The Role of Regulatory T Cells and Their Therapeutic Potential in Hypertensive Disease of Pregnancy: A Literature Review.

Hypertensive disorders of pregnancy (HDP), including preeclampsia (PE) and gestational hypertension (GH), are major causes of maternal and foetal morbidity and mortality. This review elucidates the role of regulatory T cells (Tregs) in the immunological aspects of HDP and explores their therapeutic potential. Tregs, which play a critical role in maintaining immune homeostasis, are crucial in pregnancy to prevent immune-mediated rejection of the foetus. The review highlights that Tregs contribute to immunological adaptation in normal pregnancy, ensuring foetal acceptance. In contrast, HDP is associated with Treg dysfunction, which is marked by decreased numbers and impaired regulatory capacity, leading to inadequate immune tolerance and abnormal placental development. This dysfunction is particularly evident in PE, in which Tregs fail to adequately modulate the maternal immune response against foetal antigens, contributing to the pathophysiology of the disorder. Therapeutic interventions aiming to modulate Treg activity represent a promising avenue for HDP management. Studies in animal models and limited clinical trials suggest that enhancing Treg functionality could mitigate HDP symptoms and improve pregnancy outcomes. However, given the multifactorial nature of HDP and the intricate regulatory mechanisms of Tregs, the review explores the complexities of translating in vitro and animal model findings into effective clinical therapies. In conclusion, while the precise role of Tregs in HDP is still being unravelled, their central role in immune regulation during pregnancy is indisputable. Further research is needed to fully understand the mechanisms by which Tregs contribute to HDP and to develop targeted therapies that can safely and effectively harness their regulatory potential for treating hypertensive diseases of pregnancy.

In Utero Transplantation of Expanded Autologous Amniotic Fluid Stem Cells Results in Long-Term Hematopoietic Engraftment.

In utero transplantation (IUT) of hematopoietic stem cells (HSCs) has been proposed as a strategy for the prenatal treatment of congenital hematological diseases. However, levels of long-term hematopoietic engraftment achieved in experimental IUT to date are subtherapeutic, likely due to host fetal HSCs outcompeting their bone marrow (BM)-derived donor equivalents for space in the hematopoietic compartment. In the present study, we demonstrate that amniotic fluid stem cells (AFSCs; c-Kit+/Lin-) have hematopoietic characteristics and, thanks to their fetal origin, favorable proliferation kinetics in vitro and in vivo, which are maintained when the cells are expanded. IUT of autologous/congenic freshly isolated or cultured AFSCs resulted in stable multilineage hematopoietic engraftment, far higher to that achieved with BM-HSCs. Intravascular IUT of allogenic AFSCs was not successful as recently reported after intraperitoneal IUT. Herein, we demonstrated that this likely due to a failure of timely homing of donor cells to the host fetal thymus resulted in lack of tolerance induction and rejection. This study reveals that intravascular IUT leads to a remarkable hematopoietic engraftment of AFSCs in the setting of autologous/congenic IUT, and confirms the requirement for induction of central tolerance for allogenic IUT to be successful. Autologous, gene-engineered, and in vitro expanded AFSCs could be used as a stem cell/gene therapy platform for the in utero treatment of inherited disorders of hematopoiesis. Stem Cells 2019;37:1176-1188.

Sheep CD34+ amniotic fluid cells have hematopoietic potential and engraft after autologous in utero transplantation.

Unmatched allogeneic in utero stem cell transplantation (IUSCT) produces poor engraftment unless the fetus has congenital immunodeficiency, probably because of maternal and fetal immune responses to injected cells. We studied the functional hematopoietic potential of transduced green fluorescent protein (GFP+) sheep amniotic fluid (AF) stem cells, before and after autologous IUSCT. CD34+ cells were selected from first trimester sheep AF, transduced overnight, and injected intravenously into NOD-SCID-gamma (NSG) mice. At 3 months, primary recipient bone marrow (BM) was injected into secondary NSG recipients. GFP+ cells were detected in the hematopoietic organs and peripheral blood of primary and secondary recipients at 3 months. Autologous IUSCT (transduced GFP+CD34+AF) was performed in fetal sheep. Six months postnatally, lamb BM was injected into secondary NSG recipients. GFP+ cells were detected in the peripheral blood of primary and secondary recipients. This confirms the hematopoietic potential of AF stem cells supporting the concept of autologous IUSCT to treat congenital hematopoietic disease.

