Risk factors and outcomes of uterine rupture in Singapore: Emerging trends.

INTRODUCTION: Uterine rupture is uncommon but has catastrophic implications on the pregnancy. A scarred uterus and abnormal placentation are known contributory factors. The aim of our study was to review the contributing factors, clinical presentation, complications and management of uterine rupture in our population in light of the changing nature of modern obstetric practices. METHODS: A retrospective observational study was conducted at KK Women's and Children's Hospital by studying proven cases of uterine rupture in the period between January 2003 and December 2014. These cases were analysed according to their past history, clinical presentation, complications, management and outcome. RESULTS: A total of 48 cases of proven uterine rupture were identified. The incidence of uterine rupture was 1 in 3,062 deliveries. The ratio of scarred uterus rupture to unscarred uterus rupture was approximately 3:1. The most common factor was previous lower segment caesarean section for the scarred group, followed by a history of laparoscopic myomectomy. Abdominal pain was the common clinical presentation in the antenatal period, while abnormal cardiotocography findings were the most common presentation in intrapartum rupture. CONCLUSION: There is a notable shift in the trend of uterine rupture cases given the increasing use of laparoscopic myomectomy and elective caesarean sections. While ruptures from these cases were few, their presentation in the antenatal period calls for diligent monitoring with informed patient involvement in their pregnancy care.

An Unusual Case of Placenta Abruption Leading to Couvelaire Uterus in a Previable Pregnancy.

Couvelaire uterus or uteroplacental apoplexy is a rare complication of abruptio placentae whose etiology is unknown. It is a clinical diagnosis made during visual inspection of the uterus. Immediate management is usually conservative and hysterectomy is usually not required. Our case highlights the importance of early recognition of a clinically unstable previable pregnant patient with suspected placenta abruption and early surgical recourse with successful emergency hysterotomy.

Knowledge of pelvic floor disorder in pregnancy.

INTRODUCTION AND HYPOTHESIS: Pelvic floor dysfunction is a common condition which can lead to distressing consequences such as urinary incontinence (UI), pelvic organ prolapse (POP) and fecal incontinence (FI). Pregnancy is a known major risk factor. This study aims to assess the level of knowledge about pelvic floor disorders among pregnant women in our local population. METHODS: A cross-sectional study was conducted in a population of pregnant women in their third trimester. A 47-question questionnaire was distributed to a random sample group. Knowledge scores were calculated. Possible predictive factors for knowledge level such as age, ethnicity, parity, ethnicity and educational levels were studied. RESULTS: Thirty-three out of 104 respondents (31.7%) reported history of urinary incontinence, 3 respondents (2.9%) reported sensation of prolapse, and 1 respondent (0.96%) reported fecal incontinence. The knowledge score for urinary incontinence was the highest at 46.2% and lowest in pelvic organ prolapse at 35.3%. Mean knowledge scores increased significantly with age (p = 0.021) and educational level (p = 0.046). The nulliparous women scored higher than the multiparous women. Age and educational level had a significant impact on multivariate analysis scores. CONCLUSIONS: The knowledge on pelvic floor disorders is poor among our local pregnant women. Healthcare professionals should place increased emphasis on advocating pelvic floor exercises for pregnant women during their routine antenatal care.

Human CD34(lo)CD133(lo) fetal liver cells support the expansion of human CD34(hi)CD133(hi) hematopoietic stem cells.

We have recently discovered a unique CD34(lo)CD133(lo) cell population in the human fetal liver (FL) that gives rise to cells in the hepatic lineage. In this study, we further characterized the biological functions of FL CD34(lo)CD133(lo) cells. Our findings show that these CD34(lo)CD133(lo) cells express markers of both endodermal and mesodermal lineages and have the capability to differentiate into hepatocyte and mesenchymal lineage cells by ex vivo differentiation assays. Furthermore, we show that CD34(lo)CD133(lo) cells express growth factors that are important for human hematopoietic stem cell (HSC) expansion: stem cell factor (SCF), insulin-like growth factor 2 (IGF2), C-X-C motif chemokine 12 (CXCL12), and factors in the angiopoietin-like protein family. Co-culture of autologous FL HSCs and allogenic HSCs derived from cord blood with CD34(lo)CD133(lo) cells supports and expands both types of HSCs.These findings are not only essential for extending our understanding of the HSC niche during the development of embryonic and fetal hematopoiesis but will also potentially benefit adult stem cell transplantations in clinics because expanded HSCs demonstrate the same capacity as primary cells to reconstitute the human immune system and mediate long-term hematopoiesis in vivo. Together, CD34(lo)CD133(lo) cells not only serve as stem/progenitor cells for liver development but are also an essential component of the HSC niche in the human FL.

