Genetically predicted body mass index and maternal outcomes of pregnancy: A two-sample Mendelian randomisation study.

OBJECTIVE: Observational studies have described associations between obesity and adverse outcomes of pregnancy but observational results are liable to influence by residual confounding. Mendelian randomisation (MR) leverages the 'natural' genetic randomisation to risk of an exposure occurring at allele assortment and conception. Similar to randomisation in a clinical trial, this limits the potential for the influence of confounding. DESIGN: A two-sample MR study. SETTING: Summary statistics from published genome wide association studies (GWAS) in European ancestry populations. POPULATION OR SAMPLE: Instrumental variants for body mass index (BMI) were obtained from a study on 434 794 females. METHODS: Inverse-variance weighted MR was used to assess the association between BMI and all outcomes. Sensitivity analyses with weighted median and MR-Egger were also performed. MAIN OUTCOME MEASURES: Female-specific genetic association estimates for outcomes were extracted from the sixth round of analysis of the FINNGEN cohort data. RESULTS: Higher genetically predicted BMI was associated with higher risk of pre-eclampsia (odds ratio [OR] per standard deviation 1.68, 95% confidence interval [CI] 1.46-1.94, P = 8.74 × 10-13 ), gestational diabetes (OR 1.67, 95% CI 1.46-1.92, P = 5.35 × 10-14 ), polyhydramnios (OR 1.40, 95% CI 1.00-1.96, P = 0.049). There was evidence suggestive of a potential association with higher risk of premature rupture of membranes (OR 1.16, 95% CI 1.00-1.36, P = 0.050) and postpartum depression (OR 1.12, 95% CI 0.99-1.27, P = 0.062). CONCLUSIONS: Higher genetically predicted BMI is associated with marked increase in risk of pre-eclampsia, gestational diabetes and polyhydramnios. The relation between genetically predicted BMI and premature rupture of membranes and postpartum depression should be assessed in further studies. Our study supports efforts to target BMI as a cardinal risk factor for maternal morbidity in pregnancy.

Interventions to enhance pre-pregnancy care for women with type 2 diabetes: A systematic review of the literature.

AIMS: The aim of the study was to examine the content and impact of interventions that have been used to increase the uptake of pre-pregnancy care for women with type 2 diabetes, and their impact on maternal and fetal outcomes. METHODS: A systematic search of multiple databases was conducted in November 2021, and updated July 2022, to identify studies assessing interventions to enhance pre-pregnancy care for women with type 2 diabetes. Over 10% of articles were screened by two reviewers at title and abstract phase, after which all selected full-text articles were screened by two reviewers. Quality assessment was conducted using the Critical Appraisal Skills Programme checklist for cohort studies. Meta-analysis was not possible due to study heterogeneity; therefore, narrative synthesis was conducted. RESULTS: Four eligible cohort studies were identified. The conclusions able to be drawn by this review were limited as women with type 2 diabetes (n = 800) were in the minority in all four studies (35%-40%) and none of the interventions were exclusively tailored for them. The uptake of pre-pregnancy care was lower in women with type 2 diabetes (8%-10%) compared with other participant groups in the studies. Pregnancy preparation indicators generally improved among all groups exposed to pre-pregnancy care, with varying impact on pregnancy outcomes. CONCLUSIONS: This review demonstrates that previous interventions have had a limited impact on pre-pregnancy care uptake in women with type 2 diabetes. Future studies should focus on tailored interventions for improving pre-pregnancy care for women with type 2 diabetes, particularly those from ethnic minorities and living in poorer communities.

MBRRACE in simulation: an evaluation of a multi-disciplinary simulation training for medical emergencies in obstetrics (MEmO).

