Association of Shift-Level Organizational Factors with Nosocomial Infection in the Neonatal Intensive Care Unit.

Objective: To evaluate the association between shift-level organizational data (unit occupancy, nursing overtime ratios [OTRs], and nursing provision ratios [NPRs]) with nosocomial infection (NI) among infants born very preterm in the neonatal intensive care unit (NICU). Study design: This was a multicenter, retrospective cohort study, including 1921 infants 230/7-326/7 weeks of gestation admitted to 3 tertiary-level NICUs in Quebec between 2014 and 2018. Patient characteristics and outcomes (NIs) were obtained from the Canadian Neonatal Network database and linked to administrative data. For each shift, unit occupancy (occupied/total beds), OTR (nursing overtime hours/total nursing hours), and NPR (number of actual/number of recommended nurses) were calculated. Mixed-effect logistic regression models were used to calculate aOR for the association of organizational factors (mean over 3 days) with the risk of NI on the following day for each infant. Results: Rate of NI was 11.5% (220/1921). Overall, median occupancy was 88.7% [IQR 81.0-94.6], OTR 4.4% [IQR 1.5-7.6], and NPR 101.1% [IQR 85.5-125.1]. A greater 3-day mean OTR was associated with greater odds of NI (aOR 1.08, 95% CI 1.02-1.15), a greater 3-day mean NPR was associated lower odds of NI (aOR 0.96, 95% CI 0.95-0.98), and occupancy was not associated with NI (aOR, 0.99, 95% CI 0.96-1.02). These findings were consistent across multiple sensitivity analyses. Conclusions: Nursing overtime and nursing provision are associated with the adjusted odds of NI among infants born very preterm in the NICU. Further interventional research is needed to infer causality.

Practice recommendations regarding parental presence in NICUs during pandemics caused by respiratory pathogens like COVID-19.

Aim: To co-create parental presence practice recommendations across Canadian NICUs during pandemics caused by respiratory pathogens such as COVID-19. Methods: Recommendations were developed through evidence, context, Delphi and Values and Preferences methods. For Delphi 1 and 2, participants rated 50 items and 20 items respectively on a scale from 1 (very low importance) to 5 (very high). To determine consensus, evidence and context of benefits and harms were presented and discussed within the Values and Preference framework for the top-ranked items. An agreement of 80% or more was deemed consensus. Results: After two Delphi rounds (n = 59 participants), 13 recommendations with the highest rated importance were identified. Consensus recommendations included 6 strong recommendations (parents as essential caregivers, providing skin-to-skin contact, direct or mothers' own expressed milk feeding, attending medical rounds, mental health and psychosocial services access, and inclusion of parent partners in pandemic response planning) and 7 conditional recommendations (providing hands-on care tasks, providing touch, two parents present at the same time, food and drink access, use of communication devices, and in-person access to medical rounds and mental health and psychosocial services). Conclusion: These recommendations can guide institutions in developing strategies for parental presence during pandemics caused by respiratory pathogens like COVID-19.

Preterm Birth, Family Income, and Intergenerational Income Mobility.

