Maternal-fetal-neonatal microbiome and outcomes associated with prematurity.

Our understanding of the premature gut microbiome has increased rapidly in recent years. However, to advance this important topic we must further explore various aspects of the maternal microbiome, neonatal microbiota, and the opportunities for microbiome modulation. We invite authors to contribute research and clinical papers to the Collection "Maternal-fetal-neonatal microbiome and outcomes associated with prematurity".

Perinatal characteristics and neonatal outcomes of singletons and twins in Chinese very preterm infants: a cohort study.

BACKGROUND: The prevalence of preterm birth has been rising, and there is a paucity of nationwide data on the perinatal characteristics and neonatal outcomes of twin deliveries of very preterm infants (VPIs) in China. This study compared the perinatal characteristics and outcomes of singletons and twins admitted to neonatal intensive care units (NICUs) in China. METHODS: The study population comprised all infants born before 32 weeks in the Chinese Neonatal Network (CHNN) between January 2019 and December 2019. Three-level and population-average generalized estimating equation (GEE)/alternating logistic regression (ALR) models were used to determine the association of twins with neonatal morbidities and the use of NICU resources. RESULTS: During the study period, there were 6634 (71.2%) singletons and 2680 (28.8%) twins, with mean birth weights of 1333.70 g and 1294.63 g, respectively. Twins were significantly more likely to be delivered by caesarean section (p < 0.01), have antenatal steroid usage (p = 0.048), have been conceived by assisted reproductive technology (ART) (p < 0.01), have a higher prevalence of maternal diabetes (p < 0.01) and be inborn (p < 0.01) than singletons. In addition, twins had a lower prevalence of small for gestational age, maternal hypertension, and primigravida mothers than singletons (all p < 0.01). After adjusting for potential confounders, twins had higher mortality rates (adjusted odds ratio [AOR] 1.28, 95% confidence interval [CI] 1.10-1.49), higher incidences of short-term composite outcomes (AOR 1.28, 95% CI 1.09-1.50), respiratory distress syndrome (RDS) (AOR 1.30, 95% CI 1.12-1.50), and bronchopulmonary dysplasia (BPD) (AOR 1.10, 95% CI 1.01-1.21), more surfactant usage (AOR 1.22, 95% CI 1.05-1.41) and prolonged hospital stays (adjusted mean ratio 1.03, 95% CI 1.00-1.06), compared to singletons. CONCLUSION: Our work suggests that twins have a greater risk of mortality, a higher incidence of RDS and BPD, more surfactant usage, and longer NICU stays than singletons among VPIs in China.

Diagnostic reasoning is associated with lower physician satisfaction with patient communication.

BACKGROUND: Prior research suggests that the quality of communication between doctors and patients influences the quality of medical care and adherence to treatment regimens, but little is known about factors that contribute to successful interactions between doctors and patients. AIM: To examine the quality of communication across the different medical specialties. METHODS: A survey questionnaire was undertaken at a large metropolitan-based hospital in Brisbane, Australia. In this initial study we surveyed 67 doctors across various specialties on a range of social cognition and personality measures. We then rated each of the specialties on the degree to which they rely on both procedures and diagnostics, as well as the extent to which they involve patient communication. RESULTS: A regression analysis using spss 26.0 was undertaken to ascertain if doctor's satisfaction with their communication was related to these three aspects of the various specialties. Results revealed that communication satisfaction was negatively related to the degree to which the specialty relies on diagnostics. No relationship emerged between reliance on procedures and communication satisfaction. Last, communication frequency was positively related to communication satisfaction. CONCLUSIONS: We propose two possible accounts for this finding regarding diagnostics: (i) the cognitive demands of diagnosis disrupt communication; and/or (ii) diagnoses are interpreted by patients as opinions with which they are sometimes motivated to disagree. Further research is needed to replicate these findings and establish the underlying mechanism.

Self-control, limited willpower and decision fatigue in healthcare settings.