The majority of maternal deaths in the UK are due to pre-existing or new-onset medical conditions, known as 'indirect deaths'. The MBRRACE report identified serious gaps in clinicians' human factors skills, including communication, leadership and teamwork, which contributed to maternal death. In response, we developed the first multi-disciplinary simulation-based training programme designed to address Medical Emergencies in Obstetrics (MEmO). Employing a mixed methods design, this study evaluated the educational impact of this training programme on the healthcare staff (n = 140), including the medical doctors (n = 91) and the midwives (n = 49). The training improved participants' clinical management of medical deterioration in pregnancy (p=.003) alongside improving their human factors skills (p=.004). Furthermore, participants reported the translation of these skills to their routine clinical practice. This flexible training is responsive to the changing national needs and contextualises the MBRRACE findings for healthcare staff. It is a promising avenue for reducing the rates of in-direct death in pregnancy. Impact statement What is already known on this subject? The majority of maternal deaths in the UK are due to pre-existing or new-onset medical conditions. The management of medical conditions in pregnancy relies on a multi-professional approach. However, serious gaps in clinicians' human factors skills, highlighted by the MBRRACE report, may contribute to maternal death. What do the results of this study add? This study evaluated the first multi-disciplinary, simulation-based training programme designed to address Medical Emergencies in Obstetrics (MEmO). Training significantly improved participants' management of medical deterioration in pregnancy and human factors skills, particularly in the areas of leadership, communication and teamwork. Moreover, the participants learning translated into their clinical practice. What are the implications of these findings for clinical practice and/or further research? The delivery of multi-disciplinary team training for all healthcare staff involved in the complex management of medical conditions in pregnancy can help develop a greater understanding of others' professional roles, and demonstrate the importance of interprofessional teamwork. Furthermore, it provides the space to reflect on team working approaches, including the leadership and professional autonomy, and their potential impact on patient care. Future research should evaluate the impact of this training on the objective outcome measures of medical emergencies in pregnancy.

Problem based review: the pregnant woman presenting to the AMU with palpitations.

Pregnant patients commonly present to the acute medical team with symptoms requiring further investigation. Palpitations are a common reason for presentation on the acute medical take, and most acute physicians will be familiar with the process of investigation. The combination of pregnancy and palpitations raises a broad differential diagnosis and can complicate the management pathway. This problem based review is designed to summarise the key issues which may arise during the management of a typical patient presenting in this way.

Streptococcus oralis meningitis in pregnancy.

While pregnancy is a time of relative immunosuppression, infective endocarditis and bacterial meningitis remain rare. We present a case of a pregnant woman with Streptococcus oralis endocarditis and meningitis. This is the first reported case of Streptococcus oralis meningitis in a patient without predisposing risk factors. This case highlights the importance of collecting blood cultures in febrile illness during pregnancy and illustrates that effective management plans can be formulated without performing invasive diagnostic tests such as transesophageal echocardiography.

Renal disease and hypertension in pregnancy.

Because women are becoming pregnant at a later age, hypertension is more commonly encountered in pregnancy. In addition, with increasing numbers of young women living with renal transplants and kidney disease, it is important for physicians to be aware of the effects of pregnancy on these diseases. A multidisciplinary approach is essential to assess and care for pregnant women with kidney disease. Pre-pregnancy counselling should be offered to all women with chronic kidney disease. A review of medication to avoid teratogenicity and optimise the disease prior to conception is the ideal. Pregnancy may be the first medical review for a young woman, who may present with a previously undiagnosed renal problem.

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.

An integrated primary care-based programme of PRE-Pregnancy cARE to improve pregnancy outcomes in women with type 2 Diabetes (The PREPARED study): protocol for a multi-method study of implementation, system adaptation and performance.