Characterisation of liver pathogenesis, human immune responses and drug testing in a humanised mouse model of HCV infection.

OBJECTIVE: HCV infection affects millions of people worldwide, and many patients develop chronic infection leading to liver cancers. For decades, the lack of a small animal model that can recapitulate HCV infection, its immunopathogenesis and disease progression has impeded the development of an effective vaccine and therapeutics. We aim to provide a humanised mouse model for the understanding of HCV-specific human immune responses and HCV-associated disease pathologies. DESIGN: Recently, we have established human liver cells with a matched human immune system in NOD-scid Il2rg(-/-) (NSG) mice (HIL mice). These mice are infected with HCV by intravenous injection, and the pathologies are investigated. RESULTS: In this study, we demonstrate that HIL mouse is capable of supporting HCV infection and can present some of the clinical symptoms found in HCV-infected patients including hepatitis, robust virus-specific human immune cell and cytokine responses as well as liver fibrosis and cirrhosis. Similar to results obtained from the analysis of patient samples, the human immune cells, particularly T cells and macrophages, play critical roles during the HCV-associated liver disease development in the HIL mice. Furthermore, our model is demonstrated to be able to reproduce the therapeutic effects of human interferon alpha 2a antiviral treatment. CONCLUSIONS: The HIL mouse provides a model for the understanding of HCV-specific human immune responses and HCV-associated disease pathologies. It could also serve as a platform for antifibrosis and immune-modulatory drug testing.

An unusual presentation of recurrent uterine rupture during pregnancy.

We describe a case of recurrent uterine rupture at the site of a previous rupture. Our patient had a history of right interstitial pregnancy with spontaneous uterine fundal rupture at 18 weeks of pregnancy. During her subsequent pregnancy, she was monitored closely by a senior consultant obstetrician. The patient presented at 34 weeks with right hypochondriac pain. She was clinically stable and fetal monitoring showed no signs of fetal distress. Ultrasonography revealed protrusion of the intact amniotic membranes in the abdominal cavity at the uterine fundus. Uterine rupture is a rare but hazardous obstetric complication. High levels of caution should be exercised in patients with a history of prior uterine rupture, as they may present with atypical symptoms. Ultrasonography could provide valuable information in such cases where there is an elevated risk of uterine rupture at the previous rupture site.

Candida glabrata sepsis associated with chorioamnionitis in an IVF twin pregnancy: Should we deliver?

We report a case of in vitro fertilization (IVF)-acquired Candida glabrata chorioamnionitis successfully treated through systemic maternal antifungal treatment prior to delivery. To the best of our knowledge, this is the first case of its kind in the literature. C. glabrata chorioamnionitis in pregnancy is rare, but the current literature suggests a very high fetal fatality in such cases. It is known to have an association with cervical stitch, amniocentesis, chorionic villous sampling, and assisted reproductive techniques such as IVF. Given the increasing global use of artificial reproductive techniques, it is important to raise awareness of this condition and highlight its potential complications. Early recognition of possible fetal infection could enable early initiation of systemic antifungal treatment. It would be prudent to consider early delivery once fetal maturity is achieved despite normal fetal monitoring.

Social oocyte freezing: a survey among Singaporean female medical students.

AIM: Social oocyte freezing has gained increasing interest worldwide. We conducted a cross-sectional survey on 129 female medical students in Singapore to assess their mindset and attitudes toward fertility and social oocyte freezing. METHODS: An anonymous online survey was conducted among female medical students in Singapore. The desired sample size was 100 participants. Their awareness of the existence of social oocyte freezing was first assessed. An information leaflet was provided subsequently, followed by a more detailed questionnaire. The questions focused on their awareness of age-related fertility decline and their intentions for social oocyte freezing if made available. RESULTS: One hundred and twenty-nine female students participated in the electronic survey, of whom 36.4% had heard of social oocyte freezing. Of these, 70% had personally considered taking up this option. However, after reading the information leaflet, only 48.9% would still consider this option. Of the total, 89.9% considered themselves too old for pregnancy after the age of 35 years, 37.2% would delay family planning for their career, 45.7% would consider social oocyte freezing to postpone family planning for their career, 46.5% would consider oocyte freezing if they had no suitable partners yet, 50.4% may consider freezing their eggs after the age of 30 years and 71.3% may be more amenable to oocyte freezing if government subsidy is available. CONCLUSION: We hypothesize that social oocyte freezing may be a viable option for single young women who wish to delay child-bearing for 'reproductive insurance', so long as this is done with appropriate informed consent with non-directive counseling.