We argue that willpower as well as its depletion may, in some circumstances, adversely impact on clinical decision-making and patient care. This psychological phenomenon has been dubbed ego depletion in social psychology. Willpower and its depletion which is known as 'ego depletion' are well-established and validated theoretical constructs in social psychology and have been studied across a range of experimental contexts. Willpower is closely related to the concept of self-control, which refers to the ability to regulate one's own behaviour and actions in order to pursue and achieve either a short- or long-term goal. We outline the clinical relevance of willpower and its depletion in relation to clinical case examples drawn from three of the authors' clinical experience with the view of developing a clinical-research agenda for future research studies. We examine willpower and its depletion in the context of three clinical case examples, which include (i) doctor-patient interactions, (ii) willpower and its depletion in relation to challenging interpersonal interactions with clinical and non-clinical work colleagues and (iii) willpower and its depletion in response to working within a challenging and unpredictable clinical environment. In contrast to the more widely recognised external resources (including space, staff allocations and night shifts), a greater understanding of how this important but under-recognised internal resource can be depleted in response to a range of different factors within clinical settings has the potential to inform and improve patient care through a renewed focus on the developing interdisciplinary clinical studies which draw upon contemporary findings from social psychology. Future work aimed at developing evidence-based interventions to help mitigate the negative impact of impaired self-control and decision fatigue within healthcare systems may in turn lead to improved patient care as well as more effective healthcare service and delivery.

Blood culture collection practices in NICU; A national survey.

Background: Sepsis is the leading cause of mortality and morbidity in neonates. Blood cultures are the gold standard in diagnosing neonatal sepsis; however, there are currently no consensus guidelines for blood culture collection in neonates and significant practice variation exists in Neonatal Intensive Care Units (NICUs) globally. Objective: To examine current practices in obtaining blood cultures in the evaluation of neonatal sepsis in NICUs across Canada. Methods: A nine-item electronic survey was sent to each of the 29 level-3 NICUs in Canada, which are equipped to provide highly specialized care for newborns. Results: Responses were received from 90% (26/29) of sites. Sixty-five percent (17/26) of sites have blood culture collection guidelines for the investigation of neonatal sepsis. Forty-eight percent (12/25) of sites routinely target 1.0 mL per culture bottle. In late-onset sepsis (LOS), 58% (15/26) of sites process one aerobic culture bottle, whereas four sites routinely add anaerobic culture bottles. In early-onset sepsis (EOS) in very low birth weight infants (BW <1.5 kg), 73% (19/26) of sites use umbilical cord blood, and 72% (18/25) use peripheral venipuncture. Two sites routinely collect cord blood for culture in EOS. Only one site applies the concept of differential time-to-positivity to diagnose central-line-associated bloodstream infection. Conclusions: There is significant practice variation in methods used to obtain blood cultures in level-3 NICUs across Canada. Standardization of blood culture collection practices can provide reliable estimates of the true incidence of neonatal sepsis and help to develop appropriate antimicrobial stewardship strategies.

Impact of Perinatal Exposure to SARS-CoV-2 Infection on Early Health Outcomes among Infants Born from 2020 to 2021 in British Columbia, Canada.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has impacted healthcare services and outcomes. We aimed to investigate healthcare resource utilization and early health outcomes of infants born to mothers with perinatal SARS-CoV-2 infection. Methods: The study included all infants born alive between February 1, 2020, and April 30, 2021, in British Columbia. We used linked provincial population-based databases including data on COVID-19 testing, birth, and health information for up to one year from birth. Perinatal COVID-19 exposure for infants was defined being born to mothers with a positive test for SARS-CoV-2 infection during pregnancy or at delivery. Cases of COVID-19-exposed infants were matched with up to four non-exposed infants by birth month, sex, birthplace, and gestational age in weeks. Outcomes included hospitalizations, emergency department visits, and in-/outpatient diagnoses. Outcomes were compared between groups using conditional logistic regression and linear mixed effects models including effect modification by maternal residence. Results: Among 52,711 live births, 484 infants had perinatal exposure to SARS-CoV-2, an incidence rate of 9.18 per 1000 live births. Exposed infants (54.6% male) had a mean gestational age of 38.5 weeks, and 99% were born in hospital. Proportions of infants requiring at least one hospitalization (8.1% vs. 5.1%) and at least one emergency department visit (16.9% vs. 12.9%) were higher among the exposed vs. unexposed infants, respectively. Among infants from the urban area, those with exposure were more likely to have respiratory infectious diseases (odds ratio: 1.74; 95% confidence intervals: 1.07, 2.84), compared with those without exposure. Interpretation. In our cohort, infants born to mothers with SARS-CoV-2 infection have increased healthcare demands in their early infancy, which warrants further investigation.