Isolation of esophageal stem cells with potential for therapy.

PURPOSE: Long-gap esophageal atresia represents a significant challenge for pediatric surgeons and current surgical approaches are associated with significant morbidity. A tissue-engineered esophagus, comprising cells seeded onto a scaffold, represents a therapeutic alternative. In this study, we aimed to determine the optimal techniques for isolation and culture of mouse esophageal epithelial cells and to isolate CD34-positive esophageal epithelial stem cells from cadaveric mouse specimens. METHODS: Primary epithelial cells were isolated from mouse esophagi by enzymatic dissociation from the mucosal layer (Dispase, Trypsin/EDTA) using three different protocols. In protocol A, isolated mucosa was minced and incubated with trypsin once. In protocol B, intact mucosal sheets underwent two trypsin incubations yielding a single-cell suspension. In protocol C, intact mucosa explants were plated epithelial side down. Epithelial cells were cultured on collagen-coated wells. RESULTS: Initial findings showed that Protocol B gave the best results in terms of yield, viability, and least contamination with different cell types and microbes. Esophageal epithelial cells isolated using Protocol B were stained for CD34 and sorted using fluorescence-activated cell sorting (FACS). Of the total cells sorted, 8.3% (2-11.3) [%median (range)] were CD34 positive. CONCLUSIONS: Our results demonstrate that mouse esophageal epithelial cells can be successfully isolated from fresh mouse esophagi using two consecutive trypsin incubations of intact mucosal sheets. Furthermore, the cells obtained using this method were successfully stained for CD34, a putative esophageal epithelial stem cell marker. Further research into the factors necessary for the successful proliferation of CD34 positive stem cell lines is needed to progress toward clinical application.

Feticide Before Termination of Pregnancy in Singleton Pregnancy - Trends in England and Wales 2012-2020, a Cross-sectional Study.

Feticide is the practice of inducing fetal demise before the termination of pregnancy. In England and Wales, it is recommended for terminations of pregnancy beyond 21+6 weeks of gestation. This project analyses the trends in feticide in singleton pregnancy in England and Wales between 2012 and 2020. This project was a retrospective study that analysed data extracted from the Health and Social Act 4 (HSA4) forms submitted to the Department of Health and Social Care (DHSC). The data extracted by the DHSC included the prevalence of feticide, methods of feticide and termination, statutory grounds, gestation, service provider, maternal age, ethnicity and obstetric history. In addition, data analysis was carried out to identify trends. Between 2012 and 2020, there were 9310 feticides in England and Wales, undertaken in 0.5% of all abortions. The prevalence of feticide fluctuated; however, there was an overall decrease from 1084 cases in 2012 to 1000 cases in 2020. Intracardiac injection of potassium chloride was the most frequent method of achieving feticide (67.2%). Just over half (55.8%) of feticides took place under Ground E of the Abortion Act 1967, with the main indication being congenital malformations of the nervous system. Two-fifths (40.2%) of feticides took place at 23 weeks, 22.8% at 22 weeks and 13.5% between 20 and 21 weeks. The remainder occurred at later gestations: 17.5% at 24-29 weeks and 5.9% beyond 29 weeks. During our study period, it was more common for feticides to be carried out as part of a medical termination than a surgical termination and 60.3% occurred in NHS hospitals. Women undergoing feticide were mostly aged 30-34 years (38.3%) and of White ethnicity (78.6%). Feticide is an essential component of comprehensive abortion care for women undergoing late second and third-trimester abortions. This study provides insight into how feticide is carried out in England and Wales and demonstrates the effect of the COVID-19 pandemic on reducing feticide prevalence. Future research should analyse in more detail the use of the different methods of feticide.

Perinatal and neurodevelopmental outcomes of fetal isolated ventriculomegaly: a systematic review and meta-analysis.

