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In August 1950, Mrs Betty Sara, aged 29 years, was confined of quadruplets in the town of Bellingen, New South Wales, which is 500 km north of Sydney. All four babies were delivered vaginally, after a confinement lasting over two and a half days.

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Background and Objectives: The multiple pregnancies associated with COVID-19 is a new and difficult condition to manage. The prognosis for rapid deterioration after the cesarean delivery is difficult to assess and needs close interdisciplinary follow-up due to pregnancy and postpartum-related changes. Materials and Methods: We report the case of a 37-year-old primigesta primipara patient who was admitted to "Elena Doamna" Clinical Hospital of Obstetrics and Gynecology at 33 weeks and 3 days of gestation with high-grade multiple pregnancies (triplets) for threatened premature birth associated with COVID-19. The patient had a history of surgically corrected atrial septal defect during childhood and currently is known to have paroxysmal supraventricular tachycardia. Tocolysis was ineffective and the decision to perform a cesarean operation was made. The diagnosis was established: primigesta, primipara, at 34 weeks of gestation, high-grade multiple pregnancy with triplets, intact membranes, threatened premature birth, surgically corrected atrial septal defect, paroxysmal supraventricular tachycardia, infection with COVID-19. The patient underwent a cesarean intervention and treatment for COVID-19 pneumonia. The intervention took place at 33 weeks and 4 days of gestation resulting in four newborns with weights between 1400 g and 1820 g and Apgar scores between 6-8. All newborns were transferred to a third-degree Neonatology ICU service due to their prematurity. The fourth newborn was not identified in any of the ultrasounds performed during pregnancy. During the postpartum period, the patient had a fulminant evolution of COVID-19 pneumonia, with rapid deterioration, needing respiratory support and antiviral treatment. Discussions: Managing high-risk obstetrical pregnancies associated with COVID-19 requires a multidisciplinary team consisting of obstetricians, anesthesiologists, neonatologists, and infectious disease doctors. Conclusion: Our case is the first to our knowledge in Romania to present an association of high-grade multiple pregancy with COVID19 moderate form, rapidly evolving postpartum, needing rapid intensive care admission, and specific treatment with Remdesivir, with good post-treatment evolution.

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BACKGROUND: We discuss the challenges of multiple pregnancy at very advanced reproductive age. CASE PRESENTATION: We present the case of a quadruplet pregnancy at the maternal age of 65 following in-vitro fertilization (IVF) with donor eggs and sperm, involving cross-border reproductive care. All children born were at 25 weeks' gestation and survived; however, poor neurodevelopmental outcome remains a major concern in one child. CONCLUSIONS: The use of reproductive technology to achieve a multiple pregnancy at such an advanced post-menopausal age generated a debate on ethical, psychosocial and medical questions. We share this debate and highlight the need to reconsider international guidelines for women of advanced reproductive age.

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BACKGROUND: Prematurity escalates the crisis of the infants a susceptible group of the society. Multiple delivery further intensifies the susceptibility of both family and health system. A comprehensive care is, thus, necessary to ensure the optimal growth and development of such multiple-births. Accompanied by trainings, challenges, and strategies, the present study was conducted based on a two-year report of comprehensive care management experience on two sets of multiple infants. METHODS: A qualitative case study approach was used to survey these two sets of premature infants (quadruplet and quintuplet) and their families. The data were collected through medical files, interviews, questionnaire, field presence, phone call and WhatsApp application, and continued follow-ups. Content analysis was performed based on survey and interventions during a period of two years in Isfahan, Iran (2018-2020). RESULTS: Case presentation and comprehensive care management are the main areas resulted from this study. The results of the study were categorized in eight challenging areas (categories) and strategies including sterility and infertility period, transition from the intrauterine to neonatal intensive care unit (NICU), discharge process, physical and developmental status, home visit and home care, development of care plan, socio-economic support, and coronavirus nightmare. CONCLUSION: Based on challenges and strategies during these two years, the situation of the multiple-birth infants and their families' needs should be identified as the first prerequisites in an inter-professional approach and in collaboration with the health providers. Isfahan University of Medical Sciences, Welfare Organization, and the charities were the parties involved with this process in our study. It was also found that developing a separate specific package of comprehensive care management plan for multiple-births is a necessity.

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Quadruplet pregnancy is a pregnancy state where four fetuses grow simultaneously inside a mother's womb. Four fetuses developing in a womb is a challenge not only to the mother but to the obstetrician who has to calculate every risk associated with such pregnancy. High order pregnancy is considered a high risk pregnancy due to increase in maternal, fetal and neonatal morbidity and mortality. So a multidisciplinary approach with early involvement of neonatologists and anesthesiologists for the assessment of such case is essential for a successful obstetric outcome. Here we present a case report of 27 years G3P1L1A1 at 33 weeks 2 days of gestation with quadruplet pregnancy with previous lower segment Cesarian section with history of ovulation induction, delivered successfully via cesarean section with successful outcome of all 1 female and 3 male babies. Keywords: case report; cesarean section; fertility agent; multiple pregnancy; pregnancy; quadruplets.

