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.

Endotracheal Tube Size Adjustments Within Seven Days of Neonatal Intubation.

BACKGROUND AND OBJECTIVES: Neonatal endotracheal tube (ETT) size recommendations are based on limited evidence. We sought to determine data-driven weight-based ETT sizes for infants undergoing tracheal intubation and to compare these with Neonatal Resuscitation Program (NRP) recommendations. METHODS: Retrospective multicenter cohort study from an international airway registry. We evaluated ETT size changes (downsizing to a smaller ETT during the procedure or upsizing to a larger ETT within 7 days) and risk of procedural adverse outcomes associated with first-attempt ETT size selection when stratifying the cohort into 200 g subgroups. RESULTS: Of 7293 intubations assessed, the initial ETT was downsized in 5.0% of encounters and upsized within 7 days in 1.5%. ETT downsizing was most common when NRP-recommended sizes were attempted in the following weight subgroups: 1000 to 1199 g with a 3.0 mm (12.6%) and 2000 to 2199 g with a 3.5 mm (17.1%). For infants in these 2 weight subgroups, selection of ETTs 0.5 mm smaller than NRP recommendations was independently associated with lower odds of adverse outcomes compared with NRP-recommended sizes. Among infants weighing 1000 to 1199 g: any tracheal intubation associated event, 20.8% with 2.5 mm versus 21.9% with 3.0 mm (adjusted OR [aOR] 0.62, 95% confidence interval [CI] 0.41-0.94); severe oxygen desaturation, 35.2% with 2.5 mm vs 52.9% with 3.0 mm (aOR 0.53, 95% CI 0.38-0.75). Among infants weighing 2000 to 2199 g: severe oxygen desaturation, 41% with 3.0 mm versus 56% with 3.5mm (aOR 0.55, 95% CI 0.34-0.89). CONCLUSIONS: For infants weighing 1000 to 1199 g and 2000 to 2199 g, the recommended ETT size was frequently downsized during the procedure, whereas 0.5 mm smaller ETT sizes were associated with fewer adverse events and were rarely upsized.

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.

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.

Congenital SARS-CoV-2 Infection in Two Neonates with Confirmation by Viral Culture of the Placenta in One Case.

Congenital infections with SARS-CoV-2 are uncommon. We describe two confirmed congenital SARS-CoV-2 infections using descriptive, epidemiologic and standard laboratory methods and in one case, viral culture. Clinical data were obtained from health records. Nasopharyngeal (NP) specimens, cord blood and placentas when available were tested by reverse transcriptase real-time PCR (RT-PCR). Electron microscopy and histopathological examination with immunostaining for SARS-CoV-2 was conducted on the placentas. For Case 1, placenta, umbilical cord, and cord blood were cultured for SARS-CoV-2 on Vero cells. This neonate was born at 30 weeks, 2 days gestation by vaginal delivery. RT-PCR tests were positive for SARS-CoV-2 from NP swabs and cord blood; NP swab from the mother and placental tissue were positive for SARS-CoV-2. Placental tissue yielded viral plaques with typical morphology for SARS-CoV-2 at 2.8 × 102 pfu/mL confirmed by anti-spike protein immunostaining. Placental examination revealed chronic histiocytic intervillositis with trophoblast necrosis and perivillous fibrin deposition in a subchorionic distribution. Case 2 was born at 36 weeks, 4 days gestation. RT-PCR tests from the mother and infant were all positive for SARS-CoV-2, but placental pathology was normal. Case 1 may be the first described congenital case with SARS-CoV-2 cultivated directly from placental tissue.

Alberta Collaborative Quality Improvement Strategies to Improve Outcomes of Moderate and Late Preterm Infants (ABC-QI) Trial: a protocol for a multicentre, stepped-wedge cluster randomized trial.

BACKGROUND: Evidence-based Practice for Improving Quality (EPIQ) is a collaborative quality improvement method adopted by the Canadian Neonatal Network that led to decreased mortality and morbidity in very preterm neonates. The Alberta Collaborative Quality Improvement Strategies to Improve Outcomes of Moderate and Late Preterm Infants (ABC-QI) Trial aims to evaluate the impact of EPIQ collaborative quality improvement strategies in moderate and late preterm neonates in Alberta, Canada. METHODS: In a 4-year, multicentre, stepped-wedge cluster randomized trial involving 12 neonatal intensive care units (NICUs), we will collect baseline data with the current practices in the first year (all NICUs in the control arm). Four NICUs will transition to the intervention arm at the end of each year, with 1 year of follow-up after the last group transitions to the intervention arm. Neonates born at 32 + 0 to 36 + 6 weeks' gestation with primary admission to NICUs or postpartum units will be included. The intervention includes implementation of respiratory and nutritional care bundles using EPIQ strategies, including quality improvement team building, quality improvement education, bundle implementation, quality improvement mentoring and collaborative networking. The primary outcome is length of hospital stay; secondary outcomes include health care costs and short-term clinical outcomes. Neonatal intensive care unit staff will complete a survey in the first year to assess quality improvement culture in each unit, and a sample will be interviewed 1 year after implementation in each unit to evaluate the implementation process. INTERPRETATION: The ABC-QI Trial will assess whether collaborative quality improvement strategies affect length of stay in moderate and late preterm neonates. It will provide detailed population-based data to support future research, benchmarking and quality improvement. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT05231200.

