Corticosteroid use in neonatal hypotension: A survey of Canadian neonatologists.

OBJECTIVE: To assess prescribing practices and perspectives regarding the use of corticosteroids in the management of neonatal hypotension. METHODS: Cross-sectional questionnaire-based electronic survey of neonatologists (n = 206) practicing at tertiary neonatal intensive care units across 30 academic centres in Canada. RESULTS: The overall response rate was 33% (72/206), with a completion rate was 94%. Most (48/72, 64%) worked in a unit that covered both inborn and outborn infants, and 53% (37/70) worked in units with >100 very low birth weight infants admitted annually. Among the 72 respondents, 39% use a loading dose, of whom most (57%) use 2 mg/kg. Dosing ranges were variable, most using either 0.5 mg/kg or 1 mg/kg, q6h. Among the 56% (40/72) of neonatologists who reported measuring cortisol before initiation of hydrocortisone, cut-offs for initiation of hydrocortisone varied from <100 to <500 nmol/L, most of whom (48%) used <100 nmol/L. Of 71 respondents, 92% (65) indicated that a randomized control trial examining the use of corticosteroids in neonatal hypotension is needed, of whom 52% (37) indicated that the intervention group should receiving hydrocortisone after one vasopressor/inotrope. CONCLUSIONS: This survey provides insight into the prescribing practices of tertiary neonatologists with regards to the use of corticosteroids in neonatal hypotension. While corticosteroids are frequently prescribed, there is variability in the indication, dosing, and duration of corticosteroid use. The findings from this survey can be used to inform further research, including a clinical trial, regarding the practice in the management of neonatal hypotension.

Building Connections with Families: Implementation of a Video-Messaging Service in the Neonatal Intensive Care Unit.

BACKGROUND: Family involvement is vital to optimize the care of infants in the neonatal intensive care unit (NICU). Various technologies have been used to support communication with parents in the NICU. The purpose of this study was to evaluate the parent and staff experience and perception of the use of a cloud-based video-messaging service in our NICU. METHODS: This study was a single center observational study conducted at Mount Sinai Hospital, Toronto, Canada. Following the implementation of a video-messaging service, parent and staff surveys were distributed to evaluate their experience and perception. RESULTS: Parent responses were positive with respect to how the service helped them feel: closer to their infant (100%) and reassured about their infant's care (100%). Nursing staff responses indicated that they perceived a benefit to parents (100%) and to their building a relationship with families (79%). However, they also identified time constraints (85%) and the use of the technology hardware (24%) as challenges. CONCLUSIONS: The use of an asynchronous video-messaging service was perceived as beneficial to both parents and staff in the NICU. Complaints pertained to the impact of the technology on nursing workflow and the difficulty using the hardware provided for use of the service.

Analytical Unreliability of 25 Hydroxy Vitamin D Measurements in Pre-Term Neonates.

BACKGROUND: Vitamin D supplementation is common practice for neonates and infants due to limited stores of vitamin D at birth. Although not commonly encountered, vitamin D toxicity can occur due to over-supplementation. However, toxic concentrations are often not included in method validation experiments, and assays often are not validated in the neonatal population. METHODS: We compared serial 25 hydroxy vitamin D [25(OH)D] measurements in pre-term neonates receiving 25(OH)D supplementation and identified 12 patients wherein concentrations of 25(OH)D were above 50 ng/mL (125 nM) that required additional investigations as the 25(OH)D results did not match the clinical picture. Available samples were compared across 4 immunoassay platforms (LIAISON XL, Roche Cobas e602, Abbott Alinity i, and Siemens Centaur XP) and LC-MS/MS. RESULTS: Concentrations of 25(OH)D observed on one individual immunoassay platform (LIAISON XL) fluctuated substantially between subsequent blood draws in select neonates with elevated concentrations. Serum samples from these patients showed variable agreement between LC-MS/MS and other immunoassay platforms. These fluctuations were not explained by the presence of 3-epimer-25(OH)D or 24,25(OH)2D. CONCLUSIONS: Although we were unable to identify a cause for the variable elevated results, our findings suggest that neonatal 25(OH)D measurements alone should not be used for assessment of nutritional monitoring, and that clinical correlation and other laboratory parameters including ionized calcium should be considered.