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The Genain Quadruplets, a genetically identical group of sisters, all developed schizophrenia by their early 20s. Beginning in the 1950s, under the direction of David Rosenthal, they have been studied extensively with a number of neurobiological, neuroradiological and neurobehavioral measures at the Intramural Program of the National Institute of Mental Health (NIMH). A major focus of research interest has been the fact that they varied greatly in the severity of their illness. The present report emphasizes the important role that Monte Buchsbaum had in their evaluation, especially with respect to neuroradiology, during their second period of study at NIMH in the 1980s. It is of special interest that Buchsbaum et al. (1984) concluded "No strong relationship is shown between these (radiological) measures and illness severity or drug responsivity." The inference, therefore, is that the differences in illness severity among the sisters were not readily attributable to differences in the amount of damaged brain, at least as could be determined by the imaging methods available in the 1980s. The current report also summarizes the results of the other studies performed on the sisters in the 1980s, to which Monte Buchsbaum contributed.

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The main purpose of this study was to compare the clinical outcomes of patients undergoing a single bundle anterior cruciate ligament reconstruction (ACL-R) of using quadrupled hamstring (4HT) autografts and two-strand tibialis anterior (2TA) allografts, and to find out the rate of graft failure and possible causes. We hypothesized that there would be no difference in the clinical outcome, and graft failure would be associated with the use of small sized allograft in young active males with high demand of sports activities. We retrospectively evaluated 222 patients (male, n=167, female, n=55) undergoing ACL-R between January 2010 and July 2014. Of 222 patients, 115 were included in the 4HT autograft group and 107 patients in the 2TA allograft group. Inclusion criteria were primary unilateral ACL-R with a minor MCL (

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OBJECTIVE: To report a rare case of quintuplets with monochorionic male quadruplets and a single female after two-blastocyst transfer. DESIGN: Case report. SETTING: University teaching hospital. PATIENT(S): A 37-year-old gravida 1, para 1, presenting after two-embryo IVF with monochorionic male quadruplets and a single female. INTERVENTION(S): Ultrasound examinations and cesarean delivery. MAIN OUTCOME MEASURE(S): Successful delivery of five live-born infants at 28 weeks and 6 days of gestation for preterm labor. RESULT(S): The patient was diagnosed with quintuplets consisting of monochorionic male quadruplets and a single female after the placement of two embryos in blastocyst stage. She was followed closely with ultrasound examinations and hospitalized at 23 weeks' gestation. Cesarean delivery was performed at 28 weeks and 6 days of gestation, with eventual discharge of all infants in healthy condition. CONCLUSION(S): This case represents successful assisted reproductive technology quintuplets with monochorionic quadruplets and a co-sibling. Higher-order monozygotic pregnancies with monochorionic quadruplets are exceedingly rare and a potential complication of IVF.

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BACKGROUND: More than 95% of higher-order multiples are born preterm and more than 90% are low birth weight, making this group of infants especially vulnerable to sudden infant death syndrome (SIDS). Emerging evidence suggests that families with twins face challenges adhering to the American Academy of Pediatrics (AAP) recommendations to reduce SIDS risks. Adherence to the AAP recommendations in families with higher-order multiples has not been described. PURPOSE: This study describes SIDS risk reduction infant care practices for higher-order multiples during the first year of life. METHODS: Mothers caring for higher-order multiple-birth infants were recruited from an online support group. An online survey was used to assess infant care practices when the infants were first brought home from the hospital as well as at the time of the survey. RESULTS: Ten mothers of triplets and 4 mothers of quadruplets responded. Less than 80% of the mothers practiced "back to sleep" immediately postdischarge. Supine sleep positioning decreased over time, particularly during daytime naps. Only 50% of the infants shared the parents' bedroom and approximately 30% bed-shared with their siblings. Sleep-time pacifier use was low. IMPLICATIONS FOR PRACTICE: Safe sleep education must include specific questions regarding home sleeping arrangements, encouragement of breast milk feedings, supine positioning, and pacifier use at every sleep for higher-order multiple infants well before discharge in order for parents to plan a safe sleep environment at home. IMPLICATIONS FOR RESEARCH: Prospective studies to identify barriers and facilitators can inform future strategies supporting adherence to safe sleep practices for higher-order multiple infants.

