Project Baby Bear: Rapid precision care incorporating rWGS in 5 California children's hospitals demonstrates improved clinical outcomes and reduced costs of care.

Genetic disorders are a leading contributor to mortality in neonatal and pediatric intensive care units (ICUs). Rapid whole-genome sequencing (rWGS)-based rapid precision medicine (RPM) is an intervention that has demonstrated improved clinical outcomes and reduced costs of care. However, the feasibility of broad clinical deployment has not been established. The objective of this study was to implement RPM based on rWGS and evaluate the clinical and economic impact of this implementation as a first line diagnostic test in the California Medicaid (Medi-Cal) program. Project Baby Bear was a payor funded, prospective, real-world quality improvement project in the regional ICUs of five tertiary care children's hospitals. Participation was limited to acutely ill Medi-Cal beneficiaries who were admitted November 2018 to May 2020, were <1 year old and within one week of hospitalization, or had just developed an abnormal response to therapy. The whole cohort received RPM. There were two prespecified primary outcomes-changes in medical care reported by physicians and changes in the cost of care. The majority of infants were from underserved populations. Of 184 infants enrolled, 74 (40%) received a diagnosis by rWGS that explained their admission in a median time of 3 days. In 58 (32%) affected individuals, rWGS led to changes in medical care. Testing and precision medicine cost $1.7 million and led to $2.2-2.9 million cost savings. rWGS-based RPM had clinical utility and reduced net health care expenditures for infants in regional ICUs. rWGS should be considered early in ICU admission when the underlying etiology is unclear.

Seizures after initiation of rewarming in cooled infants with hypoxic ischaemic encephalopathy.

BACKGROUND: Seizures after initiation of rewarming from therapeutic hypothermia for neonatal encephalopathy are well recognised but not easy to predict. METHODS: A secondary analysis was performed of NEOLEV2 trial data, a multicentre randomised trial of levetiracetam versus phenobarbital for neonatal seizures. Enrolled infants underwent continuous video EEG (cEEG) monitoring. The trial data were reviewed for 42 infants with seizures during therapeutic hypothermia and 118 infants who received therapeutic hypothermia but had no seizures on cEEG. RESULTS: Overall, 112 of 160 (70%) had cEEG monitoring continued until rewarming was completed. Of the 42 infants with prior seizures, there were 30 infants with valid cEEG available and seizures occurred following the initiation of rewarming in 8 (26.6%). For the 118 seizure-naive infants, 82 (69.5%) continued cEEG until either rewarming was completed or 90 h of age and none had documented seizures. CONCLUSION: Overall, just over a quarter of infants with prior seizures had cEEG evidence of at least one seizure in the 24 h after initiation of rewarming but no seizure-naive infant had cEEG evidence of seizure(s) on rewarming. Critically, by reporting the two groups separately, the data can provide guidance on the duration of EEG monitoring. IMPACT: Infants with hypoxic ischaemic encephalopathy who have cEEG evidence of seizures during therapeutic hypothermia have a significant risk of further seizures on rewarming. For infants with hypoxic ischaemic encephalopathy but no cEEG evidence of seizures during therapeutic hypothermia, there is very little risk of de novo seizures. Ongoing work utilising large cohorts may generate EEG criteria that refine estimates of risk for rewarming seizures. Based on current experience, if seizures have occurred during therapeutic hypothermia for hypoxic ischaemic encephalopathy, the EEG monitoring should be continued during rewarming and for 12 h thereafter to minimise the risk of missing an event.

Maternal mental health after infant discharge: a quasi-experimental clinical trial of family integrated care versus family-centered care for preterm infants in U.S. NICUs.