Importance: Preterm birth (PTB) has been associated with lower income in adulthood, but associations with intergenerational income mobility and the role of family socioeconomic status (SES) as modifying factor are unclear. Objectives: To assess whether the association between PTB and income differs according to family SES at birth and to assess the association between PTB and intergenerational income mobility. Design, Setting, and Participants: This study comprised a matched cohort of live births in Canada between January 1, 1990, and December 31, 1996, with follow-up until December 31, 2018. Statistical analysis was performed between May 2023 and March 2024. Exposure: Preterm birth, defined as birth between 24 and 37 weeks' gestational age (with gestational age subcategories of 34-36, 32-33, 28-31, and 24-27 weeks) vs early and full term births (gestational age, 37-41 weeks). Main Outcomes and Measures: Associations between PTB and annual adulthood income in 2018 Canadian dollars were assessed overall (current exhange rate: $1 = CAD $1.37) and stratified by family income quintiles, using generalized estimating equation regression models. Associations between PTB and percentile rank change (ie, difference between the rank of individuals and their parents in the income distribution within their respective generations) and upward or downward mobility (based on income quintile) were assessed using linear and multinomial logistic regressions, respectively. Results: Of 1.6 million included births (51.1% boys and 48.9% girls), 6.9% infants were born preterm (5.4% born at 34-36 weeks, 0.7% born at 32-33 weeks, 0.5% born at 28-31 weeks, and 0.2% born at 24-27 weeks). After matching on baseline characteristics (eg, sex, province of birth, and parental demographics) and adjusting for age and period effects, PTB was associated with lower annual income (mean difference, CAD -$687 [95% CI, -$788 to -$586]; 3% lower per year), and the differences were greater among those belonging to families in the lowest family SES quintile (mean difference, CAD -$807 [95% CI, -$998 to -$617]; 5% lower per year). Preterm birth was also associated with lower upward mobility and higher downward mobility, particularly for those born earlier than 31 weeks' gestational age (24-27 weeks: mean difference in percentile rank change, -8.7 percentile points [95% CI, -10.5 to -6.8 percentile points]). Conclusions and Relevance: In this population-based matched cohort study, PTB was associated with lower adulthood income, lower upward social mobility, and higher downward mobility, with greater differences among those belonging to economically disadvantaged families. Interventions to optimize socioeconomic outcomes of preterm-born individuals would need to define target population considering SES.

Late-Onset Sepsis among Extremely Preterm Infants of 24-28 Weeks Gestation: An International Comparison in 10 High-Income Countries.

INTRODUCTION: Despite advances in neonatal care, late-onset sepsis remains an important cause of preventable morbidity and mortality. Neonatal late-onset sepsis rates have decreased in some countries, while in others they have not. Our objective was to compare trends in late-onset sepsis rates in 9 population-based networks from 10 countries and to assess the associated mortality within 7 days of late-onset sepsis. METHODS: We performed a retrospective population-based cohort study. Infants born at 24-28 weeks' gestation between 2007 and 2019 were eligible for inclusion. Late-onset sepsis was defined as a positive blood or cerebrospinal fluid culture. Late-onset sepsis rates were calculated for 3 epochs (2007-11, 2012-15, and 2016-19). Adjusted risk ratios (aRRs) for late-onset sepsis were calculated for each network. RESULTS: Of a total of 82,850 infants, 16,914 (20.4%) had late-onset sepsis, with Japan having the lowest rate (7.1%) and Spain the highest (44.6%). Late-onset sepsis rates decreased in most networks and remained unchanged in a few. Israel, Sweden, and Finland showed the largest decrease in late-onset sepsis rates. The aRRs for late-onset sepsis showed wide variations between networks. The rate of mortality temporally related to late-onset sepsis was 10.9%. The adjusted mean length of stay for infants with late-onset sepsis was increased by 5-18 days compared to infants with no late-onset sepsis. CONCLUSIONS: One in 5 neonates of 24-28 weeks' gestation develops late-onset sepsis. Wide variability in late-onset sepsis rates exists between networks with most networks exhibiting improvement. Late-onset sepsis was associated with increased mortality and length of stay.

Early Bubble CPAP Protocol Implementation and Rates of Death or Severe BPD.

BACKGROUND: A multidisciplinary comprehensive protocol to use bubble continuous positive airway pressure (bCPAP) as the primary respiratory support in the delivery room (DR) and the NICU was introduced. With this study, we aimed to assess the association of this change with respiratory outcomes over time. METHODS: Infants with gestational age <32 weeks and birth weight <1250 g admitted between January 2012 and June 2020 were included and categorized into 4 periods, including pre-implementation (P0: 2012-2014), and post-implementation (P1: 2014-2016, P2: 2016-2018, P3: 2018-2020). The primary outcome was the rates of death and severe bronchopulmonary dysplasia (BPD), and the secondary outcomes included the rates of DR and NICU intubation ≤7 days of age, need of surfactant, and pneumothorax. Multivariate logistic regression models accounting for relevant risk factors were used to calculate adjusted odds ratios (ORs). RESULTS: The study included 440 infants (P0 = 90, P1 = 91, P2 = 128, P3 = 131). Over time, more infants were free of BPD (P < .001), and the rates of death and severe BPD decreased significantly: P1 = OR 1.21 (95% confidence interval [CI] 0.56-2.67), P2 = OR 0.45 (95% CI 0.20-0.99), and P3 = OR 0.37 (95% CI 0.15-0.84). DR intubation decreased from 66% (P0) to 24% (P3) in the entire cohort (P < .001) and from 96% (P0) to 40% (P3) in infants <26 weeks of age (P < .001). The need for NICU intubation was similar (P = .98), with a decreased need for surfactant (P = .001) occurring at higher FiO2 (P0 = 0.35 vs P3 = 0.55, P < .001). Pneumothorax rates were unchanged. CONCLUSIONS: In very preterm infants, the implementation of a comprehensive bCPAP protocol led to a significant and consistent improvement in respiratory practices and the rates of death and severe BPD.

