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The association of salivary caffeine levels with serum concentrations in premature infants with apnea of prematurity

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Abstract

The purpose of this paper is to verify whether the concentrations of caffeine in saliva are comparable to serum concentrations in preterm infants who are treated with caffeine for apnea of prematurity. This is a prospective observational study. Eligible participants were newborn infants < 37 weeks of gestational age treated with oral or intravenous caffeine for apnea of prematurity. Two paired samples of saliva and blood were collected per patient. Tube solid-phase microextraction coupled online to capillary liquid chromatography with diode array detection was used for analysis. A total of 47 infants with a median gestational age of 28 [26–30] weeks and a mean of 1.11 ± 0.4 kg of birth weight. Median postmenstrual age, when samples were collected, was 31 [29–33] weeks. Serum caffeine median levels of 19.30 μg/mL [1.9–53.90] and salivary caffeine median levels of 16.36 μg/mL [2.20–56.90] were obtained. There was a strong positive Pearson’s correlation between the two variables r = 0.83 (p < 0.001).

Conclusion: The measurement of salivary caffeine concentrations after intravenous or oral administration offers an alternative to serum caffeine monitoring in apnea of prematurity. Measurement of salivary concentration minimizes blood draws, improves blood conservation, and subsequently minimizes painful procedures in premature infants.

What is Known:

• Salivary sampling may be useful when is applied to extremely low birth weight infant, in whom blood sampling must be severely restricted.

What is New:

• The measurement of caffeine salivary concentrations after intravenous or oral administration offers an alternative to serum caffeine monitoring in apnoea of prematurity.

• Salivary sampling may be a valid non-invasive alternative that could be used to individualize and optimize caffeine dose.

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Abbreviations

AOP:

Apnea of prematurity

GA:

Gestational age

HPLC:

High-pressure liquid chromatography

IV:

Intravenous

NICU:

Neonatal intensive care unit

O:

Oral

PMA:

Postmenstrual age

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Acknowledgements

The authors would like to thank the staff and the nurses of the Neonatology Division for the dedication and support to this project. The authors thank Elena Ramirez Saenz and Luis González Batanero for their support in the writing and revision of language, grammar, and terminology.

Funding

The authors are grateful to VLC-BIOMED program, project 04-CAFE-CINETIC-VERDU-SAENZ-2016-A. ASG and MVT acknowledge RETICS funded by the PN 2018–2021 (Spain), ISCIII- Sub-Directorate General for Research Assessment and Promotion and the European Regional Development Fund (FEDER), reference RD16/0022/0001.

Author information

Authors and Affiliations

  1. Neonatal Research Group, Health Research Institute La Fe, University and Polytechnic Hospital La Fe, Valencia, Spain

    Ana García-Robles, Álvaro Solaz-García, Consuelo Cháfer Pericás, Máximo Vento & Pilar Sáenz González

  2. MINTOTA Research Group, Departament de Química Analítica. Facultat de Química, Universitat de València, Valencia, Spain

    Jorge Verdú-Andrés

  3. Division of Pharmacy, University and Polytechnic Hospital La Fe, Valencia, Spain

    José Luis Poveda Andrés & Henry Daniel Ponce-Rodriguez

  4. Data Science Unit, Health Research Institute La Fe, University and Polytechnic Hospital La Fe, Valencia, Spain

    Antonio José Cañada-Martínez

  5. Division of Neonatology, University and Polytechnic Hospital La Fe, Valencia, Spain

    Máximo Vento & Pilar Sáenz González

Authors
  1. Ana García-Robles
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  2. Álvaro Solaz-García
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  3. Jorge Verdú-Andrés
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  6. Consuelo Cháfer Pericás
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  7. Henry Daniel Ponce-Rodriguez
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  9. Pilar Sáenz González
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Contributions

AGR, ASG, MVT, JVA, JPA, CHP, and PSG were all involved in development of the study. AGR, ASG and PSG prepared the initial draft of the manuscript and set up the database infrastructure for the intervention. ACM performed statistical analyses. JVA and HDPR performed analytical sample procedures. All authors read, contributed to editing, and approved the final manuscript.

Corresponding author

Correspondence to Pilar Sáenz González.

Ethics declarations

Ethics approval

The study protocol was reviewed and approved by the Institutional Review Board of our hospital (approval identification code: GIP-CAF-2017–01/408). Written informed consent was obtained from the parents of all patients before inclusion in the study.

Consent to participate

All legal representatives of patients consent their participation after receiving patient information and consents.

Conflict of interest

The authors declare no competing interests.

Disclaimer

The authors confirm that if their article is published in ANC, they will notify the relevant parties accordingly so that the preprint version can be linked to the published record.

Additional information

Communicated by Daniele De Luca

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García-Robles, A., Solaz-García, Á., Verdú-Andrés, J. et al. The association of salivary caffeine levels with serum concentrations in premature infants with apnea of prematurity. Eur J Pediatr 181, 4175–4182 (2022). https://doi.org/10.1007/s00431-022-04628-z

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  • DOI: https://doi.org/10.1007/s00431-022-04628-z

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