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.

Association of low hemoglobin at birth and neurodevelopmental outcomes in preterm neonates ≤28 weeks' gestation: a retrospective cohort study.

OBJECTIVE: To compare neurodevelopmental outcomes at 18-24 months corrected age (CA) for preterm infants who had hemoglobin levels <120 g/l versus those with hemoglobin level ≥120 g/l at birth. METHODS: We included infants of ≤28 weeks gestational age (GA) born between January 2009 and June 2018. The primary outcome was neurodevelopmental impairment (NDI) at 18-24 months. Multivariable logistic regression was applied to determine the association. RESULTS: Of the 2351 eligible neonates, 351 (14.9%) had hemoglobin levels <120 g/L at birth. Of the 2113 surviving infants, 1534 (72.5%) underwent developmental follow-up at 18-24 months CA. There was no statistically significant difference in ND outcomes between the two groups. The composite outcome of death or NDI was significantly higher in the low hemoglobin group. CONCLUSION: In preterm infants ≤28 weeks GA, initial hemoglobin <120 g/L at birth was not associated with neurodevelopmental impairment at 18-24 months CA among survivors.

Use of Intravenous Albumin: A Guideline From the International Collaboration for Transfusion Medicine Guidelines.

BACKGROUND: Albumin is used commonly across a wide range of clinical settings to improve hemodynamics, to facilitate fluid removal, and to manage complications of cirrhosis. The International Collaboration for Transfusion Medicine Guidelines developed guidelines for the use of albumin in patients requiring critical care, undergoing cardiovascular surgery, undergoing kidney replacement therapy, or experiencing complications of cirrhosis. METHODS: Cochairs oversaw the guideline development process and the panel included researchers, clinicians, methodologists, and a patient representative. The evidence informing this guideline arises from a systematic review of randomized clinical trials and systematic reviews, in which multiple databases were searched (inception through November 23, 2022). The panel reviewed the data and formulated the guideline recommendations using Grading of Recommendations Assessment, Development and Evaluation methodology. The guidelines were revised after public consultation. RESULTS: The panel made 14 recommendations on albumin use in adult critical care (three recommendations), pediatric critical care (one recommendation), neonatal critical care (two recommendations), cardiovascular surgery (two recommendations), kidney replacement therapy (one recommendation), and complications of cirrhosis (five recommendations). Of the 14 recommendations, two recommendations had moderate certainty of evidence, five recommendations had low certainty of evidence, and seven recommendations had very low certainty of evidence. Two of the 14 recommendations suggested conditional use of albumin for patients with cirrhosis undergoing large-volume paracentesis or with spontaneous bacterial peritonitis. Twelve of 14 recommendations did not suggest albumin use in a wide variety of clinical situations where albumin commonly is transfused. CONCLUSIONS: Currently, few evidence-based indications support the routine use of albumin in clinical practice to improve patient outcomes. These guidelines provide clinicians with actionable recommendations on the use of albumin.

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.

Pre-pregnancy body mass index, gestational diabetes mellitus, and gestational weight gain: individual and combined effects on fetal growth.

