Abstract

Objective

The benefits of antibiotic treatment during pregnancy are immediate, but there may be long-term risks to the developing child. Prior studies show an association between early life antibiotics and obesity, but few have examined this risk during pregnancy.

Subjects

To evaluate the association of maternal antibiotic exposure during pregnancy on childhood BMI-z at 5 years, we conducted a retrospective cohort analysis. Using electronic health record data from seven health systems in PCORnet, a national distributed clinical research network, we included children with same-day height and weight measures who could be linked to mothers with vital measurements during pregnancy. The primary independent variable was maternal outpatient antibiotic prescriptions during pregnancy (any versus none). We examined dose response (number of antibiotic episodes), spectrum and class of antibiotics, and antibiotic episodes by trimester. The primary outcome was child age- and sex-specific BMI-z at age 5 years.

Results

The final sample was 53,320 mother–child pairs. During pregnancy, 29.9% of mothers received antibiotics. In adjusted models, maternal outpatient antibiotic prescriptions during pregnancy were not associated with child BMI-z at age 5 years (β = 0.00, 95% CI −0.03, 0.02). When evaluating timing during pregnancy, dose-response, spectrum and class of antibiotics, there were no associations of maternal antibiotics with child BMI-z at age 5 years.

Conclusion

In this large observational cohort, provision of antibiotics during pregnancy was not associated with childhood BMI-z at 5 years.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Additional information

“The views expressed in this article do not necessarily represent the views of the US Government, the Department of Health and Human Services or the National Institutes of Health.”

List of members of the PCORnet Antibiotics and Childhood Growth Study Group is listed below Acknowledgement

References

  1. 1.

    Ogden CL, Carroll MD, Fryar CD, Flegal KM. Prevalence of Obesity among adults and young: United States, 2011-4. Hyattsville, MD: National Center for Health Statistics; 2015. NCHSData Brief, no 219.

  2. 2.

    Woo Baidal JA, Locks LM, Cheng ER, Blake-Lamb TL, Perkins ME, Taveras EM. Risk factors for childhood obesity in the first 1,000 days: a systematic review. Am J Prev Med. 2016;50:761–79.

  3. 3.

    Cox LM, Blaser MJ. Antibiotics in early life and obesity. Nat Rev Endocrinol. 2015;11:182–90.

  4. 4.

    Block JP, Bailey LC, Gillman MW, Lunsford D, Daley MF, Eneli I, et al, on behalf of PCORnet Antibiotics and Childhood Growth Study Group. Early antibiotic exposure and weight outcomes in young children. Pediatrics. 2018; In Press.

  5. 5.

    Ailes EC, Summers AD, Tran EL, Gilboa SM, Arnold KE, Meaney-Delman D, et al. Antibiotics dispensed to privately insured pregnant women with urinary tract infections - United States, 2014. MMWR Morb Mortal Wkly Rep. 2018;67:18–22.

  6. 6.

    Trasande L, Blustein J, Liu M, Corwin E, Cox LM, Blaser MJ. Infant antibiotic exposures and early-life body mass. Int J Obes. 2013;37:16–23.

  7. 7.

    Saari A, Virta LJ, Sankilampi U, Dunkel L, Saxen H. Antibiotic exposure in infancy and risk of being overweight in the first 24 months of life. Pediatrics. 2015;135:617–26.

  8. 8.

    Bailey LC, Forrest CB, Zhang P, Richards TM, Livshits A, DeRusso PA. Association of antibiotics in infancy with early childhood obesity. JAMA Pediatr. 2014;168:1063–9.

  9. 9.

    Scott FI, Horton DB, Mamtani R, Haynes K, Goldberg DS, Lee DY, et al. Administration of antibiotics to children before age 2 years increases risk for childhood obesity. Gastroenterology. 2016;151:120–9. e5

  10. 10.

    Mueller NT, Whyatt R, Hoepner L, Oberfield S, Dominguez-Bello MG, Widen EM, et al. Prenatal exposure to antibiotics, cesarean section and risk of childhood obesity. Int J Obes. 2015;39:665–70.

  11. 11.

    Mor A, Antonsen S, Kahlert J, Holsteen V, Jorgensen S, Holm-Pedersen J, et al. Prenatal exposure to systemic antibacterials and overweight and obesity in Danish schoolchildren: a prevalence study. Int J Obes. 2015;39:1450–5.

  12. 12.

    Cassidy-Bushrow AE, Burmeister C, Havstad S, Levin AM, Lynch SV, Ownby DR, et al. Prenatal antimicrobial use and early-childhood body mass index. Int J Obes. 2018;42:1–7.

  13. 13.

    Poulsen MN, Pollak J, Bailey-Davis L, Hirsch AG, Glass TA, Schwartz BS. Associations of prenatal and childhood antibiotic use with child body mass index at age 3 years. Obesity. 2017;25:438–44.

  14. 14.

    Fleurence RL, Curtis LH, Califf RM, Platt R, Selby JV, Brown JS. Launching PCORnet, a national patient-centered clinical research network. J Am Med Inform Assoc. 2014;21:578–82.

  15. 15.

    Curtis LH, Brown J, Platt R. Four health data networks illustrate the potential for a shared national multipurpose big-data network. Health Aff. 2014;33:1178–86.

  16. 16.

    Brown JS, Holmes JH, Shah K, Hall K, Lazarus R, Platt R. Distributed health data networks: a practical and preferred approach to multi-institutional evaluations of comparative effectiveness, safety, and quality of care. Med Care. 2010;48(6 Suppl):S45–51.

  17. 17.

    Block JP, Bailey LC, Gillman MW, Lunsford D, Boone-Heinonen J, Cleveland LP, et al. The PCORnet antibiotics and childhood growth study: process for cohort creation and cohort description. Acad Pediatr. 2018.