BACKGROUND: The number of women of childbearing age with Type 2 diabetes(T2DM) is increasing, and they now account for > 50% of pregnancies in women with pre-existing diabetes. Diabetes pregnancies without adequate pre-pregnancy care have higher risk for poor outcomes (miscarriages, birth-defects, stillbirths) and are associated with increased complications (caesarean deliveries, macrosomic babies, neonatal intensive-care admissions). The risks and costs of these pregnancies can be reduced with pregnancy preparation (HbA1c, ≤ 6.5%, 5 mg folic acid and stopping potentially harmful medicines). However, 90% of women with T2DM, most of whom are based in primary care, are not adequately prepared for pregnancy. This study will evaluate a programme of primary care-based interventions (decision-support systems; pre-pregnancy care-pathways; pregnancy-awareness resources; professional training; and performance monitoring) to improve pregnancy preparation in women with T2DM. METHODS: The study aims to optimise the programme interventions and estimate their impact on pregnancy preparation, pre-pregnancy care uptake and pregnancy outcomes. To evaluate this multimodal intervention, we will use a multi-method research design following Complex Adaptive Systems (CAS) theory, refining the interventions iteratively during the study. Thirty GP practices with ≥ 25 women with T2DM of reproductive age (18-45 years) from two South London boroughs will be exposed to the intervention. This will provide > 750 women with an estimated pregnancy incidence of 80-100 to study. The research involves: a clinical audit of processes and outcomes; a process evaluation informing intervention feasibility, implementation, and behaviour change; and a cost-consequences analysis informing future economic evaluation. Performance data will be collected via audits of GP systems, hospital antenatal clinics and pregnancy outcomes. Following CAS theory, we will use repeated measurements to monitor intervention impact on pregnancy preparation markers at 4-monthly intervals over 18-months. We will use performance and feasibility data to optimise intervention effects iteratively. The target performance for the intervention is a 30% increase in the proportion of women meeting pre-pregnancy care criteria. DISCUSSION: The primary output will be development of an integrated programme of interventions to improve pregnancy preparation, pre-pregnancy care uptake, and reduce adverse pregnancy outcomes in women with T2DM. We will also develop an implementation plan to support the introduction of the interventions across the NHS. TRIAL REGISTRATION: ISRCTN47576591 ; February 8, 2022.

Feeding practices and blood lead levels in infants in Nagpur, India.

In a hospital-based cross-sectional study of 200 infants age 4-9 months in an Indian city (Nagpur), the authors determined the prevalence of elevated blood lead level (EBLL) and mean blood lead levels with respect to feeding patterns, i.e., breastfed or fed with formula or dairy milk. The blood lead levels in this study population ranged from 0.048 microg/dl to 42.944 microg/dl; the mean blood lead level was 10.148 microg/dl (+/- 9.128); EBLL prevalence was 38.2%. EBLL risk factors included removal of house paint in the past year, odds ratio (OR), 5.6 (95% confidence interval [CI], 1.6-19.65); use of surma (eye cosmetic), OR 4.27 (95% CI, 1.39-13.08); maternal use of sindur (vermillion), OR 2.118 (95% CI, 1.07-4.44). Feeding method (breastfed or not) did not appear to have an effect on blood lead level. In non-breastfed infants, boiling of water was significantly associated with EBLL, OR 1.97 (95% CI, 1.01-3.84).

Metabolic emergencies in pregnancy.

In pregnancy, women are more likely to develop certain metabolic disturbances as a result of the physiological changes that occur. Diabetic ketoacidosis and hypoglycaemia occur at increased frequency in women with pre-existing and gestational diabetes, and starvation ketoacidosis can present towards the end of pregnancy and can cause severe illness. Peripartum hyponatraemia is increasingly recognised and can be associated with maternal and neonatal morbidity. This review describes these conditions in detail as well as treatment priorities and the impact on both mother and baby.

Provision of acute medicine services for pregnant women in UK hospitals: Data from the Society for Acute Medicine Benchmarking Audit 2019.

BACKGROUND: Medical problems during pregnancy are the leading cause of maternal mortality in the UK. Pregnant women often present through acute services to the medical team, requiring timely access to appropriate services, physicians trained to manage medical problems in pregnancy, with locally agreed guidance available. METHODS: Data were collected through the Society for Acute Medicine Benchmarking Audit, a national audit of service delivery and patient care in acute medicine over a 24 hour period. RESULTS: One hundred and thirty hospitals participated: 5.5% had an acute medicine consultant trained in obstetric medicine, and 38% of hospitals had a named lead for maternal medicine. This was not related to hospital size (p = 0.313). Sixty-four units had local guidelines for medical problems in pregnancy; 43% had a local guideline for venous thromboembolism in pregnancy. Centres with a named lead had more guidelines (p = 0.019). CONCLUSION: Current provision of services within acute medicine for pregnant women does not meet national recommendations.

