Hemodynamic management of congenital diaphragmatic hernia: the role of targeted neonatal echocardiography.

Congenital diaphragmatic hernia (CDH) is a major congenital anomaly, resulting from the herniation of abdominal contents into the thoracic cavity, thereby impeding the proper development of the lungs and pulmonary vasculature. CDH severity correlates with a spectrum of pulmonary hypoplasia, pulmonary hypertension (PHT), and cardiac dysfunction, constituting the pathophysiological triad of this complex condition. The accurate diagnosis and effective management of PHT and cardiac dysfunction is pivotal to optimizing patient outcomes. Targeted neonatal echocardiography is instrumental in delivering real-time data crucial for the bespoke, pathophysiology-targeted hemodynamic management of CDH-associated PHT.

COVID-19 Pandemic-Related Changes in Rates of Neonatal Abstinence Syndrome.

This cross-sectional study examines COVID-19 pandemic­related changes in rates of neonatal abstinence syndrome (NAS) and whether infants in urban or rural areas and those with low socioeconomic status were disproportionately affected.

Should we "eliminate" PDA shunt in preterm infants? A narrative review.

The patent ductus arteriosus frequently poses a significant morbidity in preterm infants, subjecting their immature pulmonary vascular bed to substantial volume overload. This, in turn, results in concurrent hypoperfusion to post-ductal organs, and subsequently alters cerebral blood flow. In addition, treatment has not demonstrated definitive improvements in patient outcomes. Currently, the optimal approach remains a subject of considerable debate with ongoing research controversy regarding the best approach. This article provides a comprehensive review of existing literature.

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".

Long-Term Neurodevelopmental Impairment among Very Preterm Infants with Sepsis, Meningitis, and Intraventricular Hemorrhage.

INTRODUCTION: Sepsis and intraventricular hemorrhage (IVH) are associated with poorer long-term neurodevelopmental outcomes in very preterm infants (VPIs), but less is known about the long-term effect of meningitis and the combined impact of both meningitis and IVH. Our objective was to examine the long-term neurodevelopmental outcomes of VPIs with late onset sepsis and meningitis, with and without IVH, in Canada. METHODS: We conducted a retrospective cohort study of all infants <29 weeks GA who were admitted to 26 tertiary-level neonatal intensive care units in the Canadian Neonatal Network (CNN) and Canadian Neonatal Follow-Up Network (CNFUN) databases, from January 1, 2010, to December 31, 2016. RESULTS: Of the 6,322 infants in the cohort, 4,575 had no infection, 1,590 had late onset culture-positive bloodstream infection (CPBSI) only, and 157 had late onset meningitis. There was a significant (p < 0.05) trend of increasing rates of significant neurodevelopmental delay (sNDI) when comparing infants with no infection (sNDI rate 15.0%), late onset CPBSI (sNDI rate 22.9%), and late onset meningitis (sNDI rate 32.0%), even after adjustment for infant characteristics. Similar trends were observed for neurodevelopmental impairment, cerebral palsy, and individual Bayley-III scores <85 for cognitive, language, and motor development. There was an additive effect of IVH in all infant categories, but there was no multiplicative effect between IVH and late onset meningitis. CONCLUSION: There was an increasing trend of adverse neurodevelopmental outcomes when infants with no infection, late onset CPBSI and late onset meningitis are compared. IVH had an additive effect.

The impact of a care bundle with an emphasis on hemodynamic assessment on the short-term outcomes in neonates with congenital diaphragmatic hernia.

OBJECTIVE: To evaluate the short-term outcomes of implementing a care bundle emphasizing frequent hemodynamic assessments by echocardiography in neonates with congenital diaphragmatic hernia (CDH). STUDY DESIGN: This was a retrospective cohort study of infants with CDH admitted to a quaternary perinatal unit from January 2013 to March 2021. The primary composite outcome was defined as mortality or use of extracorporeal membrane oxygenation or need for respiratory support at discharge. RESULTS: We identified 37 and 20 CDH infants in Epoch I and II, respectively. More patch repairs (50% vs. 21.9%, p = 0.035) and echocardiograms (6[4-8] vs. 1[0-5], p = 0.003) were performed in Epoch II. While there were no differences in the primary outcome, there was a reduction in mortality in Epoch II (0% vs. 27%, p = 0.01). CONCLUSION: With the implementation of a CDH care bundle with an emphasis on hemodynamic assessment, we demonstrated a significant reduction in mortality.