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.

Neuroprotection care bundle implementation is associated with improved long-term neurodevelopmental outcomes in extremely premature infants.

OBJECTIVE: To study the impact of an evidence-based neuroprotection care (NPC) bundle on long-term neurodevelopmental impairment (NDI) in infants born extremely premature. STUDY DESIGN: An NPC bundle targeting predefined risk factors for acute brain injury in extremely preterm infants was implemented. We compared the incidence of composite outcome of death or severe neurodevelopmental impairment (sNDI) at 21 months adjusted age pre and post bundle implementation. RESULTS: Adjusting for confounding factors, NPC bundle implementation associated with a significant reduction in death or sNDI (aOR, 0.34; 95% CI 0.17-0.68; P = 0.002), mortality (aOR, 0.31; 95% CI (0.12-0.79); P = 0.015), sNDI (aOR, 0.37; 95% CI: 0.12-0.94; P = 0.039), any motor, language, or cognitive composite score <70 (aOR, 0.48; 95% CI: 0.26-0.90; P = 0.021). CONCLUSION: Implementation of NPC bundle targeting predefined risk factors is associated with a reduction in mortality or sNDI in extremely preterm infants.

Antimicrobial Stewardship at Birth in Preterm Infants: Not Just About a Decrease!

BACKGROUND: Early-onset sepsis results in increased morbidity and mortality in preterm infants. Antimicrobial Stewardship Programs (ASPs) address the need to balance adverse effects of antibiotic exposure with the need for empiric treatment for infants at the highest risk for early-onset sepsis. METHODS: All preterm infants <34 weeks gestational age born during a 6-month period before (January 2017-June 2017) and a 6-month period after (January 2019-June 2019) implementation of ASP in May 2018 were reviewed. The presence of perinatal sepsis risk factors, eligibility for, versus treatment with initial empiric antibiotics was compared. RESULTS: Our cohort comprised 479 infants with a mean of 30 weeks gestation and birth weight of 1400 g. Demographics were comparable, with more Cesarean section deliveries in the post-ASP cohort. Any sepsis risk factor was present in 73.6% versus 68.4% in the pre- versus post-ASP cohorts (P = 0.23). Fewer infants were treated with antibiotics in the later cohort (60.4%) compared with the earlier cohort (69.7%; P = 0.04). Despite the presence of risk factors (preterm labor in 93% and rupture of membranes in 60%), 42% of infants did not receive initial antibiotics. Twenty percent with no perinatal sepsis risk factors were deemed low-risk and not treated. CONCLUSIONS: Implementation of a neonatal ASP decreased antibiotic initiation at birth. Antibiotic use decreased (appropriately) in the subgroup with no perinatal sepsis risk factors. Of concern, some infants were not treated despite risk factors, such as preterm labor/rupture of membrane. Neonatal ASP teams need to be aware of potentially unintended consequences of their initiatives.

Fluid handling and blood flow patterns in neonatal respiratory distress syndrome versus transient tachypnea: a pilot study.

BACKGROUND: Cardiovascular and renal adaptation in neonates with Respiratory Distress Syndrome (RDS) and Transient Tachypnea of the Newborn (TTN) may be different. METHODS: Neonates ≥32 weeks were diagnosed with RDS or TTN based on clinical, radiologic and lung sonographic criteria. Weight loss, feeding, urine output, and sodium levels were recorded for the first 3 days, and serial ultrasounds assessed central and organ Doppler blood flow. A linear mixed model was used to compare the two groups. RESULTS: Twenty-one neonates were included, 11 with TTN and 10 with RDS. Those with RDS showed less weight loss (- 2.8 +/- 2.7% versus - 5.6 +/- 3.4%), and less enteral feeds (79.2 vs 116 ml/kg/day) than those with TTN, despite similar fluid prescription. We found no difference in urine output, or serum sodium levels. Doppler parameters for any renal or central parameters were similar. However, Anterior Cerebral Artery maximum velocity was lower (p = 0.03), Superior Mesenteric Artery Resistance Index was higher in RDS, compared to TTN (p = 0.02). CONCLUSION: In cohort of moderately preterm to term neonates, those with RDS retained more fluid and were fed less on day 3 than those with TTN. While there were no renal or central blood flow differences, there were some cerebral and mesenteric perfusion differences which may account for different pathophysiology and management.

