Respiratory support

Furosemide Safety in Preterm Infants at Risk for Bronchopulmonary Dysplasia: A Randomized Clinical Trial

Posted on by Jeannine Sato

The Journal of Pediatrics • April 2025

Access article on PubMed.

Greenberg RG, Lang J, Smith PB, Shekhawat P, Courtney SE, Hudak ML, Moya F, Iyengar A, Eldemerdash A, Bloom B, Go M, Hanna M, Rhein L, Aliaga S, Lewis T, Febre A, Kiefer AS, Bhatt-Mehta V, Khoury JA, Selewski D, Anand R, Martz K, Payne EH, Zimmerman KO, Benjamin DK Jr, Laughon M; Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee.

The objective of this study was to evaluate the safety of furosemide in preterm infants at the risk of developing bronchopulmonary dysplasia (BPD). This multicenter, randomized, dose-escalating, placebo-controlled trial enrolled infants born <29 weeks gestational age at 7-28 days postnatal age and at risk for BPD. In preterm infants, furosemide did not increase the overall incidence of AEs, hearing loss, or nephrocalcinosis, but did increase the incidence of electrolyte abnormalities. Furosemide given for 28 consecutive days was not associated with a difference in moderate-to-severe BPD or death at 36 weeks postmenstrual age.

Safety of sildenafil in premature infants at risk of bronchopulmonary dysplasia: Rationale and methods of a phase II randomized trial

Posted on by Kayla Korzekwinski

Contemporary Clinical Trials Communications • December 2022

Access article on PubMed.

Lang JE, Hornik CD, Martz K, Jacangelo J, Anand R, Greenberg R, Hornik C, Zimmerman K, Smith PB, Benjamin DK, Laughon M
Bronchopulmonary dysplasia (BPD) is a disease of chronic respiratory insufficiency stemming from premature birth and iatrogenic lung injury leading to many complications. BPD is the most common pulmonary sequela of prematurity and is often fatal; however, there remains no FDA-approved therapies to treat or prevent BPD. Sildenafil is increasingly used off-label in premature infants despite scant safety and efficacy data. We developed the phase II SIL02 trial to describe the safety, pharmacokinetics and preliminary effectiveness of intravenous and enteral sildenafil in premature infants at risk for BPD.

Hospital-acquired Pneumonia and Ventilator-associated Pneumonia in Children: A Prospective Natural History and Case-Control Study

Posted on by Kayla Korzekwinski

Pediatric Infectious Disease Journal • August 2020

Access article on PubMed.

Ericson JE, McGuire J, Michaels MG, Schwarz A, Frenck R, Deville JG, Agarwal S, Bressler AM, Gao J, Spears T, Benjamin DK, Smith PB, Bradley, JS

We examined laboratory and clinical features that might improve pediatric hospital-acquired and ventilator-associated bacterial pneumonias (HABP/VABP) trial efficiency by identifying risk factors predisposing children to HABP/VABP and describing the epidemiology of pediatric HABP/VABP. Food and Drug Administration-defined HABP/VABP occurred in 10%-12% of pediatric patients admitted to ICUs. Risk factors vary by age group.

Dosing and Safety of Off-label Use of Caffeine Citrate in Premature Infants

Posted on by Kayla Korzekwinski

Journal of Pediatrics • August 2019

Access article on PubMed.

Puia-Dumitrescu M, Smith PB, Zhao J, Soriano A, Payne EH, Harper B, Bendel-Stenzel E, Moya F, Chhabra R, Ku L, Laughon M, Wade KC

Aim to characterize the dosing and safety of off-label caffeine citrate in a contemporary cohort of extremely premature infants. We used electronic health records (2010-2013) from 4 neonatal intensive care units to identify infants of ≤28 weeks of gestational age exposed to caffeine citrate. Of 410 infants with a median (IQR) gestational age of 26 (24-27) weeks, 95% received caffeine citrate for >0 days. Infants received a median (IQR) daily dose of 8 (5-10) mg/kg/day. Incidences of clinical events on day of caffeine citrate exposure were death 2%, patent ductus arteriosus ligation 12%, and medical and surgical necrotizing enterocolitis 5% and 4%, respectively.

Comparative efficacy and safety of late surfactant preparations: a retrospective study

Posted on by Kayla Korzekwinski

Journal of Perinatology • November 2021

Access article on PubMed.