Antenatal corticosteroid administration and attention-deficit/hyperactivity disorder in childhood: a regression discontinuity study.

BACKGROUND: Antenatal corticosteroids reduce respiratory morbidity in preterm infants, but their use during late preterm gestation (34-36 weeks) is limited because their safety for longer-term child neurodevelopment is unclear. We sought to determine if fetuses with higher probability of exposure to antenatal corticosteroids had increased rates of prescriptions for attention-deficit/hyperactivity disorder (ADHD) medication in childhood, using a quasiexperimental design that better controls for confounding than existing observational studies. METHODS: We identified 16 358 children whose birthing parents were admitted for delivery between 31 + 0 (31 weeks, 0 days) and 36 + 6 weeks' gestation in 2000-2013, using a perinatal data registry from British Columbia, Canada, and linked their records with population-based child ADHD medication data (2000-2018). We used a regression discontinuity design to capitalize on the fact that pregnancies presenting for delivery immediately before and immediately after the clinical cut-off for antenatal corticosteroid administration of 34 + 0 weeks' gestation have very different levels of exposure to corticosteroids, but are otherwise similar with respect to confounders. RESULTS: Over a median follow-up period of 9 years, 892 (5.5%) children had 1 or more dispensations of ADHD medication. Children whose birthing parents were admitted for delivery just before the corticosteroid clinical cut-off of 34 + 0 weeks' gestation did not appear to be more likely to be prescribed ADHD medication than those admitted just after the cut-off (rate ratio 1.1, 95% confidence interval [CI] 0.8 to 1.6; 1.3 excess cases per 100 children, 95% CI -2.5 to 5.7). INTERPRETATION: We found little evidence that children with higher probability of exposure to antenatal corticosteroids have higher rates of ADHD prescriptions in childhood, supporting the safety of antenatal corticosteroids for this neurodevelopmental outcome.

Maternal and neonatal trauma following operative vaginal delivery.

BACKGROUND: Operative vaginal delivery (OVD) is considered safe if carried out by trained personnel. However, opportunities for training in OVD have declined and, given these shifts in practice, the safety of OVD is unknown. We estimated incidence rates of trauma following OVD in Canada, and quantified variation in trauma rates by instrument, region, level of obstetric care and institutional OVD volume. METHODS: We conducted a cohort study of all singleton, term deliveries in Canada between April 2013 and March 2019, excluding Quebec. Our main outcome measures were maternal trauma (e.g., obstetric anal sphincter injury, high vaginal lacerations) and neonatal trauma (e.g., subgaleal hemorrhage, brachial plexus injury). We calculated adjusted and stabilized rates of trauma using mixed-effects logistic regression. RESULTS: Of 1 326 191 deliveries, 38 500 (2.9%) were attempted forceps deliveries and 110 987 (8.4%) were attempted vacuum deliveries. The maternal trauma rate following forceps delivery was 25.3% (95% confidence interval [CI] 24.8%-25.7%) and the neonatal trauma rate was 9.6 (95% CI 8.6-10.6) per 1000 live births. Maternal and neonatal trauma rates following vacuum delivery were 13.2% (95% CI 13.0%-13.4%) and 9.6 (95% CI 9.0-10.2) per 1000 live births, respectively. Maternal trauma rates remained higher with forceps than with vacuum after adjustment for confounders (adjusted rate ratio 1.70, 95% CI 1.65-1.75) and varied by region, but not by level of obstetric care. INTERPRETATION: In Canada, rates of trauma following OVD are higher than previously reported, irrespective of region, level of obstetric care and volume of OVD among hospitals. These results support a reassessment of OVD safety in Canada.

A Survey on Variation in Diagnosis and Treatment of Chorioamnionitis in Tertiary Centres in Canada.

