Cody Arnold

All Publications

• Effect of reduced versus usual lipid emulsion dosing on bilirubin neurotoxicity and neurodevelopmental impairment in extremely preterm infants: study protocol for a randomized controlled trial. BMC pediatrics Holzapfel, L. F., Arnold, C., Tyson, J. E., Shapiro, S. M., Reynolds, E. W., Pedroza, C., Stephens, E. K., Kleinfeld, A., Huber, A. H., Rysavy, M. A., Del Mar Romero Lopez, M., Khan, A. M. 2023; 23 (1): 347

  Abstract

  BACKGROUND: Bilirubin neurotoxicity (BN) occurs in premature infants at lower total serum bilirubin levels than term infants and causes neurodevelopmental impairment. Usual dose lipid infusions in preterm infants may increase free fatty acids sufficiently to cause bilirubin displacement from albumin, increasing passage of unbound bilirubin (UB) into the brain leading to BN and neurodevelopmental impairment not reliably identifiable in infancy. These risks may be influenced by whether cycled or continuous phototherapy is used to control bilirubin levels.OBJECTIVE: To assess differences in wave V latency measured by brainstem auditory evoked responses (BAER) at 34-36weeks gestational age in infants born≤750g or<27weeks' gestational age randomized to receive usual or reduced dose lipid emulsion (half of the usual dose) irrespective of whether cycled or continuous phototherapy is administered.METHODS: Pilot factorial randomized controlled trial (RCT) of lipid dosing (usual and reduced) with treatment groups balanced between cycled or continuous phototherapy assignment. Eligible infants are born at≤750g or<27weeks' gestational age enrolled in the NICHD Neonatal Research Network RCT of cycled or continuous phototherapy. Infants will randomize 1:1 to reduced or usual dose lipid assignment during the first 2weeks after birth and stratified by phototherapy assignment. Free fatty acids and UB will be measured daily using a novel probe. BAER testing will be performed at 34-36weeks postmenstrual age or prior to discharge. Blinded neurodevelopmental assessments will be performed at 22-26months. Intention-to-treat analyses will be performed with generalized linear mixed models with lipid dose and phototherapy assignments as random effects covariates, and assessment for interactions. Bayesian analyses will be performed as a secondary analysis.DISCUSSION: Pragmatic trials are needed to evaluate whether lipid emulsion dosing modifies the effect of phototherapy on BN. This factorial design presents a unique opportunity to evaluate both therapies and their interaction. This study aims to address basic controversial questions about the relationships between lipid administration, free fatty acids, UB, and BN. Findings suggesting a reduced lipid dose can diminish the risk of BN would support the need for a large multicenter RCT of reduced versus usual lipid dosing.TRIAL REGISTRATION: Clinical Trials.gov, NCT04584983, Registered 14 October 2020, https://clinicaltrials.gov/ct2/show/NCT04584983 Protocol version: Version 3.2 (10/5/2022).

  View details for DOI 10.1186/s12887-023-04149-0

  View details for PubMedID 37430233

• Increasing early exposure to mother's own milk in premature newborns. Journal of perinatology : official journal of the California Perinatal Association Balasundaram, M., Land, R., Miller, S., Profit, J., Porter, M., Arnold, C., Sivakumar, D. 2022

  Abstract

  OBJECTIVE: Increase the proportion of ≤33 weeks newborns exposed to mother's own milk (MOM) oral care by 12h of age by 20% over 2 years to support a healthier microbiome.STUDY DESIGN: We implemented interventions to support early expression of colostrum and reliable delivery of resultant MOM to premature newborns. Statistical process control charts were used to track progress and provide feedback to staff. Proportions of newborns exposed to MOM by 12h were compared relative to baseline.RESULTS: There were 46, 66, and 46 newborns in the baseline, implementation, and sustainability periods, respectively. The primary outcome improved from 48% to 61% in the implementation period (relative change 1.27, 95% CI 0.89, 1.81, p=0.2), to 69% in sustainability period (relative to baseline 1.45, 95% CI 1.02, 2.08, p=0.03).CONCLUSION: An interdisciplinary team-based, multicycle, quality improvement intervention resulted in increased rates of early exposure to MOM.