Background: Isolated fetal ventriculomegaly can have a range of consequences, ranging from mild neurodevelopmental delay to perinatal death; the extent of these consequences often depend on the severity of ventriculomegaly. This systematic review and meta-analysis aims to investigate the impact of the degree of ventricular dilatation on the risk of neurodevelopmental delay and adverse perinatal outcomes in fetuses diagnosed with isolated fetal ventriculomegaly from gestational week 15 onwards. Methods: PubMed, Embase, Scopus and the Cochrane Library were searched electronically to identify studies investigating the prognosis of mild and/or severe isolated fetal ventriculomegaly. Articles were included if they reported neurodevelopmental or perinatal outcomes in fetuses prenatally diagnosed with isolated fetal ventriculomegaly from week 15 of gestation and onwards. Studies were excluded if they reported on non-isolated ventriculomegaly (IVM), failed to specify the degree of ventriculomegaly, were non-English papers, animal studies or published outside of the 21-year period of interest. Study quality was assessed by two independent reviewers using a modified version of the Newcastle-Ottawa Quality Assessment Scale. Ventriculomegaly was defined as either mild or severe when ventricular diameter measured as 10-15 or >15 mm, respectively. Meta-analyses were conducted for adverse neurodevelopmental outcome, intrauterine fetal demise and infant mortality. Results: Following the removal of duplicates, the search yielded 2,452 citations, of which 23 studies were included and 8 were eligible for meta-analysis. There were 767 and 347 cases of mild and severe isolated fetal ventriculomegaly, respectively. Adverse outcomes were consistently reported at a higher rate in severe cases than mild. The relative risks of adverse neurodevelopmental outcome, intrauterine fetal demise and infant mortality were 4.24 [95% confidence interval (CI): 2.46-7.30], 4.46 (95% CI: 1.64-12.11) and 6.02 (95% CI: 1.73-21.00), respectively, upon comparison of mild versus severe cases of isolated fetal ventriculomegaly. Conclusions: The likelihood of adverse neurodevelopmental and perinatal outcomes, including intrauterine and infant mortality, is increased in severe isolated fetal ventriculomegaly compared to mild isolated fetal ventriculomegaly.

Revolutionising healing: Gene Editing's breakthrough against sickle cell disease.

Recent advancements in gene editing illuminate new potential therapeutic approaches for Sickle Cell Disease (SCD), a debilitating monogenic disorder caused by a point mutation in the ß-globin gene. Despite the availability of several FDA-approved medications for symptomatic relief, allogeneic hematopoietic stem cell transplantation (HSCT) remains the sole curative option, underscoring a persistent need for novel treatments. This review delves into the growing field of gene editing, particularly the extensive research focused on curing haemoglobinopathies like SCD. We examine the use of techniques such as CRISPR-Cas9 and homology-directed repair, base editing, and prime editing to either correct the pathogenic variant into a non-pathogenic or wild-type one or augment fetal haemoglobin (HbF) production. The article elucidates ways to optimize these tools for efficacious gene editing with minimal off-target effects and offers insights into their effective delivery into cells. Furthermore, we explore clinical trials involving alternative SCD treatment strategies, such as LentiGlobin therapy and autologous HSCT, distilling the current findings. This review consolidates vital information for the clinical translation of gene editing for SCD, providing strategic insights for investigators eager to further the development of gene editing for SCD.

Placenta as a reservoir of stem cells: an underutilized resource?

