Fishing in Murky Waters: The Challenging Route to Diagnosing Twin-Twin Transfusion Syndrome in a Resource-Limited Humanitarian Setting, A Case Study

Fishing in Murky Waters: The Challenging Route to Diagnosing Twin-Twin Transfusion Syndrome in a Resource-Limited Humanitarian Setting, A Case Study | 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 Fishing in Murky Waters: The Challenging Route to Diagnosing Twin-Twin Transfusion Syndrome in a Resource-Limited Humanitarian Setting, A Case Study Jerom Okot, Henry Ochola, Michael Job Aeku, James Nelson Okema, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4429074/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Twin-to-twin transfusion syndrome (TTTS), though rare, poses risks for fetal demise if undetected. This late-diagnosed TTTS case from South Sudan demonstrates persistent challenges in identifying high-risk pregnancies in humanitarian settings. Case presentation: A 38-year-old multigravida at unknown weeks gestation presented with fever, labour pains, drainage of liquor, and fetal hand prolapse. Her antenatal care only reported non-specific symptoms without most diagnostics. Evaluation revealed malaria, suspected twin pregnancy, and malpresentation. Ultrasound confirmed polyhydramnios and a suspicious intrauterine mass concerning for TTTS. Undiagnosed TTTS became apparent only during emergent cesarean delivery, finding a demised anomalous donor twin. The acute intrapartum decompensation pointed to late-stage V TTTS preventing intervention. While the viable preterm neonate survived, risks from demise were avoidable through earlier detection. Conclusion This case reinforces literature on missed screening opportunities to recognize TTTS before Quintero staging with poorer prognoses. Subtle signs like sudden abdominal enlargement during third trimester were likely overlooked due to limited access to comprehensive ultrasound and Doppler surveillance. Strengthening displacement-sensitive antenatal protocols, building frontline imaging capacity, improving provider awareness, and prompt referrals could help mitigate TTTS-related morbidity and mortality in marginalized populations. Global health efforts must address these persisting care gaps in pregnancy surveillance and access to specialty care, especially in humanitarian settings. Twin to twin transfusion syndrome Background Twin-to-twin transfusion syndrome (TTTS) occurs in 10–15% of monochorionic twins and arises from arterial-venous anastomoses on the shared placenta, leading to unbalanced flow from one fetus (the "donor") to another (the "recipient") ( 1 , 2 ). The pathophysiology arises from the incomplete division between the fetal circulations that creates vascular communications which lead to inadequately balanced blood flow and compensation between the fetuses ( 3 ). The recipient twin progressively accumulates excess circulating volume in the setting of hyperdynamic cardiac function and downstream hemodynamic changes. Meanwhile, the donor twin experiences progressively diminished circulating volume resulting from persistent net transfer towards the recipient ( 4 ). This results in oligohydramnios around the donor and polyhydramnios around the recipient, with twin discordance in size, weight and amniotic fluid. If left untreated, this imbalanced perfusion and transfusion ongoing in utero culminates in up to 70–100% mortality from heart failure, hydrops, entanglement of cords or preterm birth ( 5 ). The reference standard for diagnosis remains comprehensive ultrasonography, characterizing features like oligo-/polyhydramnios sequence, “stuck” twin, and bladder signaling in addition to growth restriction or cardiac dysfunction ( 6 ). Cardinal symptoms reported by pregnant women - such as sudden-onset abdominal swelling, pelvic pressure or dyspnea - may also alert providers. Definitive treatment is fetoscopic laser coagulation to permanently ablate placental vascular communications ( 7 ). This has led to improved survival of at least one twin in 56–100% of TTTS cases and reduced neurological morbidity compared to other invasive interventions like amnioreduction ( 8 ). However, optimal outcomes rely on delivery at experienced, high-volume fetal therapy centers before potential losses or end-organ sequelae ( 9 ). Access to specialized teams for treatment poses challenges globally, even in high-income countries. In regions with few fetal therapy resources, few data exist on coupled detection-to-delivery trajectories in TTTS. This likely contributes towards preventable losses, where early surveillance and diagnosis could prompt life-saving referrals. Our case helps illustrate such pitfalls in marginalized