The Current State of Neonatal Neurodevelopmental Follow-up Programs in North America: A Children's Hospitals Neonatal Consortium Report.

OBJECTIVE: This study aimed to determine neonatal neurodevelopmental follow-up (NDFU) practices across academic centers. STUDY DESIGN: This study was a cross-sectional survey that addressed center-specific neonatal NDFU practices within the Children's Hospitals Neonatal Consortium (CHNC). RESULTS: Survey response rate was 76%, and 97% of respondents had a formal NDFU program. Programs were commonly staffed by neonatologists (80%), physical therapists (77%), and nurse practitioners (74%). Median gestational age at birth identified for follow-up was ≤32 weeks (range 26-36). Median duration was 3 years (range 2-18). Ninety-seven percent of sites used Bayley Scales of Infant and Toddler Development, but instruments used varied across ages. Scores were recorded in discrete electronic data fields at 43% of sites. Social determinants of health data were collected by 63%. Care coordination and telehealth services were not universally available. CONCLUSION: NDFU clinics are almost universal within CHNC centers. Commonalities and variances in practice highlight opportunities for data sharing and development of best practices. KEY POINTS: · Neonatal NDFU clinics help transition high-risk infants home.. · Interdisciplinary neonatal intensive care unit follow-up brings together previously separated outpatient service lines.. · This study reviews the current state of neonatal NDFU in North America..

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.

Introduction of a Warming Bundle to Reduce Hypothermia in Neonatal Surgical Patients.

INTRODUCTION: Hypothermia in the neonatal surgical population has been linked with significant morbidity and mortality. Our goal was to decrease intra and postoperative hypothermia. INTERVENTION: In November 2021, a radiant warmer and hat were included along with standard warming methods prior to the start of General Surgery procedures to minimize episodes of hypothermia. PRIMARY OUTCOME: Core body temperature was measured pre, intra and post-operatively. METHODS: Data were prospectively collected from electronic medical records from July 2021 to March 2023. A retrospective analysis was performed. Hypothermia was defined as a temperature <36.5C. Control charts were created to analyze the effect of interventions. RESULTS: A total of 277 procedures were identified; 226 abdominal procedures, 31 thoracic, 14 skin/soft tissue and 6 anorectal. The median post-natal age was 36.1 weeks (IQR: 33.2-39.2), with a pre-surgical weight of 2.3 kg (IQR: 1.6-3.0) and operative duration of 181 min (IQR: 125-214). Hat and warmer data were unavailable for 59 procedures, both hat and warmer were used for 51 % procedures, hat alone for 29 %, warmer alone for 10 % and neither for 10 % of procedures. Over time there was a significant increase in hat utilization while warmer usage was unchanged. There was a significant increase in the mean lowest intra-operative temperature and decrease in proportion of hypothermic patients intra-operatively and post-operatively. CONCLUSIONS: The inclusion of a radiant warmer and hat decreased the proportion of hypothermic patients during and after surgery. Further studies are necessary to analyze the impact on surgical outcomes. LEVEL OF EVIDENCE: III.

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.

Implementation of an ultrasound-guided approach for arterial line placements in neonates-quality improvement project.

OBJECTIVE: Our goal was to improve placement success rates for peripheral arterial line (PAL) placements by introducing an ultrasound-guided (USg) approach. Our aim was to maintain success rates over 70% within 18 months. STUDY DESIGN: Interventions included development of a training curriculum, and procedure standardization. Among 302 patients, 115 underwent USg catheter placement; the traditional method was used in 187 patients. Outcome measures were first-attempt and overall success rates. Process measures were proportion of PALs placed under US guidance, trainer availability, and trainee sign-off. Line complications were balancing measures. Statistical process control charts were used to monitor metrics. RESULTS: Sustained improvement was seen with the USg approach. The USg approach had first and overall attempt success by the trainers (i.e., independent users) of 83.7% (77/92) and 96.5% (111/115), compared to 50.3% (82/163) and 73.8% (138/187) with the traditional approach. CONCLUSION: Introducing the USg approach had a significant impact on PAL placement success in neonatal patients.