BACKGROUND: Involvement in caregiving and tailored support services may reduce the risk of mental health symptoms for mothers after their preterm infant's neonatal intensive care unit (NICU) discharge. We aimed to compare Family-Centered Care (FCC) with mobile-enhanced Family-Integrated Care (mFICare) on post-discharge maternal mental health symptoms. METHOD: This quasi-experimental study enrolled preterm infant (≤ 33 weeks)/parent dyads from three NICUs into sequential cohorts: FCC or mFICare. We analyzed post-discharge symptoms of perinatal post-traumatic stress disorder (PTSD) and depression using intention-to-treat and per protocol approaches. RESULTS: 178 mothers (89 FCC; 89 mFICare) completed measures. We found no main effect of group assignment. We found an interaction between group and stress, indicating fewer PTSD and depression symptoms among mothers who had higher NICU-related stress and received mFICare, compared with mothers who had high stress and received FCC (PTSD: interaction ß=-1.18, 95% CI: -2.10, -0.26; depression: interaction ß=-0.76, 95% CI: -1.53, 0.006). Per protocol analyses of mFICare components suggested fewer PTSD and depression symptoms among mothers who had higher NICU stress scores and participated in clinical team rounds and/or group classes, compared with mothers who had high stress and did not participate in rounds or classes. CONCLUSION: Overall, post-discharge maternal mental health symptoms did not differ between the mFICare and FCC groups. However, for mothers with high levels of stress during the NICU stay, mFICare was associated with fewer post-discharge PTSD and depression symptoms.

Mobile-Enhanced Family-Integrated Care for Preterm Infants: Nurse and Physician Views About Implementation.

BACKGROUND: The mobile-enhanced family-integrated care (mFICare) model addresses inconsistencies in family-centered care (FCC) delivery, with an evidence-based bundle of staff training, parent participation in rounds, parent classes, parent peer mentors, expanded role for parents in infant caregiving, and a parent-designed app. PURPOSE: Our aim was to explore the views of neonatal intensive care unit (NICU) nurses and physicians about mFICare implementation, including what worked well and what could be improved. METHODS: As part of a larger study to compare mFICare with FCC, we invited registered nurses, nurse practitioners, and fellow and attending physicians at the 3 study sites to participate in a survey about mFICare implementation. Data were analyzed with descriptive statistics and thematic analysis. RESULTS: The majority of the 182 respondents with experience delivering mFICare positively rated parent-led rounds, parent classes, parent skills acquisition, and the nurse-family relationship resulting from participation in mFICare. Respondents were less familiar or neutral regarding the parent peer mentor and app components of mFICare. Most respondents agreed that the mFICare program improved parent empowerment, and they shared suggestions for optimizing implementation. Physicians experienced more challenges with parent participation in rounds than nurses. Three themes emerged from the free-text data related to emotional support for parents, communication between staff and parents, and the unique experiences of families receiving mFICare. IMPLICATIONS FOR PRACTICE AND RESEARCH: The mFICare program was overall acceptable to nurses and physicians, and areas for improvement were identified. With implementation refinement, mFICare can become a sustainable model to enhance delivery of FCC in NICUs.

Parent Readiness for Their Preterm Infant's Neonatal Intensive Care Unit Discharge.

This study aims to examine the influence of hospital experience factors on parental discharge readiness, accounting for key background characteristics. Parents/guardians of infants 33 weeks of gestation or less at birth receiving neonatal intensive care at 6 sites were enrolled from April 2017 to August 2018. Participants completed surveys at enrollment, 3 weeks later, and at discharge. Multiple regression analysis assessed relationships between parental experience, well-being, and perceived readiness for infant discharge, adjusting for socioenvironmental, infant clinical, and parent demographic characteristics. Most (77%) of the 139 parents reported high levels of readiness for their infant's discharge and 92% reported high self-efficacy at discharge. The multiple regression model accounted for 40% of the variance in discharge readiness. Perceptions of family-centered care accounted for 12% of the variance; measures of parent well-being, anxiety, and parenting self-efficacy accounted for an additional 16% of the variance; parent characteristics accounted for an additional 9%; and infant characteristics accounted for less than 3% of the variance. Parental perceptions of the family-centeredness of the hospital experience, anxiety, and parenting self-efficacy accounted for a substantial proportion of the variance in readiness for discharge scores among parents of preterm infant. These influential perceptions are potentially modifiable by nursing-led interventions.

Relationship between social support and post-discharge mental health symptoms in mothers of preterm infants.