  View details for DOI 10.1038/s41372-022-01376-8

  View details for PubMedID 35396577

• Increasing Length of Stay in the NICU for Premature Newborns: Good or Bad? Pediatrics Arnold, C., Davis, A. S. 2021

  View details for DOI 10.1542/peds.2020-032748

  View details for PubMedID 33510033

• Cycled Phototherapy Dose-Finding Study for Extremely Low-Birth-Weight Infants: A Randomized Clinical Trial. JAMA pediatrics Arnold, C., Tyson, J. E., Pedroza, C., Carlo, W. F., Stevenson, D. K., Wong, R., Dempsey, A., Khan, A., Fonseca, R., Wyckoff, M., Moreira, A., Lasky, R. 2020

  Abstract

  Importance: Cycled (intermittent) phototherapy (PT) might adequately control peak total serum bilirubin (TSB) level and avoid mortality associated with usual care (continuous PT) among extremely low-birth-weight (ELBW) infants (401-1000 g).Objective: To identify a cycled PT regimen that substantially reduces PT exposure, with an increase in mean peak TSB level lower than 1.5 mg/dL in ELBW infants.Design, Setting, and Participants: This dose-finding randomized clinical trial of cycled PT vs continuous PT among 305 ELBW infants in 6 US newborn intensive care units was conducted from March 12, 2014, to November 14, 2018.Interventions: Two cycled PT regimens (≥15 min/h and ≥30 min/h) were provided using a simple, commercially available timer to titrate PT minutes per hour against TSB level. The comparator arm was usual care (continuous PT).Main Outcomes and Measures: Mean peak TSB level and total PT hours through day 14 in all 6 centers and predischarge brainstem auditory-evoked response wave V latency in 1 center. Mortality and major morbidities were secondary outcomes despite limited power.Results: Consent was requested for 452 eligible infants and obtained for 305 (all enrolled) (mean [SD] birth weight, 749 [152] g; gestational age, 25.7 [1.9] weeks; 81 infants [27%] were multiple births; 137 infants [45%] were male; 112 [37%] were black infants; and 107 [35%] were Hispanic infants). Clinical and demographic characteristics of the groups were similar at baseline. After a preplanned interim analysis of 100 infants, the regimen of 30 min/h or more was discontinued, and the study proceeded with 2 arms. Comparing 128 infants receiving PT of 15 min/h or more with 128 infants receiving continuous PT among those surviving to 14 days, mean peak TSB levels were 7.1 vs 6.4 mg/dL (adjusted difference, 0.7; 95% CI, 0.4-1.1 mg/dL) and mean total PT hours were 34 vs 72 (adjusted difference, -39; 95% CI, -45 to -32). Wave V latency adjusted for postmenstrual age was similar in 37 infants receiving 15 min/h or more of PT and 33 infants receiving continuous PT: 7.42 vs 7.32 milliseconds (difference, 0.10; 95% CI, -0.11 to 0.30 millisecond). The relative risk for death was 0.79 (95% CI, 0.40-1.54), with a risk difference of -4.5% (95% CI, -10.9 to 2.0). Morbidities did not differ between groups.Conclusions and Relevance: Cycled PT can substantially reduce total PT with little increase in peak TSB level. A large, randomized trial is needed to assess whether cycled PT would increase survival and survival without impairment in small, preterm infants.Trial Registration: ClinicalTrials.gov Identifier: NCT01944696.

  View details for DOI 10.1001/jamapediatrics.2020.0559

  View details for PubMedID 32338720

• Phototherapy and the Risk of Photo-Oxidative Injury in Extremely Low Birth Weight Infants CLINICS IN PERINATOLOGY Stevenson, D. K., Wong, R. J., Arnold, C. C., Pedroza, C., Tyson, J. E. 2016; 43 (2): 291-?

  Abstract

  Phototherapy has been used to treat newborns with jaundice for more than 50 years with the presumption that it is safe and effective for all infants. In fact, this presumption may not be true for all infants, especially the smallest and most immature. The safety and efficacy of phototherapy have never really been questioned or adequately tested in the latter, yet clinical applications of phototherapy have been further refined as its mechanisms of action have been better understood and alternative light sources have become available. This article addresses what is known about the possible risks of photo-oxidative injury in extremely low birth weight infants.