Background: Pre-pregnancy body mass index (BMI), gestational diabetes mellitus (GDM), and gestational weight gain (GWG) are interlinked and may play a complex role in fetal growth. We aimed to examine the relationship between pre-pregnancy BMI, GDM, GWG, and fetal growth outcomes and explore the contribution of GDM and GWG to the relationship between Pre-pregnancy obesity/overweight and large-for-gestational-age (LGA) in a prospective cohort. Methods: We prospectively recruited women in the first trimester and having one-step GDM screened with a 75-g oral glucose tolerance test between 24 and 28 weeks of gestation (n = 802). Outcomes included LGA, small-for-gestational-age (SGA), and preterm birth. To assess the individual and cumulative associations between pre-pregnancy BMI, GDM, GWG, and these outcomes, we used multivariate logistic regression analysis. Furthermore, we employed structural equation modeling (SEM) to investigate the mediating role of GDM and excessive GWG in the correlation between pre-pregnancy overweight/obesity and LGA. Results: Pre-pregnancy obesity, GDM, and excessive GWG were all independently associated with increased odds of LGA. Inadequate GWG was associated with higher odds of preterm birth. Compared with women unexposed to pre-pregnancy overweight/obesity, GDM, or excessive GWG, women exposed any two conditions had higher odds for LGA (AOR 3.18, 95% CI 1.25-8.11) and women with coexistence of all had the highest odds for LGA (AOR 8.09, 95% CI 2.18-29.97). The mediation analysis showed that GDM explained 18.60% (p < 0.05) of the total effect of pre-pregnancy overweight/obesity on LGA, and GWG explained 17.44% (p < 0.05) of the total effect. Conclusion: Pre-pregnancy obesity/overweight, GDM, and excessive GWG are associated with higher odds of fetal growth disturbances as individual factors and when they co-exist. The effect of pre-pregnancy overweight/obesity on LGA is partially achieved through GDM and excessive GWG.

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).

Postnatal Steroids Use for Bronchopulmonary Dysplasia in a Quaternary Care NICU.

OBJECTIVE: Intercenter variation and trends in postnatal steroids (PNS) use among preterm infants for prevention or treatment of bronchopulmonary dysplasia (BPD) is known. Understanding intracenter PNS use patterns facilitate implementation of center-specific change interventions to optimize outcomes.This study aimed to (i) quantify the proportion of infants who received PNS, and describe the timing, type, trends over time, regimen used, and deviations, and (2) describe the clinical characteristics and unadjusted outcomes of infants who received PNS. STUDY DESIGN: This was a cohort study in a quaternary neonatal intensive care unit including infants born at less than 33 weeks, and who received PNS for prevention or treatment of BPD between 2011 and 2021. Following data were included: proportion of babies who received PNS; type of PNS; age at initiation and duration; trends over time; deviation from published regimen; morbidity, mortality, and cointerventions. RESULTS: One hundred and eighty four infants (8% of <33 week' infants) received PNS. The median (interquartile range [IQR]) gestational age and birth weight were 25 (24-26) weeks and 720 (625-841) grams, respectively. The median (IQR) day of initiation and duration of PNS use were 29 (19-38) and 10 (10-22) days, respectively. One hundred and fifty-seven (85%) infants received dexamethasone (DX) and 22 (12%) received hydrocortisone as the first PNS course, and 71 (39%) infants received multiple courses. The proportion of infants receiving PNS remained unchanged, but the cumulative median dose received for BPD per patient increased by 56%. Nearly one-third of cumulative PNS dose came from PNS used for non-BPD indications. Forty-six percent infants had a deviation from published regimen (±20% deviation in duration or ±10% deviation in dose). Survival, survival without major morbidity, moderate-to-severe BPD, and technology dependence at discharge were 87, 2, 91, and 67%, respectively. CONCLUSION: Increased variation in PNS use, deviation from published regimen, and concurrent PNS exposure from non-BPD indication offer insights into implementing interventions to improve processes. KEY POINTS: · In this quaternary NICU, 8% of infants born before 33 weeks were administered postnatal steroids (PNS).. · The percentage of infants given PNS remained stable; however, the cumulative dose per patient for BPD rose.. · The study identified targeted interventions to minimize clinical practice variations at the center..

Outcomes of SARS-CoV-2 infection in early pregnancy-A systematic review and meta-analysis.

