total abdominal ultrasound with biliary sludge. The pregnant woman had no known risk factors for ectopic and/or heterotopic pregnancy. The initial diagnostic suspicions were hyperemesis gravidarum or acute pancreatitis. During hospitalization, she fluctuated between periods of clinical improvement and worsening of abdominal pain, but serial laboratory control had a favorable and benign evolution. On the 30th day of hospitalization, the patient developed spontaneous abortion, respiratory failure, and cardiorespiratory arrest. Necropsy showed heterotopic pregnancy in the pancreas, amniotic embolism, and consequent disseminated intravascular coagulation. CONCLUSION Obstetricians should suspect heterotopic pregnancy in patients with an acute abdomen. The gold standard diagnostic method for this condition is laparoscopy. In the present case, the authors consider that pancreatic pregnancy allowed the introduction of fetal antigens and/or amniotic fluid into the maternal bloodstream, leading to amniotic embolism and consequent disseminated intravascular coagulation. Amniotic Fluid Embolism Heterotopic Pregnancy Ectopic Pregnancy Case Report Obstetric Complication Figures Figure 1 Figure 2 Figure 3 BACKGROUND Heterotopic pregnancy (HP) consists of the simultaneous occurrence of an intrauterine pregnancy and an ectopic pregnancy. This condition can be asymptomatic, simulate an acute abdomen, or even progress to hypovolemic shock ( 1 ). It is estimated that the incidence of spontaneous HP is 1:30,000 pregnancies, but when associated with in vitro fertilization, it can reach 1:100 pregnancies. Furthermore, the presence of an intrauterine pregnancy often delays its diagnosis and early intervention, as the increase in β-HCG ends up being attributed to the intrauterine pregnancy ( 2 ). Amniotic embolism (AE) occurs when amniotic fluid or fetal tissue fragments enter the maternal circulation, which can cause pulmonary hypertension, cardiovascular collapse, disseminated intravascular coagulation (DIC), and high mortality rates ( 3 ). Despite the existence of known risk factors such as eclampsia, polyhydramnios, and uterine rupture, the condition is considered unpredictable given its rarity (1:80,000 pregnancies) ( 4 ). Both diseases – HP and AE - are rare, and diagnosis can be challenging. Here we report a heterotopic pregnancy that evolved with amniotic embolism and an unfavorable maternal outcome. CASE PRESENTATION A 20-year-old pregnant woman, married, gravida 2, para 1, had a gestational age of 9 weeks and 6 days at the time of hospital admission. Underwent low-risk prenatal care, and had no comorbidities, allergies, previous surgeries or daily use medications. She was a former smoker (10 pack-years), and denied a history of alcoholism or drug addiction. Her father died at the age of 37 from a heart attack, her younger sister had asthma, and her mother was healthy. She was referred to the High-Risk Maternity Hospital with symptoms of epigastric pain, nausea, and vomiting, despite symptomatic medications already administered during previous medical care. The patient presented a laboratory test with increased lipase of 205 U/L (reference 8 to 78 U/L) and an abdominal ultrasound with biliary sludge, both performed at a previous medical consultation. Therefore, the initial diagnostic suspicions were hyperemesis gravidarum or acute pancreatitis. During the first month of hospitalization at the Maternity Hospital, a daily clinical assessment was carried out. The pregnant woman fluctuated between periods of clinical improvement and worsening of abdominal pain, but serial laboratory control had a favorable and benign evolution. During this period, additional investigation tests were also carried out. A new ultrasound of the abdomen, 18 days after hospital admission, did not show lithiasis or alterations in the bile duct/pancreas (Fig. 1 ). A new obstetric ultrasound, 21 days after admission, demonstrated a single fetus, a crown rump length of 66 mm, present cardiac activity, and 12 weeks and 6 days of gestation (Fig. 2 ). Magnetic Resonance Imaging (MRI) cholangioresonance, 23 days after admission, evidenced a common bile duct of normal caliber, a gallbladder without evidence of stones, the absence of urinary lithiasis or dilatation of the collecting system, and a normal pancreas (Fig. 3 ). An upper digestive endoscopy, 27 days after admission, revealed Los Angeles grade B erosive esophagitis and gastric corpus enanthema. In this context, Obstetrics also activated the Gastroenterology, General Surgery and Psychiatry teams to assist in the management of the case. According to the General Surgery assessment, there was no surgical indication upon admission. Gastroenterology advised starting Proton Pump Inhibitor in full dose and