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

Contemporary Clinical Trials Communications December 2022

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.

 

Ampicillin dosing in premature infants for early-onset sepsis: exposure-driven efficacy, safety, and stewardship

Journal of Perinatology July 2022

Le J, Greenberg RG, Yoo Y, Clark RH, Benjamin DK Jr., Zimmerman KO, Cohen-Wolkowiez M, Wade K

 

This study simulated ampicillin concentrations in newborns to define optimal ampicillin dosing for empiric early-onset sepsis (EOS) therapy in preterm neonates. For EOS in preterm infants, two ampicillin doses (50 mg/kg) provided optimal bactericidal exposures, while minimizing potential toxicity.

 

 

Safety of sildenafil in extremely premature infants: a phase I trial

Journal of Perinatology January 2022

Jackson W, Gonzalez D, Smith PB, Ambalavanan N, Atz A, Sokol GM, Hornik CD, Stewart D, Mundakel G, Poindexter BB, Ahlfeld SK, Mills M, Cohen-Wolkowiez M, Martz K, Hornik CP, Laughon MM; on behalf of the Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee

 

This study sought to characterize the safety of sildenafil in premature infants. Safety was evaluated based on adverse events (AEs), transaminase levels, and mean arterial pressure monitoring. There was one serious AE related to the study drug involving hypotension associated with a faster infusion rate than specified by the protocol. There were no AEs related to elevated transaminases. Sildenafil was well tolerated by the study population. Drug administration times and flush rates require careful attention to prevent infusion-related hypotension associated with faster infusions of IV sildenafil in premature infants.

 

 

Early-onset sepsis in term infants admitted to neonatal intensive care units (2011-2016)

Journal of Perinatology • January 2021

Bech Polcwiartek L, Smith PB, Benjamin DK, Zimmerman KO, Love A, Tiu L, Murray S, Kang P, Ebbesen F, Hagstrøm S, Clark RH, Greenberg RG

This study investigated characteristics of term infants culture-evaluated for early-onset sepsis (EOS) in neonatal intensive care units (NICUs), frequencies of organisms causing EOS, and factors associated with EOS. EOS was most commonly caused by group B Streptococcus. Lower EOS risk was associated with low Apgar score, Cesarean delivery, small for gestational age, prenatal antibiotic exposure, and positive or unknown maternal GBS screening result. Increased risk was associated with prolonged rupture of membranes, maternal age <19 years, vasopressor treatment, and ventilator support.

Probiotic Use and Safety in the Neonatal Intensive Care Unit: A Matched Cohort Study

Journal of Pediatrics • July 2020

Gray KD, Messina JA, Cortina C, Owens T, Fowler M, Foster M, Gbadegesin S, Clark RH, Benjamin DK, Zimmerman KO, Greenberg RG

This study sought to determine the prevalence of probiotic administration in infants born preterm over time, as well as the association between probiotic administration and select adverse outcomes. Probiotic use increased over the study period and varied among neonatal intensive care units. Probiotic administration was associated with a decrease in NEC and death, and an increase in Candida infection, but no increase in bloodstream infection or meningitis.

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Authors’ response to thrombocytopenia following exchange transfusion in neonates

Journal of Perinatology • July 2020

Wolf MF, Childers J, Gray KD, Chivily C, Glenn M, Jones L, Kpa M, McMannen T, Reyes I, Zimmerman KO, Clark RH, Greenberg RG

A letter from the author in response to comment on “Exchange transfusion safety and outcomes in neonatal hyperbilirubinemia.”

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Medications and In-hospital Outcomes in Infants Born at 22-24 Weeks Gestation

Journal of PerinatologyFebruary 2020

Puia-Dumitrescu M, Younge N, Benjamin DK, Lawson K, Hume C, Hill K, Mengistu J, Wilson A, Zimmerman ZO, Ahmad K, Greenberg RG; on behalf of the Best Pharmaceuticals for Children Act – Pediatric Trials Network

This study evaluated the most commonly used medications and in-hospital morbidities and mortality in infants born 22-24 weeks of gestation. It was a multicenter retrospective cohort study of infants born 22-24 weeks of gestation, from 2006-2016, without major congenital anomalies and with available medication data obtained from neonatal intensive care units managed by the Pediatrix Medical Group. A large number of medications were used in periviable infants. There was a high prevalence of in-hospital morbidities, and survival of this population increased over the study period.

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

Journal of Pediatrics • August 2019.

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.

 

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National Survey of Neonatal Intensive Care Unit Medication Safety Practices

American Journal of Perinatology • November 2018.

Greenberg RG, Smith PB, Bose C, Clark RH, Cotten CM, DeRienzo C.

We conducted a detailed survey to identify medication safety practices among a large network of United States neonatal intensive care units (NICUs). We created a 53-question survey to assess 300 U.S. NICU’s demographics, medication safety practices, adverse drug event (ADE) reporting, and ADE response plans.

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Prevalence and safety of diazoxide in the neonatal intensive care unit

Journal of Perinatology • November 2018.

Laughon MM, Benjamin DK Jr, Capparelli EV, Kearns GL, Berezny K, Paul IM, Wade K, Barrett J, Smith PB, Cohen-Wolkowiez M.

Diazoxide is used to treat infants with persistent hypoglycemia, but the prevalence of its use and adverse effects are not well described. We report demographic and clinical characteristics of infants treated with diazoxide in neonatal intensive care units (NICUs).

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