Adapting obstetric and neonatal services during the COVID-19 pandemic: a scoping review.

BACKGROUND: The provision of care to pregnant persons and neonates must continue through pandemics. To maintain quality of care, while minimizing physical contact during the Severe Acute Respiratory Syndrome-related Coronavirus-2 (SARS-CoV2) pandemic, hospitals and international organizations issued recommendations on maternity and neonatal care delivery and restructuring of clinical and academic services. Early in the pandemic, recommendations relied on expert opinion, and offered a one-size-fits-all set of guidelines. Our aim was to examine these recommendations and provide the rationale and context to guide clinicians, administrators, educators, and researchers, on how to adapt maternity and neonatal services during the pandemic, regardless of jurisdiction. METHOD: Our initial database search used Medical subject headings and free-text search terms related to coronavirus infections, pregnancy and neonatology, and summarized relevant recommendations from international society guidelines. Subsequent targeted searches to December 30, 2020, included relevant publications in general medical and obstetric journals, and updated society recommendations. RESULTS: We identified 846 titles and abstracts, of which 105 English-language publications fulfilled eligibility criteria and were included in our study. A multidisciplinary team representing clinicians from various disciplines, academics, administrators and training program directors critically appraised the literature to collate recommendations by multiple jurisdictions, including a quaternary care Canadian hospital, to provide context and rationale for viable options. INTERPRETATION: There are different schools of thought regarding effective practices in obstetric and neonatal services. Our critical review presents the rationale to effectively modify services, based on the phase of the pandemic, the prevalence of infection in the population, and resource availability.

Lung Ultrasound for Prediction of Bronchopulmonary Dysplasia in Extreme Preterm Neonates: A Prospective Diagnostic Cohort Study.

OBJECTIVES: To evaluate the diagnostic and predictive ability of lung ultrasound at 3 time points in the first 2 weeks after birth for predicting bronchopulmonary dysplasia (BPD) among infants <29 weeks of gestational age. STUDY DESIGN: This was a prospective, diagnostic cohort study. Lung ultrasound was performed on days 3, 7, and 14 after birth and lung ultrasound scores (LUS) were calculated in blinded fashion. Diagnostic test characteristics and area under receiver operating characteristic (AUROC) curves were calculated. RESULTS: A total of 152 infants were enrolled with mean (SD) gestational age of 25.8 (1.5) weeks gestation. Of them, 87 (57%) infants were diagnosed with BPD. The LUS were significantly higher in infants diagnosed with BPD compared with those without BPD at all scan time points (P < .01). The score of >10 at all 3 time points had higher sensitivity (0.89, 0.89, and 0.77), specificity (0.87, 0.90, and 0.92), and corresponding clinically important positive and negative likelihood ratios. The AUROC for LUS at the 3 time points were 0.96, 0.97, and 0.95 on day 3, 7, and 14, respectively. Compared with the model using clinical characteristics, LUS alone had higher AUROC (P < .05 for all 3 time points). CONCLUSIONS: In this cohort, LUS in the first 2 weeks after birth had a very high predictive value for the diagnosis of BPD among infants of <29 weeks of gestation. TRIAL REGISTRATION: ClinicalTrials.govNCT04756297.

Fetal Surgery for Open Spina Bifida in Canada: Initial Results.