Does the use of higher versus lower oxygen concentration improve neurodevelopmental outcomes at 18-24 months in very low birthweight infants?

BACKGROUND: Immediately after birth, the oxygen saturation is between 30 and 50%, which then increases to 85-95% within the first 10 min. Over the last 10 years, recommendations regarding the ideal level of the initial fraction of inspired oxygen (FiO2) for resuscitation in preterm infants have changed from 1.0, to room air to low levels of oxygen (< 0.3), up to moderate concentrations (0.3-0.65). This leaves clinicians in a challenging position, and a large multi-center international trial of sufficient sample size that is powered to look at safety outcomes such as mortality and adverse neurodevelopmental outcomes is required to provide the necessary evidence to guide clinical practice with confidence. METHODS: An international cluster, cross-over randomized trial of initial FiO2 of 0.3 or 0.6 during neonatal resuscitation in preterm infants at birth to increase survival free of major neurodevelopmental outcomes at 18 and 24 months corrected age will be conducted. Preterm infants born between 230/7 and 286/7 weeks' gestation will be eligible. Each participating hospital will be randomized to either an initial FiO2 concentration of either 0.3 or 0.6 to recruit for up to 12 months' and then crossed over to the other concentration for up to 12 months. The intervention will be initial FiO2 of 0.6, and the comparator will be initial FiO2 of 0.3 during respiratory support in the delivery room. The sample size will be 1200 preterm infants. This will yield 80% power, assuming a type 1 error of 5% to detect a 25% reduction in relative risk of the primary outcome from 35 to 26.5%. The primary outcome will be a composite of all-cause mortality or the presence of a major neurodevelopmental outcome between 18 and 24 months corrected age. Secondary outcomes will include the components of the primary outcome (death, cerebral palsy, major developmental delay involving cognition, speech, visual, or hearing impairment) in addition to neonatal morbidities (severe brain injury, bronchopulmonary dysplasia; and severe retinopathy of prematurity). DISCUSSION: The use of supplementary oxygen may be crucial but also potentially detrimental to preterm infants at birth. The HiLo trial is powered for the primary outcome and will address gaps in the evidence due to its pragmatic and inclusive design, targeting all extremely preterm infants. Should 60% initial oxygen concertation increase survival free of major neurodevelopmental outcomes at 18-24 months corrected age, without severe adverse effects, this readily available intervention could be introduced immediately into clinical practice. TRIAL REGISTRATION: The trial was registered on January 31, 2019, at ClinicalTrials.gov with the Identifier: NCT03825835.

CPAP Versus NIPPV Postextubation in Preterm Neonates: A Comparative-Effectiveness Study.

