Antibiotic use in early childhood and risk of obesity: longitudinal analysis of a national cohort

Abstract

Background

Taking oral antibiotics during childhood has been linked with an increased risk of childhood obesity. This study assessed any potential association in number of courses of antibiotics taken between 2–3 and 4–5 years of age and body mass trajectory up to age 5.

Methods

The study was a secondary analysis of 8186 children and their parents from the infant cohort of the Irish National Longitudinal Study of Children. Antibiotic use was measured by parental recall between ages 2–3 and 4–5. Longitudinal models described the relationship between antibiotic exposure and body mass index (BMI) standard deviation scores and binary outcomes, and examined interactions between covariates, which included socioeconomic status, diet assessed by food frequency questionnaires and maternal BMI.

Results

Any antibiotic usage between 2 and 3 years did not predict risk of overweight or obesity at age 5. Four or more courses of antibiotics between 2 and 3 years were independently associated with obesity at age 5 (odds ratio 1.6, 95% confidence interval 1.11–2.31). Effect size was modest (coefficient + 0.09 body mass SD units, standard error 0.04, P = 0.037). Maternal BMI modified the relationship: ≥ 4 courses of antibiotics between 2 and 3 years were associated with a + 0.12 body mass SD units increase in weight at age 5 among children of normal-weight mothers (P = 0.035), but not in children of overweight mothers.

Conclusions

Number of antibiotic courses, rather than antibiotic use, may be an important factor in any link between early antibiotic exposure and subsequent childhood obesity. Research is needed to confirm differential effects on babies of normal versus overweight/obese mothers independent of socioeconomic factors.

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References

  1. 1.

    Reilly JJ, Kelly J. Long-term impact of overweight and obesity in childhood and adolescence on morbidity and premature mortality in adulthood: systematic review. Int J Obes (Lond). 2011;35:891–8.

    Article  CAS  Google Scholar 

  2. 2.

    Allison DB, Downey M, Atkinson RL, Billington CJ, Bray GA, Eckel RH, et al. Obesity as a disease: a white paper on evidence and arguments commissioned by the Council of the Obesity Society. Obesity (Silver Spring). 2008;16:1161–77.

    Article  Google Scholar 

  3. 3.

    Lloyd LJ, Langley-Evans SC, McMullen S. Childhood obesity and adult cardiovascular disease risk: a systematic review. Int J Obes (Lond). 2010;34:18–28.

    Article  CAS  Google Scholar 

  4. 4.

    Lauby-Secretan B, Scoccianti C, Loomis D, Grosse Y, Bianchini F, Straif K, et al. Body fatness and cancer–viewpoint of the IARC Working Group. N Engl J Med. 2016;375:794–8.

    Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Yajnik CS. The lifecycle effects of nutrition and body size on adult adiposity, diabetes and cardiovascular disease. Obes Rev. 2002;3:217–24.

    Article  CAS  PubMed  Google Scholar 

  6. 6.

    McLeod GF, Fergusson DM, John Horwood L, Carter FA. Adiposity and psychosocial outcomes at ages 30 and 35. Soc Psychiatry Psychiatr Epidemiol. 2016;51:309–18.

    Article  PubMed  Google Scholar 

  7. 7.

    Chaiton M, Sabiston C, O’Loughlin J, McGrath JJ, Maximova K, Lambert M. A structural equation model relating adiposity, psychosocial indicators of body image and depressive symptoms among adolescents. Int J Obes (Lond). 2009;33:588–96.

    Article  CAS  Google Scholar 

  8. 8.

    Reinhardt C, Reigstad CS, Backhed F. Intestinal microbiota during infancy and its implications for obesity. J Pediatr Gastroenterol Nutr. 2009;48:249–56.

    Article  PubMed  Google Scholar 

  9. 9.

    Musso G, Gambino R, Cassader M. Obesity, diabetes, and gut microbiota: the hygiene hypothesis expanded? Diabetes Care. 2010;33:2277–84.

    Article  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Backhed F, Roswall J, Peng Y, Feng Q, Jia H, Kovatcheva-Datchary P, et al. Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe. 2015;17:852.

    Article  CAS  PubMed  Google Scholar 

  11. 11.