health systems. Understanding where hidden prevalence may remain in displaced or low-resource populations could also spotlight needed interventions, whether through capacity-building, provider education or temporary surgical missions. Case presentation A 38-year-old female, G 11 P 10 + 0 at unknown weeks of gestation admitted at rural Ugandan Health Center level IV, in in a rural Lamwo District, Northern Uganda. She was received as a referral from a remote Health Centre II, a low-level health facility in neighboring South Sudan due to arm prolapse in labour for further management. The patient had a 5-day history intermittent high-grade fever followed by a 3 day report of labour-like pain associated with per-vaginal drainage of clear, odorless fluid. She reported feeling fetal kicks and no per-vaginal bleeding, lower urinary tract symptoms, headache, nausea, or vomiting. Attended antenatal clinic 7 times at the referral site, booked in first trimester; screened sero-negative for syphilis and Human Immuno-deficiency Virus (HIV); received ferrous sulphate, folate, tetanus-toxoid, mebendazole, and fansidar; had normal blood pressures; normal abdominal palpation findings but no other tests or obstetric scan were done. Had no recurrent illness during this pregnancy. Pre-referral, no tests were done but the patient was pre-medicated with oral paracetamol. All her previous pregnancies were singleton, delivered vaginally, however, the last pregnancy was preterm at 28 weeks of gestation that died in 4 hours postpartum (cause of death unknown). Had no known chronic medical illness and reported change of paternity since the preceding pregnancy following death of her first spouse due to an unknown cause. A peasant who resides with her 9 offspring in South Sudan, a farm homestead and reported no more fertility desire. Clinical findings On Examination, she was in pain with a self-reported pain scale of 7/10, mild dehydration and febrile (38.6 o C) but no pallor or jaundice. Was normotensive (blood pressure: 120/75mmHg) with normal pulse rate, 90 beats per minute. The obstetric exam found a symphysial-fundal length of 37cm, cephalic fetal presentation, oblique lie, normal fetal heart rate (130beats per minute), a descent of 5/5th palpable, and 1–2 uterine contractions in 10 minutes each lasting 10–20 seconds. Sterile speculum vaginal exam revealed odorless liquor with a positive pooling test, fetal hand prolapsed into the vagina, cervical dilation of 3cm but no cord. Initial laboratory tests were done: - positive malaria rapid diagnostic test, full blood count (mild leukocytosis: 12x10 9 , thrombocytopenia: 92x10 9 , and normal hemoglobin level: 13.3g/dl), blood group A rhesus positive and normal urine dipstick. Obstetric scan revealed a single live fetus at 36 weeks and 5 days of gestation, estimated weight of 2954grams, mild polyhydramnios, compound presentation, and a suspicious intrauterine mass. At this point, the diagnosis was latent labour with early rupture of membranes, hand prolapse, and severe malaria with mild thrombocytopenia. On the admission day, she was on intravenous (IV) artesunate 127mg at 0,12 and 24 hours followed by oral (po) artemether-lumefantrine (80/480mg) 12 hourly for 3 days, po paracetamol 1g 8 hourly for 3 days, and IV ceftriaxone 1gm od for 5 days. The patient was counselled for an emergency caesarean section due to fetal hand prolapse and bilateral tubal ligation, informed consent was obtained, blood was booked, and the patient was preloaded with 1 liter of IV normal saline fluids. After the IV fluids, the caesarean section was done under spinal anesthesia through a Pfannenstiel skin incision, found an intact gravid uterus, a lower uterine segment incision was made delivered a live baby boy, weight 2500 grams, APGAR score of 8 and 10 at 1 and 5 minutes respectively. Also, delivered a second dead fetus, indistinguishable sex, compressed on the left aspect of the uterus, and weighed 200g. One placenta was delivered by controlled cord traction and the uterus closed. Bilateral tubal ligation was done by Parkland’s technique and the abdominal wall layer closed step-wisely. The estimated blood loss was about 400 milliliters. At this stage, diamniotic monochorionic twin pregnancy with late-stage V TTTS was diagnosed retrospectively. Postoperatively, the patient received maintenance IV fluids, analgesics, IV metronidazole, and the drugs prescribed on admission. The newborn commenced breastfeeding and was well. Both baby and mother were discharged in good condition on the third post-operative day. Discussion This case illustrates key challenges surrounding diagnosis and management of TTTS in low-resource