Abstract
Background
Prior studies of early antibiotic use and growth have shown mixed results, primarily on cross-sectional outcomes. This study examined the effect of oral antibiotics before age 24 months on growth trajectory at age 2–5 years.
Methods
We captured oral antibiotic prescriptions and anthropometrics from electronic health records through PCORnet, for children with ≥1 height and weight at 0–12 months of age, ≥1 at 12–30 months, and ≥2 between 25 and 72 months. Prescriptions were grouped into episodes by time and by antimicrobial spectrum. Longitudinal rate regression was used to assess differences in growth rate from 25 to 72 months of age. Models were adjusted for sex, race/ethnicity, steroid use, diagnosed asthma, complex chronic conditions, and infections.
Results
430,376 children from 29 health U.S. systems were included, with 58% receiving antibiotics before 24 months. Exposure to any antibiotic was associated with an average 0.7% (95% CI 0.5, 0.9, p < 0.0001) greater rate of weight gain, corresponding to 0.05 kg additional weight. The estimated effect was slightly greater for narrow-spectrum (0.8% [0.6, 1.1]) than broad-spectrum (0.6% [0.3, 0.8], p < 0.0001) drugs. There was a small dose response relationship between the number of antibiotic episodes and weight gain.
Conclusion
Oral antibiotic use prior to 24 months of age was associated with very small changes in average growth rate at ages 2–5 years. The small effect size is unlikely to affect individual prescribing decisions, though it may reflect a biologic effect that can combine with others.
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Code availability
R code developed for the analyses reported here are available at https://github.com/PEDSnet/pcornet_abx_growth_study/tree/main/lt_trajectory_analysis. Additionally, Daymont et al. have made an implementation of their anthropometric data evaluation algorithm available at https://github.com/carriedaymont/growthcleanr.
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Acknowledgements
The PCORnet Childhood Antibiotic Study Team includes a diverse group of investigators, research staff, clinicians, community members, and parent caregivers. All members of the team including the study’s Executive Antibiotic Stakeholder Advisory Group (EASAG) contributed to the study design, data acquisition, and interpretation of results. The Study Team would like to thank the leaders of the participating PCORnet Clinical Research Networks (CRNs) and PCORnet Coordinating Center as well as members of the PCORI team for their support and commitment to this project. Finally, the study team is grateful to the patients, families, and clinicians at CDRN member health systems for the sharing of health-related information via PCORnet, without which the study would not have been possible.
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LCB, MB, JPB, DL, and CBF conceived the study. LCB, MM, CEH, JER, JLS, and RT contributed to study data acquisition and preparation. MB, MM, LCB, RT, and CBF conducted the analyses. LCB drafted the paper, and MB, MM, and CBF contributed detailed revisions. JPB, DL, and CBF supervised the Antibiotics and Childhood Growth study. All authors contributed to critical assessment of results and provided critical review of the paper.
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This work was supported through the Patient-Centered Outcomes Research Institute (PCORI) Program Award (OBS-1505-30699). All statements in this paper are solely those of the authors and do not necessarily represent the views of PCORI, its Board of Governors, or Methodology Committee. The authors declare no competing interests.
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Bailey, L.C., Bryan, M., Maltenfort, M. et al. Antibiotics prior to age 2 years have limited association with preschool growth trajectory. Int J Obes 46, 843–850 (2022). https://doi.org/10.1038/s41366-021-01023-w
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DOI: https://doi.org/10.1038/s41366-021-01023-w
