Outcomes of Uterine Rupture in the Setting of the Unscarred Compared With the Scarred Uterus.

Uterine rupture is a rare obstetric complication that is associated with maternal and neonatal morbidity and mortality. The aim of this study was to examine uterine rupture and its outcomes in the setting of the unscarred compared with the scarred uterus. A retrospective observational cohort study was performed examining all cases of uterine rupture in three tertiary care hospitals in Dublin, Ireland, over a 20-year period. The primary outcome was perinatal mortality rate with uterine rupture, which was 11.02% (95% CI 6.5-17.3). There was no significant difference in perinatal mortality between cases of scarred and unscarred uterine rupture. Unscarred uterine rupture was associated with higher maternal morbidity , defined as major obstetric hemorrhage or hysterectomy.

Drug use in pregnancy in Ireland's capital city: A decade of trends and outcomes.

OBJECTIVE: The aim of this study was to present contemporary trends in opiate use disorder (OUD) and substance use in pregnancy in Ireland, with associated obstetric outcomes, over the last ten years. STUDY DESIGN: This retrospective observational cohort study was conducted at an Irish tertiary maternity unit. All women with OUD or substance use in pregnancy delivered under this service between 2010 and 2019 were included. Drug-exposure was self-reported. Data was collected by combining electronic and hand-held patient records. Trends and outcomes were analysed by year of delivery. Approval for the study was granted by the institution's clinical governance committee. RESULTS: Of the 82,669 women delivered, 525 had OUD or substance use in pregnancy (1 in every 160 women booking). 11.6% were homeless, 20.0% were in full-time employment and 91.0% smoked tobacco in pregnancy. 66.3% had a history of psychiatric disorders. Over the ten years, there was a significant reduction in women delivered with OUD or substance use in pregnancy (0.8 % to 0.4 %, RR 0.55, 95 % CI 0.36-0.85), significant reduction in the proportion of women on Opioid-Substitute-Treatment (OST, RR 0.66 95 % CI 0.51-0.87) and an increase in mean maternal age (30.7to32.0 years). Rates of cocaine and cannabis consumption increased (20.6 %, RR 3.8, 95 % CI 1.57-9.44: 24.0 %, RR 3.7, 95 % CI 1.58-8.86 respectively). The maternal mortality rate was 380.9:100,000 births. The perinatal mortality rate was 15.6:1000 births. The preterm birth rate was 17.9 %, with a mean birth weight of 2832 g. The rate of NICU admission was 52.0 % and the mean length of stay was 22.4 days. Amongst the smaller OUD population, the rate of NICU admission for Neonatal Abstinence Syndrome (NAS) and treatment for NAS increased over the study timeframe (36.0 %, RR 2.97, 95 % CI 1.86-4.75: 28.5 %, RR 2.92, 95 % CI 1.70-5.0 respectively). CONCLUSIONS: The obstetric population attending an Irish antenatal service with opiate use disorder or substance exposure is reducing in size with older patients, less opioid substitute therapy and increasing cocaine and cannabis use. These women have high rates of maternal and perinatal morbidity and mortality. Specialist antenatal addiction services, coordinated by the drug-liaison midwife, are critical in adapting care to respond to this dynamic and vulnerable patient cohort.

Midwives' personal and professional attitudes towards women's delivery choices, interventions and neonatal care.

OBJECTIVES: Caesarean section (CS) rates in middle- and high-income countries are rising partly due to maternal request. This study aimed to explore the personal and professional attitudes of midwives and nurses towards women's delivery choices, interventions and neonatal care. METHODS: Midwifery and nursing staff at the Coombe hospital were asked to complete a questionnaire concerning decisions for elective CS and neonatal care. The midwives' responses were divided into multiparous and nulliparous according to their own parity. RESULTS: Multiparae and nulliparae did not differ on their personal preferences for their own baby. Only 3% wanted an elective CS in a normal, healthy pregnancy but this increased to 80.2% when there was a breech presentation and 42% if the estimated fetal weight was >4.5 kg. These numbers and trends were very close to the midwives' professional recommendations under the same circumstances. The lower threshold for full resuscitation and ICU care was at 23 and 24 weeks gestation for both personal and professional recommendations. In the case of severely premature babies or babies with a poor prognosis, 54% stated that the approach to neonatal care was correct. CONCLUSIONS: Overall, midwives' professional views reflected what they would want for themselves and their babies. Only 3% recommended an elective CS in a normal, healthy pregnancy making it unlikely that midwives' attitudes are driving the rise in CS rates in Ireland.

Genetically defined individual reference ranges for tryptase limit unnecessary procedures and unmask myeloid neoplasms.