BACKGROUND AND OBJECTIVES: Nasal intermittent positive pressure ventilation (NIPPV) has been shown to be superior to nasal continuous positive airway pressure (CPAP) postextubation in preterm neonates. However, studies have not permitted high CPAP pressures or rescue with other modes. We hypothesized that if CPAP pressures >8 cmH2O and rescue with other modes were permitted, CPAP would be noninferior to NIPPV. METHODS: We conducted a pragmatic, comparative-effectiveness, noninferiority study utilizing network-based real-world data from 22 Canadian NICUs. Centers self-selected CPAP or NIPPV as their standard postextubation mode for preterm neonates <29 weeks' gestation. The primary outcome was failure of the initial mode ≤72 hours. Secondary outcomes included failure ≤7 days, and reintubation ≤72 hours and ≤7 days. Groups were compared using a noninferiority adjusted risk-difference (aRD) margin of 0.05, and margin of no difference. RESULTS: A total of 843 infants extubated to CPAP and 974 extubated to NIPPV were included. CPAP was not noninferior (and inferior) to NIPPV for failure of the initial mode ≤72 hours (33.0% vs 26.3%; aRD 0.07 [0.03 to 0.12], Pnoninferiority(NI) = .86), and ≤7 days (40.7% vs 35.8%; aRD 0.09 [0.05 to 0.13], PNI = 0.97). However, CPAP was noninferior (and equivalent) to NIPPV for reintubation ≤72 hours (13.2% vs 16.1%; aRD 0.01 [-0.05 to 0.02], PNI < .01), and noninferior (and superior) for reintubation ≤7 days (16.4% vs 22.8%; aRD -0.04 [-0.07 to -0.001], PNI < .01). CONCLUSIONS: CPAP was not noninferior to NIPPV for failure ≤72 hours postextubation; however, it was noninferior to NIPPV for reintubation ≤72 hours and ≤7 days. This suggests CPAP may be a reasonable initial postextubation mode if alternate rescue strategies are available.

Process and Outcome Measures for Infants Born Moderate and Late Preterm in Tertiary Canadian Neonatal Intensive Care Units.

OBJECTIVE: To describe the prevalence of and between-center variations in care practices and clinical outcomes of moderate and late preterm infants (MLPIs) admitted to tertiary Canadian neonatal intensive care units (NICUs). STUDY DESIGN: This was a retrospective cohort study including infants born at 320/7 through 366/7 weeks of gestation and admitted to 25 NICUs participating in the Canadian Neonatal Network between 2015 and 2020. Patient characteristics, process measures represented by care practices, and outcome measures represented by clinical in-hospital and discharge outcomes were reported by gestational age weeks. NICUs were compared using indirect standardization after adjustment for patient characteristics. RESULTS: Among 25 669 infants (17% of MLPIs born in Canada during the study period) included, 45% received deferred cord clamping, 7% had admission hypothermia, 47% received noninvasive respiratory support, 11% received mechanical ventilation, 8% received surfactant, 40% received antibiotics in the first 3 days, 4% did not receive feeding in the first 2 days, and 77% had vascular access. Mortality, early-onset sepsis, late-onset sepsis, or necrotizing enterocolitis occurred in <1% of the study cohort. Median (IQR) length of stay was 14 (9-21) days among infants discharged home from the admission hospital and 5 (3-9) days among infants transferred to community hospitals. Among infants discharged home, 33% were discharged on exclusive breastmilk and 75% on any breastmilk. There were significant variations between NICUs in all process and outcome measures. CONCLUSIONS: Care practices and outcomes of MLPIs varied significantly between Canadian NICUs. Standardization of process and outcome quality measures for this population will enable benchmarking and research, facilitating systemwide improvements.

Association of Exclusive Breast Milk Intake and Outcomes in Infants With Uncomplicated Gastroschisis: A National Cohort Study.

BACKGROUND: Enteral feeding is an essential part of the management of infants with gastroschisis. We hypothesized that exclusive breast milk is associated with improved neonatal outcomes. METHODS: We conducted a retrospective review of infants with uncomplicated gastroschisis through the Canadian Pediatric Surgery Network (CAPSNet) and Canadian Neonatal Network (CNN). The primary outcome was time to full enteral feeds. RESULTS: We identified 411 infants with gastroschisis treated at CAPSNet centres from 2014 to 2022. 144 patients were excluded due to gestational age <32 weeks, birth weight <1500 g, other congenital anomalies, or complicated gastroschisis. Of the remaining 267 participants, 78% (n = 209) received exclusive breast milk diet in the first 28 days of life, whereas 22% (n = 58) received supplemental or exclusive formula. Infants who received exclusive breast milk experienced higher time to reach full enteral feeding (median 24 vs 22 days, p = 0.047) but were more likely to have undergone delayed abdominal closure (32% vs 17%, p = 0.03). After adjustment, there were no significant differences between groups in time to reach full enteral feeds, duration of parenteral nutrition, or length of stay. Infants who received supplemental or exclusive formula had a similar risk of necrotizing enterocolitis (4% vs 3%) but were less likely to transition to exclusive breast milk at discharge (73% vs 11%, p < 0.001). CONCLUSION: Early use of exclusive breast milk in infants with uncomplicated gastroschisis is associated with similar outcomes compared to supplemental or exclusive formula. Patients who received supplemental or exclusive formula were unlikely to transition to exclusive breastfeeding by discharge. LEVEL OF EVIDENCE: Level IIb (Individual Cohort Study).