Antibiotic use in Canadian neonatal intensive care units: a national survey for developing antimicrobial stewardship targets.

A survey was conducted among Canadian tertiary neonatal intensive care units. Of the 27 sites who responded, 9 did not have any form of antimicrobial stewardship, and 11 used vancomycin for empirical coverage in late-onset-sepsis evaluations. We detected significant variations in the diagnostic criteria for urinary tract infection and ventilator-associated pneumonia.

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.

Fluid overload in newborns undergoing abdominal surgery: a retrospective study.

BACKGROUND: Fluid management in newborns undergoing surgery can be challenging due to difficulties in accurately assessing volume status in context of high fluid needs perioperatively and postoperative third-space fluid loss. Fluid overload can be associated with an increase in neonatal morbidity and mortality. OBJECTIVE: Our objective was to determine the burden of fluid overload and to evaluate their associations with adverse effects among infants undergoing abdominal surgery at a tertiary perinatal center. METHODS: Patients from our Neonatal Intensive Care Unit who underwent abdominal surgery from January 2017 to June 2019 were included in this retrospective cohort study. Fluid balance was assessed based on the maximum percentage change in body weight at 3- and 7-postoperative days. RESULTS: Sixty infants were included, with a median [interquartile range] gestational age (GA) of 29 [25-36] weeks and birth weight of 1240 [721-2871] grams. The median daily actual fluid intake was significantly higher than the prescribed fluid intake in the first 7 postoperative days (163 vs. 145 mL/kg, p < .01). The median maximum change of body weight by postoperative days 3 and 7 were 6% [3-13] and 11% [5-17], respectively. A 1% increase in weight within the first 3 postoperative days was associated with a 0.6-day increase for invasive ventilatory support (p = .012). The correlation was still significant after adjusting for GA (p = .033). CONCLUSION: Fluid overload within the first 3 postoperative days was associated with an increase in ventilator support among infants. Careful attention to fluid management may affect the optimization of outcomes for newborns undergoing abdominal surgery.

Targeted neonatal echocardiography for patent ductus arteriosus in neonates reduces the surgical ligation rate without affecting healthcare outcomes.

Background: Surgical ligation of patent ductus arteriosus (PDA) can be associated with long-term morbidity and adverse outcomes in neonates. Targeted neonatal echocardiography (TNE) has been increasingly used to improve the hemodynamic management. We aimed to evaluate the preoperative assessment impacts of the hemodynamic significance of PDA using TNE on PDA ligation rates and neonatal outcomes. Methods: This observational study included preterm infants who underwent PDA ligation during two epochs (Epoch I: January 2013 to December 2014; Epoch II: January 2015 to June 2016). During Epoch II, a comprehensive TNE assessment was performed preoperatively to evaluate the hemodynamic significance of PDA. Primary outcome was the incidence of PDA ligation. Secondary outcomes included the incidence of postoperative cardiorespiratory instabilities, individual morbidities, and the composite outcome of death. Results: A total of 69 neonates underwent PDA ligation. No difference in baseline demographics was found between the epochs. The incidence of PDA ligation in very low birth weight (VLBW) infants was lower during Epoch II than Epoch I [7.5% vs. 14.6%, rate ratio =0.51 (95% confidence interval =0.30-0.88)]. No differences were observed between epochs in the proportion of VLBW infants who developed post-operative hypotension or oxygenation failure. The composite outcome of death or major morbidity did not significantly differ between Epoch I and Epoch II (91.1% vs. 94.1%, P=1.000). Conclusions: Incorporating TNE into a standardized hemodynamic assessment program, we demonstrated a 49% reduction in PDA ligation rate without any increase in postoperative cardiopulmonary instability or short-term neonatal morbidities in a cohort of VLBW infants.

Effectiveness of a neonatal intensive care unit-specific antimicrobial stewardship program: A ten-year review.

