Risk factors for progression from severe maternal morbidity to death: a national cohort study.

Women continue to die unnecessarily during or after pregnancy in the developed world. The aim of this analysis was to compare women with severe maternal morbidities who survived with those who died, to quantify the risk associated with identified factors to inform policy and practice to improve survival

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Perinatal mortality and congenital anomalies in babies of women with type 1 or type 2 diabetes in England, Wales, and Northern Ireland: population based study

Objective To provide perinatal mortality and congenital anomaly rates for babies born to women with type 1 or type 2 diabetes in England, Wales, and Northern Ireland. Design National population based pregnancy cohort. Setting 231 maternity units in England, Wales, and Northern Ireland. Participants 2359 pregnancies to women with type 1 or type 2 diabetes who delivered between 1 March 2002 and 28 February 2003. Main outcome measures Stillbirth rates; perinatal and neonatal mortality; prevalence of congenital anomalies. Results Of 2359 women with diabetes, 652 had type 2 diabetes and 1707 had type 1 diabetes. Women with type 2 diabetes were more likely to come from a Black, Asian, or other ethnic minority group (type 2, 48.8%; type 1, 9.1%) and from a deprived area (type 2, 46.3% in most deprived fifth; type 1, 22.8%). Perinatal mortality in babies of women with diabetes was 31.8/1000 births. Perinatal mortality was comparable in babies of women with type 1 (31.7/1000 births) and type 2 diabetes (32.3/1000) and was nearly four times higher than that in the general maternity population. 141 major congenital anomalies were confirmed in 109 offspring. The prevalence of major congenital anomaly was 46/1000 births in women with diabetes (48/1000 births for type 1 diabetes; 43/1000 for type 2 diabetes), more than double that expected. This increase was driven by anomalies of the nervous system, notably neural tube defects (4.2-fold), and congenital heart disease (3.4-fold). Anomalies in 71/109 (65%) offspring were diagnosed antenatally. Congenital heart disease was diagnosed antenatally in 23/42 (54.8%) offspring; anomalies other than congenital heart disease were diagnosed antenatally in 48/67 (71.6%) offspring. Conclusion Perinatal mortality and prevalence of congenital anomalies are high in the babies of women with type 1 or type 2 diabetes. The rates do not seem to differ between the two types of diabetes