OBJECTIVE: Clinical detection and management of chorioamnionitis is challenging given the gold-standard for diagnosis remains placental pathology, the results of which are only available after delivery. Moreover, recommended diagnostic criteria for clinical chorioamnionitis have evolved over time. The goal of this study was to describe trends and differences in chorioamnionitis diagnostic and management practices in Canada. METHODS: We surveyed obstetric care providers participating in the Canadian Preterm Birth Network. Questionnaires were distributed electronically to all 29 sites and completed by 1 maternal-fetal medicine investigator at each site. RESULTS: The response rate was 82.8% (n = 24). There was considerable variation in the clinical criteria used to diagnose chorioamnionitis with 9 of 22 sites stating this occurs "frequently" or "very frequently." Isolated fever was "always" or "most of the time" used as an indication to start empiric antibiotic therapy in 14 of 24 sites, and 21 of 23 sites used the same diagnostic criteria for term and preterm deliveries. Placental histology (15 sites) and white blood cell count (14 sites) were the most common clinical tests performed to confirm chorioamnionitis. A combination of ampicillin and aminoglycoside antibiotics was used at 12 sites. Another frequently used antibiotic therapy was cefazolin and metronidazole (4 sites). CONCLUSION: There is a wide variation in practices for the diagnosis and management of chorioamnionitis across Canada. The results of this study will guide efforts to improve and standardize the management of this condition.

Factors Associated with Umbilical Venous Catheter Malposition in Newborns: A Tertiary Center Experience.

OBJECTIVE: Umbilical venous catheters (UVC) are widely used in neonatal intensive care (NICU). Noncentral catheter position is known to be associated with multiple adverse complications; however, risk factors for catheter malposition are unclear. This work aimed to identify clinical risk factors and complications associated with UVC malposition in neonates admitted in an NICU. STUDY DESIGN: A retrospective chart review was performed of inborn babies admitted to BC Women's Hospital NICU with UVC inserted in their first 7 days between July 2016 and June 2018. Infant and maternal demographic, radiograph, UVC-related data, and complications were reviewed. RESULTS: A total of 257 infants had UVC placed; 158 (61%) and 99 (39%) were in central and noncentral positions after initial placement, respectively. Of initially central-placed UVCs, a further 35 (22%) were pulled back or migrated to malposition on follow-up X-ray. Multivariable logistic regression analysis revealed the use of larger UV (5 Fr) catheter (odds ratio [OR]: 2.5, 95% confidence interval [CI]: 1.1-5.6, p = 0.026) and escalation of respiratory support mode (OR: 1.7, 95% CI: 1.0-2.8, p = 0.049) as significant predictors of catheter malposition. CONCLUSION: Noncentral UVC position as well as migration were common after initial placement in this cohort. The use of larger size UV catheters and increasingly invasive respiratory support were risk factors associated with higher incidence of UVC malposition. Ongoing surveillance of UVC position is thus recommended. KEY POINTS: · More than one-third of UV catheters were not in central position after the initial placement.. · Large size UV catheters and increasingly invasive respiratory support were risk factors for UV malposition.. · High incidence of UVC migration was found after initial central placement, warranting surveillance..

Quantifying Proximal Collecting Tubule Deficiency in Angiotensin-Converting Enzyme Inhibitor and Angiotensin II Receptor Blocker Fetopathy.

INTRODUCTION: Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers (AAs) are used for several indications, with cessation recommended in pregnancy due to toxic effects. AA fetopathy phenotype is similar to renal tubular dysgenesis including reduced proximal convoluted tubules (PCTs). Our study aimed to quantify the reduction of PCTs in fetuses and infants with prenatal exposure to AAs. MATERIALS AND METHODS: We identified 5 fetal AA exposure cases that underwent autopsy at our institution between 2011 and 2018 and compared with 5 gestational age-matched controls. Immunohistochemistry with CD10 and epithelial membrane antigen (EMA) was utilized. RESULTS: CD10 and EMA identified a median PCT density of 19.0% ± 12.3% in AA fetopathy patients, significantly less than controls (52.8% ± 4.4%; p < 0.0001). One case with in utero cessation had a PCT density of 34.2% ± 0.2%. Among other AA fetopathy findings, 1 case demonstrated unilateral renal vein thrombosis and 4 had hypocalvaria. CONCLUSIONS: We have quantified the reduction in AA fetopathy PCT density, and demonstrated in utero cessation may recover PCT differentiation. Future studies may benefit from calculating PCT percentage as a potential biomarker to correlate with post-natal renal function and maternal factors including medication type, dosage, duration, and time from medication cessation.