OBJECTIVE: To evaluate the change in consumption of specific antibiotics in a neonatal intensive care unit after the implementation of an antimicrobial stewardship program (ASP). DESIGN: Retrospective cohort study between January 1, 2010, and December 31,2019. SETTING: The neonatal intensive care unit at British Columbia Women's Hospital (Vancouver Canada), a tertiary-care center. PATIENTS: Admitted neonates prescribed antibiotics. METHODS: We implemented an ASP with an early implementation phase starting in January 2014 (period 2) and a later phase starting in January 2017 (period 3). Patient demographics were collected, including birth weight, gestational age, history of necrotizing enterocolitis (NEC), and surgical operations from existing databases. Interrupted time-series analysis was used, and comparison of antibiotic days of therapy (DOT) averages were conducted across the preimplementation period (period 1), period 2, and period 3 regarding total patients and subgroups. RESULTS: We identified 4,512 infants. There was a significant decrease in DOT from 472 (95% confidence interval [CI], 431-517) in period 1 to 405 (95% CI, 367-446) in period 2 to 313 (95% CI, 280-350) in period 3. We detected a significant decrease in the use of ampicillin, aminoglycosides, cloxacillin, and linezolid but not in vancomycin or cefotaxime. Subgroup analyses of infants <1,500 g and those without NEC or surgery showed decreases in the use of cloxacillin, aminoglycosides, and linezolid. CONCLUSIONS: The implementation of an ASP was associated with a significant decrease in the overall DOT and use of certain antibiotics. This study presents important targets for ongoing ASP work.

Left ventricular dysfunction in the immediate post-natal period.

Background: Our objective was to examine the clinical presentation, echocardiographic findings, and outcomes of newborns presenting with left ventricle (LV) dysfunction in the first 48 hours of life without perinatal asphyxia or structural heart disease. We hypothesize that LV dysfunction may occur due to maladaptation to extrauterine life. Methods: This is a retrospective cohort analysis including infants born in a quaternary perinatal centre. Late preterm and term neonates who were diagnosed with left ventricular dysfunction at less than 48 hours of life were identified using an echocardiography clinical laboratory's database and extracorporeal life support database. LV dysfunction was defined as m-mode fractional shortening (FS) <28% or ejection fraction (EF) <50% on echocardiography or reduced function reported by a cardiologist. Data extracted included patient & maternal demographics, echocardiogram parameters, clinical status, and medications. The primary outcome measure was time to recovery of LV function based on echocardiography. Results: Of the 69 patients identified, 19 patients were included in the final analysis. The mean gestational age was 38 weeks. Thirteen (68%) infants did not have an underlying cause identified despite extensive work-up. Four (21%) infants had exposure to maternal illicit drug use during pregnancy. Three infants died, and all infants without identifiable etiologies had recovery of LV function within 14 days of life. Conclusions: LV dysfunction can occur during the abrupt transition from fetal to neonatal circulation and can be associated with maternal illicit drug use.

Variability in antimicrobial use among infants born at <33 weeks gestational age.

Excessive antimicrobial use is associated with adverse neonatal outcomes. In our cohort of 27,163 infants born at <33 weeks gestational age, the first week after birth accounted for the highest rates of antimicrobial use, and variability across sites persisted after adjustment for patient characteristics correlated with illness severity.

Acute kidney injury among preterm infants receiving nonsteroidal anti-inflammatory drugs: A pilot study.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are a frequently prescribed class of medications in the neonatal intensive care unit (NICU). We aimed to reveal acute kidney injury (AKI) epidemiology in NSAID-exposed premature infants admitted to the NICU using a standardized definition and determine the percentage of NSAID-exposed patients with adequate serum creatinine (SCr) monitoring. METHODS: This retrospective study compared infants born at ≤34 weeks gestational age who received NSAID for intraventricular hemorrhage prophylaxis (prophylaxis group) or symptomatic treatment for patent ductus arteriosus (PDA; treatment group) between January and December 2014 at a tertiary NICU. All available SCr and 12-h urine output (UO) values were recorded from admission until day seven post-NSAID exposure. AKI incidence was determined using the neonatal modified Kidney Disease Improving Global Outcomes classification, defined as an increase in SCr (i.e., 1.5 fold rise from previous SCr measurement within seven days or 26.5 mmol/L increase within 48 h) or UO < 1 mL/kg/hour, excluding the first 24 h of life. RESULTS: We identified 70 eligible subjects; 32 received prophylactic NSAIDs, and 38 received indomethacin or ibuprofen for treating symptomatic PDA. AKI incidence for the entire cohort was 23% (16/70). The prophylaxis group had a significantly lower AKI rate than the treatment group (9% vs. 34%; p = 0.014). The treatment group had a higher proportion of infants with adequate SCr monitoring during NSAID treatment than the prophylaxis group (87% vs. 13%, p < 0.001). CONCLUSION: NSAID-associated AKI occurred in approximately one-quarter of premature infants overall, and the AKI incidence was higher in infants treated with NSAIDs for the symptomatic treatment of PDA than in those receiving prophylactic treatment during the first day of life. Standardized protocols for monitoring daily SCr and UO after exposure should be implemented for all neonates with NSAID exposure to improve early AKI recognition and management.