INTRODUCTION: Both embryonic and adult tissues are sources of stem cells with therapeutic potential but with some limitations in the clinical practice such as ethical considerations, difficulty in obtaining and tumorigenicity. As an alternative, the placenta is a foetal tissue that can be obtained during gestation and at term, and it represents a reservoir of stem cells with various potential. SOURCES OF DATA: We reviewed the relevant literature concerning the main stem cells that populate the placenta. AREAS OF AGREEMENT: Recently, the placenta has become useful source of stem cells that offer advantages in terms of proliferation and plasticity when compared with adult cells and permit to overcome the ethical and safety concern inherent in embryonic stem cells. In addition, the placenta has the advantage of containing epithelia, haematopoietic and mesenchymal stem cells. These stem cells possess immunosuppressive properties and have the capacity of suppress in vivo inflammatory responses. AREAS OF CONTROVERSY: Some studies describe a subpopulation of placenta stem cells expressing pluripotency markers, but for other studies, it is not clear whether pluripotent stem cells are present during gestation beyond the first few weeks. Particularly, the expression of some pluripotency markers such as SSEA-3, TRA-1-60 and TRA-1-81 has been reported by us, but not by others. GROWING POINTS: Placenta stem cells could be of great importance after delivery for banking for autologous and allogeneic applications. The beneficial effects of these cells may be due to secretion of bioactive molecules that act through paracrine actions promoting beneficial effects. AREAS TIMELY FOR DEVELOPING RESEARCH: Understanding the role of placenta stem cells during pregnancy and their paracrine actions could help in the study of some diseases that affect the placenta during pregnancy.

Regulatory T cell niche in the bone marrow, a new player in Haematopoietic stem cell transplantation.

Challenges in haematopoietic stem cell transplantation such as low bone marrow (BM) engraftment, graft versus host disease (GvHD) and the need for long-term immunosuppression could be addressed using T regulatory cells (Tregs) resident in the tissue of interest, in this case, BM Tregs. Controlling the adverse immune response in haematopoietic stem cell transplantation (HSCT) and minimising the associated risks such as infection and secondary cancers due to long-term immunosuppression is a crucial aspect of clinical practice in this field. While systemic immunosuppressive therapy could achieve reasonable GvHD control in most patients, related side effects remain the main limiting factor. Developing more targeted immunosuppressive strategies is an unmet clinical need and is the focus of several ongoing research projects. Tregs are a non-redundant sub-population of CD4+ T cells essential for controlling the immune homeostasis. Tregs are known to be reduced in number and function in autoimmune conditions. There is considerable interest in these cells as cell therapy products since they can be expanded in vitro and infused into patients. These trials have found Treg therapy to be safe, well-tolerated, and with some early signs of efficacy. However, Tregs are a heterogeneous subpopulation of T cells, and several novel subpopulations have been identified in recent years beyond the conventional thymic (tTregs) and peripheral (pTregs). There is increasing evidence for the presence of resident and tissue-specific Tregs. Bone marrow (BM) Tregs are one example of tissue-resident Tregs. BM Tregs are enriched within the marrow, serving a dual function of immunosuppression and maintenance of haematopoietic stem cells (HSCs). HSCs maintenance is achieved through direct suppression of HSCs differentiation, maintaining a proliferating pool of HSCs, and promoting the development of functional stromal cells that support HSCs. In this review, we will touch upon the biology of Tregs, focusing on their development and heterogeneity. We will focus on the BM Tregs from their biology to their therapeutic potential, focusing on their use in HSCT.

Trends in Termination of Pregnancy for Foetal Urological Abnormalities in England and Wales: a Cross-Sectional Study.

The detection of developmental abnormalities in the foetus is considered an essential component of antenatal screening. Among the most frequently identified sonographically, and possibly one of the easiest recognised, are those affecting the urinary tract, with an incidence of 1-4 in 1000 pregnancies. As such, foetal urological abnormalities represent up to 30% of all prenatally diagnosed congenital anomalies. We analysed information recorded on the Health and Social Act 4 (HSA4) forms submitted to the Department of Health and Social Care (DHSC) for 2015 to 2019. There were 915 cases of termination of pregnancy for foetal urological anomaly between 2015 and 2019 in England and Wales, representing 0.09% of total abortions. There has been a steady increase in cases, from 186 in 2015 to 222 in 2018, followed by a more recent decline in 2019 to 172. All 915 cases were justified under Ground E of The Abortion Act 1967. Most terminations of pregnancy for foetal urological anomaly were carried out at 20 weeks gestation. Isolated urinary tract single diagnoses were the commonest, with megacystis being the most prevalent, followed by bilateral renal agenesis and bilateral cystic kidneys. Nearly a third of cases (32.2%) were performed in women aged 30-34 years, and almost 4/5 of women (78.7%) were of White ethnicity. Foetal urological abnormality is a complex issue affecting a significant minority of pregnant women. When severe abnormalities are detected by prenatal diagnosis, most women choose to terminate the pregnancy.