INTRODUCTION: Available data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and pregnancy outcomes mostly refer to women contracting the infection during advanced pregnancy or close to delivery. There is limited information on the association between SARS-CoV-2 infection in early pregnancy and outcomes thereof. MATERIAL AND METHODS: We aimed to systematically review the maternal, fetal and neonatal outcomes following SARS-CoV-2 infection in early pregnancy, defined as <20 weeks of gestation (PROSPERO Registration 2020 CRD42020177673). Searches were carried out in PubMed, Medline, EMBASE, and Scopus databases from January 2020 until April 2023 and the WHO database of publications on coronavirus disease 2019 (COVID-19) from December 2019 to April 2023. Cohort and case-control studies on COVID-19 occurring in early pregnancy that reported data on maternal, fetal, and neonatal outcomes were included. Case reports and studies reporting only exposure to SARS-CoV-2 or not stratifying outcomes based on gestational age were excluded. Data were extracted in duplicate. Meta-analyses were conducted when appropriate, using R meta (R version 4.0.5). RESULTS: A total of 18 studies, 12 retrospective and six prospective, were included in this review, reporting on 10 147 SARS-CoV-2-positive women infected in early pregnancy, 9533 neonates, and 180 882 SARS-CoV-2 negative women. The studies had low to moderate risk of bias according to the Newcastle-Ottawa quality assessment Scale. The studies showed significant clinical and methodological heterogeneity. A meta-analysis could be performed only on the outcome miscarriage rate, with a pooled random effect odds ratio of 1.44 (95% confidence interval 0.96-2.18), showing no statistical difference in miscarriage in SARS-CoV-2-infected women. Individual studies reported increased incidences of stillbirth, low birthweight and preterm birth among neonates born to mothers affected by COVID-19 in early pregnancy; however, these results were not consistent among all studies. CONCLUSIONS: In this comprehensive systematic review of available evidence, we identified no statistically significant adverse association between SARS-CoV-2 infection in early pregnancy (before 20 weeks of gestation) and fetal, neonatal, or maternal outcomes. However, a 44% increase in miscarriage rate is concerning and further studies of larger sample size are needed to confirm or refute our 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.

Efficacy and safety of dexmedetomidine for analgesia and sedation in neonates: a systematic review.

Opioids and benzodiazepines have historically been employed for pain relief; however, they are associated with detrimental long-term neurodevelopmental consequences. Dexmedetomidine, a highly selective alpha-2-adrenoreceptor agonist, has piqued interest as a viable alternative for neonates, owing to its potential analgesic and neuroprotective attributes. We conducted a systematic review to assess the efficacy and safety of dexmedetomidine utilization in neonates. We conducted a comprehensive search of Ovid, MEDLINE, EMBASE, PubMed, Cochrane, and CINAHL, spanning from January 2010 to September 2022. Our review encompassed six studies involving 252 neonates. Overall, dexmedetomidine may be effective in achieving sedation and analgesia. Furthermore, it may reduce the need for adjunctive sedation or analgesia, shorten the time to extubation, decrease the duration of mechanical ventilation, and accelerate the attainment of full enteral feeds. Notably, no significant adverse effects associated with dexmedetomidine were reported. Nevertheless, additional well-designed studies to establish both the efficacy and safety of dexmedetomidine in neonatal care are needed.

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.

Neurodevelopmental outcomes of preterm neonates receiving rescue inhaled nitric oxide in the first week of age: a cohort study.

OBJECTIVE: To assess the neurodevelopmental outcomes of preterm neonates who received inhaled nitric oxide (iNO) in the first week of age for hypoxaemic respiratory failure (HRF). METHODS: In this retrospective cohort study, we included neonates born at <29 weeks gestational age (GA) between January 2010 and December 2018 who had a neurodevelopmental assessment at 18-24 months corrected age (CA) at one of the Canadian Neonatal Follow-Up Network clinics. The primary outcome was neurodevelopmental impairment (NDI). We performed propensity score-matched analysis to compare the outcomes of those who received and did not receive iNO. RESULTS: Of the 5612 eligible neonates, 460 (8.2%) received iNO in the first week of age. Maternal age, receipt of antenatal corticosteroids, GA and birth weight were lower in the iNO group compared with the no-iNO group. Neonates in the iNO group had higher illness severity scores and higher rates of preterm prolonged rupture of membranes and were small for GA. Severe brain injury, bronchopulmonary dysplasia and mortality were higher in the iNO group. Of the 4889 survivors, 3754 (77%) neonates had follow-up data at 18-24 months CA. After propensity score matching, surviving infants who received rescue iNO were not associated with higher odds of NDI (adjusted OR 1.34; 95% CI 0.85 to 2.12). CONCLUSIONS: In preterm neonates <29 weeks GA with HRF, rescue iNO use was not associated with worse neurodevelopmental outcomes among survivors who were assessed at 18-24 months CA.