Impact of outreach education program on outcomes of neonates with hypoxic ischemic encephalopathy.

AIM: To evaluate the impact of outreach education targeting neuroprotection on outcomes of outborn infants with moderate-to-severe hypoxic ischemic encephalopathy (HIE). METHODS: A retrospective cohort study of infants admitted with moderate-to-severe HIE was conducted following the implementation of outreach education in January 2016. Key interventions were early identification and referral of infants with encephalopathy utilizing telemedicine and a centralized communication system, hands-on simulation, and interactive case discussion and dissemination of clinical management guidelines and educational resources. The association between the intervention and a composite outcome of death and/or severe brain injury on brain magnetic resonance imaging (MRI) was tested controlling for the confounding factors. RESULTS: Of 165 neonates, 37 (22.4%) died and/or had a severe brain injury. This outcome decreased from 35% (27/77) to 11% (10/88) following the implementation of outreach education (P<0.001). Eligible infants not undergoing therapeutic hypothermia within 6 hours from birth decreased from 19.5% (15/77) to 4.5% (4/88). The use of inotropes decreased from 49.3% (38/77) to 19.6% (13/88). Any core temperature below 33°C was recorded for 20/53 (38%) before and 16/78 (21%) after, while those within the target range of 33°C to 34°C at admission to a tertiary care facility increased from (15/53) 28% to (51/88) 58%. Outreach education was independently associated with decreased composite outcome of death and/or severe brain injury on MRI (adjusted odds ratio 0.2; 95% confidence interval 0.07 to 0.52). CONCLUSION: Outreach education targeting neuroprotection for infants with moderate-to-severe HIE was associated with a reduction in death and/or severe brain injury.

Telemedicine-guided thoracentesis of tension pneumothorax in a term newborn.

We describe a case of a term female infant born in a rural community hospital and who developed a left-sided spontaneous tension pneumothorax shortly after birth. We used telemedicine to guide the family physician and healthcare team at the referring hospital to perform a life-saving thoracentesis using an intravenous cannula. The cannula was kept in place to drain the persistent pneumothorax during transportation to the pediatric intensive care unit at the tertiary hospital.

Intubation Competence During Neonatal Fellowship Training.

OBJECTIVES: To characterize neonatal-perinatal medicine fellows' progression toward neonatal intubation procedural competence during fellowship training. METHODS: Multi-center cohort study of neonatal intubation encounters performed by neonatal-perinatal medicine fellows between 2014 through 2018 at North American academic centers in the National Emergency Airway Registry for Neonates. Cumulative sum analysis was used to characterize progression of individual fellows' intubation competence, defined by an 80% overall success rate within 2 intubation attempts. We employed multivariable analysis to assess the independent impact of advancing quarter of fellowship training on intubation success. RESULTS: There were 2297 intubation encounters performed by 92 fellows in 8 hospitals. Of these, 1766 (77%) were successful within 2 attempts. Of the 40 fellows assessed from the start of training, 18 (45%) achieved procedural competence, and 12 (30%) exceeded the deficiency threshold. Among fellows who achieved competence, the number of intubations to meet this threshold was variable, with an absolute range of 8 to 46 procedures. After adjusting for patient and practice characteristics, advancing quarter of training was independently associated with an increased odds of successful intubation (adjusted odds ratio: 1.10; 95% confidence interval 1.07-1.14). CONCLUSIONS: The number of neonatal intubations required to achieve procedural competence is variable, and overall intubation competence rates are modest. Although repetition leads to skill acquisition for many trainees, some learners may require adjunctive educational strategies. An individualized approach to assess trainees' progression toward intubation competence is warranted.

Relative effectiveness and safety of pharmacotherapeutic agents for patent ductus arteriosus (PDA) in preterm infants: a protocol for a multicentre comparative effectiveness study (CANRxPDA).

