Faculty Bibliography

BACKGROUND:In neonatology, many of our patients require respiratory support for a variety of pathologies. However, there is little data regarding objective parameters to help guide this support. Decisions regarding the optimal level of support for each patient remain largely subjective. The electrical activity of the diaphragm (Edi) is a measure of neural respiratory drive and inspiratory load. This could serve as a useful tool to provide objective data regarding respiratory status, which in turn may aid in decision-making about optimal respiratory support. OBJECTIVES/OBJECTIVE: The primary objective of this study was to compare Edi metrics in infants who required invasive mechanical ventilation with those who remained on noninvasive modes of ventilation. The secondary objective was to compare the rates and severity of bronchopulmonary dysplasia (BPD) in the two groups. DESIGN/METHODS/METHODS: This was a prospective observational pilot study. Infants admitted to the neonatal ICUs (NICUs) at Hassenfeld Children's Hospital and Bellevue Hospital Center, born at a gestational age of 26-32 weeks and weighing >500 grams, were eligible for the study. An Edi catheter (Maquet Critical Care AB, Solna, Sweden) was placed within the first 24 hours of life and remained in place for 72 hours. Subjects were weaned or escalated on their respiratory support based on current unit practice guidelines. They were separated into two groups: those who required invasive mechanical ventilation and those who did not. Paired Student's t-tests, chi-square tests, and Mann-Whitney tests were used to evaluate statistical significance (p ≤ 0.05). RESULTS:A total of 29 subjects were enrolled: 15 in the intubated group and 14 in the noninvasive group. Edi minimum was significantly lower, and delta Edi (the difference between Edi peak and minimum) was higher in the non-intubated group. There were no statistical differences in Edi peaks between the groups, although there was a trend toward higher peaks in the noninvasive group. Additionally, BPD outcomes were not statistically different. CONCLUSIONS: The lower Edi minimum in the non-intubated group suggests less severe lung disease and milder respiratory distress syndrome (RDS), requiring less stimulus and external support to generate adequate distending pressure to maintain alveolar patency at end-expiration. The higher delta Edi indicates a greater intrinsic ability to generate an adequate tidal volume for ventilation. There is wide variation in practice regarding modes of ventilation, both invasive and noninvasive, with no clear best practice. We lack objective data to guide our practice. This study is the first to examine Edi metrics as a monitoring tool to assess the degree of disease severity and sufficiency of support provided. Our results suggest that using Edi metrics may provide more data to help standardize and guide clinical practice.

OBJECTIVE:To compare resting energy expenditure (REE) among premature infants exposed to recorded maternal heartbeat and voice (MHV) vs. ambient noise. STUDY DESIGN/METHODS:A prospective, randomized crossover pilot trial evaluating the effect of MHV on REE using indirect calorimetry in hemodynamically stable premature infants born at 26-34 weeks' gestation. MHV recordings were digitally overlapped, and exposure sequence was randomized. RESULT/RESULTS:Among 34 measurements from seventeen subjects, REE was significantly lower during MHV exposure compared to ambient noise (61.4 ± 10.3 vs. 70.9 ± 10.3 kcal/kg/day, p = 0.0001). Mean heart rate was also significantly lower with MHV (144 ± 13 vs. 150 ± 11 bpm, p = 0.028), with no differences in other vital signs. CONCLUSION/CONCLUSIONS:REE of premature infants decreased during exposure to MHV when compared with ambient noise. MHV may serve as a potential noninvasive therapeutic intervention to improve metabolic efficiency in premature infants, potentially helping with improved growth.

OBJECTIVE:To compare regional splanchnic oxygenation (SrSO2) levels and clinical outcomes between infants who received minimal enteral nutrition (MEN) during Therapeutic Hypothermia (TH), and those who did not. STUDY DESIGN/METHODS:A prospective, interventional cohort study with a historic control group at two Regional Perinatal Centers (NCT05471336). RESULTS:Participant demographics and clinical illness severity were similar between MEN (n = 40) and control (n = 40) groups. There were no significant safety events. SrSO2 levels were normal in both groups throughout. Subjects that received MEN experienced fewer central line days (5.8 v 6.9, p = 0.005) and higher rates of human milk feeding (77% v 46%, p = 0.010), and achieved full oral feeds sooner (9.9 v 13.4 days, p = 0.043). CONCLUSION/CONCLUSIONS:Splanchnic tissue oxygenation was normal in both groups, and similar between groups throughout TH. Providing MEN during TH appears safe and effective, resulting in several important clinical benefits.

