Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Early caffeine therapy and clinical outcomes in extremely preterm infants

Journal of Perinatology volume 33, pages 134–140 (2013)Cite this article

Subjects

Abstract

Objective:

To determine if early caffeine (EC) therapy is associated with decreased bronchopulmonary dysplasia (BPD) or death, decreased treatment of patent ductus arteriosus (PDA), or shortened duration of ventilation.

Study Design:

In a retrospective cohort of 140 neonates ⩽1250 g at birth, infants receiving EC (initiation <3 days of life) were compared with those receiving late caffeine (LC, initiation ⩾3 days of life) using logistic regression.

Result:

Of infants receiving EC, 25% (21/83) died or developed BPD compared with 53% (30/57) of infants receiving LC (adjusted odds ratio (aOR) 0.26, 95% confidence interval (CI) 0.09 to 0.70; P<0.01). PDA required treatment in 10% of EC infants versus 36% of LC infants (aOR 0.28, 95%CI 0.10 to 0.73; P=0.01). Duration of mechanical ventilation was shorter in infants receiving EC (EC, 6 days; LC, 22 days; P<0.01).

Conclusion:

Infants receiving EC therapy had improved neonatal outcomes. Further studies are needed to determine if caffeine prophylaxis should be recommended for preterm infants.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Fanaroff AA, Stoll BJ, Wright LL, Carlo WA, Ehrenkranz RA, Stark AR et al. Trends in neonatal morbidity and mortality for very low birthweight infants. Am J Obstet Gynecol 2007; 196 (2): 147 e141-e148.

    Article  PubMed  Google Scholar 

  2. Stoll BJ, Hansen NI, Bell EF, Shankaran S, Laptook AR, Walsh MC et al. Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network. Pediatrics 2010; 126 (3): 443–456.

    Article  PubMed  Google Scholar 

  3. Baraldi E, Filippone M . Chronic lung disease after premature birth. N Engl J Med 2007; 357 (19): 1946–1955.

    Article  CAS  PubMed  Google Scholar 

  4. Schmidt B, Roberts R, Millar D, Kirpalani H . Evidence-based neonatal drug therapy for prevention of bronchopulmonary dysplasia in very-low-birth-weight infants. Neonatology 2008; 93 (4): 284–287.

    Article  PubMed  Google Scholar 

  5. Laughon MM, Smith PB, Bose C . Prevention of bronchopulmonary dysplasia. Semin Fetal Neonatal Med 2009; 14 (6): 374–382.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Cotton RB, Stahlman MT, Bender HW, Graham TP, Catterton WZ, Kovar I . Randomized trial of early closure of symptomatic patent ductus arteriosus in small preterm infants. J Pediatr 1978; 93 (4): 647–651.

    Article  CAS  PubMed  Google Scholar 

  7. Brooks JM, Travadi JN, Patole SK, Doherty DA, Simmer K . Is surgical ligation of patent ductus arteriosus necessary? The Western Australian experience of conservative management. Arch Dis Child Fetal Neonatal Ed 2005; 90 (3): F235–F239.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Marshall DD, Kotelchuck M, Young TE, Bose CL, Kruyer L, O'Shea TM . Risk factors for chronic lung disease in the surfactant era: a North Carolina population-based study of very low birth weight infants. North Carolina Neonatologists Association. Pediatrics 1999; 104 (6): 1345–1350.

    Article  CAS  PubMed  Google Scholar 

  9. Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A et al. Caffeine therapy for apnea of prematurity. N Engl J Med 2006; 354 (20): 2112–2121.

    Article  CAS  PubMed  Google Scholar 

  10. Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A et al. Long-term effects of caffeine therapy for apnea of prematurity. N Engl J Med 2007; 357 (19): 1893–1902.

    Article  CAS  PubMed  Google Scholar 

  11. Davis PG, Schmidt B, Roberts RS, Doyle LW, Asztalos E, Haslam R et al. Caffeine for Apnea of Prematurity trial: benefits may vary in subgroups. J Pediatr 2010; 156 (3): 382–387.

    Article  CAS  PubMed  Google Scholar 

  12. Laughon MM, Langer JC, Bose CL, Smith PB, Ambalavanan N, Kennedy KA et al. Prediction of bronchopulmonary dysplasia by postnatal age in extremely premature infants. Am J Respir Crit Care Med 2011; 183 (12): 1715–1722.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Tyson JE, Parikh NA, Langer J, Green C, Higgins RD . Intensive care for extreme prematurity--moving beyond gestational age. N Engl J Med 2008; 358 (16): 1672–1681.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Clark RH, Bloom BT, Spitzer AR, Gerstmann DR . Reported medication use in the neonatal intensive care unit: data from a large national data set. Pediatrics 2006; 117 (6): 1979–1987.

    Article  PubMed  Google Scholar 

  15. Dukhovny D, Lorch SA, Schmidt B, Doyle LW, Kok JH, Roberts RS et al. Economic evaluation of caffeine for apnea of prematurity. Pediatrics 2011; 127 (1): e146–e155.

    Article  PubMed  Google Scholar 

  16. Aranda JV, Turmen T, Davis J, Trippenbach T, Grondin D, Zinman R et al. Effect of caffeine on control of breathing in infantile apnea. J Pediatr 1983; 103 (6): 975–978.