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OBJECTIVES: The aim of this study is to describe the experience and outcome of higher order multiple (HOM) births in a private tertiary health facility in Nigeria. MATERIALS AND METHODS: This was a retrospective review of records of HOM over 3 years in a private tertiary health facility in Nigeria. Relevant data on HOM births were extracted from both the patients' case notes, admission registers and maternity ward and delivery records of the hospital using a predesigned pro forma. Data were analyzed using Statistical Package for Social Sciences Version 22.0. RESULTS: The prevalence of HOM births was 0.72% of 1950 births over the 3 years study period; while for triplets, quadruplets, and quintuplets were 0.56%, 0.1% and 0.05%, respectively. The mean gestational age was 32 ± 3 weeks, and all except three sets of triplets were by Assisted Reproductive Technology (ART). Respiratory distress syndrome, neonatal jaundice, and neonatal sepsis accounted for more than 80% of the neonatal complications noted in HOM births. However, there was no significant difference between neonatal survival of HOM as compared to twin deliveries, P = 0.08. CONCLUSION: HOM is becoming increasingly common in Nigeria. The strongest risk factor is ART, and neonatal complications are common reinforcing the need to streamline ART protocols in Nigeria.

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BACKGROUND: Little attention has been placed on the unique iron demands that may exist in women with multiple gestations. This merits attention because iron deficiency (ID) during pregnancy is associated with adverse pregnancy outcomes that are known to be more prevalent in multiple births. OBJECTIVE: We characterized longitudinal changes in iron status across pregnancy in a cohort of healthy women with multiple gestations and identified determinants of maternal ID and anemia. DESIGN: A group of 83 women carrying twins, triplets, or quadruplets (aged 20-46 y) was recruited from 2011 to 2014. Blood samples obtained during pregnancy (∼24 wk; n = 73) and at delivery (∼35 wk; n = 61) were used to assess hemoglobin, serum ferritin (SF), soluble transferrin receptor (sTfR), hepcidin, serum iron, erythropoietin, serum folate, vitamin B-12, C-reactive protein, and interleukin-6. RESULTS: The prevalence of tissue ID (sTfR >8.5 mg/L) increased significantly from pregnancy to delivery (9.6% compared with 23%, P = 0.03). Women with depleted iron stores (SF <12 µg/L, n = 20) during pregnancy had a 2-fold greater risk of anemia at delivery, and 25% (n = 5) developed iron deficiency anemia (IDA). Overall, 44.6% of women studied (n = 37/83) were anemic at delivery, and 18% of women (n = 11/61) had IDA. Erythropoietin during pregnancy was significantly negatively associated with hemoglobin at delivery. Women with erythropoietin >75th percentile during pregnancy exhibited a 3-fold greater risk of anemia, suggesting that erythropoietin is a sensitive predictor of anemia at delivery. Inflammation was present at delivery, which limited the utility of ferritin or hepcidin as iron-status indicators at delivery. CONCLUSIONS: ID and anemia are highly prevalent in women with multiple gestations. Additional screening and iron supplementation may be warranted in this high-risk population given the known associations between ID anemia and adverse maternal and neonatal outcomes. This trial was registered at clinicaltrials.gov as NCT01582802.

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The aim of the report was to present a method of zygosity determination in multiple pregnancy. The study wascarried out on same-sex neonates born as a result of spontaneous quadruplet pregnancy. Zygosity was determinedby DNA profiling. The pregnancy was confirmed to be polyzygotic. DNA profiling may be used as a method ofzygosity determination in multiple pregnancy.

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INTRODUCTION: Hirschsprung's disease is a congenital colonic aganglionosis, usually presented as inability or difficulty in passing of meconium, chronic and persistent obstipation, maleficent feeding, vomiting, distension and lethargy. CASE PRESENTATION: We presented a case of an in-vitro conceived quadruplet premature neonate who presented with pneumoperitoneum caused by transverse colon spontaneous perforation and microcolon appearance of distal bowel, treated by resection and temporary colostomy turns to be a rare manifestation of Hirschsprung's disease. CONCLUSION: Assisted reproductive technologies increases chances for multiple pregnancies and may increase chance for major congenital anomalies. Rare manifestation of Hirschsprung's disease is spontaneous pneumoperitoneum which remains a surgical emergency. Delay in recognizing and treatment can significantly worsen prognosis. In neonate with intestinal perforation one should consider Hirschsprung's disease.