BACKGROUND: Social support is associated with decreased symptoms of postpartum mood and anxiety disorders (PMAD) in mothers of healthy infants, but less is known about social support and PMADs in mothers with preterm infants. The purpose of this study was to examine the relationship between social support and symptoms of PMADs reported by mothers in the months following hospital discharge of their preterm infant. METHODS: Mothers of infants less than 33 weeks gestational age were enrolled from neonatal intensive care units (NICU) at 6 sites. Mothers completed PMAD measures of depression, anxiety and post-traumatic stress approximately 3 months following their infant's discharge. Multivariable regression was used to evaluate relationships between social support and PMAD measures. RESULTS: Of 129 mothers, 1 in 5 reported clinically significant PMAD symptoms of: depression (24%), anxiety (19%), and post-traumatic stress (20%). Social support was strongly inversely associated with all 3 PMADs. Social support explained between 21% and 26% of the variance in depression, anxiety and post-traumatic stress symptoms. CONCLUSION: Increased social support may buffer PMAD symptoms in mothers of preterm infants after discharge. Research is needed to determine effective screening and interventions aimed at promoting social support for all parents during and following their infant's hospitalisation.

Neonatal outcomes from a quasi-experimental clinical trial of Family Integrated Care versus Family-Centered Care for preterm infants in U.S. NICUs.

BACKGROUND: Family Integrated Care (FICare) benefits preterm infants compared with Family-Centered Care (FCC), but research is lacking in United States (US) Neonatal Intensive Care Units (NICUs). The outcomes for infants of implementing FICare in the US are unknown given differences in parental leave benefits and health care delivery between the US and other countries where FICare is used. We compared preterm weight and discharge outcomes between FCC and mobile-enhanced FICare (mFICare) in the US. METHODS: In this quasi-experimental study, we enrolled preterm infant (≤ 33 weeks)/parent dyads from 3 NICUs into sequential cohorts: FCC or mFICare. Our primary outcome was 21-day change in weight z-scores. Our secondary outcomes were nosocomial infection, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), and human milk feeding (HMF) at discharge. We used intention-to-treat analyses to examine the effect of the FCC and mFICare models overall and per protocol analyses to examine the effects of the mFICare intervention components. FINDINGS: 253 infant/parent dyads participated (141 FCC; 112 mFICare). There were no parent-related adverse events in either group. In intention-to-treat analyses, we found no group differences in weight, ROP, BPD or HMF. The FCC cohort had 2.6-times (95% CI: 1.0, 6.7) higher odds of nosocomial infection than the mFICare cohort. In per-protocol analyses, we found that infants whose parents did not receive parent mentoring or participate in rounds lost more weight relative to age-based norms (group-difference=-0.128, CI: -0.227, -0.030; group-difference=-0.084, CI: -0.154, -0.015, respectively). Infants whose parents did not participate in rounds or group education had 2.9-times (CI: 1.0, 9.1) and 3.8-times (CI: 1.2, 14.3) higher odds of nosocomial infection, respectively. CONCLUSION: We found indications that mFICare may have direct benefits on infant outcomes such as weight gain and nosocomial infection. Future studies using implementation science designs are needed to optimize intervention delivery and determine acute and long-term infant and family outcomes. CLINICAL TRIAL REGISTRATION: NCT03418870 01/02/2018.

Comparison of family centered care with family integrated care and mobile technology (mFICare) on preterm infant and family outcomes: a multi-site quasi-experimental clinical trial protocol.

BACKGROUND: Family Centered Care (FCC) has been widely adopted as the framework for caring for infants in the Neonatal Intensive Care Unit (NICU) but it is not uniformly defined or practiced, making it difficult to determine impact. Previous studies have shown that implementing the Family Integrated Care (FICare) intervention program for preterm infants in the NICU setting leads to significant improvements in infant and family outcomes. Further research is warranted to determine feasibility, acceptability and differential impact of FICare in the US context. The addition of a mobile application (app) may be effective in providing supplemental support for parent participation in the FICare program and provide detailed data on program component uptake and outcomes. METHODS: This exploratory multi-site quasi-experimental study will compare usual FCC with mobile enhanced FICare (mFICare) on growth and clinical outcomes of preterm infants born at or before 33 weeks gestational age, as well as the stress, competence and self-efficacy of their parents. The feasibility and acceptability of using mobile technology to gather data about parent involvement in the care of preterm infants receiving FCC or mFICare as well as of the mFICare intervention will be evaluated (Aim 1). The effect sizes for infant growth (primary outcome) and for secondary infant and parent outcomes at NICU discharge and three months after discharge will be estimated (Aim 2). DISCUSSION: This study will provide new data about the implementation of FICare in the US context within various hospital settings and identify important barriers, facilitators and key processes that may contribute to the effectiveness of FICare. It will also offer insights to clinicians on the feasibility of a new mobile application to support parent-focused research and promote integration of parents into the NICU care team in US hospital settings. TRIAL REGISTRATION: ClinicalTrials.gov, ID NCT03418870. Retrospectively registered on December 18, 2017.