settings. The subtle signs of TTTS were likely missed during routine antenatal care for this patient from South Sudan, ultimately leading to an adverse outcome. While the classic features were eventually noted such as polyhydramnios, and growth discordance earlier detection of the twin pregnancy may have been possible with risk-based screening incorporating first trimester ultrasound and Doppler studies as availability allowed ( 2 ). However, the remote setting and displaced status of this patient hindered access to such diagnostics, a recognized barrier in similar humanitarian contexts ( 10 ). Consequently, progression to more severe Quintero staging could not be halted pharmacologically or through laser intervention ( 2 ). This mirrors other low-income cases where late TTTS diagnosis limited options for fetal therapy. Undiagnosed TTTS also posed delivery challenges once unrecognized severe growth discrepancy and malpresentation came to light. Accessing emergency cesarean capabilities in such a remote setting averted likely adverse outcomes for the second twin but this may not be feasible for all patients ( 11 ). Notably, this case adds to limited literature on TTTS in displaced or low-resource populations. While successful introduction of laser surgery has been demonstrated elsewhere, preventing late diagnoses remains paramount ( 12 ). This reinforces the value of raising TTTS awareness and building frontline ultrasound capabilities for earlier detection where possible ( 10 ). More population data on TTTS-attributable morbidity could also strengthen the impetus for such health systems strengthening. In low-income regions, complex fetal disorders like TTTS continue posing diagnostic and therapeutic challenges. As illustrated through this case, opportunities exist for quality improvement through risk-appropriate antenatal screening, telehealth support of providers, patient education and enhanced surgical capacity-building ( 2 , 12 ). Reporting this experience from South Sudan thus highlights where global health resources could be focused to improve care for vulnerable women and babies. Conclusion This case report presents a late-diagnosed and undiagnosed TTTS in a low-resource humanitarian setting, resulting in demise of the donor twin. The subtle signs pointing to TTTS during pregnancy were likely overlooked due to limitations in diagnostic capacity and prenatal screening protocols in the region. While the surviving twin was ultimately delivered via emergency cesarean, earlier detection could have allowed for specialist referral, fetal intervention, and possible prevention of a demise. Key clinical takeaways highlight persistent gaps in identifying high-risk pregnancies in displaced or low-resource populations, leading to missed opportunities for mitigating morbidity and mortality from conditions like TTTS. Strengthening frontline screening with ultrasound, improving provider knowledge, and enhancing coordination for referrals and transport are imperative to pick up danger signs earlier. smoothly. More widespread data on TTTS-attributable adverse outcomes could also inform health policy and resource allocation in vulnerable settings. This case stresses the importance of investing in healthcare infrastructure and delivery systems serving pregnant women in low-income regions. Reporting experiences such as this brings awareness to where global health efforts must be focused to advance maternal-fetal medicine in areas struggling with access barriers. Knowledge-sharing around successful introduction of specialized capabilities like foetoscopic surgery elsewhere provides hope for incrementally tackling complex conditions like TTTS at the margins of the healthcare system. Declarations Acknowledgement We acknowledge medical student from Gulu University Conflict of interest None Funding There was no funding for this study. Consent to publish. Mother consented for this to be published. Data availability declaration Data on the history and management of the mother and baby are available upon reasonable request from the first Author Ethic approval and consent to participate. the mother provided informed consent for the case to be published, a copy of written informed consent attached below. Figure 1 References Fisk NM, Duncombe GJ, Sullivan MHF. The Basic and Clinical Science of Twin–Twin Transfusion Syndrome. Placenta. 2009;30(5):379–90. Lewi L, Jani J, Blickstein I, Huber A, Gucciardo L, Van Mieghem T et al. The outcome of monochorionic diamniotic twin gestations in the era of invasive fetal therapy: a prospective cohort study. Am J Obstet Gynecol. 