maintaining a diet as accepted. Psychiatry recommended starting Sertraline 25mg per day and maintaining outpatient follow-up. On the 30th day on the ward, during a medical visit, the patient was lying in bed with a blood pression of 70/40 mmHg, a heart rate > 100 bpm, an O2 saturation of 85%, an Glasgow Coma Scale of 14, and a blood glucose of 31 mg/dl, she was hypocolored, with petechiae disseminated to the trunk and limbs and vaginal bleeding. She was urgently taken to the Obstetric Center. Volume correction and intravenous hypoglycemia were initiated. Laboratory tests were urgently collected. Due to signs of respiratory failure, orotracheal intubation was performed with bilateral and symmetric ventilation in all pleuropulmonary fields. Central venous access was attempted in the right subclavian without success. External jugular venous access at the right was then punctured, and intravenous potassium and bicarbonate replacement were immediately started. After this, the patient developed two cardiorespiratory arrests within 42 minutes, which were reversed. Eleven minutes after reestablishing her heart rhythm, she presented a third cardiorespiratory arrest, being resuscitated for 22 minutes, but without success, and with medium-fixed pupils. Maternal death was declared. Necropsy showed HP in the pancreas, signs of pulmonary AE, and consequent DIC. Furthermore, the uterine cavity was empty, indicating that there was a spontaneous abortion of the topical pregnancy. DISCUSSION AND CONCLUSION This report addresses the case of a HP with a pancreatic gestational implant that is complicated by AE. The incidence of HP has increased in recent decades due to the dissemination of assisted reproduction techniques and infertility treatments ( 1 ). Furthermore, the risk factors for HP are closely related to those for ectopic pregnancy, including a history of pelvic inflammatory disease, previous pelvic surgery, and previous tubal pathologies. Approximately 71% of women with HP have at least one risk factor for ectopic pregnancy, and 10% have three or more ( 5 ). However, in the described case, none of these factors were present, which may have made early diagnosis difficult. The fallopian tubes are the most common site of ectopic gestational implantation, with 95% of cases located in the ampulla, infundibulum, or isthmus. Abdominal implants are rare and comprise 0.9–1.4% of cases of ectopic pregnancy ( 6 ). Regarding pancreatic implantation, specifically, there are only 3 cases described in the literature ( 7 – 9 ). The clinical presentation of a pancreatic gestational implant is nonspecific, and there are no characteristic manifestations to differentiate it from acute pancreatitis. Moreover, serum levels of β-HCG, progesterone, amylase, or lipase, as well as transvaginal ultrasound, are of little use for diagnosis ( 7 ). Abdominal ultrasound can contribute to the diagnosis of HP by detecting, in addition to the intrauterine gestational sac, a heterogeneous extrauterine adnexal mass with hyperechogenic margins, peritrophoblastic flow, yolk sac, fetal parts, and cardiac activity ( 6 ). However, in the described case, imaging tests did not contribute to diagnostic elucidation. This contrasts with the perspective of some authors, who suggest that ultrasound and MRI may be useful in the investigation of abdominal HP ( 7 , 10 , 11 ). Currently, laparoscopy is the gold standard for diagnosing ectopic pregnancy, including pancreatic ectopic pregnancy, and subsequent histological evaluation is also important for confirmation ( 7 ). Late diagnosis of HP can cause significant morbidity and mortality ( 5 ). The pregnant woman in the present case, for instance, developed AE. The pathophysiology of AE involves the introduction of amniotic fluid and/or fetal components into the maternal circulation, generating intense pulmonary vasoconstriction and bronchoconstriction. These effects are considered to be caused not only by physical obstruction but also by the intense release of inflammatory cytokines as an immune-mediated response to foreign components ( 4 ). Some factors that predispose to this condition are uterine trauma, advanced maternal age, multiparity, induction of labor, cesarean section, placenta previa, eclampsia, polyhydramnios, curettage, and kidney diseases ( 3 ). In the present case, the authors consider that pancreatic pregnancy may have led to the introduction of fetal antigens and/or amniotic fluid into the maternal bloodstream, leading to an unfavorable outcome. The clinical presentation of AE may include hypoxemia, sudden maternal collapse, DIC, and acute fetal distress ( 2 ). The evolution of patients is typically biphasic, with pulmonary hypertension and right ventricular failure at the beginning, followed by left ventricular