INTRODUCTION: Patent ductus arteriosus (PDA) is the most common cardiovascular problem that develops in preterm infants and evidence regarding the best treatment approach is lacking. Currently available medical options to treat a PDA include indomethacin, ibuprofen or acetaminophen. Wide variation exists in PDA treatment practices across Canada. In view of this large practice variation across Canadian neonatal intensive care units (NICUs), we plan to conduct a comparative effectiveness study of the different pharmacotherapeutic agents used to treat the PDA in preterm infants. METHODS AND ANALYSIS: A multicentre prospective observational comparative-effectiveness research study of extremely preterm infants born <29 weeks gestational age with an echocardiography confirmed PDA will be conducted. All participating sites will self-select and adhere to one of the following primary pharmacotherapy protocols for all preterm babies who are deemed to require treatment.Standard dose ibuprofen (10 mg/kg followed by two doses of 5 mg/kg at 24 hours intervals) irrespective of postnatal age (oral/intravenous).Adjustable dose ibuprofen (oral/intravenous) (10 mg/kg followed by two doses of 5 mg/kg at 24 hours intervals if treated within the first 7 days after birth. Higher doses of ibuprofen up to 20 mg/kg followed by two doses of 10 mg/kg at 24 hours intervals if treated after the postnatal age cut-off for lower dose as per the local centre policy).Acetaminophen (oral/intravenous) (15 mg/kg every 6 hours) for 3-7 days.Intravenous indomethacin (0.1-0.3 mg/kg intravenous every 12-24 hours for a total of three doses). OUTCOMES: The primary outcome is failure of primary pharmacotherapy (defined as need for further medical and/or surgical/interventional treatment following an initial course of pharmacotherapy). The secondary outcomes include components of the primary outcome as well as clinical outcomes related to response to treatment or adverse effects of treatment. SITES AND SAMPLE SIZE: The study will be conducted in 22 NICUs across Canada with an anticipated enrollment of 1350 extremely preterm infants over 3 years. ANALYSIS: To examine the relative effectiveness of the four treatment strategies, the primary outcome will be compared pairwise between the treatment groups using χ2 test. Secondary outcomes will be compared pairwise between the treatment groups using χ2 test, Student's t-test or Wilcoxon rank sum test as appropriate. To further examine differences in the primary and secondary outcomes between the four groups, multiple logistic or linear regression models will be applied for each outcome on the treatment groups, adjusted for potential confounders using generalised estimating equations to account for within-unit-clustering. As a sensitivity analysis, the difference in the primary and secondary outcomes between the treatment groups will also be examined using propensity score method with inverse probability weighting approach. ETHICS AND DISSEMINATION: The study has been approved by the IWK Research Ethics Board (#1025627) as well as the respective institutional review boards of the participating centres. TRIAL REGISTRATION NUMBER: NCT04347720.

Neurodevelopmental outcomes of preterm infants conceived by assisted reproductive technology.

BACKGROUND: There have been concerns about the development of children conceived through assisted reproductive technology. Despite multiple studies investigating the outcomes of assisted conception, data focusing specifically on the neurodevelopmental outcomes of infants conceived through assisted reproductive technology and born preterm are limited. OBJECTIVE: This study aimed to evaluate and compare the neurodevelopmental outcomes of preterm infants born at <29 weeks' gestation at 18 to 24 months' corrected age who were conceived through assisted reproductive technology and those who were conceived naturally. STUDY DESIGN: This retrospective cohort study included inborn, nonanomalous infants, born at <29 weeks' gestation between January 1, 2010, and December 31, 2016, who had a neurodevelopmental assessment at 18 to 24 months' corrected age at any of the 10 Canadian Neonatal Follow-Up Network clinics. The primary outcome was neurodevelopmental impairment at 18 to 24 months, defined as the presence of any of the following: cerebral palsy; Bayley-III cognitive, motor, or language composite score of <85; sensorineural or mixed hearing loss; and unilateral or bilateral visual impairment. Secondary outcomes included mortality, composite of mortality or neurodevelopmental impairment, significant neurodevelopmental impairment, and each component of the primary outcome. We compared outcomes between infants conceived through assisted reproductive technology and those conceived naturally, using bivariate and multivariable analyses after adjustment. RESULTS: Of the 4863 eligible neonates, 651 (13.4%) were conceived using assisted reproductive technology. Maternal age; education level; and rates of diabetes mellitus, receipt of antenatal corticosteroids, and cesarean delivery were higher in the assisted reproduction group than the natural conception group. Neonatal morbidity and death rates were similar except for intraventricular hemorrhage, which was lower in the assisted reproduction group (33% [181 of 546] vs 39% [1284 of 3318]; P=.01). Of the 4176 surviving infants, 3386 (81%) had a follow-up outcome at 18 to 24 months' corrected age. Multivariable logistic regression adjusting for gestational age, antenatal steroids, sex, small for gestational age, multiple gestations, mode of delivery, maternal age, maternal education, pregnancy-induced hypertension, maternal diabetes mellitus, and smoking showed that infants conceived through assisted reproduction was associated with lower odds of neurodevelopmental impairment (adjusted odds ratio, 0.67; 95% confidence interval, 0.52-0.86) and the composite of death or neurodevelopmental impairment (adjusted odds ratio, 0.67; 95% confidence interval, 0.54-0.84). Conception through assisted reproductive technology was associated with decreased odds of a Bayley-III composite cognitive score of <85 (adjusted odds ratio, 0.68; 95% confidence interval, 0.48-0.99) and composite language score of <85 (adjusted odds ratio, 0.67; 95% confidence interval, 0.50-0.88). CONCLUSION: Compared with natural conception, assisted conception was associated with lower odds of adverse neurodevelopmental outcomes, especially cognitive and language outcomes, at 18 to 24 months' corrected age among preterm infants born at <29 weeks' gestation. Long-term follow-up studies are required to assess the risks of learning disabilities and development of complex visual-spatial and processing skills in these children as they reach school age.