Strategies and interventions for improving safety culture in Australian Emergency Departments: A modified Delphi study.

BACKGROUND: Patient safety and safety culture are critical for quality healthcare delivery in general and in Emergency Departments (EDs) in particular. The aim of this study is to identify strategies that may contribute to the improvement and maintenance of patient safety culture and which are considered most feasible in the ED environment. METHODS: A two-step modified Delphi method with 11 experts' panel was performed to establish consensus. A list of potential expert participants with a background in patient safety culture in EDs was compiled through the professional networks of the supervisory team. Snowball sampling was used to identify additional possible participants. The expert panel included key leaders in the emergency medicine community in Queensland, Australia: patient safety experts and researchers, patient safety directors, and healthcare providers in an Australian ED The study ran from September 2018 to December 2018. The tool used in Round 1 in this study was developed through triangulating the outcomes of a review of literature, results from a survey of ED staff and findings from semi-structured interviews with key stakeholders in ED. The results from Round 1 informed the development of the Round 2 tool. The responses from the Delphi Round 1 tool were analysed as both qualitative data and quantitative data. The responses from the Delphi Round 2 tool were treated as quantitative data and analysed with the SPSS software. Consensus was calculated based on more than 80% agreement in collapsed categories 1 and 2 (or 4 and 5) of the five-point Likert scale. RESULTS: Only six strategies out of 17 (35%) achieved consensus for both importance and feasibility. These strategies may therefore be considered the most important and feasible key strategies for improving safety culture in EDs. Seven strategies (41.1%) achieved consensus for importance, but not for feasibility and four strategies (23.55%) did not achieve consensus for either importance or feasibility. CONCLUSIONS: This study offers practical solutions for safety culture improvement in the ED context. Six key strategies were seen as both important and feasible and these grouped into three main themes; leadership through agenda setting, operational management approaches to reinforce the agenda and commitment, and systems and structures to reinforce the agenda and monitor progress.

Ecologically enhanced healthcare at the Mater hospitals: the intersection between sustainable delivery, Pope Francis' care of the common home and indigenous land care in an era of climate challenges.

The changes we are causing to our global environment now threaten everyone's health. As such, health systems and professionals should consider environmental sustainability as part of good health and care. Climate change is only one of the global challenges we face, but the problems presented by ignoring it, and the immediate health benefits offered by addressing it, are too significant for health professionals to ignore. High-quality healthcare depends on addressing the social and environmental determinants of health and disease, more so in rural and indigenous areas. The Mater Hospital's reconciling Francis' global holistic approach to local Aboriginal expertise addresses both needs at the same time.

Retrieval medicine and pre-hospital care in remote Australia.

Retrieval medicine and pre-hospital care in remote Australia are challenging, requiring competencies in major trauma, high-risk obstetrics, critical care in adults and children, severe mental health-related agitation and envenomation. They keep a city-based retrieval and pre-hospital care doctor on their toes. Cultural fluencies to enhance care for Aboriginal and remote communities are critical during the long hours taken for the patient journey from the accident scene or clinic to definitive care.

Enteroviral and herpes simplex virus central nervous system infections in infants < 90 days old: a Paediatric Investigators' Collaborative Network on Infections in Canada (PICNIC) study.

BACKGROUND: The relative contribution of viruses to central nervous system (CNS) infections in young infants is not clear. For viral CNS infections, there are limited data on features that suggest HSV etiology or on predictors of unfavorable outcome. METHODS: In this cross-sectional retrospective study, seven centers from the Pediatric Investigators Collaborative Network on Infections in Canada identified infants < 90 days of age with CNS infection proven to be due to enterovirus (EV) or herpes simplex virus (HSV) January 1, 2013 through December 31, 2014. RESULTS: Of 174 CNS infections with a proven etiology, EV accounted for 103 (59%) and HSV for 7 (4%). All HSV cases and 41 (40%) EV cases presented before 21 days of age. Four HSV cases (57%) and 5 EV cases (5%) had seizures. Three (43%) HSV and 23 (23%) EV cases lacked cerebrospinal fluid (CSF) pleocytosis. HSV cases were more likely to require ICU admission (p = 0.010), present with seizures (p = 0.031) and have extra-CNS disease (p < 0.001). Unfavorable outcome occurred in 12 cases (11% of all EV and HSV infections) but was more likely following HSV than EV infection (4 (57%) versus 8 (8%); p = 0.002). CONCLUSIONS: Viruses accounted for approximately two-thirds of proven CNS infections in the first 90 days of life. Empiric therapy for HSV should be considered in suspected CNS infections in the first 21 days even in the absence of CSF pleocytosis unless CSF parameters are suggestive of bacterial meningitis. Neurodevelopmental follow-up should be considered in infants whose course of illness is complicated by seizures.