2008;199(5):514.e1-514.e8. Quintero RA, Mueller OT, Martínez JM, Arroyo J, Gilbert-Barness E, Hilbelink D, et al. Twin–twin transfusion syndrome in a dizygotic monochorionic–diamniotic twin pregnancy. J Matern Fetal Neonatal Med. 2003;14(4):279–81. Snowise S, Moise KJ, Johnson A, Bebbington MW, Papanna R. Donor Death After Selective Fetoscopic Laser Surgery for Twin–Twin Transfusion Syndrome. Obstet Gynecol. 2015;126(1):74–80. Brown DL, Benson CB, Driscoll SG, Doubilet PM. Twin-twin transfusion syndrome: sonographic findings. Radiology. 1989;170(1):61–3. Blickstein I. Twin-to-twin transfusion syndrome. Am J Obstet Gynecol. 1990;163(2):677. Ruano R, De Lourdes Brizot M, Liao AW, Zugaib M. Selective Fetoscopic Laser Photocoagulation of Superficial Placental Anastomoses for the Treatment of Severe Twin-Twin Transfusion Syndrome. Clinics. 2009;64(2):91–6. Senat MV, Deprest J, Boulvain M, Paupe A, Winer N, Ville Y. Endoscopic Laser Surgery versus Serial Amnioreduction for Severe Twin-to-Twin Transfusion Syndrome. N Engl J Med. 2004;351(2):136–44. Bamberg C, Hecher K. Update on twin-to-twin transfusion syndrome. Best Pract Res Clin Obstet Gynaecol. 2019;58:55–65. Matias A, Montenegro N, Areias J. Anticipating twin–twin transfusion syndrome in monochorionic twin pregnancy. Is there a role for nuchal translucency and ductus venosus blood flow evaluation at 11–14 weeks? Twin Res. 2000;3(02):65–70. Iwo-Amah RS, Wekere FCC, Amadi SC, Kwosah JN. Emergency caesarean section and its sequelae in a tertiary hospital in Niger Delta, Nigeria. Int J Reprod Contracept Obstet Gynecol. 2021;10(12):4372. Spruijt MS, Lopriore E, Steggerda J, Slaghekke S, Van Klink F. Twin-twin transfusion syndrome in the era of fetoscopic laser surgery: antenatal management, neonatal outcome and beyond. Expert Rev Hematol. 2020;13(3):259–67. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies 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-4429074","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":308275636,"identity":"f5609511-cb61-4c36-8d19-eda8e9294995","order_by":0,"name":"Jerom Okot","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABCklEQVRIiWNgGAWjYDACHgglw8ZwAMyQAxEHHuDXwtgAomBajMFaEojRAuMngngM+LTw8xw+/uBnmw0PH+PhYx8+5tikzw87/BBoi52cbgN2LZK9bYmNvW1pQIcdS545c1ta7sbbaQZALcnGZgewazE4z2PYwNt2GKjljDEz77bDuRtnJ4C0HEjchkdL41+wlvOfgVr+pxvOTv+AX8vZHsNmqC3MQC0HEuSlc/DbItlzLHG2zDmwX4wZZ25LNtwgnVNwIMEAt1/4eZIPfHxTZiMnP+PwY4aP2+zk5Wenb/7wocJODpcWMGBkAxISUBUGYNoAj3Iw+AOyrwHClm8gpHoUjIJRMApGGgAAFzxiptuTeKUAAAAASUVORK5CYII=","orcid":"","institution":"Gulu University","correspondingAuthor":true,"prefix":"","firstName":"Jerom","middleName":"","lastName":"Okot","suffix":""},{"id":308275637,"identity":"a7d59e82-614d-48b3-b927-03ee24660847","order_by":1,"name":"Henry Ochola","email":"","orcid":"","institution":"London School of Hygiene \u0026 Tropical Medicine","correspondingAuthor":false,"prefix":"","firstName":"Henry","middleName":"","lastName":"Ochola","suffix":""},{"id":308275638,"identity":"4ca4061b-3228-4abf-bfe2-6ec07e1e6002","order_by":2,"name":"Michael Job Aeku","email":"","orcid":"","institution":"International Rescue Committee","correspondingAuthor":false,"prefix":"","firstName":"Michael","middleName":"Job","lastName":"Aeku","suffix":""},{"id":308275639,"identity":"9652d807-7c7a-4807-a6a5-270bc773acd3","order_by":3,"name":"James Nelson Okema","email":"","orcid":"","institution":"Gulu University","correspondingAuthor":false,"prefix":"","firstName":"James","middleName":"Nelson","lastName":"Okema","suffix":""},{"id":308275640,"identity":"ee811651-0582-41a0-bd59-cfeade358f94","order_by":4,"name":"Simple Ouma","email":"","orcid":"","institution":"Gulu University","correspondingAuthor":false,"prefix":"","firstName":"Simple","middleName":"","lastName":"Ouma","suffix":""},{"id":308275641,"identity":"9b66ad20-e455-49ee-a146-7c3274bce058","order_by":5,"name":"Francis Pebalo Pebolo","email":"","orcid":"","institution":"Gulu University","correspondingAuthor":false,"prefix":"","firstName":"Francis","middleName":"Pebalo","lastName":"Pebolo","suffix":""}],"badges":[],"createdAt":"2024-05-16 07:06:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4429074/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4429074/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":92826356,"identity":"3bd27755-a776-4762-9139-60e678ee7cce","added_by":"auto","created_at":"2025-10-06 04:31:57","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":374736,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4429074/v1/fc8bea00-8164-4706-8a78-9aac7c8f61d7.