    Anglemyer A, Horvath HT, Bero L. Healthcare outcomes assessed with observational study designs compared with those assessed in randomized trials. Cochrane Database Syst Rev. 2014;4:Mr000034.

    Google Scholar 

  12. 12.

    Azad MB, Moossavi S, Owora A, Sepehri S. Early-life antibiotic exposure, gut microbiota development, and predisposition to obesity. Nestle Nutr Inst Workshop Ser. 2017;88:67–79.

    Article  PubMed  Google Scholar 

  13. 13.

    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.

    Article  PubMed  Google Scholar 

  14. 14.

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

    Article  CAS  Google Scholar 

  15. 15.

    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.

    Article  CAS  Google Scholar 

  16. 16.

    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.

    Article  PubMed  Google Scholar 

  17. 17.

    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 (Silver Spring). 2017;25:438–44.

    Article  CAS  PubMed Central  Google Scholar 

  18. 18.

    Li DK, Chen H, Ferber J, Odouli R. Infection and antibiotic use in infancy and risk of childhood obesity: a longitudinal birth cohort study. Lancet Diabetes Endocrinol. 2017;5:18–25.

    Article  PubMed  Google Scholar 

  19. 19.

    Dror T, Dickstein Y, Dubourg G, Paul M. Microbiota manipulation for weight change. Microb Pathog. 2017;106:146–61.

    Article  CAS  PubMed  Google Scholar 

  20. 20.

    Gerber JS, Bryan M, Ross RK, Daymont C, Parks EP, Localio AR, et al. Antibiotic exposure during the first 6 months of life and weight gain during childhood. JAMA. 2016;315:1258–65.

    Article  CAS  PubMed  Google Scholar 

  21. 21.

    Shao X, Ding X, Wang B, Li L, An X, Yao Q, et al. Antibiotic exposure in early life increases risk of childhood obesity: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2017;8:170.

    Article  Google Scholar 

  22. 22.

    Partap U, Allcock SH, Parker E, Gurdasani D, Young EH, Sandhu MS. Association between early life antibiotic use and childhood overweight and obesity: a narrative review. Glob Health Epidemiol Genom. 2018;3:e18.

    Article  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Miller SA, Wu RKS, Oremus M. The association between antibiotic use in infancy and childhood overweight or obesity: a systematic review and meta-analysis. Obes Rev. 2018;19:1463–75.

    Article  CAS  PubMed  Google Scholar 

  24. 24.

    Rasmussen SH, Shrestha S, Bjerregaard LG, Angquist LH, Baker JL, Jess T, et al. Antibiotic exposure in early life and childhood overweight and obesity: a systematic review and meta-analysis. Diabetes Obes Metab. 2018;20:1508–14.

    Article  PubMed  Google Scholar 

  25. 25.

    Quail A, Williams J, McCrory C, Murray A, Thornton M. Sample design and response in wave 1 of the Infant Cohort (at 9 months) of Growing Up In Ireland. Dublin: Office of the Minister for Children and Youth Affairs, Department of Health and Children; 2011.

  26. 26.

    Pan H, Cole TJ. LMSgrowth, a Microsoft Excel add-into access growth references based on the LMS method. Version 2.77. 11017 ed 2012. http://www.healthforchildren.co/uk/. Accessed 1 Nov 2015.

  27. 27.

    Kelleher CC, Viljoen K, Khalil H, Somerville R, O’Brien J, Shrivastava A, et al. Longitudinal follow-up of the relationship between dietary intake and growth and development in the lifeways cross-generation cohort study 2001–2013. Proc Nutr Soc. 2014;73:118–31.

    Article  PubMed  Google Scholar 

  28. 28.

    Wrieden WL, Longbottom PJ, Adamson AJ, Ogston SA, Payne A, Haleem MA, et al. Estimation of typical food portion sizes for children of different ages in Great Britain. Br J Nutr. 2008;99:1344–53.

    Article  CAS  PubMed  Google Scholar 

  29. 29.

    Food Standards Agency. McCance and Widdowson’s the composition of foods. 7th ed. London: Royal Society of Chemistry; 2014.

    Google Scholar 

  30. 30.

    Bates D, Mächler M, Bolker B, Walker S. Fitting linear mixed-effects models using lme4. arXiv preprint arXiv:1406.5823; 2014.

  31. 31.