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

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

Blood culture collection practices in NICU; A national survey.

Background: Sepsis is the leading cause of mortality and morbidity in neonates. Blood cultures are the gold standard in diagnosing neonatal sepsis; however, there are currently no consensus guidelines for blood culture collection in neonates and significant practice variation exists in Neonatal Intensive Care Units (NICUs) globally. Objective: To examine current practices in obtaining blood cultures in the evaluation of neonatal sepsis in NICUs across Canada. Methods: A nine-item electronic survey was sent to each of the 29 level-3 NICUs in Canada, which are equipped to provide highly specialized care for newborns. Results: Responses were received from 90% (26/29) of sites. Sixty-five percent (17/26) of sites have blood culture collection guidelines for the investigation of neonatal sepsis. Forty-eight percent (12/25) of sites routinely target 1.0 mL per culture bottle. In late-onset sepsis (LOS), 58% (15/26) of sites process one aerobic culture bottle, whereas four sites routinely add anaerobic culture bottles. In early-onset sepsis (EOS) in very low birth weight infants (BW <1.5 kg), 73% (19/26) of sites use umbilical cord blood, and 72% (18/25) use peripheral venipuncture. Two sites routinely collect cord blood for culture in EOS. Only one site applies the concept of differential time-to-positivity to diagnose central-line-associated bloodstream infection. Conclusions: There is significant practice variation in methods used to obtain blood cultures in level-3 NICUs across Canada. Standardization of blood culture collection practices can provide reliable estimates of the true incidence of neonatal sepsis and help to develop appropriate antimicrobial stewardship strategies.

Association of Hospital Resource Utilization With Neurodevelopmental Outcomes in Neonates With Hypoxic-Ischemic Encephalopathy.

Importance: Intercenter variation exists in the management of hypoxic-ischemic encephalopathy (HIE). It is unclear whether increased resource utilization translates into improved neurodevelopmental outcomes. Objective: To determine if higher resource utilization during the first 4 days of age, quantified by hospital costs, is associated with survival without neurodevelopmental impairment (NDI) among infants with HIE. Design, Setting, and Participants: Retrospective cohort analysis of neonates with HIE who underwent therapeutic hypothermia (TH) at US children's hospitals participating in the Children's Hospitals Neonatal Database between 2010 and 2016. Data were analyzed from December 2021 to December 2022. Exposures: Infants who survived to 4 days of age and had neurodevelopmental outcomes assessed at greater than 11 months of age were divided into 2 groups: (1) death or NDI and (2) survived without NDI. Resource utilization was defined as costs of hospitalization including neonatal neurocritical care (NNCC). Data were linked with Pediatric Health Information Systems to quantify standardized costs by terciles. Main Outcomes and Measures: The main outcome was death or NDI. Characteristics, outcomes, hospitalization, and NNCC costs were compared. Results: Among the 381 patients who were included, median (IQR) gestational age was 39 (38-40) weeks; maternal race included 79 (20.7%) Black mothers, 237 (62.2%) White mothers, and 58 (15.2%) mothers with other race; 80 (21%) died, 64 (17%) survived with NDI (combined death or NDI group: 144 patients [38%]), and 237 (62%) survived without NDI. The combined death or NDI group had a higher rate of infants with Apgar score at 10 minutes less than or equal to 5 (65.3% [94 of 144] vs 39.7% [94 of 237]; P < .001) and a lower rate of infants with mild or moderate HIE (36.1% [52 of 144] vs 82.3% [195 of 237]; P < .001) compared with the survived without NDI group. Compared with low-cost centers, there was no association between high- or medium-hospitalization cost centers and death or NDI. High- and medium-EEG cost centers had lower odds of death or NDI compared with low-cost centers (high vs low: OR, 0.30 [95% CI, 0.16-0.57]; medium vs low: OR, 0.29 [95% CI, 0.13-0.62]). High- and medium-laboratory cost centers had higher odds of death or NDI compared with low-cost centers (high vs low: OR, 2.35 [95% CI, 1.19-4.66]; medium vs low: OR, 1.93 [95% CI, 1.07-3.47]). High-antiseizure medication cost centers had higher odds of death or NDI compared with low-cost centers (high vs. low: OR, 3.72 [95% CI, 1.51-9.18]; medium vs low: OR, 1.56 [95% CI, 0.71-3.42]). Conclusions and Relevance: Hospitalization costs during the first 4 days of age in neonates with HIE treated with TH were not associated with neurodevelopmental outcomes. Higher EEG costs were associated with lower odds of death or NDI yet higher laboratory and antiseizure medication costs were not. These findings serve as first steps toward identifying aspects of NNCC that are associated with outcomes.