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Fishing in Murky Waters: The Challenging Route to Diagnosing Twin-Twin Transfusion Syndrome in a Resource-Limited Humanitarian Setting, A Case Study","fulltext":[{"header":"Background","content":"\u003cp\u003eTwin-to-twin transfusion syndrome (TTTS) occurs in 10\u0026ndash;15% of monochorionic twins and arises from arterial-venous anastomoses on the shared placenta, leading to unbalanced flow from one fetus (the \"donor\") to another (the \"recipient\") (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). The pathophysiology arises from the incomplete division between the fetal circulations that creates vascular communications which lead to inadequately balanced blood flow and compensation between the fetuses (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). The recipient twin progressively accumulates excess circulating volume in the setting of hyperdynamic cardiac function and downstream hemodynamic changes. Meanwhile, the donor twin experiences progressively diminished circulating volume resulting from persistent net transfer towards the recipient (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). This results in oligohydramnios around the donor and polyhydramnios around the recipient, with twin discordance in size, weight and amniotic fluid. If left untreated, this imbalanced perfusion and transfusion ongoing in utero culminates in up to 70\u0026ndash;100% mortality from heart failure, hydrops, entanglement of cords or preterm birth (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe reference standard for diagnosis remains comprehensive ultrasonography, characterizing features like oligo-/polyhydramnios sequence, \u0026ldquo;stuck\u0026rdquo; twin, and bladder signaling in addition to growth restriction or cardiac dysfunction (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Cardinal symptoms reported by pregnant women - such as sudden-onset abdominal swelling, pelvic pressure or dyspnea - may also alert providers. Definitive treatment is fetoscopic laser coagulation to permanently ablate placental vascular communications (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). This has led to improved survival of at least one twin in 56\u0026ndash;100% of TTTS cases and reduced neurological morbidity compared to other invasive interventions like amnioreduction (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). However, optimal outcomes rely on delivery at experienced, high-volume fetal therapy centers before potential losses or end-organ sequelae (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Access to specialized teams for treatment poses challenges globally, even in high-income countries.\u003c/p\u003e \u003cp\u003eIn regions with few fetal therapy resources, few data exist on coupled detection-to-delivery trajectories in TTTS. This likely contributes towards preventable losses, where early surveillance and diagnosis could prompt life-saving referrals. Our case helps illustrate such pitfalls in marginalized health systems. Understanding where hidden prevalence may remain in displaced or low-resource populations could also spotlight needed interventions, whether through capacity-building, provider education or temporary surgical missions.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 38-year-old female, G\u003csub\u003e11\u003c/sub\u003eP\u003csub\u003e10\u003c/sub\u003e\u0026thinsp;+\u0026thinsp;0 at unknown weeks of gestation admitted at rural Ugandan Health Center level IV, in in a rural Lamwo District, Northern Uganda. She was received as a referral from a remote Health Centre II, a low-level health facility in neighboring South Sudan due to arm prolapse in labour for further management.\u003c/p\u003e \u003cp\u003eThe patient had a 5-day history intermittent high-grade fever followed by a 3 day report of labour-like pain associated with per-vaginal drainage of clear, odorless fluid. She reported feeling fetal kicks and no per-vaginal bleeding, lower urinary tract symptoms, headache, nausea, or vomiting. Attended antenatal clinic 7 times at the referral site, booked in first trimester; screened sero-negative for syphilis and Human Immuno-deficiency Virus (HIV); received ferrous sulphate, folate, tetanus-toxoid, mebendazole, and fansidar; had normal blood pressures; normal abdominal palpation findings but no other tests or obstetric scan were done. Had no recurrent illness during this pregnancy. Pre-referral, no tests were done but the patient was pre-medicated with oral paracetamol. All her previous pregnancies were singleton, delivered vaginally, however, the last pregnancy was preterm at 28 weeks of gestation that died in 4 hours postpartum (cause of death unknown). Had no known chronic medical illness and reported change of paternity since the preceding pregnancy following death of her first spouse due to an unknown cause. A peasant who resides with her 9 offspring in South Sudan, a farm homestead and reported no more fertility desire.