    Bolker B, Su Y-S. Coefplot2: coefficient plots. R package version 0132; 2011.

  32. 32.

    Schwartz BS, Pollak J, Bailey-Davis L, Hirsch AG, Cosgrove SE, Nau C, et al. Antibiotic use and childhood body mass index trajectory. Int J Obes (Lond). 2015;40:615–21.

    Article  CAS  PubMed Central  Google Scholar 

  33. 33.

    Ajslev TA, Andersen CS, Gamborg M, Sørensen TIA, Jess T. Childhood overweight after establishment of the gut microbiota: the role of delivery mode, pre-pregnancy weight and early administration of antibiotics. Int J Obes (Lond). 2011;35:522–9.

    Article  CAS  Google Scholar 

  34. 34.

    Murphy R, Stewart AW, Braithwaite I, Beasley R, Hancox RJ, Mitchell EA. Antibiotic treatment during infancy and increased body mass index in boys: an international cross-sectional study. Int J Obes (Lond). 2014;38:1115–9.

    Article  Google Scholar 

  35. 35.

    Langdon A, Crook N, Dantas G. The effects of antibiotics on the microbiome throughout development and alternative approaches for therapeutic modulation. Genome Med. 2016;8:39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. 36.

    Collado MC, Isolauri E, Laitinen K, Salminen S. Distinct composition of gut microbiota during pregnancy in overweight and normal-weight women. Am J Clin Nutr. 2008;88:894–9.

    Article  CAS  PubMed  Google Scholar 

  37. 37.

    Collado MC, Isolauri E, Laitinen K, Salminen S. Effect of mother’s weight on infant’s microbiota acquisition, composition, and activity during early infancy: a prospective follow-up study initiated in early pregnancy. Am J Clin Nutr. 2010;92:1023–30.

    Article  CAS  PubMed  Google Scholar 

  38. 38.

    Linabery AM, Nahhas RW, Johnson W, Choh AC, Towne B, Odegaard AO, et al. Stronger influence of maternal than paternal obesity on infant and early childhood body mass index: the Fels Longitudinal Study. Pediatr Obes. 2013;8:159–69.

    Article  CAS  PubMed  Google Scholar 

  39. 39.

    Cattaneo A, Monasta L, Stamatakis E, Lioret S, Castetbon K, Frenken F, et al. Overweight and obesity in infants and pre-school children in the European Union: a review of existing data. Obes Rev. 2010;11:389–98.

    Article  CAS  PubMed  Google Scholar 

  40. 40.

    Roy SM, Chesi A, Mentch F, Xiao R, Chiavacci R, Mitchell JA, et al. Body mass index (BMI) trajectories in infancy differ by population ancestry and may presage disparities in early childhood obesity. J Clin Endocrinol Metab. 2015;100:1551–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. 41.

    Berkey CS, Colditz GA. Adiposity in adolescents: change in actual BMI works better than change in BMI z score for longitudinal studies. Ann Epidemiol. 2007;17:44–50.

    Article  PubMed  Google Scholar 

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Funding

The National Study Longitudinal of Childhood—Growing Up in Ireland is funded by the Department of Children and Youth Affairs in Ireland. DK was funded by a stipend from Trinity College Dublin.

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Authors

Contributions

DK contributed to study design, data analysis, and manuscript writing and review. AK contributed to study design and data analysis. TOD contributed to study design, manuscript writing, and manuscript review. CH contributed to study design, data analysis, and manuscript writing and review. All authors approved the final version of the manuscript.

Corresponding author

Correspondence to Dervla Kelly.

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Ethical approval

This study was approved by a specially-convened Research Ethics Committee of The National Study Longitudinal of Childhood—Growing Up in Ireland.

Conflict of interest

No financial or nonfinancial benefits have been received or will be received from any party related directly or indirectly to the subject of this article.

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Alan Kelly: RIP, 5th October 2015. Dublin, Ireland.

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Kelly, D., Kelly, A., O’Dowd, T. et al. Antibiotic use in early childhood and risk of obesity: longitudinal analysis of a national cohort. World J Pediatr 15, 390–397 (2019). https://doi.org/10.1007/s12519-018-00223-1

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Keywords

  • Antibiotics
  • Body mass index
  • Early childhood
  • Infants
  • Obesity