OBJECTIVE: Fetal myelomeningocele closure results in better infant outcomes than postnatal closure at the cost of potential prematurity and maternal morbidity. Our aim is to describe the setup of a fetal myelomeningocele closure program in Canada and document its outcomes. METHODS: We conducted a retrospective review of all open fetal myelomeningocele closure surgeries performed at the Ontario Fetal Centre in its first 3 years of operation (2017-2020). Maternal and fetal baseline characteristics, surgical details, pregnancy outcomes, and infant follow-up until 1 year of age were recorded. RESULTS: Twenty-seven women underwent fetal myelomeningocele closure surgery, 10 of whom (37%) resided outside of Ontario. Mean gestational age at surgery was 25.0 ± 0.7 weeks. All surgeries were technically uncomplicated and no fetal deaths occurred. There was a significant negative correlation between increasing experience and skin-to-skin surgical time (R²â€¯= 0.36; P = 0.001). Of the 26 patients who have delivered, 4 (15.4%) experienced preterm prelabour rupture of membranes. Mean gestational age at delivery was 34.9±3.0 weeks. All but 1 patient delivered by cesarean. Maternal complications occurred in 9 women (34.6%). There were no maternal deaths, but 3 (11.5%) infant deaths. Of the 14 surviving infants who have reached at least 1 year of age, 5 (35.7%) underwent ventriculo-peritoneal shunting. Of the 9 infants who have not yet reached 1 year of age, 3 (33.3%) underwent endoscopic third ventriculostomy and none underwent shunting. CONCLUSION: Fetal open spina bifida closure can be performed in Canada, with results similar to those reported by other international expert centres. Long-term follow-up is ongoing.

Development of a Core outcome set for fetal Myelomeningocele (COSMiC): study protocol.

BACKGROUND: Open spina bifida (OSB) is one of the most common congenital central nervous system defects and leads to long-term physical and cognitive disabilities. Open fetal surgery for OSB improves neurological outcomes and reduces the need for ventriculoperitoneal shunting, compared to postnatal surgery, but is associated with a significant risk of prematurity and maternal morbidity. Fetoscopic surgery comes with less maternal morbidity, yet the question remains whether the procedure is neuroprotective and reduces prematurity. Comparison of outcomes between different treatment options is challenging due to inconsistent outcome reporting. We aim to develop and disseminate a core outcome set (COS) for fetal OSB, to ensure that outcomes relevant to all stakeholders are collected and reported in a standardised fashion in future studies. METHODS: The COS will be developed using a validated Delphi methodology. A systematic literature review will be performed to identify outcomes previously reported for prenatally diagnosed OSB. We will assess maternal (primary and subsequent pregnancies), fetal, neonatal and childhood outcomes until adolescence. In a second phase, we will conduct semi-structured interviews with stakeholders, to ensure representation of additional relevant outcomes that may not have been reported in the literature. We will include patients and parents, as well as health professionals involved in the care of these pregnancies and children (fetal medicine specialists, fetal surgeons, neonatologists/paediatricians and allied health). Subsequently, an international group of key stakeholders will rate the importance of the identified outcomes using three sequential online rounds of a modified Delphi Survey. Final agreement on outcomes to be included in the COS, their definition and measurement will be achieved through a face-to-face consensus meeting with all stakeholder groups. Dissemination of the final COS will be ensured through different media and relevant societies. DISCUSSION: Development and implementation of a COS for fetal OSB will ensure consistent outcome reporting in future clinical trials, systematic reviews and clinical practice guidelines. This will lead to higher quality research, better evidence-based clinical practice and ultimately improved maternal, fetal and long-term childhood outcomes. TRIAL REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) CRD42018104880 . Registered on December 5, 2018. Core Outcome Measures in Effectiveness Trials (COMET): 1187.

Review of guidelines and recommendations from 17 countries highlights the challenges that clinicians face caring for neonates born to mothers with COVID-19.

AIM: This review examined how applicable national and regional clinical practice guidelines and recommendations for managing neonates born to mothers with COVID-19 mothers were to the evolving pandemic. METHODS: A systematic search and review identified 20 guidelines and recommendations that had been published by May 25, 2020. We analysed documents from 17 countries: Australia, Brazil, Canada, China, France, India, Italy, Japan, Saudi Arabia, Singapore, South Africa, South Korea, Spain, Sweden, Switzerland, the UK and the United States. RESULTS: The documents were based on expert consensus with limited evidence and were of variable, low methodological rigour. Most did not provide recommendations for delivery methods or managing symptomatic infants. None provided recommendations for post-discharge assimilation of potentially infected infants into the community. The majority encouraged keeping mothers and infants together, subject to infection control measures, but one-third recommended separation. Although breastfeeding or using breastmilk was widely encouraged, two countries specifically prohibited this. CONCLUSION: The guidelines and recommendations for managing infants affected by COVID-19 were of low, variable quality and may be unsustainable. It is important that transmission risks are not increased when new information is incorporated into clinical recommendations. Practice guidelines should emphasise the extent of uncertainty and clearly define gaps in the evidence.

