. 2022 Apr;46(4):843-850.

doi: 10.1038/s41366-021-01023-w. Epub 2022 Jan 8.

Antibiotics prior to age 2 years have limited association with preschool growth trajectory

L Charles Bailey^{1

2}, Matthew Bryan^{3

4}, Mitchell Maltenfort³, Jason P Block⁵, Rachel Teneralli³, Douglas Lunsford⁶, Janne Boone-Heinonen⁷, Ihuoma Eneli⁸, Casie E Horgan⁹, Pi-I D Lin⁵, Juliane S Reynolds⁹, Anthony E Solomonides¹⁰, David Janicke¹¹, Jessica L Sturtevant⁹, Sengwee Toh⁹, Elsie Taveras⁵, Bradley M Appelhans¹², David Arterburn¹³, Matthew F Daley¹⁴, Amanda Dempsey¹⁵, Lara R Dugas¹⁶, Jonathan Finkelstein¹⁷, Stephanie L Fitzpatrick¹⁸, Andrea Goodman¹⁹, Matthew J Gurka²⁰, William J Heerman²¹, Michael Horberg²², Md Jobbayer Hossain²³, Daniel S Hsia²⁴, Carmen R Isasi²⁵, Elyse O Kharbanda²⁶, Mary Jo Messito²⁷, Kathleen Murphy¹⁹, Kevin O'Bryan²⁸, Holly L Peay²⁹, Micah T Prochaska³⁰, Jon Puro³¹, Maria Rayas³², Marc B Rosenman³³, Bradley Taylor³⁴, Jeffrey J VanWormer³⁵, Zachary Willis³⁶, Samrat Yeramaneni³⁷, Christopher B Forrest^{3

4}; PCORnet Antibiotics and Childhood Growth Study Group

Collaborators, Affiliations

Collaborators

PCORnet Antibiotics and Childhood Growth Study Group:
Brad Appelhans, David Arterburn, Andrew Brickman, Matthew F Daley, Arthur Davidson, Elizabeth Dawson-Hahn, Amanda Dempsey, Lara R Dugas, Jonathan Finkelstein, Stephanie L Fitzpatrick, Matthew J Gurka, Andrea Goodman, William J Heerman, Michael Horberg, Md Jobayer Hossain, Daniel S Hsia, Jenny Ingber, Carmen R Isasi, Melanie Jay, Elyse Kharbanda, Peter Margolis, M James, Mary Jo Messito, Kathleen Murphy, Kevin O'Bryan, Holly Peay, Micah T Prochaska, Jon Puro, Goutham Rao, Maria Rayas, Marc Rosenman, H Robert, Bradley Taylor, Alfredo Tirado-Ramos, Jeffrey VanWormer, Zachary Willis, Samrat Yeramaneni