Metabolic acidosis rather than hypo/hypercapnia in the first 72 hours of life associated with intraventricular hemorrhage in preterm neonates.

AIM: Safe limits of arterial partial pressure of carbon dioxide (PaCO2) and acidosis in premature infants are not well defined. Both respiratory and systemic illness along with center-specific ventilation strategies contribute to PaCO2 fluctuations and acid-base imbalances during the critical time period of first 72 h of life. This study evaluated the association between early blood gas parameters and intraventricular hemorrhage (IVH) in preterm infants. METHODS: This retrospective observational study included neonates with a gestational age (GA) of ≤29 wks, who had at least 7 blood gas analysis done within the first 72 h of life. By adjusting for known variables that predispose to IVH, multivariable logistic regression analysis was used to study the association of PaCO2 and acid-base measures with the risk of IVH. RESULTS: Between 2013-2016, among 272 neonates who met inclusion criteria and were assessed for IVH on cranial ultrasound within first week of life, 101 neonates [mean GA of 25 ± 1.5 wks] had IVH and 171 neonates [mean GA of 25 ± 1.6 wks] had normal scans. After adjustment for confounding variables, higher values of maximum lactate (OR = 1.18, 95% CI = 1.1-1.3, p < .0001) and maximum base deficit (OR = 1.19, 95% CI = 1.1-1.2, p < .0001) within 72 h of life increased the likelihood of any grade of IVH. However, time-weighted average PaCO2, maximum and minimum PaCO2 had no statistically significant effect on the risk of IVH. The relationship remained unchanged even when moderate-severe IVH was considered as the primary outcome. CONCLUSION: Severe metabolic acidosis rather than hypo/hypercapnia during the first 72 h of life was associated with higher odds of IVH in infants born at ≤29 wks of gestation. Future studies determining levels of PaCO2 that is safe for premature brain would need to control for the metabolic component of acidosis.

Neuroprotection Care Bundle Implementation to Decrease Acute Brain Injury in Preterm Infants.

BACKGROUND: We assessed the impact of an evidence-based neuroprotection care bundle on the risk of brain injury in extremely preterm infants. METHODS: We implemented a neuroprotection care bundle consisting of a combination of neuroprotection interventions such as minimal handling, midline head position, deferred cord clamping, and protocolization of hemodynamic and respiratory managements. These interventions targeted risk factors for acute brain injury in extremely preterm infants (born at gestational age less than 29 weeks) during the first three days of birth. Implementation occurred in a stepwise manner, including care bundle development by a multidisciplinary care team based on previous evidence and experience, standardization of outcome assessment tools, and education. We compared the incidence of the composite outcome of acute preterm brain injury or death preimplementation and postimplementation. RESULTS: Neuroprotection care bundle implementation associated with a significant reduction in acute brain injury risk factors such as the use of inotropes (24% before, 7% after, P value < 0.001) and fluid boluses (37% before, 19% after, P value < 0.001), pneumothorax (5% before, 2% after, P value = 0.002), and opioid use (19% before, 7% after, P value < 0.001). Adjusting for confounding factors, the neuroprotection care bundle significantly reduced death or severe brain injury (adjusted odds ratio, 0.34; 95% confidence interval, 0.20 to 0.59; P value < 0.001) and severe brain injury (adjusted odds ratio, 0.31; 95% confidence interval, 0.17 to 0.58; P < 0.001). CONCLUSIONS: Implementation of neuroprotection care bundle targeting predefined risk factors is feasible and effective in reducing acute brain injury in extremely preterm infants.