A randomized clinical trial of therapeutic hypothermia mode during transport for neonatal encephalopathy.

OBJECTIVE: To determine if temperature regulation is improved during neonatal transport using a servo-regulated cooling device when compared with standard practice. STUDY DESIGN: We performed a multicenter, randomized, nonmasked clinical trial in newborns with neonatal encephalopathy cooled during transport to 9 neonatal intensive care units in California. Newborns who met institutional criteria for therapeutic hypothermia were randomly assigned to receive cooling according to usual center practices vs device servo-regulated cooling. The primary outcome was the percentage of temperatures in target range (33°-34°C) during transport. Secondary outcomes included percentage of newborns reaching target temperature any time during transport, time to target temperature, and percentage of newborns in target range 1 hour after cooling initiation. RESULTS: One hundred newborns were enrolled: 49 to control arm and 51 to device arm. Baseline demographics did not differ with the exception of cord pH. For each subject, the percentage of temperatures in the target range was calculated. Infants cooled using the device had a higher percentage of temperatures in target range compared with control infants (median 73% [IQR 17-88] vs 0% [IQR 0-52], P < .001). More subjects reached target temperature during transport using the servo-regulated device (80% vs 49%, P <.001), and in a shorter time period (44 ± 31 minutes vs 63 ± 37 minutes, P = .04). Device-cooled infants reached target temperature by 1 hour with greater frequency than control infants (71% vs 20%, P < .001). CONCLUSIONS: Cooling using a servo-regulated device provides more predictable temperature management during neonatal transport than does usual care for outborn newborns with neonatal encephalopathy.

Perioperative Quality Improvement in Children's Hospitals Neonatal Consortium NICUs.

Infants admitted to NICUs in children's hospitals represent a different population than those in a traditional birth hospital. The patients in a children's hospital NICU often have the most complex neonatal diagnoses and are cared for by various subspecialists. The Children's Hospitals Neonatal Consortium is a collaborative of more than 40 NICUs that collect data and perform quality improvement (QI) work across the United States and Canada. The collaborative's database provides an opportunity to benchmark clinical outcomes for this specialized population and to support the QI efforts. In this review, we summarize the success of individual collaborative QI projects focused on improving the care of the neonate in the perioperative period related to clinical team handoffs, postoperative hypothermia prevention, and improvement of postoperative pain management. The collaborative's experience can serve as a model for other national collaboratives seeking to support QI efforts.

A Multicenter Collaborative to Improve Postoperative Pain Management in the NICU.

OBJECTIVES: This quality improvement initiative aimed to decrease unrelieved postoperative pain and improve family satisfaction with pain management. METHODS: NICUs within the Children's Hospitals Neonatal Consortium that care for infants with complex surgical problems participated in this collaborative. Each of these centers formed multidisciplinary teams to develop aims, interventions, and measurement strategies to test in multiple Plan-Do-Study-Act cycles. Centers were encouraged to adopt evidence-based interventions from the Clinical Practice Recommendations, which included pain assessment tools, pain score documentation, nonpharmacologic treatment measures, pain management guidelines, communication of a pain treatment plan, routine discussion of pain scores during team rounds, and parental involvement in pain management. Teams submitted data on a minimum of 10 surgeries per month, spanning from January to July 2019 (baseline), August 2019 to June 2021 (improvement work period), and July 2021 to December 2021 (sustain period). RESULTS: The percentage of patients with unrelieved pain in the 24-hour postoperative period decreased by 35% from 19.5% to 12.6%. Family satisfaction with pain management measured on a 3-point Likert scale with positive responses ≥2 increased from 93% to 96%. Compliance with appropriate pain assessment and numeric documentation of postoperative pain scores according to local NICU policy increased from 53% to 66%. The balancing measure of the percentage of patients with any consecutive sedation scores showed a decrease from 20.8% at baseline to 13.3%. All improvements were maintained during the sustain period. CONCLUSIONS: Standardization of pain management and workflow in the postoperative period across disciplines can improve pain control in infants.