Affiliations

¹ Departments of Pediatrics and Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA, USA. baileyc@chop.edu.
² Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. baileyc@chop.edu.
³ Departments of Pediatrics and Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
⁴ Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁵ Division of Chronic Disease Research Across the Lifecourse (CoRAL), Department of Population Medicine, Harvard Pilgrim Health Care Institute, Harvard Medical School, Boston, MA, USA.
⁶ North Fork School District, Utica, OH, USA.
⁷ School of Public Health, Oregon Health & Science University, Portland, OR, USA.
⁸ Nationwide Children's Hospital, Columbus, OH, USA.
⁹ Division of Therapeutics Research and Infectious Disease Epidemiology, Department of Population Medicine, Harvard Pilgrim Health Care Institute, Harvard Medical School, Boston, MA, USA.
¹⁰ Center for Biomedical Research Informatics, North Shore University Health System, Evanston, IL, USA.
¹¹ Department of Clinical and Health Psychology, College of Public Health and Health Professions, University of Florida, Gainesville, FL, USA.
¹² Rush University Medical Center, Chicago, IL, USA.
¹³ Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA.
¹⁴ Institute for Health Research, Kaiser Permanente Colorado, Aurora, CO, USA.
¹⁵ University of Colorado, Denver, CO, USA.
¹⁶ Public Health Sciences, Loyola University, Chicago, IL, USA.
¹⁷ Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, CA, USA.
¹⁸ Center for Health Research, Kaiser Permanente Northwest, Portland, OR, USA.
¹⁹ Genetic Alliance, Washington, DC, USA.
²⁰ Department of Health Outcomes and Biomedical Informatics, University of Florida, Gainesville, FL, USA.
²¹ Vanderbilt University Medical Center, Nashville, TN, USA.
²² Kaiser Permanente Mid-Atlantic Permanente Research Institute, Rockville, MD, USA.
²³ Nemours/A I Dupont Hospital for Children, Wilmington, DE, USA.
²⁴ Pennington Biomedical Research Center, Baton Rouge, LA, USA.
²⁵ Albert Einstein College of Medicine, New York, NY, USA.
²⁶ HealthPartners Institute, Minneapolis, MN, USA.
²⁷ NYU School of Medicine, New York, NY, USA.
²⁸ Washington University School of Medicine, St. Louis, MO, USA.
²⁹ RTI International, Research Triangle Park, NC, USA.
³⁰ University of Chicago, Chicago, IL, USA.
³¹ OCHIN, Inc., Portland, OR, USA.
³² UT Health San Antonio, San Antonio, TX, USA.
³³ Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
³⁴ Medical College of Wisconsin, Milwaukee, WI, USA.
³⁵ Marshfield Clinic Research Institute, Marshfield, WI, USA.
³⁶ Department of Pediatrics, University of North Carolina, Chapel Hill, NC, USA.
³⁷ Baylor Scott & White Research Institute, Dallas, TX, USA.

PMID: 34999718
PMCID: PMC8967797
DOI: 10.1038/s41366-021-01023-w

Antibiotics prior to age 2 years have limited association with preschool growth trajectory

L Charles Bailey et al. Int J Obes (Lond). 2022 Apr.

. 2022 Apr;46(4):843-850.

doi: 10.1038/s41366-021-01023-w. Epub 2022 Jan 8.

Authors

Collaborators

PCORnet Antibiotics and Childhood Growth Study Group:
Brad Appelhans, David Arterburn, Andrew Brickman, Matthew F Daley, Arthur Davidson, Elizabeth Dawson-Hahn, Amanda Dempsey, Lara R Dugas, Jonathan Finkelstein, Stephanie L Fitzpatrick, Matthew J Gurka, Andrea Goodman, William J Heerman, Michael Horberg, Md Jobayer Hossain, Daniel S Hsia, Jenny Ingber, Carmen R Isasi, Melanie Jay, Elyse Kharbanda, Peter Margolis, M James, Mary Jo Messito, Kathleen Murphy, Kevin O'Bryan, Holly Peay, Micah T Prochaska, Jon Puro, Goutham Rao, Maria Rayas, Marc Rosenman, H Robert, Bradley Taylor, Alfredo Tirado-Ramos, Jeffrey VanWormer, Zachary Willis, Samrat Yeramaneni