Suspected twin anemia polycythemia sequence in a dichorionic, diamniotic twin pregnancy: a case report.

BACKGROUND: Twin anemia polycythemia sequence is a rare complication in monochorionic twin pregnancy. CASE PRESENTATION: We describe a case of dichorionic twin pregnancy presenting with suspected twin anemia polycythemia sequence. A 31-year-old White female, on her third pregnancy, had a routine ultrasound scan at 12 weeks gestation, which demonstrated a dichorionic twin pregnancy with one placenta located in the anterior wall and the other in the posterior wall of the uterus. At 21 weeks, a scan demonstrated a 24% growth discordance between the two fetuses with normal Doppler studies and amniotic fluid. At 27 weeks, one twin showed signs of anemia and the other polycythemia; the fetal middle cerebral artery peak systolic velocity was high in the anemic fetus and low in the polycythemic twin (1.8 and 0.5 multiples of the median). An intrauterine blood transfusion was carried out and this increased the fetal hemoglobin concentration in the anemic twin from 3.5 to 12.5 g/dL. At 29 weeks, delivery by cesarean section was carried out because of evidence from middle cerebral artery peak systolic velocity of recurrence of anemia in one twin and worsening polycythemia in the co-twin; at birth the hemoglobin concentrations were 5.6 and 24.9 g/dL, respectively. Histopathological examination confirmed dichorionicity with no communicating vessels between the two placentas. CONCLUSIONS: This is the first case of twin anemia polycythemia sequence in a dichorionic, diamniotic twin pregnancy where intrauterine blood transfusion was used to prolong the pregnancy by almost 2 weeks in a "twin anemia polycythemia sequence-like" setting.

Clinical value of placental examination for paediatricians.

The placenta contains valuable clinical information that is linked to fetal development, neonatal morbidity and mortality, and future health outcomes. Both gross inspection and histopathological examination of the placenta may identify intrinsic or secondary placental lesions, which can contribute directly to adverse neonatal outcomes or indicate the presence of an unfavourable intrauterine environment. Placental examination therefore forms an essential component of the care of high-risk neonates and at perinatal post-mortem examination. In this article, we describe the clinical value of placental examination for paediatricians and perinatal clinicians. We discuss common pathological findings on general inspection of the placenta with photographic examples and provide an overview of the placental pathological examination, including how to interpret key findings. We also address the medico-legal and financial implications of placental examinations and describe current and future clinical considerations for clinicians in regard to placental examination.

Regulatory T cells in the peripheral blood of women with gestational diabetes: a systematic review and meta-analysis.

Background: Gestational diabetes (GDM) affects approximately 14% of pregnancies globally and is associated with short- and long-term complications for both the mother and child. In addition, GDM has been linked to chronic low-grade inflammation with recent research indicating a potential immune dysregulation in pathophysiology and a disparity in regulatory T cells. Objective: This systematic review and meta-analysis aimed to determine whether there is an association between GDM and the level of Tregs in the peripheral blood. Methods: Literature searches were conducted in PubMed, Embase, and Ovid between the 7th and 14th of February 2022. The inclusion criteria were any original studies published in the English language, measuring differentiated Tregs in women with GDM compared with glucose-tolerant pregnant women. Meta-analysis was performed between comparable Treg markers. Statistical tests were used to quantify heterogeneity: τ 2, χ 2, and I 2. Study quality was assessed using a modified version of the Newcastle-Ottawa scale. Results: The search yielded 223 results: eight studies were included in the review and seven in the meta-analysis (GDM = 228, control = 286). Analysis of Tregs across all trimesters showed significantly lower Treg numbers in women with GDM (SMD, -0.76; 95% CI, -1.37, -0.15; I 2 = 90%). This was reflected in the analysis by specific Treg markers (SMD -0.55; 95% CI, -1.04, -0.07; I 2 = 83%; third trimester, five studies). Non-significant differences were found within subgroups (differentiated by CD4+FoxP3+, CD4+CD127-, and CD4+CD127-FoxP3) of both analyses. Conclusion: GDM is associated with lower Treg numbers in the peripheral maternal blood. In early pregnancy, there is clinical potential to use Treg levels as a predictive tool for the subsequent development of GDM. There is also a potential therapeutic intervention to prevent the development of GDM by increasing Treg populations. However, the precise mechanism by which Tregs mediate GDM remains unclear. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42022309796.

