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  • Clinical Research Article
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Anesthesia, extremely premature infants and full-scale intelligence quotient at 5 years of age

Pediatric Research (2025)Cite this article

A Correction to this article was published on 23 April 2025

This article has been updated

Abstract

Background

To determine the association between exposure to Food and Drug Administration (FDA) warned anesthetics in premature infants and their full-scale intelligence quotient (FSIQ) score at 5 years of age.

Methods

Premature infants born <27 weeks gestational age (GA) between January 2006 and December 2012 with FDA anesthetic exposure status were included. Exposures included volatile anesthetics, propofol, benzodiazepines, ketamine, chloral hydrate, and barbiturates/phenobarbital. Exposure was treated as a binary variable with infants stratified into those who were or were not exposed to any FDA warned drug. Associations were explored using univariable and multivariable regressions.

Results

238 (61.5%) of 387 eligible infants had available FSIQ scores. Of these, 110 (46.2%) were exposed to warned anesthetics. Unadjusted and adjusted imputed case associations (95% CI) between FDA warned anesthetics and FSIQ were −5 (−10 to −2, p = 0.014) and −2 (−7 to 3, p = 0.528) points. An unobserved confounder(s) the strength of severe IVH [−9 points (−15 to −3)] would be required to overturn the directional association between FDA exposure and FSIQ in our complete case model.

Conclusion

Premature infants exposed to anesthetics flagged by the FDA showed no significant reduction in FSIQ at 5 years of age.

Impact

  • It is unclear whether early exposure to anesthetics in premature infants born <27 weeks gestation is associated with full-scale intelligence quotient (FSIQ) at 5 years of age.

  • Our retrospective cohort study included 387 premature infants born <27 weeks gestational age. FSIQ scores were available for 238/387 at 5 years of age of which 110 were exposed to Food and Drug Administration (FDA) warned anesthetic drugs.

  • After missing data imputation and adjustment for maternal and neonatal characteristics, no significant associations were found between FDA warned anesthetic exposure and FSIQ.

  • No adjusted volatile anesthetic or opioid dosage effect was associated with FSIQ.

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Fig. 1: Flow diagram of study cohort.
Fig. 2: Full-scale intelligence quotient (FSIQ) at 5 years of age of preterm infants exposed to.

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Data availability

In accordance with the Alberta Health Services Data Disclosure Agreement, we are not able to provide or make the data available for any purpose to a third party without the prior written consent of Alberta Health Services, Calgary, Alberta.

Change history

  • 22 April 2025

    The original online version of this article was revised: In the sentence beginning ‘We additionally included infant characteristics...’ in this article, the value ‘(BPD, NEC (≥stage 3)’ should have read ‘(BPD, NEC (≥stage 2)’.

  • 23 April 2025

    A Correction to this paper has been published: https://doi.org/10.1038/s41390-025-04065-2

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Acknowledgements

This work was supported by the Canadian Anesthesia Research Foundation as part of a Canadian Anesthesiologists’ Society Resident Research Grant awarded to Dr. Joanna Moser.

Author information

Authors and Affiliations

  1. Department of Anesthesiology, Perioperative and Pain Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

    Joanna J. Fifen, Andrew Walker & Debbie McAllister

  2. Alberta Health Services, Calgary, AB, Canada

    Joanna J. Fifen, Andrew Walker, Amina Benlamri, Selphee Tang, Sue Makarchuk, Abhay Lodha & Debbie McAllister

  3. Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

    Mujtaba Siddique

  4. Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB, Canada

    Arijit Lodha

  5. Department of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

    Amina Benlamri, Abhay Lodha & Debbie McAllister

  6. Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

    Abhay Lodha & Debbie McAllister

  7. Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

    Abhay Lodha

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  1. Joanna J. Fifen
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Contributions

J.J. Fifen drafted the initial version of the manuscript. M. Siddique and A. Lodha were involved in critical review and revision of the manuscript. J.J. Fifen, A. Lodha, D. McAllister, and A. Benlamri conceptualized and designed the study, were involved in the acquisition and interpretation of the data, and critical review and revision of the manuscript. A. Walker was involved in data acquisition, statistical analysis and interpretation of the data and critical review and revision of the manuscript. S. Tang was involved in the acquisition and interpretation of the data and critical review and revision of the manuscript. S. Makarchuk completes neurodevelopment assessments of the premature infants seen in the neonatal follow-up clinic and was involved in critical review and revision of the manuscript.

Corresponding author

Correspondence to Debbie McAllister.

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Competing interests

The authors declare no competing interests.

Consent to participate

The Conjoint Health Research Ethics Board (CHREB ID: REB16-0632, University of Calgary, Calgary, Alberta, Canada) granted the researchers a waiver of consent.

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The original online version of this article was revised: In the sentence beginning ‘We additionally included infant characteristics...’ in this article, the value ‘(BPD, NEC (≥stage 3)’ should have read ‘(BPD, NEC (≥stage 2)’.

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Fifen, J.J., Siddique, M., Lodha, A. et al. Anesthesia, extremely premature infants and full-scale intelligence quotient at 5 years of age. Pediatr Res (2025). https://doi.org/10.1038/s41390-025-04023-y

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