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Caffeine citrate for apnea of prematurity—One dose does not fit all a prospective study

Journal of Perinatology volume 41, pages 2292–2297 (2021)Cite this article

Subjects

Abstract

Background

Caffeine citrate is the most frequently used medication in preterm neonates for the prevention of apnea of prematurity. There is no accepted consensus regarding the optimal caffeine citrate dosing. In this study, we evaluate clinical responses of premature neonates to standard-dose caffeine citrate treatment.

Methods

A prospective observational study conducted at the NICU at Sheba Medical Center (3/2016-2/2017). The study population included preterm neonates born at a gestational age (GA) < 33 weeks and treated with caffeine citrate according to the local NICU protocol.

Results

The study cohort included 66 preterm neonates of GA < 33 weeks. Thirty infants were defined as responders and 36 as nonresponders to 7.5 mg/kg caffeine citrate treatment, and they required a further dose increase to 10 mg/kg. Infants in the nonresponders group were born at earlier GA than responders (29 vs. 31 weeks, respectively, P = 0.004). The nonresponders required a significantly longer hospital stay (56 vs. 46 days, P = 0.014), and longer supplemental oxygen support (18 vs 2 days, P = 0.008).

Conclusions

Caffeine citrate initiation at higher doses is safe and does not require routine serum levels monitoring. It might be more effective for controlling apnea of prematurity in preterm neonates born ≤29 weeks of gestation.

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Fig. 1: Caffeine citrate treatment protocol.
Fig. 2: Flowchart of the study population.

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Data availability

All the data presented in the manuscript is available upon request from the corresponding author.

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Author information

Authors and Affiliations

  1. Department of Neonatology, Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Tel-Hashomer, Israel

    Chava Rosen, Camilia Taran, Marwan Hanna & Tzipora Strauss

  2. The Talpiot Medical Leadership Program, Sheba Medical Center, Tel-Hashomer, Israel

    Chava Rosen

  3. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Chava Rosen, Itai Gueta, Ronen Loebstein, Tzipora Strauss & Havatzelet Yarden-Bilavsky

  4. Institute of Clinical Pharmacology and Toxicology, Sheba Medical Center, Tel Hashomer, Israel

    Itai Gueta, Ronen Loebstein & Havatzelet Yarden-Bilavsky

  5. Department of Internal Medicine A, Sheba Medical Center, Tel Hashomer, Israel

    Itai Gueta

  6. Department of Pediatrics A, Schneider Children’s Medical Center, Petach Tikva, both affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Havatzelet Yarden-Bilavsky

Authors
  1. Chava Rosen
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  2. Camilia Taran
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  7. Havatzelet Yarden-Bilavsky
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Contributions

CR designed the study, performed data collection; analyzed and interpreted the data and co-wrote the manuscript. CT assisted in data collection from patients’ files and managing nurses, assisted in drafting the initial manuscript; and analyzed the data. MH assisted in data collection and supervised the adherence to the caffeine citrate protocol and analyzed the data and assisted in drafting the initial manuscript. IG and RL assisted in study design, data collection, data analysis, and statistics. HY-B assisted in study design, data collection, data analysis, and statistics and co-wrote the manuscript. TS designed, coordinated, and conducted the study, including analysis and interpretation of data, and co-wrote the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Chava Rosen.

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Competing interests

The authors declare no competing interests.

Ethics approval

The study protocol was approved by the institutional review board of the Sheba Medical Center.

Consent to participate

The study cohort included 70 preterm neonates with a GA < 33 weeks whose parents signed informed written consent.

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Rosen, C., Taran, C., Hanna, M. et al. Caffeine citrate for apnea of prematurity—One dose does not fit all a prospective study. J Perinatol 41, 2292–2297 (2021). https://doi.org/10.1038/s41372-021-01172-w

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