Transcutaneous bilirubin levels in extremely preterm infants less than 30 weeks gestation.

OBJECTIVE: The primary objective of this study was to determine the relationship between transcutaneous bilirubin (TcB) levels and total serum bilirubin (TSB) levels in extremely preterm infants. STUDY DESIGN: We conducted a prospective multicenter study of extremely preterm infants less than 30 weeks gestation in California. Difference between paired TcB and TSB values were compared based on gestational age, birth weight, maternal race/ethnicity, chronological age as well as during and after phototherapy. RESULTS: TSB values ranged from 0 to 12.6 mg/dl and the TcB values ranged from 0 to 14.2 mg/dl. TSB was predicted with a high degree of accuracy at TSB = 2.37 + 0.54 (TcB) with r = 0.786. There was good correlation across gestational age, birth weight, race/ethnic, chronological age subgroups as well as during and after phototherapy. CONCLUSION: Our study supports the use of TcB as a screening tool for monitoring jaundice in extremely preterm infants.

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.

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.

Project Console: a quality improvement initiative for neonatal abstinence syndrome in a children's hospital level IV neonatal intensive care unit.

OBJECTIVE: To improve care for infants with neonatal abstinence syndrome. DESIGN: Infants with a gestational age of ≥35 weeks with prenatal opioid exposure were eligible for our quality improvement initiative. Interventions in our Plan-Do-Study-Act cycles included physician consensus, re-emphasis on non-pharmacological treatment, the Eat Sleep Console method to measure functional impairment, morphine as needed, clonidine and alternative soothing methods for parental unavailability (volunteer cuddlers and automated sleeper beds). Pre-intervention and post-intervention outcomes were compared. RESULTS: Length of stay decreased from 31.8 to 10.5 days (p<0.0001) without an increase in readmissions. Composite pharmacotherapy exposure days decreased from 28.7 to 5.5 (p<0.0001). This included reductions in both morphine exposure days (p<0.0001) and clonidine exposure days (p=0.01). Fewer infants required pharmacotherapy (p=0.02). CONCLUSIONS: Our study demonstrates how a comprehensive initiative can improve care for infants with neonatal abstinence syndrome in an open-bay or a high-acuity neonatal intensive care unit when rooming-in is not available or other comorbidities are present.

What parents want to know about caring for their preterm infant: A longitudinal descriptive study.

OBJECTIVES: To describe the characteristics of parent knowledge needs and skill acquisition over the course of their infant's neonatal intensive care unit hospitalization. METHODS: 148 parents/guardians of infants ≤33 week gestation enrolled during the usual care phase of a multi-site quasi-experimental study, completing weekly surveys about their learning needs for the coming week and skills learned in the past week. RESULTS: The topics of most interest or concern for parents included feeding their infant and their infant's medical course. Knowledge needs varied by phase of hospitalization (early, middle, late) and by parent age, prior parenting experience, infant gestational age and hospital length of stay. The most common skills learned related to feeding and basic infant care. The number of skills parents reported learning each week varied by parent age, gender, and education. CONCLUSIONS: Parents of preterm infants expressed specific learning needs and acquisition of skills that varied over the course of the hospitalization and by parent and infant characteristics. PRACTICE IMPLICATIONS: The findings can be used to improve parent learning experiences so that they can become full partners in their infant's caregiving and are better prepared to care for their infant after discharge. STUDY REGISTRATION: ClinicalTrials.gov, ID NCT03418870.

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.

Levetiracetam Versus Phenobarbital for Neonatal Seizures: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: There are no US Food and Drug Administration-approved therapies for neonatal seizures. Phenobarbital and phenytoin frequently fail to control seizures. There are concerns about the safety of seizure medications in the developing brain. Levetiracetam has proven efficacy and an excellent safety profile in older patients; therefore, there is great interest in its use in neonates. However, randomized studies have not been performed. Our objectives were to study the efficacy and safety of levetiracetam compared with phenobarbital as a first-line treatment of neonatal seizures. METHODS: The study was a multicenter, randomized, blinded, controlled, phase IIb trial investigating the efficacy and safety of levetiracetam compared with phenobarbital as a first-line treatment for neonatal seizures of any cause. The primary outcome measure was complete seizure freedom for 24 hours, assessed by independent review of the EEGs by 2 neurophysiologists. RESULTS: Eighty percent of patients (24 of 30) randomly assigned to phenobarbital remained seizure free for 24 hours, compared with 28% of patients (15 of 53) randomly assigned to levetiracetam (P < .001; relative risk 0.35 [95% confidence interval: 0.22-0.56]; modified intention-to-treat population). A 7.5% improvement in efficacy was achieved with a dose escalation of levetiracetam from 40 to 60 mg/kg. More adverse effects were seen in subjects randomly assigned to phenobarbital (not statistically significant). CONCLUSIONS: In this phase IIb study, phenobarbital was more effective than levetiracetam for the treatment of neonatal seizures. Higher rates of adverse effects were seen with phenobarbital treatment. Higher-dose studies of levetiracetam are warranted, and definitive studies with long-term outcome measures are needed.