A national survey of the enteral feeding practices in Canadian neonatal intensive care units.

AIM: Nutrition affects the growth and neurodevelopmental outcomes of preterm infants, yet controversies exist about the optimal enteral feeding regime. The objective of this study was to compare enteral feeding guidelines in Canadian neonatal intensive care units (NICUs). METHOD: The research team identified key enteral feeding practices of interest. Canadian Neonatal Network site investigators at 30 Level 3 NICUs were contacted to obtain a copy of their 2016 to 2017 feeding guidelines for infants who weighed less than 1,500 g at birth. Each guideline was reviewed to compare recommendations around the selected feeding practices. RESULTS: Five of the 30 NICUs did not have a feeding guideline. The other 25 NICUs used 22 different enteral feeding guidelines. The guidelines in 40% of those NICUs recommend commencing minimal enteral nutrition (MEN) within 24 hours of birth and maintaining that same feeding volume for 24 to 96 hours. In 40% of NICUs, the guideline recommended that MEN be initiated at a volume of 5 to 10 mL/kg/day for infants born at <1,000 g. Guidelines in all 25 NICUs recommend the use of bovine-based human milk fortifier (HMF), and in 56% of NICUs, it is recommended that HMF be initiated at a total fluid intake of 100 mL/kg/day. Guidelines in only 16% of NICUs recommended routine gastric residual checks. Donor milk and probiotics are used in 76% and 72% of the 25 NICUs, respectively. CONCLUSION: This study revealed substantial variability in recommended feeding practices for very low birth weight infants, underscoring the need to establish a national feeding guideline for this vulnerable group.

Third-generation cephalosporin-resistant urinary tract infections in children presenting to the paediatric emergency department.

BACKGROUND: The incidence of antibiotic-resistant urinary tract infections (UTIs) in children is increasing. The purpose of this study was to describe the incidence, clinical characteristics, and risk factors for third-generation cephalosporin-resistant UTIs presenting to the paediatric emergency department (ED). METHODS: This was a retrospective cohort study conducted at British Columbia Children's Hospital. Children aged 0 to 18 years old presenting to the ED between July 1, 2013 and June 30, 2014 and were found to have UTI due to Enterobacteriaceae and Pseudomonas species were included. Patient demographics, clinical features, laboratory findings, and outcomes were compared using standard statistical analyses. Risk factors for resistant UTIs were analyzed using multiple logistic regression analysis. RESULTS: There were 294 eligible patients. The median age was 27.4 months. A third-generation cephalosporin-resistant organism was identified in 36 patients (12%). Patients with resistant UTI had lower rates of appropriate empiric antibiotic therapy (25% versus 95.3%, P<0.05), higher rates of hospitalization (38.9% versus 21.3%, P<0.05), higher rates of undergoing a voiding cystourethrogram (19.4% versus 5.0%, P<0.05), and higher rates of UTI recurrence within 30 days (13.9% versus 4.7%, P<0.05). In multivariate analysis, recent hospitalization (odds ratio [OR] 4.3, confidence interval [CI] 1.2 to 16) and antibiotic therapy (OR 3.5, CI 1.5 to 8.5) within the previous 30 days were risk factors for resistant UTI. CONCLUSIONS: Third-generation cephalosporin-resistant organisms account for a significant proportion of community-acquired paediatric UTIs. Recent hospitalization and antibiotic use are associated with increased risk of resistant UTI.

RAPIDOMICS: rapid genome-wide sequencing in a neonatal intensive care unit-successes and challenges.