failure during or immediately after delivery ( 12 ). The respiratory system is often compromised in the initial phase, progressing to acute respiratory distress syndrome or pulmonary edema. Coagulopathy is also a common feature, observed in 83% of patients, and may lead to the need for hysterectomy and massive transfusions ( 2 ). The diagnosis of AE is one of exclusion, and the differential diagnosis includes obstetric conditions such as uterine rupture and eclampsia, as well as placental abruption, and non-obstetric conditions such as pulmonary embolism and pneumothorax ( 2 ). The definitive diagnosis is usually established only after death, through the findings found at the autopsy, as occurred in the case described above, and maternal mortality rates can reach 25% ( 12 ). The treatment of AE is mainly supportive, depending on the clinical presentation. Initial management should focus on aggressive treatment of shock by providing high-quality cardiopulmonary resuscitation, as patients often present with sudden cardiovascular collapse ( 13 ). Facing this case, the authors of the present study consider that pancreatic pregnancy allowed the introduction of fetal antigens and/or amniotic fluid into the maternal bloodstream, leading to AE and consequent DIC. Therefore, obstetricians should suspect HP in patients with an acute abdomen, and the gold standard diagnostic method for this condition is laparoscopy. To date, there are no cases of HP associated with AE described in the literature. The authors highlight the difficulty faced in diagnosing HP, even in a large maternity hospital, which has technological support and a multidisciplinary team. Medicine is a science of probability, therefore, rare and infrequent diseases such as HP require a high level of diagnostic suspicion to be identified early and well managed. However, the fact that the patient in question had no known risk factors for HP and presented imaging tests without alterations certainly delayed her diagnosis. Abbreviations AE Amniotic Embolism DIC Disseminated Intravascular Coagulation HP Heterotopic Pregnancy MRI Magnetic Resonance Imaging Declarations Ethics approval and consent to participate This study was reviewed and approved by the Ethics Committee for Research on Human Beings of Clinics Hospital Complex of University Federal of Parana, CAAE 69643523.8.0000.0096. Consent for publication Written informed consent for publication was obtained from two responsible family members. Documentation of the written consent will be provided to the journal upon request. Availability of data and materials The data and materials analyzed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding No funding was received for conducting this study. Authors’ contributions GS, ECH and CTR: study concept and writing the manuscript. ACSA and MCPF: collection of patient’s information. APP, NLECS and DJN: critical revision of the manuscript for intellectual content. All authors have approved the final manuscript. Acknowledgements Not applicable. References Černiauskaitė M, Vaigauskaitė B, Ramašauskaitė D, Šilkūnas M. Spontaneous Heterotopic Pregnancy: Case Report and Literature Review. Medicina (B Aires) [Internet]. 2020 Aug 1 [cited 2023 Sep 8];56(8):1–5; doi:10.3390/medicina56080365 Nguyen KP, Hudspeth M, Milestone H. Spontaneous Heterotopic Pregnancy: Diagnosis and Management. Case Rep Obstet Gynecol. 2022;2022; doi:10.1155/2022/2994808 Dedhia JD, Mushambi MC. Amniotic fluid embolism. Continuing Education in Anesthesia Critical Care & Pain. 2007 Oct;7(5):152–6; doi:10.1016/j.bjae.2018.05.002 Haftel A, Chowdhury YS. Amniotic Fluid Embolism. StatPearls [Internet]. 2023 Jul 3 [cited 2023 Sep 16]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK559107/ Maleki A, Khalid N, Rajesh Patel C, El-Mahdi E. The rising incidence of heterotopic pregnancy: Current perspectives and associations with in-vitro fertilization. Eur J Obstet Gynecol Reprod Biol. 2021 Nov;266:138–44; doi:10.1016/j.ejogrb.2021.09.031 Chukus A, Tirada N, Restrepo R, Reddy NI. Uncommon implantation sites of ectopic pregnancy: Thinking beyond the complex adnexal mass. Radiographics. 2015 May 1;35(3):946–59; doi:10.1148/rg.2015140202 Guan Z, Li HF, Guo LL, Yang X. Management of pancreatic ectopic pregnancy. Taiwan J Obstet Gynecol. 2015 Oct 1;54(5):629–31; doi:10.1016/j.tjog.2015.08.022 Dmowski WP, Rana N, Ding J, Wu WT. Retroperitoneal subpancreatic ectopic pregnancy following in vitro fertilization in a patient with previous bilateral salpingectomy: How did it get there? J Assist Reprod Genet. 2002;19(2):90–3; doi:10.1023/a:1014451932539 Ferland R, Chadwick D, O’Brien JA, Granai CO 3rd. An ectopic pregnancy in the upper retroperitoneum following in vitro fertilization and embryo transfer. Obstet Gynecol. 