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

Best Pharmaceuticals for Children Act–Pediatric Trials Network Steering Committee

Research output: Contribution to journalArticle

Abstract

Objective: To characterize the dosing and safety of off-label caffeine citrate in a contemporary cohort of extremely premature infants. Study design: 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. Safety outcomes included death, bronchopulmonary dysplasia, necrotizing enterocolitis, spontaneous intestinal perforation, intraventricular hemorrhage, patent ductus arteriosus ligation, seizures, and arrhythmias. We used multivariable logistic regression to evaluate the association of caffeine citrate exposure with clinical events. Results: 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. Bronchopulmonary dysplasia occurred in 37% of infants and was not associated with caffeine dose. Increased caffeine citrate dose was associated with lower odds of patent ductus arteriosus ligation and necrotizing enterocolitis. Conclusions: Caffeine citrate was used in extremely premature infants at younger gestation, at higher doses, and for longer durations than recommended on the drug label. Increased caffeine citrate exposure, dose, or therapy duration was not associated with increased risk of necrotizing enterocolitis.

Original languageEnglish (US)
Pages (from-to)27-32.e1
JournalJournal of Pediatrics
Volume211
DOIs
StatePublished - Aug 1 2019

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Off-Label Use
Premature Infants
Safety
Necrotizing Enterocolitis
Patent Ductus Arteriosus
Extremely Premature Infants
Ligation
Bronchopulmonary Dysplasia
Gestational Age
Intestinal Perforation
caffeine citrate
Electronic Health Records
Neonatal Intensive Care Units
Caffeine
Cardiac Arrhythmias
Seizures
Logistic Models
Hemorrhage
Pregnancy
Incidence

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health

Cite this

Best Pharmaceuticals for Children Act–Pediatric Trials Network Steering Committee (2019). Dosing and Safety of Off-label Use of Caffeine Citrate in Premature Infants. Journal of Pediatrics, 211, 27-32.e1. https://doi.org/10.1016/j.jpeds.2019.04.028
Best Pharmaceuticals for Children Act–Pediatric Trials Network Steering Committee. / Dosing and Safety of Off-label Use of Caffeine Citrate in Premature Infants. In: Journal of Pediatrics. 2019 ; Vol. 211. pp. 27-32.e1.
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abstract = "Objective: To characterize the dosing and safety of off-label caffeine citrate in a contemporary cohort of extremely premature infants. Study design: 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. Safety outcomes included death, bronchopulmonary dysplasia, necrotizing enterocolitis, spontaneous intestinal perforation, intraventricular hemorrhage, patent ductus arteriosus ligation, seizures, and arrhythmias. We used multivariable logistic regression to evaluate the association of caffeine citrate exposure with clinical events. Results: 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. Bronchopulmonary dysplasia occurred in 37{\%} of infants and was not associated with caffeine dose. Increased caffeine citrate dose was associated with lower odds of patent ductus arteriosus ligation and necrotizing enterocolitis. Conclusions: Caffeine citrate was used in extremely premature infants at younger gestation, at higher doses, and for longer durations than recommended on the drug label. Increased caffeine citrate exposure, dose, or therapy duration was not associated with increased risk of necrotizing enterocolitis.",
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Best Pharmaceuticals for Children Act–Pediatric Trials Network Steering Committee 2019, 'Dosing and Safety of Off-label Use of Caffeine Citrate in Premature Infants', Journal of Pediatrics, vol. 211, pp. 27-32.e1. https://doi.org/10.1016/j.jpeds.2019.04.028

Dosing and Safety of Off-label Use of Caffeine Citrate in Premature Infants. / Best Pharmaceuticals for Children Act–Pediatric Trials Network Steering Committee.

In: Journal of Pediatrics, Vol. 211, 01.08.2019, p. 27-32.e1.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Dosing and Safety of Off-label Use of Caffeine Citrate in Premature Infants

AU - Best Pharmaceuticals for Children Act–Pediatric Trials Network Steering Committee

AU - Puia-Dumitrescu, Mihai

AU - Smith, P. Brian

AU - Zhao, Jian

AU - Soriano, Angela

AU - Payne, Elizabeth H.

AU - Harper, Barrie

AU - Bendel-Stenzel, Ellen

AU - Moya, Fernando

AU - Chhabra, Rakesh

AU - Ku, Lawrence

AU - Laughon, Matthew

AU - Wade, Kelly C.

AU - Furda, Gary

AU - Benjamin, Danny

AU - Capparelli, Edmund

AU - Kearns, Gregory L.

AU - Paul, Ian

AU - Hornik, Christoph

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Y1 - 2019/8/1

N2 - Objective: To characterize the dosing and safety of off-label caffeine citrate in a contemporary cohort of extremely premature infants. Study design: 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. Safety outcomes included death, bronchopulmonary dysplasia, necrotizing enterocolitis, spontaneous intestinal perforation, intraventricular hemorrhage, patent ductus arteriosus ligation, seizures, and arrhythmias. We used multivariable logistic regression to evaluate the association of caffeine citrate exposure with clinical events. Results: 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. Bronchopulmonary dysplasia occurred in 37% of infants and was not associated with caffeine dose. Increased caffeine citrate dose was associated with lower odds of patent ductus arteriosus ligation and necrotizing enterocolitis. Conclusions: Caffeine citrate was used in extremely premature infants at younger gestation, at higher doses, and for longer durations than recommended on the drug label. Increased caffeine citrate exposure, dose, or therapy duration was not associated with increased risk of necrotizing enterocolitis.

AB - Objective: To characterize the dosing and safety of off-label caffeine citrate in a contemporary cohort of extremely premature infants. Study design: 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. Safety outcomes included death, bronchopulmonary dysplasia, necrotizing enterocolitis, spontaneous intestinal perforation, intraventricular hemorrhage, patent ductus arteriosus ligation, seizures, and arrhythmias. We used multivariable logistic regression to evaluate the association of caffeine citrate exposure with clinical events. Results: 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. Bronchopulmonary dysplasia occurred in 37% of infants and was not associated with caffeine dose. Increased caffeine citrate dose was associated with lower odds of patent ductus arteriosus ligation and necrotizing enterocolitis. Conclusions: Caffeine citrate was used in extremely premature infants at younger gestation, at higher doses, and for longer durations than recommended on the drug label. Increased caffeine citrate exposure, dose, or therapy duration was not associated with increased risk of necrotizing enterocolitis.

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Best Pharmaceuticals for Children Act–Pediatric Trials Network Steering Committee. Dosing and Safety of Off-label Use of Caffeine Citrate in Premature Infants. Journal of Pediatrics. 2019 Aug 1;211:27-32.e1. https://doi.org/10.1016/j.jpeds.2019.04.028