Provincial Review of Adherence to Age-specific Guidelines for Umbilical Hernia Repair and Trends in Management.

BACKGROUND: Umbilical hernia (UH) is a common pediatric condition, for which delaying surgical repair for asymptomatic UH until after age 3 is recommended due to a high incidence of spontaneous closure. We aimed to determine the adherence to guidelines, rate of urgent surgical repair, outcomes, cost, and interinstitutional referral patterns of UH repair in the province of Quebec (Canada). METHODS: This was a population-based retrospective cohort study of children 28 days to 17 years old who underwent UH repair between 2010 and 2020 using health administrative databases. Children who had multiple procedures, or prolonged peri-operative stays were excluded. Early repair was defined as elective surgery at or under age 3. RESULTS: Of the 3215 children, 1744 (54.2%) were female, and 1872 (58.2%) were treated in a tertiary children's hospital. Guidelines were respected for 2853 out of 3215 children (89.7%). Patients living over 75 km from their treating hospitals (OR 2.36, 95% CI 1.33-4.16, P < 0.01), with pre-existing comorbidities (OR, 2.82; 95% CI, 1.96-4.05; P < 0.001), or being treated in a tertiary center (OR 2.10, 95% CI 1.45-3.03, P < 0.001) had a higher risk of early repair. Repair at or under age 3 and urgent surgery were associated with significant cost increases of 411$ (P < 0.001) and 558$ (P < 0.001), respectively. CONCLUSION: Quebec has a high rate of adherence to age-specific guidelines for UH repair. Future research should explore factors that explain transfers into tertiary centers, and the extent to which these reflect efficient use of resources. LEVEL OF EVIDENCE: level III. TYPE OF STUDY: Retrospective comparative study.

Intravenous immunoglobulin for patients with unexplained recurrent implantation failure: a 6-year single center retrospective review of clinical outcomes.

The effectiveness of intravenous immunoglobulin (IVIg) for patients with unexplained recurrent implantation failure (uRIF) remains debated. We retrospectively analysed outcomes of uRIF patients treated with IVIg compared to a separate control uRIF cohort within our center (01/2014-12/2021). Primary outcomes included live birth, miscarriage, or transfer failure. We documented IVIg side effects and maternal/fetal outcomes. Logistic regression analysis was used to assess for association of IVIg exposure with outcomes and adjust for confounders. The study included 143 patients, with a 2:1 ratio of controls to patients receiving IVIg treatment. Patient characteristics were similar between groups. There was higher live birth rate (LBR) in patients receiving IVIg (32/49; 65.3%) compared to controls (32/94; 34%); p < 0.001). When stratifying patients into moderate and severe uRIF (respectively 3-4 and [Formula: see text] 5 previous good quality blastocyst transfer failures), only patients with severe uRIF benefited from IVIg (LBR (20/29 (69%) versus 5/25 (20%) for controls, p = 0.0004). In the logistic regression analysis, IVIg was associated with higher odds of live birth (OR 3.64; 95% CI 1.78-7.67; p = 0.0004). There were no serious adverse events with IVIg. IVIg can be considered in well selected patients with [Formula: see text] 5 previous unexplained, high quality blastocyst transfer failures. A randomized controlled trial is needed to confirm these findings.

Validation of a Costing Algorithm and Cost Drivers for Neonates Admitted to the Neonatal Intensive Care Unit.