Efficacy and safety of fenofibrate in combination with phototherapy for the treatment of neonatal hyperbilirubinemia: a systematic review and meta-analyses.

Phototherapy is the standard treatment for neonatal jaundice. We aimed to review the efficacy and safety of fenofibrate as an adjunct therapy. Twelve databases were searched and a systematic review and meta-analysis were conducted. Mean change (MC), mean difference (MD), and risk ratios (RR) with a 95% confidence interval (CI) were calculated using a random effects model. The GRADE approach was used to evaluate the evidence's certainty. Nine randomized trials were included. The MC of total serum bilirubin (mg/dL) was significant at 12, 24, 36, 48, and 72 h with respective MC (95% CI) values of -0.46 (-0.61, -0.310), -1.10 (-1.68, -0.52), -2.06 (-2.20, -1.91), -2.15 (-2.74, -1.56), and -1.13 (-1.71, -0.55). The FEN + PT group had a shorter duration of phototherapy (MD: -14.36 h; 95% CI: -23.67, -5.06) and a shorter hospital stay (MD: -1.40 days; 95% CI: -2.14, -0.66). There was no significant difference in the risk of complications (RR: 0.89; 95% CI: 0.54, 1.46) or the need for exchange transfusion (RR: 0.58; 95% CI: 0.12, 2.81). The certainty of the evidence was very low for all outcomes. In conclusion, fenofibrate might be a safe adjunct to neonatal phototherapy. Larger randomized controlled trials are needed for the confirmation of these results.

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.

Parent-reported health outcomes at preschool age in preterm survivors: a population-based cohort study.

OBJECTIVE: Literature on health status (HS) and health-related quality of life of preterm survivors at preschool age is sparse. Further, little is known about the relationship between parent-reported HS outcomes and standardised neurodevelopmental outcomes measured in preterm survivors at preschool age. Our objective was to evaluate parent-reported child HS outcomes and their relationship to neurodevelopmental outcomes at 36 months of age in very preterm survivors. DESIGN: Prospective population-based cohort study. SETTING: Perinatal follow-up programme. PATIENTS: Infants <31 weeks' gestational age born from 2014 to 2016. OUTCOME MEASURES: Parents completed the Health Status Classification System for Pre-School Children questionnaire at 36 months. At the same age, neurodevelopmental assessments were completed to determine neurodevelopmental impairment (NDI). NDI was categorised as none, 'mild' or 'significant' (moderate or severe cerebral palsy, Bayley Scales of Infant and Toddler Development - Third Edition <70, blind or required hearing aid). RESULTS: Of 118 children, 87 (73.7%) parents reported their child had an HS concern (mild: 61 (51%); moderate: 16 (13.6%); and severe: 10 (8.5%)). Mild and significant NDIs were observed in 17 (14.4%) and 14 (11.9%) children, respectively. For the 14 (12%) children with significant NDI, 7 (50.0%) parents reported severe and 4 (28.6%) reported moderate concerns. Conversely, for 26 (22%) children with parent-reported moderate to severe concerns, 11 (42.3%) met the criteria for significant NDI. There was a moderate positive correlation between parental concern and NDI status (Spearman correlation=0.46, p<0.0001). CONCLUSIONS: Parental HS concerns only moderately correlated with the NDI status. Of the 12% of children with significant NDI, only half of the parents reported severe HS concerns.