Genetic disorders are one of the leading causes of infant mortality and are frequent in neonatal intensive care units (NICUs). Rapid genome-wide sequencing (GWS; whole genome or exome sequencing (ES)), due to its diagnostic capabilities and immediate impacts on medical management, is becoming an appealing testing option in the NICU setting. RAPIDOMICS was a trio-based rapid ES pilot study of 25 babies with suspected genetic disorders in the BC Women's Hospital NICU. ES and bioinformatic analysis were performed after careful patient ascertainment. Trio analysis was performed using an in-house pipeline reporting variants in known disease-causing genes. Variants interpreted by the research team as definitely or possibly causal of the infant's phenotype were Sanger validated in a clinical laboratory. The average time to preliminary diagnosis was 7.2 days. Sanger validation was pursued in 15 patients for 13 autosomal dominant and 2 autosomal recessive disorders, with an overall diagnostic rate (partial or complete) of 60%.Conclusion: In total, 72% of patients enrolled had a genomic diagnosis achieved through ES, multi-gene panel testing or chromosomal microarray analysis. Among these, there was an 83% rate of significant and immediate impact on medical decision-making directly related to new knowledge of the diagnosis. Health service implementation challenges and successes are discussed. What is Known: • Rapid genome-wide sequencing in the neonatal intensive care setting has a greater diagnostic hit rate and impact on medical management than conventional genetic testing. However, the impact of consultation with genetics and patient ascertainment requires further investigation. What is New: • This study demonstrates the importance of genetic consultation and careful patient selection prior to pursuing exome sequencing (ES). • In total, 15/25 (60%) patients achieved a diagnosis through ES and 18/25 (72%) through ES, multi-gene panel testing or chromosomal microarray analysis with 83% of those having immediate effects on medical management.

Challenges of expedition medicine in Antarctica.

Expedition medicine in Antarctica requires a broad spectrum of clinical competencies ranging from resuscitation medicine and trauma care to treating minor illness, safety awareness and safety induction. It remains a challenging environment to practise as a single unassisted physician is required to assess, acutely treat (medications, procedures) and complete follow-up consultation.

Use of sildenafil in an infant with persistent pulmonary hypertension secondary to lung and renal hypoplasia - a case report.

BACKGROUND: Premature preterm rupture of membranes (PPROM) is reported to be associated with high rates of neonatal mortality and morbidity. Sildenafil has been used in infants with persistent pulmonary hypertension of newborn (PPHN) due to congenital diaphragmatic hernia (CDH) and bronchopulmonary dysplasia (BPD). Recently, Sildenafil has been evaluated as an alternative or adjunctive pulmonary vasodilator. This case report illustrates the use of early sildenafil for PPHN and right ventricular dysfunction in an unusual setting of lung and renal hypoplasia. CASE PRESENTATION: A male infant was born at 37 weeks with a birth weight of 2840 g. Rupture of membranes developed at approximately 24 weeks of gestational age (GA). Bilateral small kidneys (< 2 standard deviations below average) were detected on ultrasound (US) examination at 30 weeks of gestation. The baby developed pneumothorax and pulmonary hypertensive crisis towards the end of the first day. An echocardiogram showed a dilated right ventricle, moderate right ventricular systolic dysfunction, hypoplastic pulmonary arteries and a large patent ductus arteriosus with bidirectional flow. The patient was sedated, paralyzed, and inhaled nitric oxide was administered to decrease the pulmonary resistance. In anticipation of persistent pulmonary hypertension due to the hypoplastic lungs and small calibre of pulmonary arteries, sildenafil was started on day of life (DOL) 5 at a dosage of 0.25 mg/kg/dose Q8H and gradually increased to 2 mg/kg/dose Q8H on DOL 9. The patient was finally extubated on DOL 7 and weaned off of non-invasive respiratory support on DOL 26. Sildenafil was gradually weaned beginning on DOL 21 and discontinued on DOL 48. Repeat echocardiogram assessment at 3 months showed complete resolution of PHT and right ventricular dilatation. CONCLUSIONS: We describe the early use of sildenafil in treating pulmonary hypertension associated with lung and renal hypoplasia in a non-CDH patient. Following this treatment the patient made a full recovery from right ventricular dysfunction.