OBJECTIVE: Neonatal intensive care units (NICUs) account for over 35% of pediatric in-hospital costs. A better understanding of NICU expenditures may help identify areas of improvements. This study aimed to validate the Canadian Neonatal Network (CNN) costing algorithm for seven case-mix groups with actual costs incurred in a tertiary NICU and explore drivers of cost. STUDY DESIGN: A retrospective cohort study of infants admitted within 24 hours of birth to a Level-3 NICU from 2016 to 2019. Patient data and predicted costs were obtained from the CNN database and were compared to actual obtained from the hospital accounting system (Coût par Parcours de Soins et de Services). Cost estimates (adjusted to 2017 Canadian Dollars) were compared using Spearman correlation coefficient (rho). RESULTS: Among 1,795 infants included, 169 (9%) had major congenital anomalies, 164 (9%) with <29 weeks' gestational age (GA), 189 (11%) with 29 to 32 weeks' GA, and 452 (25%) with 33 to 36 weeks' GA. The rest were term infants: 86 (5%) with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia, 194 (11%) requiring respiratory support, and 541 (30%) admitted for other reasons. Median total NICU costs varied from $6,267 (term infants admitted for other reasons) to $211,103 (infants born with <29 weeks' GA). Median daily costs ranged from $1,613 to $2,238. Predicted costs correlated with actual costs across all case-mix groups (rho range 0.78-0.98, p < 0.01) with physician and nursing representing the largest proportion of total costs (65-82%). CONCLUSION: The CNN algorithm accurately predicts NICU total costs for seven case-mix groups. Personnel costs account for three-fourths of in-hospital total costs of all infants in the NICU. KEY POINTS: · Very preterm infants born below 33 weeks of gestation account for most of NICU resource use.. · Human resources providing direct patient care represented the largest portion of costs.. · The algorithm strongly predicted total costs for all case-mix groups..

Corrected Age at Bayley Assessment and Developmental Delay in Extreme Preterms.

BACKGROUND AND OBJECTIVES: Research on outcomes of prematurity frequently examines neurodevelopment in the toddler years as an end point, but the age range at examination varies. We aimed to evaluate whether the corrected age (CA) at Bayley-III assessment is associated with rates of developmental delay in extremely preterm children. METHODS: This retrospective cohort study included children born at <29 weeks' gestation who were admitted in the Canadian Neonatal Network between 2009 and 2017. The primary outcomes were significant developmental delay (Bayley-III score <70 in any domain) and developmental delay (Bayley-III score <85 in any domain). To assess the association between CA at Bayley-III assessment and developmental delay, we compared outcomes between 2 groups of children: those assessed at 18 to 20 months' CA and 21-24 months. RESULTS: Overall, 3944 infants were assessed at 18-20 months' CA and 881 at 21-24 months. Compared with infants assessed at 18-20 months, those assessed at 21-24 months had higher odds of significant development delay (20.0% vs 12.5%; adjusted odds ratio, 1.75; 95% confidence interval [CI], 1.41-2.13) and development delays (48.9% vs 41.7%, adjusted odds ratio 1.33; 95% CI, 1.11-1.52). Bayley-III composite scores were on average 3 to 4 points lower in infants evaluated at 21-24 months' CA (for instance, adjusted mean difference and 95% CI for language: 3.49 [2.33-4.66]). Conversely, rates of cerebral palsy were comparable (4.6% vs 4.7%) between the groups. CONCLUSIONS: Bayley-III assessments performed at 21-24 months' CA were more likely to diagnose a significant developmental delay compared with 18- to 20-month assessments in extremely preterm children.

Association between maternal hypertension and infant neurodevelopment in extremely preterm infants.

OBJECTIVE: To examine the association between maternal hypertension during pregnancy and neurodevelopmental impairment (NDI) at 24 months post-menstrual age in extremely preterm infants. STUDY DESIGN: Using data from two tertiary neonatal units (2011-2017) for infants born at 23 + 0 to 28 + 6 weeks, we investigated outcomes of NDI related to maternal hypertension and small-for-gestational-age (SGA) status. RESULTS: Of 1019 pre-term infants, 647 had complete data and were included in the analysis. Ninety-six (15%) had maternal hypertension exposure; 25 (4%) were also SGA. Infants with maternal hypertension showed a higher odds of any NDI (aOR: 2.29, 95% CI = 1.36-3.87) and significant NDI (aOR: 2.01, 95% CI = 1.02-3.95). The combination of hypertension and SGA further elevated this risk (aOR for any NDI: 4.88, 95% CI = 1.80-13.22; significant NDI: 6.91, 95% CI = 2.50-19.12). CONCLUSION: Maternal hypertension during pregnancy elevates the risk of NDI in extremely preterm infants, more so when combined with SGA.