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eClinical findings\u003c/h2\u003e \u003cp\u003eOn Examination, she was in pain with a self-reported pain scale of 7/10, mild dehydration and febrile (38.6\u003csup\u003eo\u003c/sup\u003eC) but no pallor or jaundice. Was normotensive (blood pressure: 120/75mmHg) with normal pulse rate, 90 beats per minute. The obstetric exam found a symphysial-fundal length of 37cm, cephalic fetal presentation, oblique lie, normal fetal heart rate (130beats per minute), a descent of 5/5th palpable, and 1\u0026ndash;2 uterine contractions in 10 minutes each lasting 10\u0026ndash;20 seconds. Sterile speculum vaginal exam revealed odorless liquor with a positive pooling test, fetal hand prolapsed into the vagina, cervical dilation of 3cm but no cord.\u003c/p\u003e \u003cp\u003eInitial laboratory tests were done: - positive malaria rapid diagnostic test, full blood count (mild leukocytosis: 12x10\u003csup\u003e9\u003c/sup\u003e, thrombocytopenia: 92x10\u003csup\u003e9\u003c/sup\u003e, and normal hemoglobin level: 13.3g/dl), blood group A rhesus positive and normal urine dipstick. Obstetric scan revealed a single live fetus at 36 weeks and 5 days of gestation, estimated weight of 2954grams, mild polyhydramnios, compound presentation, and a suspicious intrauterine mass. At this point, the diagnosis was latent labour with early rupture of membranes, hand prolapse, and severe malaria with mild thrombocytopenia.\u003c/p\u003e \u003cp\u003eOn the admission day, she was on intravenous (IV) artesunate 127mg at 0,12 and 24 hours followed by oral (po) artemether-lumefantrine (80/480mg) 12 hourly for 3 days, po paracetamol 1g 8 hourly for 3 days, and IV ceftriaxone 1gm od for 5 days. The patient was counselled for an emergency caesarean section due to fetal hand prolapse and bilateral tubal ligation, informed consent was obtained, blood was booked, and the patient was preloaded with 1 liter of IV normal saline fluids. After the IV fluids, the caesarean section was done under spinal anesthesia through a Pfannenstiel skin incision, found an intact gravid uterus, a lower uterine segment incision was made delivered a live baby boy, weight 2500 grams, APGAR score of 8 and 10 at 1 and 5 minutes respectively. Also, delivered a second dead fetus, indistinguishable sex, compressed on the left aspect of the uterus, and weighed 200g. One placenta was delivered by controlled cord traction and the uterus closed. Bilateral tubal ligation was done by Parkland\u0026rsquo;s technique and the abdominal wall layer closed step-wisely. The estimated blood loss was about 400 milliliters. At this stage, diamniotic monochorionic twin pregnancy with late-stage V TTTS was diagnosed retrospectively. Postoperatively, the patient received maintenance IV fluids, analgesics, IV metronidazole, and the drugs prescribed on admission. The newborn commenced breastfeeding and was well. Both baby and mother were discharged in good condition on the third post-operative day.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis case illustrates key challenges surrounding diagnosis and management of TTTS in low-resource settings. The subtle signs of TTTS were likely missed during routine antenatal care for this patient from South Sudan, ultimately leading to an adverse outcome.\u003c/p\u003e \u003cp\u003eWhile the classic features were eventually noted such as polyhydramnios, and growth discordance earlier detection of the twin pregnancy may have been possible with risk-based screening incorporating first trimester ultrasound and Doppler studies as availability allowed (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). However, the remote setting and displaced status of this patient hindered access to such diagnostics, a recognized barrier in similar humanitarian contexts (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Consequently, progression to more severe Quintero staging could not be halted pharmacologically or through laser intervention (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). This mirrors other low-income cases where late TTTS diagnosis limited options for fetal therapy.