First case of desmosterolosis diagnosed by prenatal whole exome sequencing.

Desmosterolosis is a rare autosomal recessive disorder of cholesterol biosynthesis resulting in multiple congenital abnormalities and syndromic intellectual disability. It is caused by defects in DHCR24, the gene encoding 3-ß-hydroxysterol-24-reductase (24-dehydrocholesterol reductase), which acts in conversion of cholesterol precursor desmosterol, hence resulting in elevated plasma desmosterol levels. To date, desmosterolosis has been reported in 10 patients. Here we report an eleventh patient with desmosterolosis, and the first one to be diagnosed antenatally. Diagnosis was made on whole exome sequencing after amniocentesis due to complex antenatal abnormalities including cerebellar hypoplasia, microgyria, aortic stenosis, and renal tract abnormalities. Sterol quantitation was subsequently done postnatally, which supported the diagnosis. Although the nonspecific features make desmosterolosis difficult to suspect, we demonstrate that disorders of cholesterol synthesis can be considered as a differential diagnosis antenatally.

Tailoring the response to COVID-19: experiences of an inner city maternity unit with a virtual patient surveillance approach.

This study outlines the characteristics and outcomes of pregnant women with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We present the success of our 'COVID Surveillance Team' - a dedicated team of midwives and medics that regularly contact patients, identifying early any need for escalation of care. Data were collected prospectively from March to September 2020. Patients are followed up by our team for 14 days following diagnosis, via telephone. Maternal and neonatal outcomes were studied. Fifty-five women were diagnosed with COVID-19. 39/55 (70.9%) were of BAME background. 10/55 (18%) had medical comorbidities. 35/55 (63.6%) were diagnosed in the 3rd trimester, 7/55 (12.7%) were postnatal. Three women (5.4%) required critical care unit admission. One was transferred to a tertiary centre for extra-corporeal membrane oxygenation (ECMO), one patient died. Of the 43 deliveries, 28 (65.1%) underwent caesarean section. 11/45 (24.4%) of babies were born preterm. Eight babies were tested for COVID-19, one was positive. Our study demonstrates most pregnant women suffer mild illness, with no adverse outcomes for mother or neonate. We highlight the success of our COVID surveillance team, that should be considered best practice and consideration should be given for adoption by other maternity units to enhance patient safety.Impact StatementWhat is already known on this subject? Many studies present maternal and neonatal characteristics and outcomes of COVID-19 infection in the pregnant population, demonstrating most patients suffer mild disease with minimal adverse outcomes.What do the results of this study add? We highlight the important work of our COVID surveillance team, and the positive impact it has had on the wellbeing and safety of our women. We believe we are the first maternity unit in the UK to adopt and report on a virtual patient surveillance approach supporting our patients and leading to increased patient safety.What are the implications of these findings for clinical practice and/or further research? Our surveillance team has proved very successful and has been described as exemplar by NHS England and promoted as best practice. This approach could be adopted by other units, within the UK and further afield, for the benefit of women's health and safety. The team has shared their guidance and standard operating procedure with maternity units across the UK.

Placenta accreta spectrum disorders - detection rate and maternal outcomes following implementation of an institutional protocol.

Placenta accreta spectrum (PAS) disorders have been on the rise in recent years with increasing caesarean rates. The purpose of this prospective observational study was to describe our detection rates and to review outcomes in PAS after the introduction of an institutional screening and management protocol. Twenty-one patients with suspected PAS over 5 years were identified. 20/21 patients had an accurate determination of placental invasion and positive correlation with surgical and histopathological examination. Early morbidity (massive haemorrhage) was found in 7/21 patients, whilst late morbidity (hospital readmission) was found in 5/21 patients. There were no maternal deaths and admissions to intensive therapy unit (ITU). In summary, our centre demonstrated a high antenatal detection rate for PAS using an evidence-based protocol. This has led to timely intervention by an experienced multidisciplinary team and excellent outcomes. Immediate and delayed postoperative counselling was effective for optimal patient understanding and experience.Impact StatementWhat is already known on this subject? With rising caesarean section rates, the incidence of placenta accreta spectrum (PAS) disorders is increasing. Despite this, most obstetricians have personally managed only a small number of patients with PAS. Moreover, there appears to be some debate over the optimal diagnostic and management strategy.What do the results of this study add? As the incidence increases, development of institutional screening and management protocol is a necessity for large units. Timely diagnosis, extensive pre and postoperative counselling and multidisciplinary teamwork ensure reduced early and late morbidity.What are the implications of these findings for clinical practice and/or further research? Evidence based screening protocols for PAS disorders reduce the likelihood of undiagnosed cases and should be developed in every unit. Consideration must also be given to standardisation of the diagnostic and management protocols, including contingency plan for emergencies.