Variations in care of neonates during therapeutic hypothermia: call for care practice bundle implementation.

BACKGROUND: Therapeutic hypothermia (TH) is the gold-standard treatment for moderate and severe neonatal encephalopathy (NE). Care during TH has implications for long-term outcomes. Outcome variability exists among neonatal intensive care units (NICUs) in Canada, but care variations are not understood well. This study examines variations in care practices for neonates with NE treated with TH in NICUs across Canada. METHODS: A non-anonymous, web-based questionnaire was emailed to tertiary NICUs in Canada providing TH for NE to assess care practices during the first days of life and neurodevelopmental follow-up. RESULTS: Ninety-two percent (24/26) responded. Centres followed national guidelines regarding the use of the modified Sarnat score to assess the initial severity of NE, the need to initiate TH within the first 6 h of birth, and the importance of follow-up. However, other practices varied, including ventilation mode, definition/treatment of hypotension, routine echocardiography, use of sedation, use of electroencephalogram (EEG), MRI timing, placental analysis, and follow-up duration. CONCLUSIONS: NICUs across Canada follow available national guidelines, but variations exist in practices for managing NE during TH. Development and implementation of a consensus-based care bundle for neonates during TH may reduce practice variability and improve outcomes. IMPACT: This survey describes the current HIE care practices and variation among tertiary centres in Canada. Variations exist in the care of neonates with NE treated with TH in NICUs across Canada. This paper Identifies areas of variation that are not discussed in detail in the national guidelines and will help to set up quality improvement initiatives. Elucidating the variation in care practices calls for the creation and implementation of a national, consensus-based care bundle, with the objective to improve the outcomes of these critically ill neonates.

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

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

Variations in practices and outcomes of neonates with hypoxic ischemic encephalopathy treated with therapeutic hypothermia across tertiary NICUs in Canada.

OBJECTIVE: To characterize variations in practices and outcomes for neonates with hypoxic-ischemic encephalopathy (HIE) treated with therapeutic hypothermia (TH) across Canadian tertiary Neonatal Intensive Care Units (NICUs). STUDY DESIGN: Retrospective study of neonates admitted for HIE and treated with TH in 24 tertiary NICUs from the Canadian Neonatal Network, 2010-2020. The two primary outcomes of mortality before discharge and MRI-detected brain injury were compared across NICUs using adjusted standardized ratios (SR) with 95% CI. RESULTS: Of the 3261 neonates that received TH, 367 (11%) died and 1033 (37%) of the 2822 with MRI results had brain injury. Overall, rates varied significantly across NICUs for mortality (range 5-17%) and brain injury (range 28-51%). Significant variations in use of inotropes, inhaled nitric oxide, blood products, and feeding during TH were identified (p values < 0.01). CONCLUSION: Significant variations exist in practices and outcomes of HIE neonates treated with hypothermia across Canada.

Opioid exposure during therapeutic hypothermia and short-term outcomes in neonatal encephalopathy.