Serum tryptase is a biomarker used to aid in the identification of certain myeloid neoplasms, most notably systemic mastocytosis, where basal serum tryptase (BST) levels >20 ng/mL are a minor criterion for diagnosis. Although clonal myeloid neoplasms are rare, the common cause for elevated BST levels is the genetic trait hereditary α-tryptasemia (HαT) caused by increased germline TPSAB1 copy number. To date, the precise structural variation and mechanism(s) underlying elevated BST in HαT and the general clinical utility of tryptase genotyping, remain undefined. Through cloning, long-read sequencing, and assembling of the human tryptase locus from an individual with HαT, and validating our findings in vitro and in silico, we demonstrate that BST elevations arise from overexpression of replicated TPSAB1 loci encoding canonical α-tryptase protein owing to coinheritance of a linked overactive promoter element. Modeling BST levels based on TPSAB1 replication number, we generate new individualized clinical reference values for the upper limit of normal. Using this personalized laboratory medicine approach, we demonstrate the clinical utility of tryptase genotyping, finding that in the absence of HαT, BST levels >11.4 ng/mL frequently identify indolent clonal mast cell disease. Moreover, substantial BST elevations (eg, >100 ng/mL), which would ordinarily prompt bone marrow biopsy, can result from TPSAB1 replications alone and thus be within normal limits for certain individuals with HαT.

Hyperbaric effects on cold stored whole blood following a military dive mission profile.

BACKGROUND: Whole blood (WB) is carried by special operations forces as part of a remote damage control resuscitation strategy. The effects of an underwater mission on the quality and coagulation profile of WB were simulated by exposure to hyperbaric pressures in a chamber. METHODS: WB units collected in CPDA-1 were exposed to three different combinations of hyperbaric pressure and duration of exposure: Group A 153.52 kPa (15.24 msw; 1.52 atm) for 4 h; n = 9, Group B 506.63 kPa (50.29 msw; 5.00 atm) for 1 h; n = 9, Group C 153.52 kPa (15.24 msw; 1.52 atm) for 1 h; n = 7. The following parameters were measured on each unit: prothrombin time/international normalized ratio, activated partial thromboplastin time, thromboelastography and concentration determinations of platelets, lactate, fibrinogen, and lactate dehydrogenase. Each sample underwent baseline, prepressurization, immediate postpressurization, and 6 h postpressurization laboratory testing. RESULTS: Six hours following hyperbaric exposure, the lactate concentration in group C was higher than prepressurization measurement and the platelet concentration in Group A was lower than prepressurization measurement. There were no changes in any of the other analyzed biochemical, coagulation and thromboelastogram parameters following exposure to hyperbaric stress. DISCUSSION: These data suggest that pressurization of WB up to 5 atm did not impact parameters tested. Changes observed in lactate and platelet count need further study, as well as complementary testing of red blood cell integrity. Further investigation of the hyperbaric extremes is necessary to determine if there is a damage inducing pressure to which WB should not be exposed.

Resolving the genetics of human tryptases: implications for health, disease, and clinical use as a biomarker.

PURPOSE OF REVIEW: To discuss our evolving understanding of the genetic variation in human tryptases and recent advances in associated clinical phenotypes. RECENT FINDINGS: Serum tryptase levels have long been used as biomarkers in clinical practice to diagnose mast cell-associated disorders and mast cell-mediated reactions but the contribution of specific secreted isoforms of human tryptases and their role(s) in health and disease has only recently begun to be illuminated. It is now recognized that hereditary alpha-tryptasemia (HαT) is a common genetic trait and the commonest cause for elevated basal serum tryptase (BST), where it can both contribute to mast cell-associated phenotypes, and potentially confound their correct diagnosis. Expression of different tryptase isoforms is now recognized to be associated with specific clinical phenotypes including clonal and nonclonal mast cell-associated disorders as well as certain asthma endotypes. These disparate impacts on clinical disorders may result from differences in enzymatic activities of mature α-tryptases and ß-tryptases, and the unique substrate profile and stability of heterotetrameric mature α/ß-tryptases recently described to naturally occur. SUMMARY: Variable copy number and isoform expression of tryptases differentially impact diseases and reactions associated with mast cells in humans. Recent advances in understanding of genetics governing BST levels have refined our understanding and the clinical use of this biomarker. In the future, incorporation of tryptase genotyping will likely be integral to the work-up and trial design of patients with phenotypes impacted by mast cells ranging from asthma to mastocytosis.

Assessment of antenatal anxiety, depression and obsessive-compulsive disorder in pregnant women in the COVID-19 era.