1991 [cited 2023 Sep 8]. Available from: https://europepmc.org/article/med/1870818 Lockhat F, Corr P, Ramphal S, Moodley J. The value of magnetic resonance imaging in the diagnosis and management of extra-uterine abdominal pregnancy. Clin Radiol. 2006 Mar;61(3):264-9; doi:10.1016/j.crad.2005.10.013. Kitade M, Takeuchi H, Kikuchi I, Shimanuki H, Kumakiri J, Kinoshita K. A case of simultaneous tubal-splenic pregnancy after assisted reproductive technology. Fertil Steril. 2005;83(4):1042.e19-1042.e21; doi:10.1016/j.fertnstert.2004.10.047. Heřman H, Tefr Faridová A, Volfová M, Hostinská E, Džuponová G, Pilka R. Amniotic fluid embolism – review and multicentric case analysis. Česká gynekologie. 2022 Aug 31;87(4); doi:10.48095/cccg2022261. Pacheco LD, Clark SL, Klassen M, Hankins GDV. Amniotic fluid embolism: principles of early clinical management. Am J Obstet Gynecol. 2020 Jan;222(1):48–52; doi:10.1016/j.ajog.2019.07.036. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 14 Nov, 2024 Read the published version in BMC Pregnancy and Childbirth → Version 1 posted Editorial decision: Revision requested 17 Jul, 2024 Reviews received at journal 04 Jul, 2024 Reviewers agreed at journal 11 Jun, 2024 Reviews received at journal 31 Jan, 2024 Reviewers agreed at journal 21 Jan, 2024 Reviewers agreed at journal 21 Jan, 2024 Reviewers invited by journal 31 Dec, 2023 Editor assigned by journal 31 Dec, 2023 Editor invited by journal 23 Dec, 2023 Submission checks completed at journal 23 Dec, 2023 First submitted to journal 19 Dec, 2023 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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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-3777853","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":263321615,"identity":"293cbac9-769b-43ca-b155-157802baa987","order_by":0,"name":"Gabriella 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echogenicity.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-3777853/v1/c099e5460da2e3128e5bc421.png"},{"id":49062011,"identity":"a2371e05-2822-4f63-9636-fb418a55f0d3","added_by":"auto","created_at":"2024-01-02 14:23:50","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":792599,"visible":true,"origin":"","legend":"\u003cp\u003eObstetric ultrasound with a single fetus, a crown rump length of 66 mm, present cardiac activity, 12 weeks and 6 days of gestation, topical.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-3777853/v1/c90a8cf70336cffe8f149943.png"},{"id":49062009,"identity":"060efbdf-3a45-43de-aace-3a72f0c4e864","added_by":"auto","created_at":"2024-01-02 14:23:50","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":212732,"visible":true,"origin":"","legend":"\u003cp\u003eMRI cholangioresonance demonstrates pancreas with preserved morphology and signal intensity with peripancreatic fat of normal appearance.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-3777853/v1/0a3ee9fe4c827ea85cc1843b.png"},{"id":69286116,"identity":"5e8f5564-f1c0-49ab-b6a8-7786ed195f5c","added_by":"auto","created_at":"2024-11-18 19:29:53","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1771148,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3777853/v1/1e0cd0ae-c8db-48ab-92c4-55093943e705.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eHeterotopic Pregnancy and Amniotic Embolism: a Case Report\u003c/p\u003e","fulltext":[{"header":"BACKGROUND","content":"\u003cp\u003eHeterotopic pregnancy (HP) consists of the simultaneous occurrence of an intrauterine pregnancy and an ectopic pregnancy. This condition can be asymptomatic, simulate an acute abdomen, or even progress to hypovolemic shock (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). It is estimated that the incidence of spontaneous HP is 1:30,000 pregnancies, but when associated with in vitro fertilization, it can reach 1:100 pregnancies. Furthermore, the presence of an intrauterine pregnancy often delays its diagnosis and early intervention, as the increase in β-HCG ends up being attributed to the intrauterine pregnancy (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAmniotic embolism (AE) occurs when amniotic fluid or fetal tissue fragments enter the maternal circulation, which can cause pulmonary hypertension, cardiovascular collapse, disseminated intravascular coagulation (DIC), and high mortality rates (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Despite the existence of known risk factors such as eclampsia, polyhydramnios, and uterine rupture, the condition is considered unpredictable given its rarity (1:80,000 pregnancies) (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eBoth diseases \u0026ndash; HP and AE - are rare, and diagnosis can be challenging. Here we report a heterotopic pregnancy that evolved with amniotic embolism and an unfavorable maternal outcome.