Lane MD, Kishnani S, Udemadu O, Danquah SE, Treadway RM, Langman A, Balevic S, Jackson WM, Laughon M, Hornik CP, Greenberg RG, Clark RH, Zimmerman KO

This study sought to characterize the use, efficacy, and safety of poractant alfa and calfactant surfactants compared to beractant in preterm infants receiving late surfactant. Compared to beractant, there is no evidence of overall superior efficacy or safety of poractant alfa.

Surfactant Administration in Preterm Infants: Drug Development Opportunities

Posted on by Kayla Korzekwinski

The Journal of Pediatrics • May 2019

Access article on PubMed.

Taylor G, Jackson W, Hornik CP, Koss A, Mantena S, Homsley K, Gattis B, Kudumu-Clavell M, Clark R, Smith PB, Laughon MM

This study evaluated how frequently surfactant is used off-label in preterm infants. The majority of surfactant given to preterm infants is administered off-label. The uptrend in administration via INSURE coincides with increased supporting evidence. The gap between FDA labeling and current clinic practice exemplifies an opportunity for label expansion, which may require additional prospective or retrospective safety and/or effectiveness data for infants of older GA and higher birth weight.

Antifungal Extraction by the Extracorporeal Membrane Oxygenation Circuit

Posted on by Kayla Korzekwinski

The Journal of ExtraCorporeal Technology • September 2017

Access article on PubMed.

Watt KM, Cohen-Wolkowiez M, Williams DC, Bonadonna DK, Cheifetz IM, Thakker D, Benjamin DK Jr, Brouwer KLR

Invasive candidiasis is common and often fatal in patients supported with extracorporeal membrane oxygenation (ECMO), and treatment relies on optimal antifungal dosing. The ECMO circuit can extract drug and decrease drug exposure, placing the patient at risk of therapeutic failure. This ex vivo study determined the extraction of antifungal drugs by the ECMO circuit. Fluconazole and micafungin were studied separately in three closed-loop circuit configurations to isolate the impact of the oxygenator, hemofilter, and tubing on circuit extraction.

Timing of Multiorgan Dysfunction among Hospitalized Infants with Fatal Fulminant Sepsis

Posted on by Kayla Korzekwinski

American Journal of Perinatology • June 2017

Access article on PubMed.

Wynn JL, Kelly MS, Benjamin DK, Clark RH, Greenberg R, Benjamin DK Jr, Smith PB

This study sought to identify the progression of specific signs of multiorgan dysfunction among infants with fatal sepsis. Hospitalized infants with fatal LOS manifest respiratory, cardiovascular, renal, immune, and hematologic dysfunction. Knowledge of these factors and their timing may be important for the development and testing of novel therapeutics to reduce sepsis mortality.

Risk Factors and In-Hospital Outcomes Following Tracheostomy in Infants

Posted on by Kayla Korzekwinski

The Journal of Pediatrics • June 2017

Access article on PubMed.

Lee JH, Smith PB, Quek MBH, Laughon MM, Clark RH, Hornik CP

This study analyzed an electronic medical record from 348 NICUs from 1997–2012 and evaluated the associations between infant demographics, diagnoses, and pre-tracheostomy cardio-pulmonary support with in-hospital mortality. It also determined the trends in use of infant tracheostomy over time. Tracheostomy is uncommonly performed in hospitalized infants, but the associated mortality is high. Risk factors for increased in-hospital mortality after tracheostomy include GA near term, SGA, and pulmonary diagnoses.

Respiratory Support for Very Low Birth Weight Infants Receiving Dexamethasone

Posted on by Kayla Korzekwinski

The Journal of Pediatrics • April 2017

Access article on PubMed.

Virkud YV, Hornik CP, Benjamin DK, Laughon MM, Clark RH, Greenberg RG, Smith PB.

To assess how neonatal intensive care units followed the American Academy of Pediatrics guidelines for use of dexamethasone in preterm infants by evaluating respiratory support at the time of dexamethasone administration. This is an observational study of infants discharged from one of 290 neonatal intensive care units from 2003 to 2010. The cohort included very low birth weight (<1500 g birth weight) infants born at ≤32 weeks gestational age. The main outcome was respiratory support at time of exposure to dexamethasone.