OBJECTIVE: To assess the mental health of pregnant women, with reference to anxiety, depression and obsessive-compulsive (OC) symptoms, during the COVID-19 pandemic. METHODS: A cross-sectional survey was conducted in Ireland during the third wave of the pandemic between February and March 2021. Psychiatric, social and obstetric information was collected from pregnant women in a Dublin maternity hospital, alongside self-reported measures of mental health status. RESULTS: Of 392 women responding, 23.7% had anxiety, scoring >9 for GAD-7 (7-item generalised anxiety disorder), 20.4% had depression, scoring >9 for PHQ-9 (9-item depression screening tool: Patient health questionnaire) and 10.3% had obsessive-compulsive disorder (OCD), scoring >13 for Yale-Brown obsessive-compulsive scale symptom checklist (Y-BOCS). Amongst self-reported OCD symptoms, there was a preponderance for obsessions rather than compulsions. Of 392 women, 36.2% described their mental health as worse during the pandemic, most frequently describing symptoms of anxiety and sleep disturbance. When analysed against test scores, self-reported worsening of mental health was significantly associated with higher scores on the GAD-7, PHQ-9 and Y-BOCS scales. The three scores were positively interrelated. Poor mental health scores were associated with self-reported strain in relationship with the baby's father, and current or previous history of mental illness. CONCLUSION: This study found high levels of depression, anxiety and OC symptoms amongst pregnant women during COVID-19. This highlights the vulnerability of this group to mental illness and the importance of enhanced screening and support during pandemics.

Small intestinal immunopathology and GI-associated antibody formation in hereditary alpha-tryptasemia.

BACKGROUND: Hereditary alpha-tryptasemia (HαT) is characterized by elevated basal serum tryptase due to increased copies of the TPSAB1 gene. Individuals with HαT frequently present with multisystem complaints, including anaphylaxis and seemingly functional gastrointestinal (GI) symptoms. OBJECTIVE: We sought to determine the prevalence of HαT in an irritable bowel syndrome cohort and associated immunologic characteristics that may distinguish patients with HαT from patients without HαT. METHODS: Tryptase genotyping by droplet digital PCR, flow cytometry, cytometry by time-of-flight, immunohistochemistry, and other molecular biology techniques was used. RESULTS: HαT prevalence in a large irritable bowel syndrome cohort was 5% (N = 8/158). Immunophenotyping of HαT PBMCs (N ≥ 27) revealed increased total and class-switched memory B cells. In the small bowel, expansion of tissue mast cells with expression of CD203c, HLA-DR, and FcεRI, higher intestinal epithelial cell pyroptosis, and increased class-switched memory B cells were observed. IgG profiles in sera from individuals with HαT (N = 21) significantly differed from those in individuals with quiescent Crohn disease (N = 20) and non-HαT controls (N = 19), with increased antibodies directed against GI-associated proteins identified in individuals with HαT. CONCLUSIONS: Increased mast cell number and intestinal epithelial cell pyroptosis in the small intestine, and class-switched memory B cells in both the gut and peripheral blood associated with IgG reactive to GI-related proteins, distinguish HαT from functional GI disease. These innate and adaptive immunologic findings identified in association with HαT are suggestive of subclinical intestinal inflammation in symptomatic individuals.

External cephalic version - A 10-year review of practice.

INTRODUCTION: Following the term breech trial (TBT), the incidence of Caesarean section secondary to breech presentations increased, from 76.9 % to 89.7 %. External Cephalic Version (ECV) is a safe effective method to reduce non-cephalic presentation at time of delivery. METHODS: Retrospective audit of all the ECV procedures performed at a tertiary women's hospital between Jan 2010 and Jan 2020. RESULTS: The success rate of ECV was 54.5 %. The rate of vaginal birth following successful ECV was 73.6 % and rate of Caesarean 26.4 %, compared to 96.4 % for those with unsuccessful ECV (P < 0.0001). Factors found to be associated with increased success rates was the use of Intravenous terbutaline (P = 0.03), fetal birth weight ≥3.5 kg (P = 0.0001) and when the procedure is performed by an experienced operator who performed over 20 ECV procedures (P < 0.0001). CONCLUSION: ECV is a safe and effective procedure to reduce Caesarean section rates secondary to breech presentation. A dedicated ECV clinic with experienced operators and the use of intravenous terbutaline could improve success rate of ECV and reduce the number of Caesareans for breech presentation.

Heritable risk for severe anaphylaxis associated with increased α-tryptase-encoding germline copy number at TPSAB1.