\u003c/p\u003e"},{"header":"CASE PRESENTATION","content":"\u003cp\u003eA 20-year-old pregnant woman, married, gravida 2, para 1, had a gestational age of 9 weeks and 6 days at the time of hospital admission. Underwent low-risk prenatal care, and had no comorbidities, allergies, previous surgeries or daily use medications. She was a former smoker (10 pack-years), and denied a history of alcoholism or drug addiction. Her father died at the age of 37 from a heart attack, her younger sister had asthma, and her mother was healthy.\u003c/p\u003e \u003cp\u003eShe was referred to the High-Risk Maternity Hospital with symptoms of epigastric pain, nausea, and vomiting, despite symptomatic medications already administered during previous medical care. The patient presented a laboratory test with increased lipase of 205 U/L (reference 8 to 78 U/L) and an abdominal ultrasound with biliary sludge, both performed at a previous medical consultation. Therefore, the initial diagnostic suspicions were hyperemesis gravidarum or acute pancreatitis.\u003c/p\u003e \u003cp\u003eDuring the first month of hospitalization at the Maternity Hospital, a daily clinical assessment was carried out. The pregnant woman fluctuated between periods of clinical improvement and worsening of abdominal pain, but serial laboratory control had a favorable and benign evolution. During this period, additional investigation tests were also carried out. A new ultrasound of the abdomen, 18 days after hospital admission, did not show lithiasis or alterations in the bile duct/pancreas (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). A new obstetric ultrasound, 21 days after admission, demonstrated a single fetus, a crown rump length of 66 mm, present cardiac activity, and 12 weeks and 6 days of gestation (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Magnetic Resonance Imaging (MRI) cholangioresonance, 23 days after admission, evidenced a common bile duct of normal caliber, a gallbladder without evidence of stones, the absence of urinary lithiasis or dilatation of the collecting system, and a normal pancreas (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). An upper digestive endoscopy, 27 days after admission, revealed Los Angeles grade B erosive esophagitis and gastric corpus enanthema.\u003c/p\u003e \u003cp\u003eIn this context, Obstetrics also activated the Gastroenterology, General Surgery and Psychiatry teams to assist in the management of the case. According to the General Surgery assessment, there was no surgical indication upon admission. Gastroenterology advised starting Proton Pump Inhibitor in full dose and maintaining a diet as accepted. Psychiatry recommended starting Sertraline 25mg per day and maintaining outpatient follow-up.\u003c/p\u003e \u003cp\u003eOn the 30th day on the ward, during a medical visit, the patient was lying in bed with a blood pression of 70/40 mmHg, a heart rate\u0026thinsp;\u0026gt;\u0026thinsp;100 bpm, an O2 saturation of 85%, an Glasgow Coma Scale of 14, and a blood glucose of 31 mg/dl, she was hypocolored, with petechiae disseminated to the trunk and limbs and vaginal bleeding. She was urgently taken to the Obstetric Center. Volume correction and intravenous hypoglycemia were initiated. Laboratory tests were urgently collected. Due to signs of respiratory failure, orotracheal intubation was performed with bilateral and symmetric ventilation in all pleuropulmonary fields. Central venous access was attempted in the right subclavian without success. External jugular venous access at the right was then punctured, and intravenous potassium and bicarbonate replacement were immediately started. After this, the patient developed two cardiorespiratory arrests within 42 minutes, which were reversed. Eleven minutes after reestablishing her heart rhythm, she presented a third cardiorespiratory arrest, being resuscitated for 22 minutes, but without success, and with medium-fixed pupils. Maternal death was declared. Necropsy showed HP in the pancreas, signs of pulmonary AE, and consequent DIC. Furthermore, the uterine cavity was empty, indicating that there was a spontaneous abortion of the topical pregnancy.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"DISCUSSION AND CONCLUSION","content":"\u003cp\u003eThis report addresses the case of a HP with a pancreatic gestational implant that is complicated by AE. The incidence of HP has increased in recent decades due to the dissemination of assisted reproduction techniques and infertility treatments (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Furthermore, the risk factors for HP are closely related to those for ectopic pregnancy, including a history of pelvic inflammatory disease, previous pelvic surgery, and previous tubal pathologies. Approximately 71% of women with HP have at least one risk factor for ectopic pregnancy, and 10% have three or more (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). However, in the described case, none of these factors were present, which may have made early diagnosis difficult.