Systematic Review and Meta-analysis of Clinical Outcomes of Early Caffeine Therapy in Preterm Neonates

Overview

Journal Br J Clin Pharmacol

Specialty Pharmacology

Date 2016 Aug 16

PMID 27526255

Citations 39

Authors

Kok Pim Kua

Shaun Wen Huey Lee

Affiliations

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Abstract

Aims: This study evaluated the therapeutic outcomes of early versus late caffeine therapy in preterm neonates.

Methods: We performed a systematic literature search in PubMed, Embase, CINAHL and CENTRAL from inception to 30 June 2016 to identify studies investigating the use of early caffeine therapy (initiated at less than 3 days of life) in preterm infants. Effect estimates were combined using random-effects meta-analysis. The primary outcomes for this study were bronchopulmonary dysplasia and mortality.

Results: The initial search found 4066 citations, of which 14 studies enrolling a total of 64 438 participants were included. The time of initiation of early caffeine therapy varied from the first 2 h to 3 days postnatal. Early caffeine therapy reduced the risk of bronchopulmonary dysplasia in both cohort studies (RR: 0.80, 95% CI: 0.66 to 0.96) and randomized controlled trials (RR: 0.67, 95% CI: 0.56 to 0.81). In cohort studies, neonates treated early with caffeine also showed decreased risks of patent ductus arteriosus, brain injury, retinopathy of prematurity and postnatal steroid use. However, the mortality rate was increased.

Conclusions: The findings suggest that early caffeine therapy is associated with reduced incidence of bronchopulmonary dysplasia and may help decrease the burden of morbidities in preterm infants.

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References

Lodha A, Seshia M, McMillan D, Barrington K, Yang J, Lee S . Association of early caffeine administration and neonatal outcomes in very preterm neonates. JAMA Pediatr. 2014; 169(1):33-8. DOI: 10.1001/jamapediatrics.2014.2223. View

Skouroliakou M, Bacopoulou F, Markantonis S . Caffeine versus theophylline for apnea of prematurity: a randomised controlled trial. J Paediatr Child Health. 2009; 45(10):587-92. DOI: 10.1111/j.1440-1754.2009.01570.x. View

Fredholm B, BATTIG K, Holmen J, Nehlig A, Zvartau E . Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol Rev. 1999; 51(1):83-133. View

Clyman R, Roman C . The effects of caffeine on the preterm sheep ductus arteriosus. Pediatr Res. 2007; 62(2):167-9. DOI: 10.1203/PDR.0b013e3180a725b1. View

Davis P, Schmidt B, Roberts R, Doyle L, Asztalos E, Haslam R . Caffeine for Apnea of Prematurity trial: benefits may vary in subgroups. J Pediatr. 2009; 156(3):382-7. DOI: 10.1016/j.jpeds.2009.09.069. View

Sankaran K, Chien L, Walker R, Seshia M, Ohlsson A . Variations in mortality rates among Canadian neonatal intensive care units. CMAJ. 2002; 166(2):173-8. PMC: 99269. View

Armanian A, Iranpour R, Faghihian E, Salehimehr N . Caffeine Administration to Prevent Apnea in Very Premature Infants. Pediatr Neonatol. 2016; 57(5):408-412. DOI: 10.1016/j.pedneo.2015.10.007. View

Henderson-Smart D, Steer P . Caffeine versus theophylline for apnea in preterm infants. Cochrane Database Syst Rev. 2010; (1):CD000273. PMC: 11380529. DOI: 10.1002/14651858.CD000273.pub2. View

Cummings J, Polin R . Noninvasive Respiratory Support. Pediatrics. 2015; 137(1). DOI: 10.1542/peds.2015-3758. View

10.

Stoll B, Hansen N, Bell E, Shankaran S, Laptook A, Walsh M . Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network. Pediatrics. 2010; 126(3):443-56. PMC: 2982806. DOI: 10.1542/peds.2009-2959. View

11.

Alexander S, Fabbro D, Kelly E, Marrion N, Peters J, Benson H . The Concise Guide to PHARMACOLOGY 2015/16: Enzymes. Br J Pharmacol. 2015; 172(24):6024-109. PMC: 4718211. DOI: 10.1111/bph.13354. View

12.

Patel R, Leong T, Carlton D, Vyas-Read S . Early caffeine therapy and clinical outcomes in extremely preterm infants. J Perinatol. 2012; 33(2):134-40. DOI: 10.1038/jp.2012.52. View

13.

Katheria A, Sauberan J, Akotia D, Rich W, Durham J, Finer N . A Pilot Randomized Controlled Trial of Early versus Routine Caffeine in Extremely Premature Infants. Am J Perinatol. 2015; 32(9):879-86. DOI: 10.1055/s-0034-1543981. View

14.

Ananth C, Liu S, Joseph K, Kramer M . A comparison of foetal and infant mortality in the United States and Canada. Int J Epidemiol. 2008; 38(2):480-9. DOI: 10.1093/ije/dyn194. View

15.

Kua K, Lee S . Systematic review and meta-analysis of clinical outcomes of early caffeine therapy in preterm neonates. Br J Clin Pharmacol. 2016; 83(1):180-191. PMC: 5338164. DOI: 10.1111/bcp.13089. View

16.

Baud O, Maury L, Lebail F, Ramful D, El Moussawi F, Nicaise C . Effect of early low-dose hydrocortisone on survival without bronchopulmonary dysplasia in extremely preterm infants (PREMILOC): a double-blind, placebo-controlled, multicentre, randomised trial. Lancet. 2016; 387(10030):1827-36. DOI: 10.1016/S0140-6736(16)00202-6. View

17.

Dobson N, Patel R, Smith P, Kuehn D, Clark J, Vyas-Read S . Trends in caffeine use and association between clinical outcomes and timing of therapy in very low birth weight infants. J Pediatr. 2014; 164(5):992-998.e3. PMC: 3992195. DOI: 10.1016/j.jpeds.2013.12.025. View

18.

Jadad A, Moore R, Carroll D, Jenkinson C, Reynolds D, Gavaghan D . Assessing the quality of reports of randomized clinical trials: is blinding necessary?. Control Clin Trials. 1996; 17(1):1-12. DOI: 10.1016/0197-2456(95)00134-4. View

19.

Wells J, Kramer G . Phosphodiesterase inhibitors as tools in cyclic nucleotide research: a precautionary comment. Mol Cell Endocrinol. 1981; 23(1):1-9. DOI: 10.1016/0303-7207(81)90112-x. View

20.

Rysavy M, Li L, Bell E, Das A, Hintz S, Stoll B . Between-hospital variation in treatment and outcomes in extremely preterm infants. N Engl J Med. 2015; 372(19):1801-11. PMC: 4465092. DOI: 10.1056/NEJMoa1410689. View