    Article  CAS  PubMed  Google Scholar 

  17. Davis JM, Bhutani VK, Stefano JL, Fox WW, Spitzer AR . Changes in pulmonary mechanics following caffeine administration in infants with bronchopulmonary dysplasia. Pediatr Pulmonol 1989; 6 (1): 49–52.

    Article  CAS  PubMed  Google Scholar 

  18. Yoder B, Thomson M, Coalson J . Lung function in immature baboons with respiratory distress syndrome receiving early caffeine therapy: a pilot study. Acta Paediatr 2005; 94 (1): 92–98.

    Article  CAS  PubMed  Google Scholar 

  19. Supinski GS, Deal Jr EC, Kelsen SG . The effects of caffeine and theophylline on diaphragm contractility. Am Rev Respir Dis 1984; 130 (3): 429–433.

    CAS  PubMed  Google Scholar 

  20. Li J, Li G, Hu JL, Fu XH, Zeng YJ, Zhou YG et al. Chronic or high dose acute caffeine treatment protects mice against oleic acid-induced acute lung injury via an adenosine A2A receptor-independent mechanism. Eur J Pharmacol 2011; 654 (3): 295–303.

    Article  CAS  PubMed  Google Scholar 

  21. Oliveira-Junior IS, Pinheiro BV, Silva ID, Salomao R, Zollner RL, Beppu OS . Pentoxifylline decreases tumor necrosis factor and interleukin-1 during high tidal volume. Braz J Med Biol Res 2003; 36 (10): 1349–1357.

    Article  CAS  PubMed  Google Scholar 

  22. Gillot I, Gouyon JB, Guignard JP . Renal effects of caffeine in preterm infants. Biol Neonate 1990; 58 (3): 133–136.

    Article  CAS  PubMed  Google Scholar 

  23. Soloveychik V, Bin-Nun A, Ionchev A, Sriram S, Meadow W . Acute hemodynamic effects of caffeine administration in premature infants. J Perinatol 2009; 29 (3): 205–208.

    Article  CAS  PubMed  Google Scholar 

  24. Blaustein MP, Golovina VA, Song H, Choate J, Lencesova L, Robinson SW et al. Organization of Ca2+ stores in vascular smooth muscle: functional implications. Novartis Found Symp 2002; 246: 125–137; discussion 137-141, 221-227.

    CAS  PubMed  Google Scholar 

  25. Whorton AR, Collawn JB, Montgomery ME, Young SL, Kent RS . Arachidonic acid metabolism in cultured aortic endothelial cells. Effect of cAMP and 3-isobutyl-1-methylxanthine. Biochem Pharmacol 1985; 34 (1): 119–123.

    Article  CAS  PubMed  Google Scholar 

  26. Clyman RI, Roman C . The effects of caffeine on the preterm sheep ductus arteriosus. Pediatr Res 2007; 62 (2): 167–169.

    Article  CAS  PubMed  Google Scholar 

  27. Hamrick SE, Hansmann G . Patent ductus arteriosus of the preterm infant. Pediatrics 2010; 125 (5): 1020–1030.

    Article  PubMed  Google Scholar 

  28. Henderson-Smart DJ, Davis PG . Prophylactic methylxanthines for endotracheal extubation in preterm infants. Cochrane Database Syst Rev 2010; (12): CD000139.

  29. Hoecker C, Nelle M, Poeschl J, Beedgen B, Linderkamp O . Caffeine impairs cerebral and intestinal blood flow velocity in preterm infants. Pediatrics 2002; 109 (5): 784–787.

    Article  PubMed  Google Scholar 

  30. Van Bel F, Van de Bor M, Stijnen T, Baan J, Ruys JH . Cerebral blood flow velocity changes in preterm infants after a single dose of indomethacin: duration of its effect. Pediatrics 1989; 84 (5): 802–807.

    CAS  PubMed  Google Scholar 

  31. Doyle LW, Cheong J, Hunt RW, Lee KJ, Thompson DK, Davis PG et al. Caffeine and brain development in very preterm infants. Ann Neurol 2010; 68 (5): 734–742.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Becky Kinkead for her critical review of this manuscript.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA

    R M Patel, D P Carlton & S Vyas-Read

  2. Children's Healthcare of Atlanta, Atlanta, GA, USA

    R M Patel, D P Carlton & S Vyas-Read

  3. Departments of Biostatistics and Bioinformatics, Grace Crum Rollins School of Public Health, Emory University, Atlanta, GA, USA

    T Leong

  4. The Children's Center for Developmental Lung Biology, Atlanta, GA, USA

    S Vyas-Read

Authors
  1. R M Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T Leong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D P Carlton
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S Vyas-Read
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R M Patel.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies the paper on the Journal of Perinatology website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Patel, R., Leong, T., Carlton, D. et al. Early caffeine therapy and clinical outcomes in extremely preterm infants. J Perinatol 33, 134–140 (2013). https://doi.org/10.1038/jp.2012.52

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jp.2012.52

Keywords

This article is cited by

Search

Advanced search

Quick links