\u003c/p\u003e \u003cp\u003eThe fallopian tubes are the most common site of ectopic gestational implantation, with 95% of cases located in the ampulla, infundibulum, or isthmus. Abdominal implants are rare and comprise 0.9\u0026ndash;1.4% of cases of ectopic pregnancy (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Regarding pancreatic implantation, specifically, there are only 3 cases described in the literature (\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe clinical presentation of a pancreatic gestational implant is nonspecific, and there are no characteristic manifestations to differentiate it from acute pancreatitis. Moreover, serum levels of β-HCG, progesterone, amylase, or lipase, as well as transvaginal ultrasound, are of little use for diagnosis (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAbdominal ultrasound can contribute to the diagnosis of HP by detecting, in addition to the intrauterine gestational sac, a heterogeneous extrauterine adnexal mass with hyperechogenic margins, peritrophoblastic flow, yolk sac, fetal parts, and cardiac activity (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). However, in the described case, imaging tests did not contribute to diagnostic elucidation. This contrasts with the perspective of some authors, who suggest that ultrasound and MRI may be useful in the investigation of abdominal HP (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Currently, laparoscopy is the gold standard for diagnosing ectopic pregnancy, including pancreatic ectopic pregnancy, and subsequent histological evaluation is also important for confirmation (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eLate diagnosis of HP can cause significant morbidity and mortality (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). The pregnant woman in the present case, for instance, developed AE. The pathophysiology of AE involves the introduction of amniotic fluid and/or fetal components into the maternal circulation, generating intense pulmonary vasoconstriction and bronchoconstriction. These effects are considered to be caused not only by physical obstruction but also by the intense release of inflammatory cytokines as an immune-mediated response to foreign components (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Some factors that predispose to this condition are uterine trauma, advanced maternal age, multiparity, induction of labor, cesarean section, placenta previa, eclampsia, polyhydramnios, curettage, and kidney diseases (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). In the present case, the authors consider that pancreatic pregnancy may have led to the introduction of fetal antigens and/or amniotic fluid into the maternal bloodstream, leading to an unfavorable outcome.\u003c/p\u003e \u003cp\u003eThe clinical presentation of AE may include hypoxemia, sudden maternal collapse, DIC, and acute fetal distress (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). The evolution of patients is typically biphasic, with pulmonary hypertension and right ventricular failure at the beginning, followed by left ventricular failure during or immediately after delivery (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). The respiratory system is often compromised in the initial phase, progressing to acute respiratory distress syndrome or pulmonary edema. Coagulopathy is also a common feature, observed in 83% of patients, and may lead to the need for hysterectomy and massive transfusions (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe diagnosis of AE is one of exclusion, and the differential diagnosis includes obstetric conditions such as uterine rupture and eclampsia, as well as placental abruption, and non-obstetric conditions such as pulmonary embolism and pneumothorax (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). The definitive diagnosis is usually established only after death, through the findings found at the autopsy, as occurred in the case described above, and maternal mortality rates can reach 25% (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe treatment of AE is mainly supportive, depending on the clinical presentation. Initial management should focus on aggressive treatment of shock by providing high-quality cardiopulmonary resuscitation, as patients often present with sudden cardiovascular collapse (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFacing this case, the authors of the present study consider that pancreatic pregnancy allowed the introduction of fetal antigens and/or amniotic fluid into the maternal bloodstream, leading to AE and consequent DIC. Therefore, obstetricians should suspect HP in patients with an acute abdomen, and the gold standard diagnostic method for this condition is laparoscopy.