\u003c/p\u003e \u003cp\u003eUndiagnosed TTTS also posed delivery challenges once unrecognized severe growth discrepancy and malpresentation came to light. Accessing emergency cesarean capabilities in such a remote setting averted likely adverse outcomes for the second twin but this may not be feasible for all patients (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eNotably, this case adds to limited literature on TTTS in displaced or low-resource populations. While successful introduction of laser surgery has been demonstrated elsewhere, preventing late diagnoses remains paramount (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). This reinforces the value of raising TTTS awareness and building frontline ultrasound capabilities for earlier detection where possible (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). More population data on TTTS-attributable morbidity could also strengthen the impetus for such health systems strengthening.\u003c/p\u003e \u003cp\u003eIn low-income regions, complex fetal disorders like TTTS continue posing diagnostic and therapeutic challenges. As illustrated through this case, opportunities exist for quality improvement through risk-appropriate antenatal screening, telehealth support of providers, patient education and enhanced surgical capacity-building (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Reporting this experience from South Sudan thus highlights where global health resources could be focused to improve care for vulnerable women and babies.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis case report presents a late-diagnosed and undiagnosed TTTS in a low-resource humanitarian setting, resulting in demise of the donor twin. The subtle signs pointing to TTTS during pregnancy were likely overlooked due to limitations in diagnostic capacity and prenatal screening protocols in the region. While the surviving twin was ultimately delivered via emergency cesarean, earlier detection could have allowed for specialist referral, fetal intervention, and possible prevention of a demise.\u003c/p\u003e \u003cp\u003eKey clinical takeaways highlight persistent gaps in identifying high-risk pregnancies in displaced or low-resource populations, leading to missed opportunities for mitigating morbidity and mortality from conditions like TTTS. Strengthening frontline screening with ultrasound, improving provider knowledge, and enhancing coordination for referrals and transport are imperative to pick up danger signs earlier. smoothly. More widespread data on TTTS-attributable adverse outcomes could also inform health policy and resource allocation in vulnerable settings.\u003c/p\u003e \u003cp\u003eThis case stresses the importance of investing in healthcare infrastructure and delivery systems serving pregnant women in low-income regions. Reporting experiences such as this brings awareness to where global health efforts must be focused to advance maternal-fetal medicine in areas struggling with access barriers. Knowledge-sharing around successful introduction of specialized capabilities like foetoscopic surgery elsewhere provides hope for incrementally tackling complex conditions like TTTS at the margins of the healthcare system.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgement\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe acknowledge medical student from Gulu University\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere was no funding for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to publish.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMother consented for this to be published.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability declaration\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData on the history and management of the mother and baby are available upon reasonable request from the first Author\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthic approval and consent to participate.\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ethe mother provided informed consent for the case to be published, a copy of written informed consent attached below. \u003cstrong\u003eFigure 1\u003c/strong\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eFisk NM, Duncombe GJ, Sullivan MHF. The Basic and Clinical Science of Twin\u0026ndash;Twin Transfusion Syndrome. Placenta. 2009;30(5):379\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLewi L, Jani J, Blickstein I, Huber A, Gucciardo L, Van Mieghem T et al. The outcome of monochorionic diamniotic twin gestations in the era of invasive fetal therapy: a prospective cohort study. Am J Obstet Gynecol. 2008;199(5):514.e1-514.e8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eQuintero RA, Mueller OT, Mart\u0026iacute;nez JM, Arroyo J, Gilbert-Barness E, Hilbelink D, et al. Twin\u0026ndash;twin transfusion syndrome in a dizygotic monochorionic\u0026ndash;diamniotic twin pregnancy. J Matern Fetal Neonatal Med. 2003;14(4):279\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSnowise S, Moise KJ, Johnson A, Bebbington MW, Papanna R. Donor Death After Selective Fetoscopic Laser Surgery for Twin\u0026ndash;Twin Transfusion Syndrome. Obstet Gynecol. 