OBJECTIVE: To assess the association between opioid exposure during therapeutic hypothermia (TH) for perinatal hypoxic-ischemic encephalopathy (HIE) and in-hospital outcomes. STUDY DESIGN: In this retrospective cohort study, linked data were accessed on infants ≥36 weeks gestation, who underwent TH for HIE, born from 2010-2016 in 23 Neonatal Intensive Care Units participating in Children's Hospitals Neonatal Consortium and Pediatric Health Information Systems. We excluded infants who received opioids for >5 days. RESULTS: The cohort (n = 1484) was categorized as No opioid [240(16.2%)], Low opioid (1-2 days) [574 (38.7%)] and High opioid group (HOG, 3-5 days) [670 (45.2%)]. After adjusting for HIE severity, opioids were not associated with abnormal MRI, but were associated with decreased likelihood of complete oral feeds at discharge. HOG had increased likelihood of prolonged hospital stay and ventilation. CONCLUSION: Opioid exposure during TH was not associated with abnormal MRI; its association with adverse short-term outcomes suggests need for cautious empiric use.

2% aqueous vs alcohol-based chlorhexidine for skin antisepsis in VLBW neonates undergoing peripheral venipuncture: a non-inferiority trial.

OBJECTIVE: To compare 2% aqueous chlorhexidine gluconate (AQC) vs. 2% chlorhexidine gluconate in 70% isopropyl alcohol (ALC) for pre-venipuncture skin antisepsis in very-low-birth-weight neonates (VLBW, birth-weight <1500 grams). STUDY DESIGN: Double-blind, non-inferiority trial randomized 199 VLBW neonates, age 2-28 days, to receive pre-venipuncture skin preparation using single application of swabstick impregnated with AQC (n = 99) or ALC (n = 100). Skin clearance rate (percentage post-cleansing skin swabs with <15 bacterial colony forming units) with a 10% non-inferiority margin for AQC was primary outcome. Absolute and relative CFU reduction and adverse skin reactions were compared. RESULTS: AQC's clearance was non-inferior to ALC (91% vs. 88%; 95% CI -6.6%, +12.4%). Median (interquartile range) absolute [61 (16, 110) vs. 63 (18, 100); p = 0.65] and relative [100% (97%, 100%) vs. 100% (99.7%, 100%); p = 0.20] CFU reductions were similar. Neither group experienced any adverse reactions. CONCLUSION: AQC may provide non-inferior skin disinfection to ALC in VLBW neonates. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01270776.

Association of Weight Changes by Three Days after Birth and Mortality and/or Severe Neurological Injury in Preterm Infants < 29 Weeks Gestational Age: A Multicenter Cohort Study.

OBJECTIVE: This study aimed to determine the range of weight loss, at 3 days postnatal age, associated with the lowest risk of mortality/short-term morbidity in preterm infants <29 weeks gestational age (GA). STUDY DESIGN: This multicenter retrospective cohort study employed data from the Canadian Neonatal Network database. The primary outcome was a composite of mortality and/or severe neurological injury. Multivariable quadratic and linear regression models which adjusted for potential confounders were built. RESULTS: A total of 9275 preterm infants (median GA 26, IQR 25, 28 weeks) were included. The optimal weight change range at day three, after adjustment for potential confounders for the primary outcomes, was -15 to -8.9%. CONCLUSIONS: There is a 'U'-shaped relationship between weight change from birth to day three and mortality and/or severe neurological injury. Interventional studies, which target weight loss within the range found in this study and evaluate the impact on neonatal outcomes, are needed to corroborate our findings.

Utilization of Therapeutic Hypothermia and Neurological Injury in Neonates with Mild Hypoxic-Ischemic Encephalopathy: A Report from Children's Hospital Neonatal Consortium.