  View details for DOI 10.1016/j.clp.2016.01.005

  View details for PubMedID 27235208

• Phototherapy in ELBW newborns: does it work? Is it safe? The evidence from randomized clinical trials. Seminars in perinatology Arnold, C., Pedroza, C., Tyson, J. E. 2014; 38 (7): 452-64

  Abstract

  Phototherapy is assumed to be both effective and safe for extremely low-birth-weight infants. Our objective was to critically assess the relevant evidence from randomized trials. In the decades-old Collaborative Phototherapy Trial, phototherapy reduced serum bilirubin but not neurodevelopmental impairments. In the recent and larger Neonatal Network Trial, aggressive phototherapy compared to conservative phototherapy reduced both peak serum bilirubin (7.0 vs. 9.8mg/dL) and profound impairment at 18-22 months adjusted age (relative risk = 0.68). However, both trials suggested that phototherapy increased deaths among the smallest infants. Conservative Bayesian analyses of ventilator-treated infants under 751g birth weight in the Network trial identified a 99% probability of increased deaths and 99% probability of reduced profound impairment with aggressive phototherapy. Potential strategies to optimize the risk/benefit ratio in achieving low serum bilirubin levels, e.g., use of lowered irradiance levels, light-emitting diode phototherapy units, cycled phototherapy, and/or porphyrin compounds, deserve rigorous evaluation.

  View details for DOI 10.1053/j.semperi.2014.08.008

  View details for PubMedID 25308614

• Outcomes following periviable birth. Seminars in perinatology Arnold, C., Tyson, J. E. 2014; 38 (1): 2-11

  Abstract

  This review is presented in three segments: (1) important background concepts, (2) recent reports from regional geographically defined cohorts, and (3) prognosis research from the National Institutes of Health Neonatal Research Network. Extending the use of intensive care to newborns of lower gestational ages will unavoidably result in a higher proportion and a higher absolute number of survivors with morbidity, unless other changes in practice offset the increased risk associated with decreasing gestational age. In geographically defined cohort studies, the proportion of periviable newborns delivered in perinatal centers and the practices around foregoing and withdrawing intensive care are two important determinants of outcomes following periviable birth. It is much easier to quantify the effect of the former than the latter. Decisions regarding comfort care vs. intensive are frequently based on gestational age as the sole predictor variable, although multiple factors can be readily used to more accurately assess the benefits and burdens of intensive care and facilitate better informed parental counseling and decision making.

  View details for DOI 10.1053/j.semperi.2013.07.002

  View details for PubMedID 24468563

• Safe sleep practices and sudden infant death syndrome risk reduction: NICU and well-baby nursery graduates. Clinical pediatrics Fowler, A. J., Evans, P. W., Etchegaray, J. M., Ottenbacher, A., Arnold, C. 2013; 52 (11): 1044-53

  Abstract

  Our primary objective was to compare parents of infants cared for in newborn intensive care units (NICUs) and infants cared for in well-baby ("general") nurseries with regard to knowledge and practice of safe sleep practices/sudden infant death syndrome risk reduction measures and guidelines. Our secondary objective was to obtain qualitative data regarding reasons for noncompliance in both populations. Sixty participants (30 from each population) completed our survey measuring safe sleep knowledge and practice. Parents of NICU infants reported using 2 safe sleep practices-(a) always placing baby in crib to sleep and (b) always placing baby on back to sleep-significantly more frequently than parents of well infants. Additional findings and implications for future studies are discussed.

  View details for DOI 10.1177/0009922813506038

  View details for PubMedID 24137040

• Variability in vancomycin use in newborn intensive care units determined from data in an electronic medical record. Infection control and hospital epidemiology Arnold, C., Clark, R., Bosco, J., Shoemaker, C., Spitzer, A. R. 2008; 29 (7): 667-70

  Abstract

  Data from an electronic medical record were used to demonstrate a large variation in the proportion of patients treated with vancomycin in 56 newborn intensive care units, which ranged from 18% to 70% . Use of oxacillin or nafcillin instead of vancomycin was rare during the first few years of the study period but was routine in 13% of the newborn intensive care units during the last few years of the study period. The use of electronic medical record data for studies of antibiotic use is discussed here.

  View details for DOI 10.1086/588589

  View details for PubMedID 18518667