Faculty Bibliography

BACKGROUND:Bronchopulmonary Dysplasia (BPD) is the most common complication associated with prematurity. Caffeine citrate is a commonly used medication in the neonatal intensive care unit (NICU) for apnea of prematurity (AOP). In the Caffeine Therapy for Apnea of Prematurity study, or CAP trial, infants who received caffeine at 5 mg/kg had reduced rates of BPD compared to the placebo group. Recently, there have been questions regarding the optimal dose of caffeine and if higher doses may have increased benefit on decreasing rates of BPD. OBJECTIVE:The objectives of this study were to determine if infants who received a higher maintenance dose of caffeine have decreased rates of BPD, decreased severity of BPD and improved neurodevelopmental outcomes compared to those who received a lower maintenance dose of caffeine. DESIGN/METHODS/METHODS:This was a retrospective, observational cohort study at a level IV NICU including infants less than 28 weeks gestational age (GA) receiving caffeine. Maternal and infant demographics and clinical data from the infant's hospital course were collected. Infants were assigned to low-dose (n = 62) or high-dose (n = 111) cohorts based on average daily caffeine dose. The low-dose cohort received an average daily dose of ≤6 mg/kg/day, while the high-dose cohort received an average daily dose of >6 mg/kg/day. BPD rates and severity were then evaluated for each subject. Neurodevelopmental follow-up Bayley scores were assessed at 6, 12, 18, and 24-month follow-up visits. Chi-square test, T test, Mann-Whitney U Test, Logistic regression, and Linear regression statistics were completed to evaluate data. RESULTS:Demographics and clinical characteristics were similar between the low and high-dose caffeine groups. The duration of caffeine in each group was similar as well. The percentage of individuals requiring invasive ventilation was similar between the two groups, however, infants in the high-dose group required less intense forms of ventilation and were on invasive ventilation for a shorter time than the low-dose group (Table 1). The rates of BPD were similar in the two groups (79% vs 78%, p = 0.92), however the severity of BPD based on Jensen Criteria was significantly different between the two groups, with lower rates of severe BPD in the high-dose group (p < 0.001) (Tables 2 and 3). Patients in the higher-dose caffeine group had higher Bayley composite scores at 6 months (p < 0.02). No significant differences were noted at later follow-up (Table 3). CONCLUSIONS:The decreased rates of severe BPD in the high-dose group, along with improved Bayley scores at 6-month follow-up suggest the potential benefit of high-dose maintenance caffeine in the extremely premature and extremely low birth weight population. Additional large, prospective studies are required to evaluate the efficacy of high-dose caffeine in preventing BPD and improving long-term outcomes in this most vulnerable population.

CONTEXT/BACKGROUND:Pediatric palliative care (PPC) consultation for infants with life-limiting conditions provides parents and caregivers with opportunities to participate in advance care planning, shared decision-making, and to receive appropriate psychosocial and spiritual supports. OBJECTIVES/OBJECTIVE:To evaluate the impact of PPC consultation on spiritual, psychosocial, and communication outcomes for infants that died in the NICU. METHODS:Retrospective chart review of infants who died in a level IV NICU over a 10-year period (2014-2024). Mann-Whitney U and Chi-square or Fisher's exact tests were used to evaluate demographic and medical differences between infants with and without PPC consultation. Regression analyses were used to evaluate the impact of PPC on psychosocial, spiritual, and communication outcomes after adjusting for relevant covariates. RESULTS:There were significant medical and demographic differences between infants with PPC and no PPC consultation. Infants with PPC consultation had significantly higher odds of referral to child life, participation in memory making activities, documentation of family meetings and advance care planning discussions, and a higher incidence rate ratio of NICU social work visits and family meetings during their admission after adjusting for potential confounders. CONCLUSION/CONCLUSIONS:PPC consultation is associated with improved psychosocial, spiritual, and communication support utilization for seriously ill NICU infants and their families.

OBJECTIVE:To compare neurodevelopmental outcomes using Bayley Scales of Infant Development (BSID), between encephalopathic neonates undergoing therapeutic hypothermia (TH), sedated with either continuous dexmedetomidine or intermittent morphine. STUDY DESIGN/METHODS:Retrospective, observational cohort study including encephalopathic neonates born between 2014 - 2022 that underwent TH at two Regional Perinatal Centres, and completed neurodevelopmental follow-up assessments. RESULTS:There were no significant differences in demographics or short-term neurologic outcomes between morphine (n = 30) and dexmedetomidine (n = 32) groups. At 12 months, median motor composite scores (104 vs 98.5, p = 0.02) and median fine motor scaled scores (SS) (11 vs 10, p = 0.01) were significantly higher in the dexmedetomidine group. Median expressive language SS were slightly higher in the morphine group (11 v 10, p = 0.05). BSID scores at 18-24 months were similar. CONCLUSION/CONCLUSIONS:This study supports the use of dexmedetomidine as first-line sedation agent during TH, given comparable 18-24 month neurodevelopmental outcomes.