Evidence-based management of pregnant women with sickle cell disease in high-income countries.

Globally, patients living with sickle cell disease are now surviving to reproductive age, with life expectancy approaching 50 years in most countries. Thus, reproductive options are now essential for patients living with the condition. However, it can be associated with maternal, delivery, and fetal complications. Outcomes may vary depending on the level of expertise and resources. In this piece we provide an optional guideline for managing sickle cell disease in pregnancy. The therapeutic option of serial exchange prophylactic transfusion has been offered in the context of a clinical trial (TAPS2).

Trends of Selective Fetal Reduction and Selective Termination in Multiple Pregnancy, in England and Wales: a Cross-Sectional Study.

Selective abortion was shown to be increasingly common in England and Wales over a 9-year period, occurring most frequently as twin to singleton reductions in the 1st trimester. We analysed the trends in selective abortion (SA) in multiple pregnancies in England and Wales between 2009 and 2018. This is a cross-sectional study looking at 1143 women with multiple pregnancies in England and Wales undergoing SA. There were a total of 1143 cases of SA between 2009 and 2018 in England and Wales, representing 0.07% of total abortions. There has been a steady increase in cases, from 90 in 2009 to 131 in 2018, with 82.3% justified under ground E of The Abortion Act 1967. The majority of SAs were carried out at 13-19 weeks gestation, and intracardiac injection of potassium chloride was the most prevalent method (75%). Twin to singleton reductions accounted for 59%, the most common form of SAs. Over half of all cases (59%) were performed in women aged 30-39 years, and 84% of all women were of White ethnicity. SA has been an option available for couples diagnosed with multiple pregnancy, especially when there are discordant anomalies. Although SA may decrease multiple pregnancy-related complications, preventative methods must be championed.

Chronic histiocytic intervillositis (CHI): current treatments and perinatal outcomes, a systematic review and a meta-analysis.

Background: Chronic histiocytic intervillositis (CHI) is a rare placental lesion with a high recurrence rate and poor perinatal outcomes. There are currently limited guidelines regarding the diagnosis of this condition in the index pregnancy and treatment where recurrence is suspected. Objective: The primary objective of this systematic review and meta-analysis was to determine the perinatal outcomes of pregnancies affected by chronic histiocytic intervillositis and to what extent they can be improved with treatment. The secondary objective was to assess the relationship between CHI lesion severity and pregnancy loss. Methods: A systematic search of Ovid Embase, Web of Science, Science Direct, PubMed, Ovid Medline, Google Scholar and CINAHL was carried out. Case reports, cohort, case-control and randomised controlled trials (RCT) detailing the perinatal outcomes of CHI pregnancies, both treated and untreated, were included. Results: No RCTs were identified. However, in a review population of 659 pregnancies, with additional 7 in case reports, CHI treatments included aspirin, prednisone, prednisolone, low molecular weight heparin (LMWH), hydroxychloroquine and adalimumab. A descriptive synthesis of data found mixed results for treatments in relation to live birth, miscarriage and fetal growth restriction outcomes. Furthermore, quantitative synthesis of 38 pregnancies revealed a non-significant improvement in live birth rate with CHI targeted treatment (OR 1.79 [95% CI 0.33-9.61] (p=0.50), while meta-analysis of CHI severity in line with pregnancy loss, in a sample of 231 pregnancies, revealed lower odds of pregnancy loss with less severe lesions (OR: 0.17 [0.03-0.80], p=0.03). Conclusions: This systematic review and meta-analysis reinforce notions surrounding the insufficient evidence for CHI treatment. It also strengthens previous hypotheses detailing the positive association between CHI lesion severity and odds of pregnancy loss. Aspirin, LMWH, prednisolone, hydroxychloroquine and adalimumab are candidates with varying levels of weak to moderate evidence supporting their use. Further prospective research is required to obtain robust evidence pertaining to treatment safety and efficacy and optimal drug regimes. Systematic Review Registration: [website], identifier CRD42021237604.