Evaluation of the association between patent ductus arteriosus approach and neurodevelopment in extremely preterm infants.

OBJECTIVE: Assess if unit-level PDA management correlates with neurodevelopmental impairment (NDI) at 18-24 months corrected postnatal age (CPA) in extremely preterm infants. STUDY DESIGN: Retrospective analysis of infants born at <29 weeks (2014-2017) across two units having distinct PDA strategies. Site 1 utilized an echocardiography-based treatment strategy aiming for accelerated closure (control). Site 2 followed a conservative approach. PRIMARY ENDPOINT: NDI, characterized by cerebral palsy, any Bayley-III composite score <85, sensorineural/mixed hearing loss, or at least unilateral visual impairment. RESULTS: 377 infants were evaluated. PDA treatment rates remained unchanged in Site 1 but eventually reached 0% in Site 2. Comparable rates of any/significant NDI were seen across both sites (any NDI: 38% vs 36%; significant NDI: 13% vs 10% for Site 1 and 2, respectively). After adjustments, NDI rates remained similar. CONCLUSION: PDA management strategies in extremely preterm newborns showed no significant impact on neurodevelopment outcomes at 18-24 months CPA.

Early cardiac function and death, severe bronchopulmonary dysplasia and pulmonary hypertension in extremely preterm infants.

BACKGROUND: Association between early cardiac function and neonatal outcomes are scarcely reported. The aim of the current study was to describe this association with death, severe bronchopulmonary dysplasia (BPD) and BPD-related pulmonary hypertension (PH). METHODS: Retrospective cohort study of infants <29 weeks born between 2015 and 2019. Infants with clinically acquired echocardiography at ≤21 days after birth were included and data were extracted by an expert masked to outcomes. RESULTS: A total of 176 infants were included. Echocardiogram was performed at a median of 9 days (IQR 5-13.5). Of these, 31 (18%) had death/severe BPD and 59 (33.5%) had death/BPD-related PH. Infants with death/severe BPD were of lower birth weight (745 [227] vs 852 [211] grams, p = 0.01) and more exposed to invasive ventilation, late-onset sepsis, inotropes and/or postnatal steroids. Early echocardiograms demonstrated decreased right ventricular [Tricuspid Annular Plane Systolic Excursion: 5.2 (1.4) vs 6.2 (1.5) cm, p = 0.03] and left ventricular function [Ejection fraction 53 (14) vs 58 (10) %, p = 0.03]. Infants with death/BPD-related PH had an increased Eccentricity index (1.35 [0.20] vs 1.26 [0.19], p = 0.02), and flat/bowing septum (19/54 [35%] vs 20/109 [18%], p = 0.021). CONCLUSIONS: In extremely premature infants, altered ventricular function and increased pulmonary pressure indices within the first 21 days after birth, were associated with the combined outcome of death/severe BPD and death/BPD-related PH. IMPACT: Decreased cardiac function on echocardiography performed during first three weeks of life is associated with severe bronchopulmonary dysplasia in extremely premature infants. In extreme preterm infants, echocardiographic signs of pulmonary hypertension in early life are associated with later BPD-related pulmonary hypertension close to 36 weeks post-menstrual age. Early cardiac markers should be further studied as potential intervention targets in this population. Our study is adding comprehensive analysis of echocardiographic data in infants born below 29 weeks gestational age.

Variations in Site-Specific Costs for Infants Born Extremely Preterm in Canadian Neonatal Intensive Care Units.

