Impact of maternal risk factors on ethnic disparities in maternal mortality:a national population-based cohort study

BackgroundEthnic disparities in maternal mortality are consistently reported. This study aimed to investigate the contribution of known risk factors including age, socioeconomic status, and medical comorbidities to observed ethnic disparities in the United Kingdom (UK).MethodsA cohort of all women who died during or up to six weeks after pregnancy in the UK 2009–2019 were identified through national surveillance. No single denominator population included data on all risk factors, therefore we used logistic regression modelling to compare to 1) routine population birth and demographic data (2015–19) (routine data comparator) and 2) combined control groups of four UK Obstetric Surveillance System studies (UKOSS) control comparator)).FindingsThere were 801 maternal deaths in the UK between 2009 and 2019 (White: 70%, Asian: 13%, Black: 12%, Chinese/Other: 3%, Mixed: 2%). Using the routine data comparator (n = 3,519,931 maternities) to adjust for demographics, including social deprivation, women of Black ethnicity remained at significantly increased risk of maternal death compared with women of white ethnicity (adjusted OR 2.43 (95% Confidence Interval 1.92–3.08)). The risk was greatest in women of Caribbean ethnicity (aOR 3.55 (2.30–5.48)). Among women of White ethnicity, risk of mortality increased as deprivation increased, but women of Black ethnicity had greater risk irrespective of deprivation. Using the UKOSS control comparator (n = 2210), after multiple adjustments including smoking, body mass index, and comorbidities, women of Black and Asian ethnicity remained at increased risk (aOR 3.13 (2.21–4.43) and 1.57 (1.16–2.12) respectively).InterpretationKnown risk factors do not fully explain ethnic disparities in maternal mortality. The impact of socioeconomic deprivation appears to differ between ethnic groups

Perinatal outcomes after admission with COVID-19 in pregnancy:a UK national cohort study

There are few population-based studies of sufficient size and follow-up duration to have reliably assessed perinatal outcomes for pregnant women hospitalised with SARS-CoV-2 infection. The United Kingdom Obstetric Surveillance System (UKOSS) covers all 194 consultant-led UK maternity units and included all pregnant women admitted to hospital with an ongoing SARS-CoV-2 infection. Here we show that in this large national cohort comprising two years’ active surveillance over four SARS-CoV-2 variant periods and with near complete follow-up of pregnancy outcomes for 16,627 included women, severe perinatal outcomes were more common in women with moderate to severe COVID-19, during the delta dominant period and among unvaccinated women. We provide strong evidence to recommend continuous surveillance of pregnancy outcomes in future pandemics and to continue to recommend SARS-CoV-2 vaccination in pregnancy to protect both mothers and babies

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

Infant birthweight and risk of childhood cancer: international population-based case control studies of 40 000 cases

Background: High birthweight is an established risk factor for childhood leukaemia. Its association with other childhood cancers is less clear, with studies hampered by low case numbers. Methods: We used two large independent datasets to explore risk associations between birthweight and all subtypes of childhood cancer. Data for 16 554 cases and 53 716 controls were obtained by linkage of birth to cancer registration records across five US states, and 23 772 cases and 33 206 controls were obtained from the UK National Registry of Childhood Tumours. US, but not UK, data were adjusted for gestational age, birth order, plurality, and maternal age and race/ethnicity. Results: Risk associations were found between birthweight and several childhood cancers, with strikingly similar results between datasets. Total cancer risk increased linearly with each 0.5 kg increase in birthweight in both the US [odds ratio 1.06 (95% confidence interval 1.04, 1.08)] and UK [1.06 (1.05, 1.08)] datasets. Risk was strongest for leukaemia [USA: 1.10 (1.06, 1.13), UK: 1.07 (1.04, 1.10)], tumours of the central nervous system [USA: 1.05 (1.01, 1.08), UK: 1.07 (1.04, 1.10)], renal tumours [USA: 1.17 (1.10, 1.24), UK: 1.12 (1.06, 1.19)] and soft tissue sarcomas [USA: 1.12 (1.05, 1.20), UK: 1.07 (1.00, 1.13)]. In contrast, increasing birthweight decreased the risk of hepatic tumours [USA: 0.77 (0.69, 0.85), UK: 0.79 (0.71, 0.89) per 0.5 kg increase]. Associations were also observed between high birthweight and risk of neuroblastoma, lymphomas, germ cell tumours and malignant melanomas. For some cancer subtypes, risk associations with birthweight were non-linear. We observed no association between birthweight and risk of retinoblastoma or bone tumours. Conclusions: Approximately half of all childhood cancers exhibit associations with birthweight. The apparent independence from other factors indicates the importance of intrauterine growth regulation in the aetiology of these diseases