  18. 18.

    Angier H, Gold R, Crawford C, POM J, JT C, Marino M, et al. Linkage methods for connecting children with parents in electronic health record and state public health insurance data. Matern Child Health J. 2014;18:2025–33.

  19. 19.

    CDC. A SAS Program for the 2000 CDC Growth Charts (ages 0 to <20 years) [cited 2018. Available from: https://www.cdc.gov/nccdphp/dnpao/growthcharts/resources/sas.htm.

  20. 20.

    Feudtner C, Hays RM, Haynes G, Geyer JR, Neff JM, Koepsell TD. Deaths attributed to pediatric complex chronic conditions: national trends and implications for supportive care services. Pediatrics. 2001;107:E99.

Download references

Acknowledgements

All statements in this manuscript are solely those of the authors and do not necessarily represent the views of PCORI, its Board of Governor, or Methodology Committee. 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 Data Research Networks (CDRNs), Patient Powered Research Networks (PPRNs), and PCORnet Coordinating Center as well as members of the PCORI team for their support and commitment to this project.

Members of the PCORnet Antibiotics and Childhood Growth Study Group:

David Arterburn12, Lauren P. Cleveland4, Jonathan Finkelstein13, Stephanie L. Fitzpatrick14, Andrea Goodman15, Michael Horberg16, Jenny Ingber17, Kathleen Murphy17, Holly Landrum Peay18, Pedro Rivera19, Juliane S. Reynolds6, Jessica L. Sturtevant6, Ivette Torres20

Funding

This work was supported through the Patient-Centered Outcomes Research Institute (PCORI) Program Award (OBS-1505-30699).

Author information

Affiliations

  1. Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA

    • William J. Heerman
  2. Institute for Health Research, Kaiser Permanente Colorado, Aurora, CO, 80014, USA

    • Matthew F. Daley
  3. School of Public Health, Oregon Health and Science University/Portland State University, Portland, OR, USA

    • Janne Boone-Heinonen
  4. Division of Chronic Disease Research Across the Lifecourse (CoRAL), Department of Population Medicine, Harvard Pilgrim Health Care Institute, Harvard Medical School, Boston, MA, USA

    • Sheryl L. Rifas-Shiman
    • , Matthew W. Gillman
    • , Chelsea Jenter
    • , Jason P. Block
    •  & Lauren P. Cleveland
  5. Applied Clinical Research Center, Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    • L. Charles Bailey
    •  & Christopher B. Forrest
  6. Therapeutics Research and Infectious Disease Epidemiology Group, Department of Population Medicine, Harvard Pilgrim Health Care Institute, Harvard Medical School, Boston, MA, USA

    • Jessica G. Young
    • , Casie E. Horgan
    • , Sengwee Toh
    • , Juliane S. Reynolds
    •  & Jessica L. Sturtevant
  7. Dr. Gillman is now Director of the Environmental Influences on Child Health Outcomes (ECHO) Program, Office of the Director, National Institutes of Health, Bethesda, MD, USA

    • Matthew W. Gillman
  8. Department of Clinical and Health Psychology, College of Public Health and Health Professions, University of Florida, Gainesville, FL, USA

    • David M. Janicke
  9. HealthPartners Institute, Department of Research, Bloomington, MN, USA

    • Elyse O. Kharbanda
  10. North Fork School District, Utica, OH, USA

    • Doug Lunsford
  11. Department of Pediatrics, New York University, Bellevue Hospital Center, New York, NY, USA

    • Mary Jo Messito
  12. Washington Permanente Medical Group, Internal Medicine, Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA

    • David Arterburn
  13. Boston Children’s Hospital, Department of Population Medicine, Harvard Pilgrim Health Care Institute, Harvard Medical School, Boston, MA, USA

    • Jonathan Finkelstein
  14. Center for Health Research, Kaiser Permanente North West, Portland, OR, USA

    • Stephanie L. Fitzpatrick
  15. Genetic Alliance PCORnet Coordinating Center, Genetic Alliance, Washington, DC, USA

    • Andrea Goodman
  16. Kaiser Permanente Mid-Atlantic Permanente Research Institute, Rockville, MD, USA

    • Michael Horberg
  17. no affiliation, New York, NY, USA

    • Jenny Ingber
    •  & Kathleen Murphy
  18. RTI International, Research Triangle Park, Triangle Park, NC, USA

    • Holly Landrum Peay
  19. OCHIN Inc, Portland, OR, USA

    • Pedro Rivera
  20. Clinical Research Department, Valley Baptist Medical Center - Harlingen, Harlingen, TX, USA

    • Ivette Torres

Authors

  1. Search for William J. Heerman in:

  2. Search for Matthew F. Daley in:

  3. Search for Janne Boone-Heinonen in:

  4. Search for Sheryl L. Rifas-Shiman in:

  5. Search for L. Charles Bailey in:

  6. Search for Christopher B. Forrest in:

  7. Search for Jessica G. Young in:

  8. Search for Matthew W. Gillman in:

  9. Search for Casie E. Horgan in:

  10. Search for David M. Janicke in:

  11. Search for Chelsea Jenter in:

  12. Search for Elyse O. Kharbanda in:

  13. Search for Doug Lunsford in:

  14. Search for Mary Jo Messito in:

  15. Search for Sengwee Toh in:

  16. Search for Jason P. Block in:

Consortia

  1. On behalf of the PCORnet Antibiotics and Childhood Growth Study Group

Conflict of interest

The authors declare that they have no conflict of interest.

Corresponding author

Correspondence to William J. Heerman.

Supplementary information

About this article

Publication history

Received

Revised

Accepted

Published

DOI

https://doi.org/10.1038/s41366-018-0316-6