Fetal spina bifida: What we tell the parents.

Worldwide, about 150 000 infants are born with spina bifida yearly, making this condition one of the most common fetal central nervous system anomalies compatible with life. Over the last decade, major changes have been introduced in the prenatal diagnosis and management of spina bifida. In this review, we provide a brief summary of the current management of fetal spina bifida and present essential information that should be provided to expecting parents when their fetus has been diagnosed with spina bifida. This information is focused around common parental questions, as encountered in our typical clinical practice, to facilitate knowledge translation.

Prospective audit and feedback on antibiotic use in neonatal intensive care: a retrospective cohort study.

BACKGROUND: Antimicrobial stewardship programs potentially lead to appropriate antibiotic use, yet the optimal approach for neonates is uncertain. Such a program was implemented in a tertiary care neonatal intensive care unit in October 2012. We evaluated the impact of this program on antimicrobial use and its association with clinical outcomes. METHODS: In a retrospective cohort study, we examined 1580 neonates who received antimicrobials in the 13-months before and 13-months during program implementation. Prospective audit and feedback was given 5 days a week on each patient who was receiving antibiotic. Pharmacy and microbiology data were linked to clinical data from the local Canadian Neonatal Network database. The primary outcome was days of antibiotic therapy per 1000 patient-days; secondary outcomes included mortality, necrotizing enterocolitis, and antibiotic duration for culture-positive and culture-negative late-onset sepsis. The breadth of antibiotic exposure was compared using the Antibiotic Spectrum Index. RESULTS: Overall antibiotic use decreased to 339 days of therapy per 1000 patient-days from 395 (14%, P < 0.001), without an increase in mortality. There was no difference in duration of therapy in culture-negative or culture-positive sepsis, rates of necrotizing enterocolitis, or breadth of antibiotic exposure. Fewer antibiotic starts occurred during program implementation (63% versus 59%, P < 0.001). The use of narrow-spectrum agents decreased (P < 0.001) whereas the use of cefotaxime increased (P = 0.016) during program implementation. CONCLUSIONS: Daily prospective audit and feedback was not associated with a change in antibiotic duration or clinical outcomes, however there were fewer babies started on antibiotics, suggesting that additional interventions are required to inform and sustain changes in antibiotic prescribing practices.

Targeted neonatal echocardiography (TNE) consult service in a large tertiary perinatal center in Canada.

OBJECTIVE: To describe the utilization and study the factors associated with the impact on clinical management of a new TNE consultation service in a perinatal center. METHODS: This retrospective cohort study included all neonates who underwent TNE consultation at the neonatal unit of Mount Sinai Hospital in Toronto, Canada (November 2011 and July 2015). The consults that had "impact" were defined as those that led to a TNE suggested change in the clinical management within 6 h of its recommendation. Logistic regression analysis was performed to identify factors associated with a change in clinical management following the consultation. RESULTS: A total of 553 consults were performed for 268 infants (gestational age: 27 ± 4 weeks and age at initial consult: 16 (5, 34) days). Patent ductus arteriosus (PDA, 61%), suspected pulmonary hypertension (PH, 27%), and systemic hypotension (SH, 9%) were the common indications. The average consultations increased from 9 in 2012-2013 to 20 per month in 2014-2015. Forty eight percent of consults had an impact on clinical management (PDA scans: 38%, PH: 58%, and SH: 81%, p < 0.01 between all). Male gender (adjusted odds ratio (95% confidence interval): 1.9 (1.0, 3.5); p = 0.04), mechanical ventilation (2.43 (1.2, 4.9); p = 0.01), and scans for PH (7.1 (2.2, 23.2); p < 0.01) and SH (2.6 (1.1, 6.5); p = 0.03) were independently associated with the impact on clinical management. TNE consults identified all incidental cases of major structural defects (n = 4), and six out of ten minor diagnoses. CONCLUSIONS: TNE consult service demonstrated an increasing utilization and a significant impact on clinical management over time especially for non-PDA indications and in situations of high-illness severity. Although, all major cardiac defects were identified, some minor congenital defects were missed by TNEs.