Infants Born to Mothers Who Were SARS-CoV-2 Positive during Pregnancy and Admitted to Neonatal Intensive Care Unit.

INTRODUCTION: Our objective was to compare neonatal outcomes and resource use of neonates born to mothers with SARS-CoV-2 positivity during pregnancy with neonates born to mothers without SARS-CoV-2 positivity. METHODS: We conducted a two-country cohort study of neonates admitted between January 1, 2020, and September 15, 2021, to tertiary neonatal intensive care unit (NICU) in Canada and Sweden. Neonates from mothers who were SARS-CoV-2 positive during pregnancy were compared with three randomly selected NICU neonates of mothers who were not test-positive, matched on gestational age, sex, and birth weight (±0.25 SD). Subgroup analyses were conducted for neonates born <33 weeks' gestation and mothers who were SARS-CoV-2 positive ≤10 days prior to birth. Primary outcome was duration of respiratory support. Secondary outcomes were in-hospital mortality, neonatal morbidity, late-onset sepsis, receipt of breast milk at discharge, and length of stay. RESULTS: There were 163 exposed and 468 matched neonates in Canada, and 303 exposed and 903 matched neonates in Sweden. There was no statistically significant difference in invasive or noninvasive respiratory support durations, mortality, respiratory and other neonatal morbidities, or resource utilizations between two groups in both countries in entire cohort and in subgroup analyses. Receipt of breast milk at discharge was lower in the Canadian neonates of mothers who were SARS-CoV-2 positive ≤10 days before birth (risk ratio 0.68, 95% CI: 0.57-0.82). CONCLUSION: Maternal SARS-CoV-2 positivity was not associated with increased durations of respiratory support, morbidities, mortality, or length of hospital stay in Canada and Sweden among neonates admitted to tertiary NICU.

Practice Summary of Antimicrobial Therapy for Commonly Encountered Conditions in the Neonatal Intensive Care Unit: A Canadian Perspective.

Neonates are highly susceptible to infections owing to their immature cellular and humoral immune functions, as well the need for invasive devices. There is a wide practice variation in the choice and duration of antimicrobial treatment, even for relatively common conditions in the NICU, attributed to the lack of evidence-based guidelines. Early decisive treatment with broad-spectrum antimicrobials is the preferred clinical choice for treating sick infants with possible bacterial infection. Prolonged antimicrobial exposure among infants without clear indications has been associated with adverse neonatal outcomes and increased drug resistance. Herein, we review and summarize the best practices from the existing literature regarding antimicrobial use in commonly encountered conditions in neonates.

Antimicrobial utilization in very-low-birth-weight infants: association with probiotic use.

OBJECTIVE: To examine the association between probiotic use and antimicrobial utilization. STUDY DESIGN: We retrospectively evaluated very-low-birth-weight (VLBW) infants admitted to tertiary neonatal intensive care units in Canada between 2014 and 2019. Our outcome was antimicrobial utilization rate (AUR) defined as number of days of antimicrobial exposure per 1000 patient-days. RESULT: Of 16,223 eligible infants, 7279 (45%) received probiotics. Probiotic use rate increased from 10% in 2014 to 68% in 2019. The AUR was significantly lower in infants who received probiotics vs those who did not (107 vs 129 per 1000 patient-days, aRR = 0.89, 95% CI [0.81, 0.98]). Among 13,305 infants without culture-proven sepsis or necrotizing enterocolitis ≥Stage 2, 5931 (45%) received probiotics. Median AUR was significantly lower in the probiotic vs the no-probiotic group (78 vs 97 per 1000 patient-days, aRR = 0.85, 95% CI [0.74, 0.97]). CONCLUSION: Probiotic use was associated with a significant reduction in AUR among VLBW infants.

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.