The increasing availability of novel therapies highlights the importance of screening newborns for rare genetic disorders so that they may benefit from early therapy, when it is most likely to be effective. Pilot newborn screening (NBS) studies are a way to gather objective evidence about the feasibility and utility of screening, the accuracy of screening assays, and the incidence of disease. They are also an optimal way to evaluate the complex ethical, legal and social implications (ELSI) that accompany NBS expansion for disorders. ScreenPlus is a consented pilot NBS program that aims to enroll over 100,000 infants across New York City. The initial ScreenPlus panel includes 14 disorders and uses an analyte-based, multi-tiered screening platform in an effort to enhance screening accuracy. Infants who receive an abnormal result are referred to a ScreenPlus provider for confirmatory testing, management, and therapy as needed, along with longitudinal capture of outcome data. Participation in ScreenPlus requires parental consent, which is obtained in active and passive manners. Patient-facing documents are translated into the ten most common languages spoken at our nine pilot hospitals, all of which serve diverse communities. At the time of consent, parents are invited to receive a series of online surveys to capture their opinions about specific ELSI-related topics, such as NBS policy, residual dried blood spot retention, and the types of disorders that should be on NBS panels. ScreenPlus has developed a stakeholder-based, collective funding model that includes federal support in addition to funding from 14 advocacy and industry sponsors, all of which have a particular interest in NBS for at least one of the ScreenPlus disorders. Taken together, ScreenPlus is a model, multi-sponsored pilot NBS program that will provide critical data about NBS for a broad panel of disorders, while gathering key stakeholder opinions to help guide ethically sensitive decision-making about NBS expansion.

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.

This review is a summary of available evidence regarding the use of near-infrared spectroscopy (NIRS) to help better guide and understand the effects of red blood cell (RBC) transfusion in neonatal patients. We review recent literature demonstrating the changes that take place in regional tissue oxygen saturation (rSO₂) resulting from RBC transfusion. We also discuss in detail if any correlation exists between rSO₂ and hemoglobin values in neonates. Finally, we review studies that have evaluated the use of NIRS as a transfusion guide during neonatal intensive care.

OBJECTIVES/OBJECTIVE:Antenatal corticosteroids (ACS) administered to mothers at risk for preterm delivery before 34 weeks has been standard care to improve neonatal outcomes. After introducing a new obstetric policy based on updated recommendations advising the administration of ACS to pregnant women at risk for late preterm (LPT) delivery (34-36 6/7 weeks), we set out to determine the short-term clinical impact on those LPT neonates. METHODS:Retrospective chart review of LPT neonates delivered at NYU Langone Medical Center both one year before and after the policy went into place. We excluded subjects born to mothers with pre-gestational diabetes, multiple gestations, and those with congenital/genetic abnormalities. We also excluded subjects whose mothers already received ACS previously in pregnancy. Subjects were divided into pre-policy and post-policy groups. Neonatal and maternal data were compared for both groups. RESULTS:388 subjects; 180 in the pre-policy and 208 in the post-policy group. This policy change resulted in a significant increase in ACS administration to mothers who delivered LPT neonates (67.3 vs. 20.6%, p<0.001). In turn, there was a significant reduction in LPT neonatal intensive care unit (NICU) admissions (44.2 vs. 54.4%, p=0.04) and need for respiratory support (27.9 vs. 42.8%, p<0.01). However, we also found an increased incidence of hypoglycemia (49.5 vs. 28.3%, p<0.001). CONCLUSIONS:This LPT ACS policy appears effective in reducing the need for LPT NICU level care overall. However, clinicians must be attentive to monitor for adverse effects like hypoglycemia, and there remains a need for better understanding of potential long-term impacts.

OBJECTIVES/OBJECTIVE:colonization rates before and after the visitor policy change, which coincided with the exponential rise of COVID-19 cases in New York City (NYC). METHODS:colonization. RESULTS:=0.02). CONCLUSIONS:colonization rate. Hospital unit leaders may need to focus on other strategies in order to reduce colonization.

BACKGROUND: RAF alterations are oncogenic drivers found in most pediatric low-grade gliomas (LGGs). Tovorafenib is an investigational, oral, selective, CNS-penetrant, small molecule, type II pan-RAF inhibitor.
METHOD(S): FIREFLY-1 (NCT04775485) is a multicenter phase 2 study evaluating the safety and efficacy of tovorafenib monotherapy. Registrational arm 1 enrolled patients with recurrent/progressive LGG harboring an activating BRAF alteration. Patients aged 6 months-25 years who progressed following >= 1 prior line of systemic therapy were eligible. Tovorafenib 420 mg/m2 (<= 600 mg) was administered weekly (tablet or liquid suspension formulation) until progression or for >= 26, 28-day cycles. The primary endpoint (arm 1) was overall response rate, as defined by RANO criteria, per independent review.
RESULT(S): As of April 14, 2022, 25 patients were enrolled to arm 1 and had >= 6 months of follow-up. Median age at enrollment was 8 years (range 3-18). Most patients had astrocytomas (92%), 48% with optic pathway involvement. Patients were heavily pretreated (56% with >= 3 prior lines of therapy), and 72% previously received MAPK pathwaytargeted agents. Tumors harbored BRAF fusions (84%) or BRAF V600E mutations (16%). Per independent assessment, partial responses (1 unconfirmed) were seen in 14 (64%) of 22 evaluable patients, with 6 additional patients having stable disease, and a clinical benefit rate of 91%. Responses were achieved in tumors with BRAF fusions and V600E mutations. Most treatment-emergent adverse events (AEs) were grade 1 or 2 (96%). The most common grade >= 3 AEs were anemia (12%), vomiting, increased blood creatinine phosphokinase and maculopapular rash (8% each). Seven patients (28%) required dose modification for treatment-related AEs; no patients discontinued tovorafenib due to AEs. Updated results, including efficacy per RAPNO assessments will be presented.
CONCLUSION(S): Tovorafenib was generally well tolerated and showed encouraging evidence of antitumor activity in children with pretreated BRAF-altered LGG