Affiliations

¹ Departments of Pediatrics and Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA, USA. baileyc@chop.edu.
² Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. baileyc@chop.edu.
³ Departments of Pediatrics and Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
⁴ Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁵ Division of Chronic Disease Research Across the Lifecourse (CoRAL), Department of Population Medicine, Harvard Pilgrim Health Care Institute, Harvard Medical School, Boston, MA, USA.
⁶ North Fork School District, Utica, OH, USA.
⁷ School of Public Health, Oregon Health & Science University, Portland, OR, USA.
⁸ Nationwide Children's Hospital, Columbus, OH, USA.
⁹ Division of Therapeutics Research and Infectious Disease Epidemiology, Department of Population Medicine, Harvard Pilgrim Health Care Institute, Harvard Medical School, Boston, MA, USA.
¹⁰ Center for Biomedical Research Informatics, North Shore University Health System, Evanston, IL, USA.
¹¹ Department of Clinical and Health Psychology, College of Public Health and Health Professions, University of Florida, Gainesville, FL, USA.
¹² Rush University Medical Center, Chicago, IL, USA.
¹³ Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA.
¹⁴ Institute for Health Research, Kaiser Permanente Colorado, Aurora, CO, USA.
¹⁵ University of Colorado, Denver, CO, USA.
¹⁶ Public Health Sciences, Loyola University, Chicago, IL, USA.
¹⁷ Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, CA, USA.
¹⁸ Center for Health Research, Kaiser Permanente Northwest, Portland, OR, USA.
¹⁹ Genetic Alliance, Washington, DC, USA.
²⁰ Department of Health Outcomes and Biomedical Informatics, University of Florida, Gainesville, FL, USA.
²¹ Vanderbilt University Medical Center, Nashville, TN, USA.
²² Kaiser Permanente Mid-Atlantic Permanente Research Institute, Rockville, MD, USA.
²³ Nemours/A I Dupont Hospital for Children, Wilmington, DE, USA.
²⁴ Pennington Biomedical Research Center, Baton Rouge, LA, USA.
²⁵ Albert Einstein College of Medicine, New York, NY, USA.
²⁶ HealthPartners Institute, Minneapolis, MN, USA.
²⁷ NYU School of Medicine, New York, NY, USA.
²⁸ Washington University School of Medicine, St. Louis, MO, USA.
²⁹ RTI International, Research Triangle Park, NC, USA.
³⁰ University of Chicago, Chicago, IL, USA.
³¹ OCHIN, Inc., Portland, OR, USA.
³² UT Health San Antonio, San Antonio, TX, USA.
³³ Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
³⁴ Medical College of Wisconsin, Milwaukee, WI, USA.
³⁵ Marshfield Clinic Research Institute, Marshfield, WI, USA.
³⁶ Department of Pediatrics, University of North Carolina, Chapel Hill, NC, USA.
³⁷ Baylor Scott & White Research Institute, Dallas, TX, USA.

PMID: 34999718
PMCID: PMC8967797
DOI: 10.1038/s41366-021-01023-w

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.

PubMed Disclaimer

Figures

**Figure 1.**
Estimated effect of antibiotic exposure on growth trajectory for large network partners. Estimates are shown for network partners with ≥10,000 children, based on fully adjusted models using episodes containing at least one narrow- (A) or broad-spectrum (B) antibiotic. Vertical bars denote 95% confidence intervals for each estimate, which correlate with the cohort size for that network partner (*cf.* Table S1).

See this image and copyright information in PMC

References

1. Chai G, Governale L, McMahon AW, Trinidad JP, Staffa J, Murphy D. Trends of outpatient prescription drug utilization in US children, 2002–2010. Pediatrics. 2012;130(1):23–31. - PubMed
1. Vaz LE, Kleinman KP, Raebel MA, Nordin JD, Lakoma MD, Dutta-Linn MM, et al. Recent trends in outpatient antibiotic use in children. Pediatrics. 2014;133(3):375–85. - PMC - PubMed
1. Bailey LC, Forrest CB, Zhang P, Richards TM, Livshits A, DeRusso PA. Association of Antibiotics in Infancy With Early Childhood Obesity. JAMA pediatrics. 2014. - PubMed
1. Jukes TH, Williams WL. Nutritional effects of antibiotics. Pharmacol Rev. 1953;5(4):381–420. - PubMed
1. Cox LM, Yamanishi S, Sohn J, Alekseyenko AV, Leung JM, Cho I, et al. Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell. 2014;158(4):705–21. - PMC - PubMed

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions

Grants and funding

OBS-1505-30699/PCORI/Patient-Centered Outcomes Research Institute/United States

LinkOut - more resources

Full Text Sources
Medical
- MedlinePlus Health Information

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Antibiotics prior to age 2 years have limited association with preschool growth trajectory

Collaborators

Affiliations

Antibiotics prior to age 2 years have limited association with preschool growth trajectory

Authors

Collaborators

Affiliations

Abstract

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical