European Journal of Pediatrics

, Volume 174, Issue 7, pp 949–956 | Cite as

High versus low-dose caffeine for apnea of prematurity: a randomized controlled trial

  • Sameh Mohammed
  • Islam Nour
  • Abd Elazeez Shabaan
  • Basma Shouman
  • Hesham Abdel-Hady
  • Nehad Nasef
Original Article


The optimum caffeine dose in preterm infants has not been well investigated. We aimed to compare the efficacy and safety of high versus low-dose caffeine citrate on apnea of prematurity (AOP) and successful extubation of preterm infants from mechanical ventilation. We compared high-dose (loading 40 mg/kg/day and maintenance of 20 mg/kg/day) versus low-dose (loading 20 mg/kg/day and maintenance of 10 mg/kg/day) caffeine citrate in preterm infants <32 weeks gestation, presented with AOP within the first 10 days of life. A total of 120 neonates (60 in each group) were enrolled. High-dose caffeine was associated with a significant reduction in extubation failure in mechanically ventilated preterm infants (p < 0.05), the frequency of apnea (p < 0.001), and days of documented apnea (p < 0.001). High-dose caffeine was associated with significant increase in episodes of tachycardia (p < 0.05) without a significant impact on physician decision to withhold caffeine.

Conclusion: The use of higher, than current standard, dose of caffeine may decrease the chance of extubation failure in mechanically ventilated preterm infants and frequency of AOP without significant side effects.

What is Known:

Caffeine therapy for treatment of apnea of prematurity has been well established over the past few years. The optimal loading and maintenance dose of caffeine in preterm infants is not well-studied.

What is New:

This double blind randomized controlled trial demonstrated that using a higher, than current standard, loading and maintenance doses of caffeine for treatment of apnea in preterm infants is well tolerated and significantly decrease the frequency of apnea.


Apnea Caffeine Mechanical ventilation Neonatal respiratory distress syndrome Preterm infant Xanthines 



Apnea of prematurity


Bronchopulmonary dysplasia


Caffeine for apnea of prematurity


Continuous positive airway pressure


Intraventricular hemorrhage


Necrotizing enterocolitis


Periventricular leukomalacia


Retinopathy of prematurity



We would like to thank the parents and families in the Neonatal Intensive Care Unit at Mansoura University Children’s Hospital. We thank Eetemad Arafa for her assistance with randomization, blinding, and drug preparation.

Conflict on interest

Authors declare that they have no significant competing financial, professional, or personal interests that might have influenced the performance or presentation of the work described in this manuscript.

Funding source

No funding sources.

Authors’ contributions

Sameh Mohammed participated in design of the study, data collection, and writing the first draft of the manuscript; Islam Nour participated in design of the study, data collection, data interpretation, and writing the manuscript; Abd Elazeez Shabaan participated in design of the study, data collection, and writing of the manuscript; Basma Shouman participated in design of the study, data collection, and writing of the manuscript; Hesham Abdel-Hady participated in design of the study, data collection, and writing of the manuscript; and Nehad Nasef participated in formulating the hypothesis, design of the study, data collection, data interpretation, statistical analysis, and writing of the manuscript. All should approve the final version of the manuscript.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Sameh Mohammed
    • 1
  • Islam Nour
    • 1
    • 2
  • Abd Elazeez Shabaan
    • 1
    • 2
  • Basma Shouman
    • 1
    • 2
  • Hesham Abdel-Hady
    • 1
    • 2
  • Nehad Nasef
    • 1
    • 2
  1. 1.Neonatal Intensive Care UnitMansoura University Children’s HospitalMansouraEgypt
  2. 2.Department of Pediatrics, Faculty of MedicineUniversity of MansouraMansouraEgypt

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