BACKGROUND: An elevated basal serum tryptase level is associated with severe systemic anaphylaxis, most notably caused by Hymenoptera envenomation. Although clonal mast cell disease is the culprit in some individuals, it does not fully explain this clinical association. OBJECTIVE: Our aim was to determine the prevalence and associated impact of tryptase genotypes on anaphylaxis in humans. METHODS: Cohorts with systemic mastocytosis (SM) and venom as well as idiopathic anaphylaxis from referral centers in Italy, Slovenia, and the United States, underwent tryptase genotyping by droplet digital PCR. Associated anaphylaxis severity (Mueller scale) was subsequently examined. Healthy volunteers and controls with nonatopic disease were recruited and tryptase was genotyped by droplet digital PCR and in silico analysis of genome sequence, respectively. The effects of pooled and recombinant human tryptases, protease activated receptor 2 agonist and antagonist peptides, and a tryptase-neutralizing mAb on human umbilical vein endothelial cell permeability were assayed using a Transwell system. RESULTS: Hereditary α-tryptasemia (HαT)-a genetic trait caused by increased α-tryptase-encoding Tryptase-α/ß1 (TPSAB1) copy number resulting in elevated BST level-was common in healthy individuals (5.6% [n = 7 of 125]) and controls with nonatopic disease (5.3% [n = 21 of 398]). HαT was associated with grade IV venom anaphylaxis (relative risk = 2.0; P < .05) and more prevalent in both idiopathic anaphylaxis (n = 8 of 47; [17%; P = .006]) and SM (n = 10 of 82 [12.2%; P = .03]) relative to the controls. Among patients with SM, concomitant HαT was associated with increased risk for systemic anaphylaxis (relative risk = 9.5; P = .007). In vitro, protease-activated receptor-2-dependent vascular permeability was induced by pooled mature tryptases but not α- or ß-tryptase homotetramers. CONCLUSIONS: Risk for severe anaphylaxis in humans is associated with inherited differences in α-tryptase-encoding copies at TPSAB1.

Trends in private maternity care in Ireland's capital during and after the Great Economic Recession 2009-2017.

BACKGROUND: Maternity care in hospitals in the Republic of Ireland is funded by a hybrid of public finance and private health insurance. AIMS: The aim of this longitudinal observational study was to investigate the annual trends in maternity care from 2009 to 2017 during and after the Great Economic Recession. METHODS: All women who delivered a singleton baby weighing ≥ 500 g during the 9 years (2009-2017) were included. Detailed clinical and sociodemographic details were computerised at the first antenatal visit by a trained midwife. Women who delivered their first baby during the study were analysed longitudinally if they delivered again during the 9 years. RESULTS: The mean age of the 73,266 women was 31.3 ± 5.6 years, 40.1% were nulliparas, and 70.3% were Irish-born. Overall, 75.2% opted for the public, 10.8% for the semi-private, and 14.0% for the private package of maternity care. Over the 9 years, the number of women choosing private and semi-private care decreased by 21.6% and 35.3%, respectively, whereas the number of women using public care increased by 12.3%. Most women opted for the same package of care in subsequent pregnancies. CONCLUSIONS: Ireland's recent economic recession was accompanied by an overall decrease in the number of women choosing private maternity care after 2009. Furthermore, economic recovery with increasing female employment after 2012 was not associated with a recovery in demand for private care. These findings have important implications for healthcare policies and for the future organisation and funding of our maternity services.

The impact of the Covid-19 pandemic on maternity services: A review of maternal and neonatal outcomes before, during and after the pandemic.

OBJECTIVE: To explore any apparent trends in maternal or neonatal outcomes during the Covid-19 pandemic by comparing the maternity outcomes before, during and after the pandemic. STUDY DESIGN: A retrospective review was performed of maternity statistics recorded on the hospital database of a large tertiary referral centre in Dublin with over 8000 deliveries per annum from 1st January to 31st July 2020. This time period represented the months prior to, during the peak and following the pandemic in Ireland. RESULTS: There was no correlation between the monthly number of Covid deaths and the monthly number of perinatal deaths (r = 0.465, NS), preterm births (r = 0.339, NS) or hypertensive pregnancies (r = 0.48, NS). Compared to the combined numbers for the same month in 2018 and 2019, there were no significant changes in perinatal deaths or preterm births in the months when Covid deaths were at their height. The rate of preterm birth was significantly less common in January-July 2020 compared to January-July in 2018/2019 (7.4 % v 8.6 %, chi-sq 4.53, P = 0.03). CONCLUSION: The was no evidence of a negative impact of the Covid-19 pandemic on maternity services, as demonstrated by maternal and neonatal outcomes.

