A national cohort study and confidential enquiry to investigate ethnic disparities in maternal mortality

Background Ethnic disparities in maternal mortality were first documented in the UK in the early 2000s but are known to be widening. This project aimed to describe the women who died in the UK during or up to a year after the end of pregnancy, to compare the quality of care received by women from different aggregated ethnic groups, and to identify any structural or cultural biases or discrimination affecting their care. Methods National surveillance data was used to identify all 1894 women who died during or up to a year after the end of pregnancy between 2009 and 18 in the UK. Their characteristics and causes of death were described. A Confidential Enquiry was undertaken to describe the quality of care women received. The care of a stratified random sample of 54 women who died during or up to a year after the end of pregnancy between 2009 and 18, (18 from the aggregated group of Black women, 19 from the Asian aggregated group and 17 from the White aggregated group) was re-examined specifically to describe any structural or cultural biases or discrimination identified. Findings There were no major differences causes of death between women from different aggregated ethnic groups, with cardiovascular disease the leading cause of death in all groups. Multiple areas of bias were identified in the care women received, including lack of nuanced care (notable amongst women from Black aggregated ethnic groups who died), microaggressions (most prominent in the care of women from Asian aggregated ethnic groups who died) and clinical, social and cultural complexity (evident across all ethnic groups). Interpretation This confidential enquiry suggests that multiple structural and other biases exist in UK maternity care. Further research on the role of microaggressions is warranted. Funding This research is funded by the National Institute for Health Research (NIHR) Policy Research Programme, conducted through the Policy Research Unit in Maternal and Neonatal Health and Care, PR-PRU-1217–21,202. MK is an NIHR Senior Investigator. SK is part funded and FCS fully funded by the National Institute for Health Research (NIHR) Applied Research Centre (ARC) West Midlands. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Macroprolactinomas and Nonfunctioning Pituitary Adenomas and Pregnancy Outcomes

Objective To examine the monitoring, management, and outcomes of pituitary tumors in pregnancy. Methods A national, prospective, observational, population-based case series study was conducted in all UK consultant-led obstetric units over 3 years using the UK Obstetric Surveillance System. In order to evaluate rates of adverse pregnancy outcomes, women with a macroprolactinoma (≥10mm) or non-functioning pituitary adenoma, diagnosed before or during pregnancy, were compared to 2 comparison groups: 1) a UKOSS cohort with singleton (n=2205) or twin (n=27) pregnancy and 2) data from the Office of National Statistics (n=2,703,102). Main outcome measures were the incidence, management, and frequency of adverse maternal and offspring outcomes of pituitary tumors in pregnancy. Results There were 71 confirmed cases of pituitary tumors in pregnancy (49 macrolactinoma, 16 non-functioning adenomas, 3 acromegaly, 3 Cushing’s disease). The women with pituitary tumors were 4 years older than comparison women (P<0.001). None of the 9 women treated with surgery or radiotherapy prior to pregnancy had symptomatic tumor expansion. This occurred in 6 out of 40 women with macroprolactinomas and 1 out of 7 non-functioning adenomas diagnosed before conception, and in 3 out of 5 women with non-functioning adenomas diagnosed in pregnancy. Two women had pituitary apoplexy, both of whom also had symptoms of expansion of tumor or surrounding pituitary tissue. To within the level of accuracy possible, there was no evidence that pituitary tumors were associated with adverse pregnancy outcomes (pregnancy-induced hypertension, preeclampsia, preterm labor, stillbirth). Women with non-functioning adenomas were more likely to have cesarean section compared to controls (RR 2.06, CI 1.26-3.36, p = 0.035). Conclusions The majority of women with macroprolactinomas and non-functioning adenomas have good pregnancy outcomes. Non-functioning pituitary adenomas occur more commonly in pregnancy than previously thought, and can present de novo with symptoms of pituitary expansion in pregnancy

Rheumatic mitral valve disease in pregnancy

A 32-year-old Nepalese woman with known rheumatic mitral valve disease presented 17 weeks into her first pregnancy with exertional breathlessness and wheezing, leading to expectoration of foamy pink liquid. Her history included percutaneous balloon mitral valvotomy at the age of 25 years, after which she had remained asymptomatic and fully active. She had three episodes of acute pulmonary oedema and was transferred to a tertiary centre for further management. An echocardiogram suggested severe mitral stenosis (mitral valve area 1.0 cm2) and pulmonary hypertension (mean pulmonary artery pressure 87 mmHg). She had further episodes of pulmonary oedema despite maximal medical therapy with diuretics, cardioselective beta blockers (dose limited because of systolic hypotension), digoxin, nitrates and anticoagulation. At 21 weeks' gestation, an emergency St Jude metallic valve was implanted. Unfortunately, intrauterine death occurred 2 days postoperatively, likely caused by pre-eclampsia or haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome. The patient recovered well and continues on warfarin and a small dose of beta blocker. </jats:p