Use of Targeted Neonatal Echocardiography and Focused Cardiac Sonography in Tertiary Neonatal Intensive Care Units: Time to Embrace It?

Focused cardiac sonography and targeted neonatal echocardiography refer to goal-directed cardiac imaging using ultrasound, typically by noncardiologic specialists. Although the former consists of a rapid qualitative assessment of cardiac function, which is usually performed by acute care practitioners, the latter refers to detailed functional echocardiography to obtain quantitative and qualitative indexes of pulmonary and systemic hemodynamics in sick neonates and is typically performed by neonatologists. Although the use of these modalities is increasing, they still remain unavailable in most North American centers providing acute care to neonates, partly because of limited data regarding their direct impact on patient care. Here we present a series of 5 cases from a large perinatal unit in which immediate availability of relevant expertise led to important and arguably life-saving clinical interventions. In 4 of these cases, focused cardiac sonography was sufficient to make the diagnosis, whereas in 1 case, clinical integration of detailed systemic hemodynamics measured on target neonatal echocardiography was required.

Further expansion of the phenotypic spectrum associated with mutations in ALDH18A1, encoding Δ¹-pyrroline-5-carboxylate synthase (P5CS).

We report on the third case of cutis laxa and progeroid features caused by a homozygous mutation in ALDH18A1 that encodes Δ¹-pyrroline-5-carboxylate-synthase (P5CS). This severely affected child, born to consanguineous parents of Pakistani origin, presented with lax, wrinkled and thin skin with dilated and tortuous subcutaneous blood vessels, corneal clouding, and hypotonia. The child had severe global developmental delay and feeding difficulties and died in infancy for an unknown reason. The proband was homozygous for a mutation in ALDH18A1, c.1923 + 1G > A which results in the production of two anomalous transcripts that are predicted to encode proteins lacking the catalytic site for the enzyme. The cellular phenotype is characterized by diminished production of collagen types I and III, altered elastin ultrastructure, and diminished cell proliferation of cultured dermal fibroblasts. This severe clinical and cellular phenotype overlaps with a broad group of neurocutaneous syndromes that include cutis laxa type II, wrinkly skin syndrome, de Barsy syndrome, and gerodermia osteodysplastica. The findings presented here emphasize the pleiotropic presentation of this group of conditions and suggest that multiple components of the extracellular matrix are perturbed in these disorders.

A role for platelet-derived growth factor-BB in rat postpneumonectomy compensatory lung growth.

Unilateral pneumonectomy leads to compensatory growth in the residual lung, the mediators of which are largely unknown. We hypothesized, based on its other known roles in lung cell growth, that platelet-derived growth factor (PDGF)-BB would be an essential mediator of postpneumonectomy compensatory lung growth. Left-sided pneumonectomies were performed on 21-d-old rats, for comparison with sham-operated or unoperated control animals. Body weights were not different between groups. Right lung weights and DNA content were significantly increased (p < 0.05), compared with controls, by 10 d after pneumonectomy. The rate of DNA synthesis was maximal on d 5 postpneumonectomy. Total right lung PDGF-B mRNA and PDGF-BB protein increased after pneumonectomy, but were apparently tightly regulated, relative to total right lung beta-actin mRNA and protein content, respectively. However, PDGF-BB expression after pneumonectomy was apparently not purely constitutive, in that daily i.p. injections of a truncated soluble PDGF beta-receptor both reduced activation of the native PDGF beta-receptor, and attenuated increased lung DNA synthesis on d 3 after pneumonectomy. These findings are consistent with a critical role for PDGF-BB in postpneumonectomy lung growth.