Isolation and freezing of human peripheral blood mononuclear cells from pregnant patients.

To analyze immune cell populations accurately, a large number of Peripheral Blood Mononuclear Cells (PBMCs) must be obtained from blood samples. Traditional manual isolation and SepMateTM isolation of PBMCs consistently yield blood-stained plasma layers and overall low numbers of CD4+ and CD8+ cells. Here, we describe an optimized protocol, using PBS with EDTA to increase PBMC yield from pregnant patients. This protocol enables analysis of CD4+, CD8+, and Regulatory T Cells and is potentially applicable to any immune cell population. For complete details on the use and execution of this protocol, please refer to the SepMateTM website https://www.stemcell.com/products/brands/SepMateTM-pbmc-isolation.html.

Is induced labour in the nullipara associated with more maternal and perinatal morbidity?

PURPOSE: To ascertain any differences in foetomaternal outcomes in induced and spontaneous labour among nulliparous women delivering at term. METHODS: A retrospective matched cohort study consisting of 403 nulliparous women induced at ≥ 292 days and 806 nulliparous women with spontaneous labour at 285-291 days. RESULTS: Compared to those in spontaneous labour, women who had induction of labour were three times more likely to have a caesarean delivery (OR 3.1, 95% CI 2.4-4.1; P < 0.001). Women who had induction of labour were 2.2 times more likely to have oxytocin augmentation (OR 2.2, 95% CI 1.7-2.8; P < 0.001), 3.6 times more likely to have epidural anaesthesia (OR 3.6, 95% CI 2.8-4.6; P < 0.001), 1.7 times more likely to have uterine hyperstimulation (OR 1.7, 95% CI 1.1-2.6), 2 times more likely to have a suspicious foetal heart rate trace (OR 2.0, 95% CI 1.5-2.6), 4.1 times more likely to have blood loss over 500 ml (OR 4.1, 95% CI 2.9-5.5; P < 0.001), and 2.9 times more likely to stay in hospital beyond 5 days (OR 2.9, 95% CI 1.5-5.6; P < 0.001). Babies born to mothers who had induction of labour were significantly more likely to have an Apgar score of <5 at 5 min and an arterial cord pH of <7.0. CONCLUSION: Compared to those with spontaneous labour, nulliparous women with induced labours are more likely to have uterine hyperstimulation, caesarean delivery, and babies with low Apgar scores. Nulliparous women should be made aware of this, as well as potential risks of expectant management during counseling.

The Theoretical Basis of In Utero Hematopoietic Stem Cell Transplantation and Its Use in the Treatment of Blood Disorders.

Since its conception, prenatal therapy has been successful in correction of mainly anatomical defects, although the range of application has been limited. Research into minimally invasive fetal surgery techniques and prenatal molecular diagnostics has facilitated the development of in utero stem cell transplantation (IUT)-a method of delivering healthy stem cells to the early gestation fetus with the hope of engraftment, proliferation, and migration to the appropriate hematopoietic compartment. An area of application that shows promise is the treatment of hematopoietic disorders like hemoglobinopathies. The therapeutic rationale of IUT with hematopoietic stem cells (HSCs) is based on the proposed advantages the fetal environment offers based on its unique physiology. These advantages include the immature immune system facilitating the development of donor-specific tolerance, the natural migration of endogenous hematopoietic cells providing space for homing and engraftment of donor cells, and the fetal environment providing HSCs with the same opportunity to survive and proliferate regardless of their origin (donor or host). Maternal immune tolerance to the fetus and placenta also implies that the maternal environment could be accepting of donor cells. In theory, the fetus is a perfect recipient for stem cell transplant. Clinically, however, IUT is yet to see widespread success calling into question these assumptions of fetal physiology. This review aims to discuss and evaluate research surrounding these key assumptions and the clinical success of IUT in the treatment of thalassemia.