2015;126(1):74\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrown DL, Benson CB, Driscoll SG, Doubilet PM. Twin-twin transfusion syndrome: sonographic findings. Radiology. 1989;170(1):61\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBlickstein I. Twin-to-twin transfusion syndrome. Am J Obstet Gynecol. 1990;163(2):677.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRuano R, De Lourdes Brizot M, Liao AW, Zugaib M. Selective Fetoscopic Laser Photocoagulation of Superficial Placental Anastomoses for the Treatment of Severe Twin-Twin Transfusion Syndrome. Clinics. 2009;64(2):91\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSenat MV, Deprest J, Boulvain M, Paupe A, Winer N, Ville Y. Endoscopic Laser Surgery versus Serial Amnioreduction for Severe Twin-to-Twin Transfusion Syndrome. N Engl J Med. 2004;351(2):136\u0026ndash;44.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBamberg C, Hecher K. Update on twin-to-twin transfusion syndrome. Best Pract Res Clin Obstet Gynaecol. 2019;58:55\u0026ndash;65.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMatias A, Montenegro N, Areias J. Anticipating twin\u0026ndash;twin transfusion syndrome in monochorionic twin pregnancy. Is there a role for nuchal translucency and ductus venosus blood flow evaluation at 11\u0026ndash;14 weeks? Twin Res. 2000;3(02):65\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIwo-Amah RS, Wekere FCC, Amadi SC, Kwosah JN. Emergency caesarean section and its sequelae in a tertiary hospital in Niger Delta, Nigeria. Int J Reprod Contracept Obstet Gynecol. 2021;10(12):4372.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSpruijt MS, Lopriore E, Steggerda J, Slaghekke S, Van Klink F. Twin-twin transfusion syndrome in the era of fetoscopic laser surgery: antenatal management, neonatal outcome and beyond. Expert Rev Hematol. 2020;13(3):259\u0026ndash;67.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Twin to twin transfusion syndrome","lastPublishedDoi":"10.21203/rs.3.rs-4429074/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4429074/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eTwin-to-twin transfusion syndrome (TTTS), though rare, poses risks for fetal demise if undetected. This late-diagnosed TTTS case from South Sudan demonstrates persistent challenges in identifying high-risk pregnancies in humanitarian settings.\u003c/p\u003e\u003ch2\u003eCase presentation:\u003c/h2\u003e \u003cp\u003eA 38-year-old multigravida at unknown weeks gestation presented with fever, labour pains, drainage of liquor, and fetal hand prolapse. Her antenatal care only reported non-specific symptoms without most diagnostics. Evaluation revealed malaria, suspected twin pregnancy, and malpresentation. Ultrasound confirmed polyhydramnios and a suspicious intrauterine mass concerning for TTTS. Undiagnosed TTTS became apparent only during emergent cesarean delivery, finding a demised anomalous donor twin. The acute intrapartum decompensation pointed to late-stage V TTTS preventing intervention. While the viable preterm neonate survived, risks from demise were avoidable through earlier detection.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThis case reinforces literature on missed screening opportunities to recognize TTTS before Quintero staging with poorer prognoses. Subtle signs like sudden abdominal enlargement during third trimester were likely overlooked due to limited access to comprehensive ultrasound and Doppler surveillance. Strengthening displacement-sensitive antenatal protocols, building frontline imaging capacity, improving provider awareness, and prompt referrals could help mitigate TTTS-related morbidity and mortality in marginalized populations. Global health efforts must address these persisting care gaps in pregnancy surveillance and access to specialty care, especially in humanitarian settings.\u003c/p\u003e","manuscriptTitle":"Fishing in Murky Waters: The Challenging Route to Diagnosing Twin-Twin Transfusion Syndrome in a Resource-Limited Humanitarian Setting, A Case Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-07 19:02:47","doi":"10.21203/rs.3.rs-4429074/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c34bc781-9dd8-4a47-a539-eb630213fe5f","owner":[],"postedDate":"June 7th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-10-06T04:23:51+00:00","versionOfRecord":[],"versionCreatedAt":"2024-06-07 19:02:47","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4429074","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4429074","identity":"rs-4429074","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}