Caesarean section rates in women in the Republic of Ireland who chose to attend their obstetrician privately: a retrospective observational study.

BACKGROUND: Caesarean section (CS) rates are increasing and there are wide variations in rates internationally and nationally. There is evidence that women who attend their obstetrician privately have a higher incidence of CS than those who attend publicly. The purpose of this observational study was to further investigate why CS rates may be higher in women who chose to attend their obstetrician privately. METHODS: This study analysed data collected as part of the clinical records by midwives at the woman's first antenatal appointment in a large European maternity hospital. All women who delivered between the years 2009 and 2017 were included. Data were analysed both cross-sectionally and longitudinally. RESULTS: Overall, 73,266 women had a singleton pregnancy and 1830 had a multiple pregnancy. Of the packages of maternity care, 75.2% chose public, 10.8% chose semiprivate and 14.0% chose private. During the study, 11,991 women attended the hospital for their first and second pregnancies. Overall, women who attended privately were older and had higher proportions of infertility treatment and history of miscarriage (all p < 0.001) compared to those publicly-funded. Private patients were more likely to have a history of infertility, a history of miscarriage, a multiple pregnancy and to be ≥35 yrs. They had lower rates of obesity, smoking and illicit drug use in pregnancy (all p < 0.001). In women who chose private care, the overall rate of CS was higher compared to women choosing publicly-funded (42.7% vs 25.3%, p < 0.001) The increase was due to an increase in elective rather than emergency CS. The increase in elective CS fell after adjustment for clinical risks. In the longitudinal analysis, 89.7% chose the same package second time around. Women who changed from public to private care for the second pregnancy were more likely to have had a previous emergency CS or admission to the Neonatal Unit. CONCLUSIONS: This study suggests that the increased CS rate in women privately insured may be attributed, in part, to the fact that women who can afford health insurance choose continuity of care from a senior obstetrician because they are risk adverse and wish to have the option of an elective CS.

Hymenoptera venom-induced anaphylaxis and hereditary alpha-tryptasemia.

PURPOSE OF REVIEW: To discuss the association between the common dominantly inherited genetic trait hereditary alpha-tryptasemia (HαT) and hymenoptera venom-induced anaphylaxis (HVA). RECENT FINDINGS: Elevated BST has been correlated with more severe systemic anaphylaxis in humans in a number of settings - most notably in HVA. Clonal mast cell disease, in particular, systemic mastocytosis, is frequently associated with elevated BST, and is a major risk factor for severe HVA. However, clonal mast cell diseases are believed to be rare, whereas HVA is relatively more common. HαT affects an estimated 3-5% of Western populations and is the common cause for elevated BST in these individuals. An association between HαT and severe HVA, as well as clonal mast cell disease has recently been demonstrated wherein this trait modifies reaction severity in venom allergic individuals. A mechanism underlying this association has been proposed through the identification of naturally occurring heterotetrameric tryptases and characterization of their unique physical attributes. SUMMARY: Here we discuss the long-standing association between elevated BST and HVA severity, how HαT fits into this landscape, and review the clinical and mechanistic evidence that supports HαT as a modifier of HVA.

Impaired angiogenesis and extracellular matrix metabolism in autosomal-dominant hyper-IgE syndrome.

There are more than 7000 described rare diseases, most lacking specific treatment. Autosomal-dominant hyper-IgE syndrome (AD-HIES, also known as Job's syndrome) is caused by mutations in STAT3. These patients present with immunodeficiency accompanied by severe nonimmunological features, including skeletal, connective tissue, and vascular abnormalities, poor postinfection lung healing, and subsequent pulmonary failure. No specific therapies are available for these abnormalities. Here, we investigated underlying mechanisms in order to identify therapeutic targets. Histological analysis of skin wounds demonstrated delayed granulation tissue formation and vascularization during skin-wound healing in AD-HIES patients. Global gene expression analysis in AD-HIES patient skin fibroblasts identified deficiencies in a STAT3-controlled transcriptional network regulating extracellular matrix (ECM) remodeling and angiogenesis, with hypoxia-inducible factor 1α (HIF-1α) being a major contributor. Consistent with this, histological analysis of skin wounds and coronary arteries from AD-HIES patients showed decreased HIF-1α expression and revealed abnormal organization of the ECM and altered formation of the coronary vasa vasorum. Disease modeling using cell culture and mouse models of angiogenesis and wound healing confirmed these predicted deficiencies and demonstrated therapeutic benefit of HIF-1α-stabilizing drugs. The study provides mechanistic insights into AD-HIES pathophysiology and suggests potential treatment options for this rare disease.