Human natural killer cells control Plasmodium falciparum infection by eliminating infected red blood cells.

Immunodeficient mouse-human chimeras provide a powerful approach to study host-specific pathogens, such as Plasmodium falciparum that causes human malaria. Supplementation of immunodeficient mice with human RBCs supports infection by human Plasmodium parasites, but these mice lack the human immune system. By combining human RBC supplementation and humanized mice that are optimized for human immune cell reconstitution, we have developed RBC-supplemented, immune cell-optimized humanized (RICH) mice that support multiple cycles of P. falciparum infection. Depletion of human natural killer (NK) cells, but not macrophages, in RICH mice results in a significant increase in parasitemia. Further studies in vitro show that NK cells preferentially interact with infected RBCs (iRBCs), resulting in the activation of NK cells and the elimination of iRBCs in a contact-dependent manner. We show that the adhesion molecule lymphocyte-associated antigen 1 is required for NK cell interaction with and elimination of iRBCs. Development of RICH mice and validation of P. falciparum infection should facilitate the dissection of human immune responses to malaria parasite infection and the evaluation of therapeutics and vaccines.

Challenges in the management of a rare case of extensive retroperitoneal haemangioma in a pregnant woman.

Haemangioma of the retroperitoneal space is a rare benign capillary malformation, which can grow significantly in pregnancy due to the multiple associated cardiovascular changes. We herein describe the case of a pregnant woman with an extensive right retroperitoneal haemangioma extending from the level of the renal hilum, across the lateral anterior abdominal wall and into the thigh. We also highlight the challenges faced in the management of the patient's delivery process. To the best of our knowledge, this is the first case of such nature and severity described in the English literature.

Induction of functional human macrophages from bone marrow promonocytes by M-CSF in humanized mice.

Engraftment of human CD34⁺ hematopoietic stem/progenitor cells into immunodeficient mice leads to robust reconstitution of human T and B cells but not monocytes and macrophages. To identify the cause underlying the poor monocyte and macrophage reconstitution, we analyzed human myeloid cell development in humanized mice and found that it was blocked at the promonocyte stage in the bone marrow. Expression of human M-CSF or GM-CSF by hydrodynamic injection of cytokine-encoding plasmid completely abolished the accumulation of promonocytes in the bone marrow. M-CSF promoted the development of mature monocytes and tissue-resident macrophages whereas GM-CSF did not. Moreover, correlating with an increased human macrophages at the sites of infection, M-CSF-treated humanized mice exhibited an enhanced protection against influenza virus and Mycobacterium infection. Our study identifies the precise stage at which human monocyte/macrophage development is blocked in humanized mice and reveals overlapping and distinct functions of M-CSF and GM-CSF in human monocyte and macrophage development. The improved reconstitution and functionality of monocytes/macrophages in the humanized mice following M-CSF expression provide a superior in vivo system to investigate the role of macrophages in physiological and pathological processes.

Cross-sectional pregnancy survey on fertility trends and pregnancy knowledge in Singapore.

AIM: Desire for children is a pertinent national health concern for Singapore due to the falling pregnancy rate. There is an urgent need to conduct a pregnancy survey for our local population to look into our local women's desire for pregnancy and family size, as well as their knowledge of the need for pregnancy supplements, fertility and pregnancy risks with the advanced age of mothers. MATERIAL AND METHODS: A cross-sectional survey was mailed to 300 women in a random sample of the female population in the South West region of Singapore. RESULTS: Three hundred women were invited to participate in our survey. Two hundred and sixty eight women (89.3%) responded. The mean age was 30.7 years (range 16-60). 41.8% were married. One in five women (21.8%) in the reproductive age group (below age 40) did not intend to have children. 70.5% of the women with tertiary education wanted children, compared to 56.4% of women with below-secondary education. Most of the respondents were aware of the risks of pregnancy with increasing maternal age, as well as the importance of folic acid, iron and calcium supplements in pregnancy. CONCLUSION: The present study helps clinicians and policymakers gain an insight into pregnancy issues in Singapore. This is important in formulating population policies and public education programs.