Case report: Hereditary angioedema in pregnancy.

Hereditary angioedema (HAE) is a rare genetic condition associated with episodic swelling due to dysfunction of bradykinin regulation pathways. This is most frequently caused by low level and/or function of the C1-esterase inhibitor protein (C1INH) which is known as hereditary angioedema with C1 inhibitor deficiency (C1INH-HAE). Pregnancy and labour can precipitate an attack, but the majority of women have an uncomplicated, spontaneous vaginal delivery. Intravenous C1INH is the first-line therapy in pregnancy and breastfeeding. It should be given if any obstetric intervention is planned. Routine prophylactic administration for uncomplicated vaginal birth is not mandatory but may be appropriate if symptoms recur frequently during the third trimester. Pregnant women with C1INH-HAE should deliver in a hospital with C1INH replacement, fiberoptic intubation and front-of-neck access equipment readily available. A documented treatment plan should be developed within a multi-disciplinary team to pre-empt complications. We describe a case of C1INH-HAE diagnosed in pregnancy.

Interprofessional teamwork for managing medical deterioration in pregnancy: what contributes to good clinical performance in simulated practice?

OBJECTIVES: To identify the patterns of teamwork displayed by interprofessional teams during simulated management of medical deterioration in pregnancy and examine whether and how they are related to clinical performance in simulated practice. DESIGN: Exploratory observational cohort study. SETTING: Interprofessional clinical simulation training with scenarios involving the management of medical deterioration in pregnant women. PARTICIPANTS: Seventeen simulated scenarios involving 62 qualified healthcare staff working within the National Health Service attending clinical simulation training (midwives (n=18), obstetricians (n=24) and medical physicians (n=20)). MAIN OUTCOME MEASURES: Teamwork behaviours over time, obtained through detailed observational analysis of recorded scenarios, using the Temporal Observational Analysis of Teamwork (TOAsT) framework. Clinician rated measures of simulated clinical performance. RESULTS: Scenarios with better simulated clinical performance were characterised by shared leadership between obstetricians and midwives at the start of the scenario, with obstetricians delegating less and midwives disseminating rationale, while both engaged in more information gathering behaviour. Towards the end of the scenario, better simulated clinical performance was associated with dissemination of rationale to the team. More delegation at the start of a scenario was associated with less spontaneous sharing of information and rationale later in the scenario. Teams that shared their thinking at the start of a scenario continued to do so over time. CONCLUSIONS: Teamwork during the opening moments of a clinical situation is critical for simulated clinical performance in the interprofessional management of medical deterioration in pregnancy. Shared leadership and the early development of the shared mental model are associated with better outcomes.

COVID-19 and maternity care in South East London: shared working and learning initiative.