OBJECTIVE: This study was aimed to describe utilization of therapeutic hypothermia (TH) in neonates presenting with mild hypoxic-ischemic encephalopathy (HIE) and associated neurological injury on magnetic resonance imaging (MRI) scans in these infants. STUDY DESIGN: Neonates ≥ 36 weeks' gestation with mild HIE and available MRI scans were identified. Mild HIE status was assigned to hyper alert infants with an exaggerated response to arousal and mild HIE as the highest grade of encephalopathy recorded. MRI scans were dichotomized as "injury" versus "no injury." RESULTS: A total of 94.5% (257/272) neonates with mild HIE, referred for evaluation, received TH. MRI injury occurred in 38.2% (104/272) neonates and affected predominantly the white matter (49.0%, n = 51). Injury to the deep nuclear gray matter was identified in (10.1%) 20 infants, and to the cortex in 13.4% (n = 14 infants). In regression analyses (odds ratio [OR]; 95% confidence interval [CI]), history of fetal distress (OR = 0.52; 95% CI: 0.28-0.99) and delivery by caesarian section (OR = 0.54; 95% CI: 0.31-0.92) were associated with lower odds, whereas medical comorbidities during and after cooling were associated with higher odds of brain injury (OR = 2.31; 95% CI: 1.37-3.89). CONCLUSION: Majority of neonates with mild HIE referred for evaluation are being treated with TH. Odds of neurological injury are over two-fold higher in those with comorbidities during and after cooling. Brain injury predominantly involved the white matter. KEY POINTS: · Increasingly, neonates with mild HIE are being referred for consideration for hypothermia therapy.. · Drift in clinical practice shows growing number of neonates treated with hypothermia as having mild HIE.. · MRI data show that 38% of neonates with mild HIE have brain injury, predominantly in the white matter..

Evaluation of transport-related outcomes for neonatal transport teams with and without physicians.

OBJECTIVE: The aim of this study was to evaluate if the presence of a physician in the neonatal transport team (NTT) affects transport-related outcomes and procedural success. DESIGN: Retrospective cohort study with propensity score matching. SETTING: Canadian national study. PATIENTS: Neonatal transports from nontertiary centres between January 2014 and December 2017. INTERVENTIONS: Comparison of transports conducted by NTTs with physicians (MD Group) and without physicians (noMD Group). MAIN OUTCOME MEASURES: The primary outcome was the change in patient acuity as measured by the transport risk index of physiologic severity (TRIPS) score. Secondary outcomes included mortality within 24 hours of NICU admission, clinical complications during transport, procedural success, and stabilization time. RESULTS: Among 9,703 eligible cases, 899 neonatal transports attended by NTTs with physicians were compared to 899 neonatal transports without physicians using propensity score matching. No differences were seen in the improvement of TRIPS score or mortality ≤24 hours of NICU admission. The MD Group had more clinical complications (7.7% versus 5.0%, P=0.02). No differences were seen in success rates of invasive procedures. The MD Group had shorter stabilization times. In multivariable analysis, the MD Group was not a significant predictor for the improvement in TRIPS score after adjustment for covariates. CONCLUSIONS: Neonatal transports conducted by teams including physicians compared to teams without physicians, did not have higher improvement in TRIPS scores and had similar success rates for procedures. These results provide insights for the planning of the structure and training of specialized interfacility neonatal transport programs.

Improving Compliance and Quality of Documentation of Cerebral Function Monitoring in a Neonatal Neurocritical Care Unit.

INTRODUCTION: Neonates admitted to neurocritical care units frequently undergo continuous bedside cerebral function monitoring (CFM). Documentation of CFM findings that are complete and accurate can augment the quality of care through improved communication. We aimed to increase the compliance with and quality of CFM documentation in the electronic medical records by 50% in our neonatal intensive care unit over 6 months. METHODS: We used the Plan-Do-Study-Act methodology, process mapping, and fishbone analysis. We implemented interventions, including the development of standardized EMR templates, face-to-face reminders at staff meetings and clinical handover sessions, and teaching on CFM interpretation. RESULTS: We evaluated 50 and 161 charts pre (August-October 2018) and postintervention (December 2018-July 2019), respectively. We improved compliance with documentation from 72% to 89% (P = 0.004); and the quality of documentation from 10% to 61% (P < 0.001). Multimodal reminders to document and educational sessions to increase familiarity with CFM interpretation effectively improved the quality of documentation. CONCLUSIONS: We improved the compliance with and the quality of CFM documentation using targeted quality improvement interventions with case-focused educational sessions, reference tools, and standardized templates. Barriers to compliance with documentation were adverse effects on the workflow that changes in the EMR system may address. A significant challenge to sustainability was the high frequency of rotating trainees. We addressed this challenge by developing mandatory electronic teaching modules that include reminders to document and a case-focused teaching curriculum; to increase awareness of the importance of CFM documentation and increase confidence in CFM interpretation.