CONTEXT/BACKGROUND:Little is known about the prevalence of goal-concordant care (GCC) in the NICU and whether it can be measured from chart data. OBJECTIVES/OBJECTIVE:To determine if GCC can be evaluated using chart data, to identify factors associated with GCC, and to evaluate the impact of pediatric palliative care (PPC) consultation on GCC. METHODS:Retrospective review of infants who died in a level IV NICU over a 10-year period (2014-2024). A structured questionnaire was used to guide independent chart abstraction for GCC outcomes between two reviewers. Cohen's kappa was used to measure reviewer agreement. Mann-Whitney U and Chi-square or Fisher's exact tests were used to evaluate differences between infants with GCC vs. no GCC. Logistic regression was used to evaluate the impact of PPC on aspects of GCC. RESULTS:78% (99/127) of patients received GCC. Reviewer agreement for determining aspects of GCC was low, however, consensus was reached for all GCC outcomes. GCC was significantly associated with religious tradition, insurance status, limitations of resuscitation, mode of death, PPC consult, any family meeting or advance care planning discussion, and more social work visits. In logistic regression, PPC consultation was not a significant predictor of GCC after adjusting for religion, insurance, time since death, length of stay, and family meetings. CONCLUSION/CONCLUSIONS:Most infants received GCC, which was able to be determined from chart data. GCC was associated with several demographic and hospitalization factors such as PPC consultation and psychosocial supports. After adjusting for confounding, PPC was not a significant predictor of GCC.

OBJECTIVE:A standardized multifaceted approach to follow-up is crucial for monitoring neurodevelopment in neonates who undergo extracorporeal membrane oxygenation (ECMO). The Pittsburgh Index for Pre-ECMO Risk (PIPER+) score, which predicts the probability of hospital mortality, may help predict adverse neurodevelopmental outcomes. This study sought to assess the neurodevelopment of neonates who were treated with ECMO in our newly developed ECMO program, by analyzing Bayley Scales of Infant Development (BSID) scores obtained at the Neonatal Comprehensive Care Program (NCCP), our neurodevelopmental follow-up clinic, through two years of age. It also aimed to determine whether neurodevelopmental outcomes in our study population were correlated to PIPER+ score, magnetic resonance imaging (MRI), or video electroencephalography (vEEG) findings. STUDY DESIGN/METHODS:We conducted a retrospective chart review of neonatal patients placed on ECMO at our institution between March 2015 and June 2023 who had at least one follow-up visit at the NCCP clinic. The relationships between neurodevelopmental outcomes, quantified by the BSID score, PIPER + score, MRI results, and vEEG abnormalities were analyzed. RESULTS:A total of 18 patients met the inclusion criteria. There was a significant negative correlation (p<0.05) between PIPER+ and BSID scores at 12 months across all developmental domains analyzed. However, this correlation was no longer significant at 24 months. The odds of the combined outcome of mortality or neurodevelopmental impairment at two years of age increased by 17% for each 1% increase in the PIPER+ score. CONCLUSIONS:Higher PIPER+ scores were associated with higher mortality in our population; they also correlated with worse neurodevelopmental outcomes at 12 months, but not at 24 months. It is important and feasible to follow neonates who underwent ECMO using a neurodevelopmental follow-up clinic.

PURPOSE/OBJECTIVE:The premature infant brain may be particularly vulnerable to anesthesia effects, but there is conflicting evidence on the association between anesthesia exposure and developmental outcomes. Twin studies can control for confounding factors. A twin cohort of premature twins provides internal control of difficulty to measure confounders and delivers added power to a study examining the effects of anesthesia on neurodevelopmental outcomes. METHODS:We conducted a retrospective cohort study of sets of premature twins and multiples born at an academic medical center, in which 1 member of the set was exposed to general anesthesia. The primary outcome was the composite scores using Bayley Scale of Infant and Toddler Development III performed at age 6 months to 18 months. Unpaired and paired analyses were performed with linear regression models, Wilcoxon signed rank test, and Mann-Whitney U test. RESULTS:We identified 81 children born at less than 32 weeks gestation within 39 sets of twins and 1 set of triplets for a total of 18 paired observations. All of the exposed infants had a single exposure to general anesthesia. There was no significant association between anesthesia exposure and a diagnosis of developmental delay (OR = 0.8; 95% confidence interval, 0.2-3.2; p = 0.99). Regression models demonstrated no association between anesthesia exposure and cognitive (96.67 vs 97.50; p = 0.74), language (98.33 vs 98.61; p = 0.94), or motor (96.25 vs 96.44; p = 0.91) composite Bayley scores. There was no association between duration of anesthesia and the 3 composite Bayley scores ( p = 0.33; p = 0.40; p = 0.74). CONCLUSION/CONCLUSIONS:Using a premature twin cohort with discordant exposure to anesthesia, our data did not demonstrate any association between anesthesia exposure and developmental delay in this vulnerable population of premature infants.