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INTRODUCTION: We would Like to present a rare case of multiple gestation following a severe event of spinal cord morbidity during a previous singleton gestation. The medical literature carries a paucity of evidence regarding the future fate of pregnancies following gestational induced intervertebral disc prolapse. CASE HISTORY: A 21 year old mother delivered a healthy boy after unbearable back pain. She subsequently developed urinary retention with laxity of the anal sphincter and underwent urgent L5-S1 discectomy. Following in vitro fertilization for infertility she conceived and was warned of the dangers of a gestation with quadruplets. The parents decided to continue the gestation regularly without intervention despite possible complications. At 31 weeks of gestation the mother delivered four normal male babies, each weighing over 1200 grams after a normal (supervised) pregnancy devoid of any back symptoms. This case demonstrates a novel clinical scenario of hitherto unreported major challenges to an established vulnerable vertebral column. DISCUSSION: To the best of our knowledge this is the first report of a multiple gestation following severe spinal column pathology demanding surgical intervention in order to prevent long term handicap. We could not even locate a series of singleton gestations following such a clinical scenario. The favorable outcome observed in this case is very encouraging and can serve to reassure potential mothers who have experienced a similar previous episode as demonstrated here. CONCLUSION: Special caution must be taken when consulting pregnant patients. From this case history we may learn that precautions such as indefinite contraception after a previous incident of massive disc prolapse may be widely unnecessary.

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OBJECTIVE: To determine the contribution of monozygotic twining to in vitro fertilization multiple births. STUDY DESIGN: We performed a retrospective analysis of the incidence of monozygotic twining in multiple births resulting from fresh embryo transfers using 2006-2010 data from the Society for Reproductive Technology Clinic Outcome Reporting System. RESULTS: The number of embryos transferred were fewer than the number of births in 0.5% (223/40950) of twin, 29% (659/2289) of triplet, and 64% (43/67) of quadruplet births resulting from transfer of fresh embryos from 2006 to 2010. In 2010, 37% of triplets and 100% of quadruplet births occurred when fewer than 3 and fewer than 4 embryos respectively were transferred. CONCLUSION: Monozygotic twinning plays a key role in the development of triplet and quadruplet pregnancies achieved through in vitro fertilization.

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OBJECTIVE: To determine the prevalence and outcome of higher order multiple (HOM) pregnancies in Lagos, Nigeria. METHODS: The mode of delivery, gestational age, pregnancy and neonatal outcome of babies delivered from HOM pregnancies were reviewed retrospectively from the labor ward and theater registers, neonatal unit admission records and medical notes in a tertiary referral centre from April 2009 to March 2012. RESULTS: Twenty-two (15, 6 and 1 set of triplets, quadruplets and quintuplet, respectively) of 6521 pregnancies delivered during the period were HOM pregnancies giving a prevalence of 3.37/1000. All the 74 babies except 12 were delivered by cesarean section. There were 18 perinatal deaths giving a perinatal mortality rate of 243 per 1000. Overall mortality was significantly associated with no antenatal booking (21 versus 5, OR: 21.0, 95% CI: 2.1-72.3, p = 0.000), gestational age ≤30 weeks (21 versus 5, OR: 46.2, 95% CI: 11.2-189.9, p = 0.000) and birth weight <1000 g for live births (p = 0.000). Mode of delivery and number of fetuses >3 were however not significantly associated with mortality. CONCLUSION: Reduction of early preterm births by proper antenatal care and close feto-maternal monitoring of HOM pregnancies will significantly reduce the resultant immediate poor outcomes for these pregnancies and their newborns.

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Type 1 diabetes (T1D) is an autoimmune disease characterized by the lack of insulin due to an autoimmune destruction of pancreatic beta cells. Here, we report a unique case of a family with naturally conceived quadruplets in which T1D was diagnosed in two quadruplets simultaneously. At the same time, the third quadruplet was diagnosed with the pre-diabetic stage. Remarkably, all four quadruplets were positive for anti-islet cell antibodies, GAD65 and IA-A2. Monozygotic status of the quadruplets was confirmed by testing 14 different short tandem repeat polymorphisms. Serological examination confirmed that all quadruplets and their father suffered from a recent enteroviral infection of EV68-71 serotype. To assess the nature of the molecular pathological processes contributing to the development of diabetes, immunocompetent cells isolated from all family members were characterized by gene expression arrays, immune-cell enumerations and cytokine-production assays. The microarray data provided evidence that viral infection, and IL-27 and IL-9 cytokine signalling contributed to the onset of T1D in two of the quadruplets. The propensity of stimulated immunocompetent cells from non-diabetic members of the family to secrete high level of IFN-α further corroborates this conclusion. The number of T regulatory cells as well as plasmacytoid and/or myeloid dendritic cells was found diminished in all family members. Thus, this unique family is a prime example for the support of the so-called 'fertile-field' hypothesis proposing that genetic predisposition to anti-islet autoimmunity is 'fertilized' and precipitated by a viral infection leading to a fully blown T1D.

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