\u003c/p\u003e \u003cp\u003eTo date, there are no cases of HP associated with AE described in the literature. The authors highlight the difficulty faced in diagnosing HP, even in a large maternity hospital, which has technological support and a multidisciplinary team. Medicine is a science of probability, therefore, rare and infrequent diseases such as HP require a high level of diagnostic suspicion to be identified early and well managed. However, the fact that the patient in question had no known risk factors for HP and presented imaging tests without alterations certainly delayed her diagnosis.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAE Amniotic Embolism\u003c/p\u003e\n\u003cp\u003eDIC Disseminated Intravascular Coagulation\u003c/p\u003e\n\u003cp\u003eHP Heterotopic Pregnancy\u003c/p\u003e\n\u003cp\u003eMRI Magnetic Resonance Imaging\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was reviewed and approved by the Ethics Committee for Research on Human Beings of Clinics Hospital Complex of University Federal of Parana, CAAE\u0026nbsp;69643523.8.0000.0096.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent for publication was obtained from two responsible family members. Documentation of the written consent will be provided to the journal upon request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data and materials analyzed during the current study are available from the corresponding author on reasonable request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was received for conducting this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGS, ECH and CTR: study concept and writing the manuscript. ACSA and MCPF: collection of patient\u0026rsquo;s information. APP, NLECS and DJN: critical revision of the manuscript for intellectual content. All authors have approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eČerniauskaitė M, Vaigauskaitė B, Rama\u0026scaron;auskaitė D, \u0026Scaron;ilkūnas M. Spontaneous Heterotopic Pregnancy: Case Report and Literature Review. Medicina (B Aires) [Internet]. 2020 Aug 1 [cited 2023 Sep 8];56(8):1\u0026ndash;5; doi:10.3390/medicina56080365\u003c/li\u003e\n \u003cli\u003eNguyen KP, Hudspeth M, Milestone H. Spontaneous Heterotopic Pregnancy: Diagnosis and Management. Case Rep Obstet Gynecol. 2022;2022; doi:10.1155/2022/2994808\u003c/li\u003e\n \u003cli\u003eDedhia JD, Mushambi MC. Amniotic fluid embolism. Continuing Education in Anesthesia Critical Care \u0026amp; Pain. 2007 Oct;7(5):152\u0026ndash;6; doi:10.1016/j.bjae.2018.05.002\u003c/li\u003e\n \u003cli\u003eHaftel A, Chowdhury YS. Amniotic Fluid Embolism. StatPearls [Internet]. 2023 Jul 3 [cited 2023 Sep 16]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK559107/\u003c/li\u003e\n \u003cli\u003eMaleki A, Khalid N, Rajesh Patel C, El-Mahdi E. The rising incidence of heterotopic pregnancy: Current perspectives and associations with in-vitro fertilization. Eur J Obstet Gynecol Reprod Biol. 2021 Nov;266:138\u0026ndash;44; doi:10.1016/j.ejogrb.2021.09.031\u003c/li\u003e\n \u003cli\u003eChukus A, Tirada N, Restrepo R, Reddy NI. Uncommon implantation sites of ectopic pregnancy: Thinking beyond the complex adnexal mass. Radiographics. 2015 May 1;35(3):946\u0026ndash;59; doi:10.1148/rg.2015140202\u003c/li\u003e\n \u003cli\u003eGuan Z, Li HF, Guo LL, Yang X. Management of pancreatic ectopic pregnancy. Taiwan J Obstet Gynecol. 2015 Oct 1;54(5):629\u0026ndash;31;\u0026nbsp;doi:10.1016/j.tjog.2015.08.022\u003c/li\u003e\n \u003cli\u003eDmowski WP, Rana N, Ding J, Wu WT. Retroperitoneal subpancreatic ectopic pregnancy following in vitro fertilization in a patient with previous bilateral salpingectomy: How did it get there? J Assist Reprod Genet. 2002;19(2):90\u0026ndash;3; doi:10.1023/a:1014451932539\u003c/li\u003e\n \u003cli\u003eFerland R, Chadwick D, O\u0026rsquo;Brien JA, Granai CO 3rd. An ectopic pregnancy in the upper retroperitoneum following in vitro fertilization and embryo transfer. Obstet Gynecol. 1991 [cited 2023 Sep 8]. Available from: https://europepmc.org/article/med/1870818\u003c/li\u003e\n \u003cli\u003eLockhat F, Corr P, Ramphal S, Moodley J. The value of magnetic resonance imaging in the diagnosis and management of extra-uterine abdominal pregnancy. Clin Radiol. 2006 Mar;61(3):264-9; doi:10.1016/j.crad.2005.10.013.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eKitade M, Takeuchi H, Kikuchi I, Shimanuki H, Kumakiri J, Kinoshita K. A case of simultaneous tubal-splenic pregnancy after assisted reproductive technology. Fertil Steril. 