Proximity to overhead power lines and childhood leukaemia: an international pooled analysis

© 2018, Cancer Research UK. Background: Although studies have consistently found an association between childhood leukaemia risk and magnetic fields, the associations between childhood leukaemia and distance to overhead power lines have been inconsistent. We pooled data from multiple studies to assess the association with distance and evaluate whether it is due to magnetic fields or other factors associated with distance from lines. Methods: We present a pooled analysis combining individual-level data (29,049 cases and 68,231 controls) from 11 record-based studies. Results: There was no material association between childhood leukaemia and distance to nearest overhead power line of any voltage. Among children living < 50 m from 200 + kV power lines, the adjusted odds ratio for childhood leukaemia was 1.33 (95% CI: 0.92–1.93). The odds ratio was higher among children diagnosed before age 5 years. There was no association with calculated magnetic fields. Odds ratios remained unchanged with adjustment for potential confounders. Conclusions: In this first comprehensive pooled analysis of childhood leukaemia and distance to power lines, we found a small and imprecise risk for residences < 50 m of 200 + kV lines that was not explained by high magnetic fields. Reasons for the increased risk, found in this and many other studies, remains to be elucidated

Metabolic profiling stratifies colorectal cancer and reveals adenosylhomocysteinase as a therapeutic target

The genomic landscape of colorectal cancer (CRC) is shaped by inactivating mutations in tumour suppressors such as APC, and oncogenic mutations such as mutant KRAS. Here we used genetically engineered mouse models, and multimodal mass spectrometry-based metabolomics to study the impact of common genetic drivers of CRC on the metabolic landscape of the intestine. We show that untargeted metabolic profiling can be applied to stratify intestinal tissues according to underlying genetic alterations, and use mass spectrometry imaging to identify tumour, stromal and normal adjacent tissues. By identifying ions that drive variation between normal and transformed tissues, we found dysregulation of the methionine cycle to be a hallmark of APC-deficient CRC. Loss of Apc in the mouse intestine was found to be sufficient to drive expression of one of its enzymes, adenosylhomocysteinase (AHCY), which was also found to be transcriptionally upregulated in human CRC. Targeting of AHCY function impaired growth of APC-deficient organoids in vitro, and prevented the characteristic hyperproliferative/crypt progenitor phenotype driven by acute deletion of Apc in vivo, even in the context of mutant Kras. Finally, pharmacological inhibition of AHCY reduced intestinal tumour burden in ApcMin/+ mice indicating its potential as a metabolic drug target in CRC

Systematic review to investigate the safety of induction and augmentation of labour among pregnant women with iron deficiency anaemia

Objective To conduct a systematic review to investigate the safety of induction and/ or augmentation of labour compared with spontaneous-onset normal labour among pregnant women with iron-deficiency anaemia. Design Systematic review Setting Studies from all countries, worldwide. Population Pregnant women with iron-deficiency anaemia at labour and delivery. Intervention Any intervention related to induction and/ or augmentation of labour. Outcome Measures Primary: Postpartum haemorrhage (PPH), heart failure and maternal death. Secondary: Emergency caesarean section, hysterectomy, admission to intensive care unit. Method We searched 10 databases, including Medline and Embase, from database inception to 01 October 2018. We included all study designs except cross-sectional studies without a comparator group, case reports, case series, ecological studies, and expert opinion. The searches were conducted by a healthcare librarian and two authors independently screened and reviewed the studies. We used the GRADE approach to ascertain risk of bias and conducted a narrative synthesis. Results We identified 3217 journal articles, 223 conference papers, 45 dissertations, and 218 registered trials. Ten articles were included for full-text review and only one was found to fulfil the eligibility criteria. This was a retrospective cohort study from India which showed that pregnant women with moderate and severe anaemia could have an increased risk of PPH if they underwent induction and/or augmentation of labour, but the evidence was weak (graded as ‘High risk of bias’). Conclusion The best approach is to prevent anaemia, but a large number of women in low-to-middle-income countries present with severe anaemia during labour. In such women, appropriate peripartum management could prevent complications and death. Our review showed that at present we do not know if induction and augmentation of labour is safe in pregnant women with iron deficiency anaemia and further research is required