OBJECTIVE: To quantify site-specific costs and their association with survival without major morbidity (SWMM) in Canada for neonates <28 weeks of gestation admitted to large tertiary neonatal intensive care units. METHODS: We conducted a retrospective analysis of infants born at <28 weeks of gestation and admitted to Canadian Neonatal Network sites from 2010 through 2021. Sites that cared for at least 50 eligible infants by gestational age in weeks over the study period were included. Using a validated costing algorithm that assessed physician, nursing, respiratory therapy, diagnostic imaging, transfusions, procedural, medication, and certain indirect costs, we calculated site and resource-specific costs in 2017 Canadian dollars (CAD) and evaluated their relationship with SWMM. RESULTS: Seven sites with 8180 (range 841-1605) eligible neonates with a mean (SD) gestation of 25.4 [1.3] weeks were included. Survival to discharge or transfer was 85.3% with a mean (SD) length of stay of 75 (46) days. The mean (SD) total and daily costs per neonate varied between $94 992 ($60 283) and $174 438 ($130 501) CAD and $1833 ($916) to $2307 ($1281) CAD, respectively. Between sites, there was no relationship between costs and SWMM. CONCLUSIONS: There was marked variation in costs and SWMM between sites in Canada with universal health care. The lack of concordance between both outcomes and costs among sites may provide possibilities for outcomes improvement and cost containment.

The proportions of term or late preterm births after exposure to early antenatal corticosteroids, and outcomes: systematic review and meta-analysis of 1.6 million infants.

OBJECTIVE: To systematically review the proportions of infants with early exposure to antenatal corticosteroids but born at term or late preterm, and short term and long term outcomes. DESIGN: Systematic review and meta-analyses. DATA SOURCES: Eight databases searched from 1 January 2000 to 1 February 2023, reflecting recent perinatal care, and references of screened articles. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials and population based cohort studies with data on infants with early exposure to antenatal corticosteroids (<34 weeks) but born at term (≥37 weeks), late preterm (34-36 weeks), or term/late preterm combined. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened titles, abstracts, and full text articles and assessed risk of bias (Cochrane risk of bias tool for randomised controlled trials and Newcastle-Ottawa scale for population based studies). Reviewers extracted data on populations, exposure to antenatal corticosteroids, and outcomes. The authors analysed randomised and cohort data separately, using random effects meta-analyses. MAIN OUTCOME MEASURES: The primary outcome was the proportion of infants with early exposure to antenatal corticosteroids but born at term. Secondary outcomes included the proportions of infants born late preterm or term/late preterm combined after early exposure to antenatal corticosteroids and short term and long term outcomes versus non-exposure for the three gestational time points (term, late preterm, term/late preterm combined). RESULTS: Of 14 799 records, the reviewers screened 8815 non-duplicate titles and abstracts and assessed 713 full text articles. Seven randomised controlled trials and 10 population based cohort studies (1.6 million infants total) were included. In randomised controlled trials and population based data, ∼40% of infants with early exposure to antenatal corticosteroids were born at term (low or very low certainty). Among children born at term, early exposure to antenatal corticosteroids versus no exposure was associated with increased risks of admission to neonatal intensive care (adjusted odds ratio 1.49, 95% confidence interval 1.19 to 1.86, one study, 5330 infants, very low certainty; unadjusted relative risk 1.69, 95% confidence interval 1.51 to 1.89, three studies, 1 176 022 infants, I2=58%, τ2=0.01, low certainty), intubation (unadjusted relative risk 2.59, 1.39 to 4.81, absolute effect 7 more per 1000, 95% confidence interval from 2 more to 16 more, one study, 8076 infants, very low certainty, one study, 8076 infants, very low certainty), reduced head circumference (adjusted mean difference -0.21, 95% confidence interval -0.29 to -0.13, one study, 183 325 infants, low certainty), and any long term neurodevelopmental or behavioural disorder in population based studies (eg, any neurodevelopmental or behavioural disorder in children born at term, adjusted hazard ratio 1.47, 95% confidence interval 1.36 to 1.60, one study, 641 487 children, low certainty). CONCLUSIONS: About 40% of infants exposed to early antenatal corticosteroids were born at term, with associated adverse short term and long term outcomes (low or very low certainty), highlighting the need for caution when considering antenatal corticosteroids. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022360079.