2005;83(4):1042.e19-1042.e21; doi:10.1016/j.fertnstert.2004.10.047.\u003c/li\u003e\n \u003cli\u003eHeřman H, Tefr Faridov\u0026aacute; A, Volfov\u0026aacute; M, Hostinsk\u0026aacute; E, Džuponov\u0026aacute; G, Pilka R. Amniotic fluid embolism \u0026ndash; review and multicentric case analysis. Česk\u0026aacute; gynekologie. 2022 Aug 31;87(4); doi:10.48095/cccg2022261.\u003c/li\u003e\n \u003cli\u003ePacheco LD, Clark SL, Klassen M, Hankins GDV. Amniotic fluid embolism: principles of early clinical management. Am J Obstet Gynecol. 2020 Jan;222(1):48\u0026ndash;52; doi:10.1016/j.ajog.2019.07.036.\u0026nbsp;\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":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Amniotic Fluid Embolism, Heterotopic Pregnancy, Ectopic Pregnancy, Case Report, Obstetric Complication","lastPublishedDoi":"10.21203/rs.3.rs-3777853/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3777853/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBACKGROUND\u003c/h2\u003e \u003cp\u003eHeterotopic pregnancy and amniotic embolism are rare conditions that can be challenging to diagnose. To date, there are no cases of heterotopic pregnancy associated with amniotic embolism described in the literature. Therefore, we report the case of a pancreatic heterotopic pregnancy, which led to amniotic embolism and an unfavorable maternal outcome.\u003c/p\u003e\u003ch2\u003eCASE PRESENTATION:\u003c/h2\u003e \u003cp\u003eA 20-year-old pregnant woman presented with nausea and abdominal pain refractory to drug treatment. She had a increased lipase of 205 U/L (reference 8 to 78 U/L) and a total abdominal ultrasound with biliary sludge. The pregnant woman had no known risk factors for ectopic and/or heterotopic pregnancy. The initial diagnostic suspicions were hyperemesis gravidarum or acute pancreatitis. During hospitalization, she fluctuated between periods of clinical improvement and worsening of abdominal pain, but serial laboratory control had a favorable and benign evolution. On the 30th day of hospitalization, the patient developed spontaneous abortion, respiratory failure, and cardiorespiratory arrest. Necropsy showed heterotopic pregnancy in the pancreas, amniotic embolism, and consequent disseminated intravascular coagulation.\u003c/p\u003e\u003ch2\u003eCONCLUSION\u003c/h2\u003e \u003cp\u003eObstetricians should suspect heterotopic pregnancy in patients with an acute abdomen. The gold standard diagnostic method for this condition is laparoscopy. In the present case, the authors consider that pancreatic pregnancy allowed the introduction of fetal antigens and/or amniotic fluid into the maternal bloodstream, leading to amniotic embolism and consequent disseminated intravascular coagulation.\u003c/p\u003e","manuscriptTitle":"Heterotopic Pregnancy and Amniotic Embolism: a Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-02 14:23:46","doi":"10.21203/rs.3.rs-3777853/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-07-17T18:08:08+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-07-04T22:45:45+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"177241589478932670977045396886324619656","date":"2024-06-11T17:44:11+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-01-31T22:50:19+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"da74c7f4-5624-409e-bf68-8e85775efb30","date":"2024-01-21T16:12:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"c2685b40-64a8-4484-913a-3e2820b0716b","date":"2024-01-21T15:33:32+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2023-12-31T08:33:07+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-12-31T08:32:11+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2023-12-23T09:04:24+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2023-12-23T09:02:12+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pregnancy and Childbirth","date":"2023-12-19T16:43:09+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a6a4622d-cadc-48f9-a5f9-a451fb2194c7","owner":[],"postedDate":"January 2nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-11-18T19:25:29+00:00","versionOfRecord":{"articleIdentity":"rs-3777853","link":"https://doi.org/10.1186/s12884-024-06969-z","journal":{"identity":"bmc-pregnancy-and-childbirth","isVorOnly":false,"title":"BMC Pregnancy and Childbirth"},"publishedOn":"2024-11-14 15:58:04","publishedOnDateReadable":"November 14th, 2024"},"versionCreatedAt":"2024-01-02 14:23:46","video":"","vorDoi":"10.1186/s12884-024-06969-z","vorDoiUrl":"https://doi.org/10.1186/s12884-024-06969-z","workflowStages":[]},"version":"v1","identity":"rs-3777853","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3777853","identity":"rs-3777853","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}