OBJECTIVES/OBJECTIVE:and fractional tissue oxygen extraction (FTOE) in stable preterm infants in the first week of life. METHODS:, splanchnic cerebral oxygen ratio (SCOR), FTOE, and regional intra-subject variability was calculated at each location at five different time intervals: 0-12 h, 12-24 h, 24-48 h, 48-72 h, and one week of life. RESULTS:=0.81). The FTOE increased in all three locations over time. Intra-subject variability was lowest in the cerebral region (1.3 % (±1.9)). CONCLUSIONS:in preterm infants.

OBJECTIVE:To screen for neurodevelopmental delays in a cohort of full-term infants born to mothers with SARS-CoV-2. STUDY DESIGN/METHODS:-3) at 16 to 18 months age. RESULTS:Of 51 subjects, twelve (24%) were below cutoff, and twenty-seven (53%) were either below or close to the cutoff in at least one developmental domain. Communication (29%), fine motor (31%), and problem-solving (24%) were the most affected domains. There were no differences in outcomes between infants born to asymptomatic and mildly symptomatic mothers. CONCLUSION/CONCLUSIONS:We observed increased risk of neurodevelopmental delays during screening of infants born at full-term to mothers with SARS-CoV-2 at 16 to 18 months age. These results highlight the urgent need for follow-up studies of infants born to mothers with SARS-CoV-2.

Near-infrared spectroscopy (NIRS) is a technology that is easy to use and can provide helpful information about organ oxygenation and perfusion by measuring regional tissue oxygen saturation (rSO2) with near-infrared light. The sensors can be placed in different anatomical locations to monitor rSO2 levels in several organs. While NIRS is not without limitations, this equipment is now becoming increasingly integrated into modern healthcare practice with the goal of achieving better outcomes for patients. It can be particularly applicable in the monitoring of pediatric patients because of their size, and especially so in infant patients. Infants are ideal for NIRS monitoring as nearly all of their vital organs lie near the skin surface which near-infrared light penetrates through. In addition, infants are a difficult population to evaluate with traditional invasive monitoring techniques that normally rely on the use of larger catheters and maintaining vascular access. Pediatric clinicians can observe rSO2 values in order to gain insight about tissue perfusion, oxygenation, and the metabolic status of their patients. In this way, NIRS can be used in a non-invasive manner to either continuously or periodically check rSO2. Because of these attributes and capabilities, NIRS can be used in various pediatric inpatient settings and on a variety of patients who require monitoring. The primary objective of this review is to provide pediatric clinicians with a general understanding of how NIRS works, to discuss how it currently is being studied and employed, and how NIRS could be increasingly used in the near future, all with a focus on infant management.

OBJECTIVE: The study aimed to evaluate the effects of inhaled iloprost on oxygenation indices in neonates with persistent pulmonary hypertension of the newborn (PPHN). STUDY DESIGN/METHODS:) were recorded. RESULTS: < 0.05), with no significant change in required mean airway pressure over that same period. There was no change in vasopressor use or clinically significant worsening of platelets count, liver, and kidney functions after initiating iloprost. CONCLUSION/CONCLUSIONS: Inhaled iloprost is well tolerated and seems to have beneficial effects in improving oxygenation indices in neonates with PPHN who do not respond to iNO. There is a need of well-designed prospective trials to further ascertain the benefits of using inhaled iloprost as an adjunct treatment in neonates with PPHN who do not respond to iNO alone. KEY POINTS/CONCLUSIONS:· Inhaled iloprost seems to have beneficial effects in improving oxygenation indices in PPHN.. · Inhaled iloprost is generally well tolerated in newborns with PPHN.. · There is a need for prospective RCTs to further ascertain the benefits of using inhaled iloprost..