Association of Co-Exposure of Antenatal Steroid and Prophylactic Indomethacin with Spontaneous Intestinal Perforation.

OBJECTIVE: To evaluate the association of a combined exposure to antenatal steroids and prophylactic indomethacin with the outcome of spontaneous intestinal perforation (SIP) among neonates born at <26 weeks of gestation or <750 g birth weight. STUDY DESIGN: We conducted a retrospective study of preterm infants admitted to Canadian Neonatal Network units between 2010 and 2018. Infants were classified into 2 groups based on receipt of antenatal steroids; the latter subgrouped as recent (≤7 days before birth) or latent (>7 days before birth) exposures. The co-exposure was prophylactic indomethacin. The primary outcome was SIP. Multivariable logistic regression analysis was used to calculate aORs. RESULTS: Among 4720 eligible infants, 4121 (87%) received antenatal steroids and 1045 (22.1%) received prophylactic indomethacin. Among infants exposed to antenatal steroids, those who received prophylactic indomethacin had higher odds of SIP (aOR 1.61, 95% CI 1.14-2.28) compared with no prophylactic indomethacin. Subgroup analyses revealed recent antenatal steroids exposure with prophylactic indomethacin had higher odds of SIP (aOR 1.67, 95% CI 1.15-2.43), but latent antenatal steroids exposure with prophylactic indomethacin did not (aOR 1.24, 95% CI 0.48-3.21), compared with the respective groups with no prophylactic indomethacin. Among those not exposed to antenatal steroids, mortality was lower among those who received prophylactic indomethacin (aOR 0.45, 95% CI 0.28-0.73) compared with no prophylactic indomethacin. CONCLUSIONS: In preterm neonates of <26 weeks of gestation or birth weight <750 g, co-exposure of antenatal steroids and prophylactic indomethacin was associated with SIP, especially if antenatal steroids was received within 7 days before birth. Among those unexposed to antenatal steroids, prophylactic indomethacin was associated with lower odds of mortality.

Predictive Models of Neurodevelopmental Outcomes After Neonatal Hypoxic-Ischemic Encephalopathy.

OBJECTIVES: To develop predictive models for death or neurodevelopmental impairment (NDI) after neonatal hypoxic-ischemic encephalopathy (HIE) from data readily available at the time of NICU admission ("early") or discharge ("cumulative"). METHODS: In this retrospective cohort analysis, we used data from the Children's Hospitals Neonatal Consortium Database (2010-2016). Infants born at ≥35 weeks' gestation and treated with therapeutic hypothermia for HIE at 11 participating sites were included; infants without Bayley Scales of Infant Development scores documented after 11 months of age were excluded. The primary outcome was death or NDI. Multivariable models were generated with 80% of the cohort; validation was performed in the remaining 20%. RESULTS: The primary outcome occurred in 242 of 486 infants; 180 died and 62 infants surviving to follow-up had NDI. HIE severity, epinephrine administration in the delivery room, and respiratory support and fraction of inspired oxygen of 0.21 at admission were significant in the early model. Severity of EEG findings was combined with HIE severity for the cumulative model, and additional significant variables included the use of steroids for blood pressure management and significant brain injury on MRI. Discovery models revealed areas under the curve of 0.852 for the early model and of 0.861 for the cumulative model, and both models performed well in the validation cohort (goodness-of-fit χ2: P = .24 and .06, respectively). CONCLUSIONS: Establishing reliable predictive models will enable clinicians to more accurately evaluate HIE severity and may allow for more targeted early therapies for those at highest risk of death or NDI.