The SARS-CoV-2 COVID-19 pandemic has had an immediate and profound impact on how healthcare systems organise and deliver services and specifically, there is a disproportionate negative impact on Black, Asian and Minority Ethnic groups and other risk factors. This has required clinical leaders to respond at pace to meet patient's care needs, while supporting staff working in a volatile, uncertain, complex and ambiguous environment. During the initial wave and then the later waves within our South East London sector, there were new challenges as everyone faced a novel disease necessitating real-time learning and reflection. Through informal conversations and networks, the clinicians highlighted in the first wave the need for a forum for clinical discussion. Using our existing South East London Local Maternity System and the evolving Maternal Medicine Networks alliance, we initiated a sharing and learning platform to support clinical decision-making for all maternity health professionals during the pandemic. Fortnightly, multidisciplinary virtual huddles were established allowing obstetric physicians, obstetricians, midwives and obstetric anaesthetists to share their clinical experience, operational and service challenges. This approach fostered and developed cross-site team working and shared learning across traditional, organisational boundaries. In South East London, prior to the introduction of universal testing in the first surge, we had a total of 65 confirmed positive cases of which 5 women were delivered due to COVID-19, 5 women required high dependency or intensive care and 3 women were intubated and ventilated. During the second and third waves, the COVID-19 Local Maternity System huddles provided monthly learning opportunities to share clinical practice, guidelines, vaccination updates and challenges with workforce. The huddles have proven to be a sustainable platform, which have built trust across the sector, facilitating effective teamwork and providing invaluable support for clinical decision-making. We describe the evolution of this structure and share our experience of working within this new clinical network during the first wave and how this established way of working facilitated collaboration during the second and third waves as staff and the system became more fatigued. The huddles have developed to become multi-professional, multisite collaborations with the whole group taking joint ownership to develop shared learning and are providing a forum for discussions for the emerging South East London's Maternal Medicine Network.

Maternal glucose homeostasis is impaired in mouse models of gestational cholestasis.

Women with intrahepatic cholestasis of pregnancy (ICP), a disorder characterised by raised serum bile acids, are at increased risk of developing gestational diabetes mellitus and have impaired glucose tolerance whilst cholestatic. FXR and TGR5 are modulators of glucose metabolism, and FXR activity is reduced in normal pregnancy, and further in ICP. We aimed to investigate the role of raised serum bile acids, FXR and TGR5 in gestational glucose metabolism using mouse models. Cholic acid feeding resulted in reduced pancreatic ß-cell proliferation and increased apoptosis in pregnancy, without altering insulin sensitivity, suggesting that raised bile acids affect ß-cell mass but are insufficient to impair glucose tolerance. Conversely, pregnant Fxr-/- and Tgr5-/- mice are glucose intolerant and have reduced insulin secretion in response to glucose challenge, and Fxr-/- mice are also insulin resistant. Furthermore, fecal bile acids are reduced in pregnant Fxr-/- mice. Lithocholic acid and deoxycholic acid, the principal ligands for TGR5, are decreased in particular. Therefore, we propose that raised serum bile acids and reduced FXR and TGR5 activity contribute to the altered glucose metabolism observed in ICP.

Troponins, Acute Coronary Syndrome and Renal Disease: From Acute Kidney Injury Through End-stage Kidney Disease.

The diagnosis of acute coronary syndromes (ACS) is heavily dependent on cardiac biomarker assays, particularly cardiac troponins. ACS, particularly non-ST segment elevation MI, are more common in patients with acute kidney injury, chronic kidney disease (CKD) and end-stage kidney disease (ESKD), are associated with worse outcomes than in patients without kidney disease and are often difficult to diagnose and treat. Hence, early accurate diagnosis of ACS in kidney disease patients is important using easily available tools, such as cardiac troponins. However, the diagnostic reliability of cardiac troponins has been suboptimal in patients with kidney disease due to possible decreased clearance of troponin with acute and chronic kidney impairment and low levels of troponin secretion due to concomitant cardiac muscle injury related to left ventricular hypertrophy, inflammation and fibrosis. This article reviews the metabolism and utility of cardiac biomarkers in patients with acute and chronic kidney diseases. Cardiac troponins are small peptides that accumulate in both acute and chronic kidney diseases due to impaired excretion. Hence, troponin concentrations rise and fall with acute kidney injury and its recovery, limiting their use in the diagnosis of ACS. Troponin concentrations are chronically elevated in CKD and ESKD, are associated with poor prognosis and decrease the sensitivity and specificity for diagnosis of ACS. Yet, the evidence indicates that the use of high-sensitivity troponins can confirm or exclude a diagnosis of ACS in the emergency room in a significant proportion of kidney disease patients; those patients in whom the results are equivocal may need longer in-hospital assessment.