Assessing the Feasibility of Providing a Real-Time Response to Seizures Detected With Continuous Long-Term Neonatal Electroencephalography Monitoring.

PURPOSE: Continuous video electroencephalography (cEEG) monitoring is the recommended gold standard of care for at-risk neonates but is not available in many Neonatal Intensive Care Units (NICUs). To conduct a randomized treatment trial of levetiracetam for the first-line treatment of neonatal seizures (the NEOLEV2 trial), we developed a monitoring infrastructure at five NICUs, implementing recent technological advancements to provide continuous video EEG monitoring and real-time response to seizure detection. Here, we report on the feasibility of providing this level of care. METHODS: Twenty-five key informant interviews were conducted with study neurologists, neonatologists, coordinators, and EEG technicians from the commercial EEG monitoring company Corticare. A general inductive approach was used to analyze these qualitative data. RESULTS: A robust infrastructure for continuous video EEG monitoring, remote review, and real-time seizure detection was established at all sites. At the time of this survey, 260 babies had been recruited and monitored for 2 to 6 days. The EEG technician review by the commercial EEG monitoring company was reassuring to families and neonatologists and led to earlier detection of seizures but did not reduce work load for neurologists. Neurologists found the automated neonatal seizure detector algorithm provided by the EEG software company Persyst useful, but the accuracy of the algorithm was not such that it could be used without review by human expert. Placement of EEG electrodes to initiate monitoring, especially after hours, remains problematic. CONCLUSIONS: Technological advancements have made it possible to provide at-risk neonates with continuous video EEG monitoring, real-time detection of and response to seizures. However, this standard of care remains unfeasible in usual clinical practice. Chief obstacles remain starting a recording and resourcing the real-time specialist review of suspect seizures.

A comparison of the effectiveness of three LED phototherapy machines, single- and double-sided, for treating neonatal jaundice in a low resource setting.

INTRODUCTION: Neonatal jaundice is one of the most common reasons for hospital admission in low resource settings. Treatment is frequently inadequate as conventional phototherapy requires frequent bulb changes. LED phototherapy has comparable efficacy to conventional phototherapy, and the bulbs last over 40,000 hours. This observational study compares the effectiveness of three LED machines, two single-sided and one double-sided in routine use in Vietnam. METHODS: We included all infants weighting ≥1500g and with jaundice diagnosed visually or by Total Serum Bilirubin (TSB) measurement at The Da Nang Hospital for Women and Children (Da Nang, Vietnam). The primary endpoint was the average hourly change in TSB over the first six hours of treatment. The secondary endpoints were duration of treatment; average hourly change in TSB over treatment, and length of stay in the neonatal unit. Multivariable analysis and bootstrap methods was performed to compare outcomes, adjusting for potential confounders. RESULTS: All outcomes were comparable in the two single-sided machines. The double-sided machine showed 54% increase in the hourly speed of TSB reduction (1.3 µmol/L/hr, 95% CI 0.3-2.3), with a 45% increase in the speed of TSB reduction over the duration of treatment (0.9 µmol/L/hr, 95% CI 0.6-1.3). In addition, the double-sided machine was associated with 21% reduction in the duration of treatment (14 hours, 95% CI 5-22) and 16% reduction of length of stay (14 hours, 95% CI 3-25). CONCLUSION: The results confirm and quantify the benefits of increasing surface-area exposure during phototherapy. Adjusted for multiple potential confounders, use of double-sided phototherapy can substantially increase the speed of TSB reduction, and substantially decrease the duration of treatment and length of stay in the NCU.