Administration of Antibiotics to Children Before Age 2 Years Increases Risk for Childhood Obesity

doi:10.1053/j.gastro.2016.03.006

Gastroenterology

Volume 151, Issue 1, July 2016, Pages 120-129.e5

https://doi.org/10.1053/j.gastro.2016.03.006 Get rights and content

Background & Aims

Childhood obesity is increasing and is associated with adult obesity. Antibiotics have been used to promote weight gain in livestock for several decades. Antibiotics are commonly prescribed for children, but it is not clear how exposure to antibiotics early in life affects risk for obesity. We performed a population-based cohort study to assess the association between antibiotic exposure before age 2 years and obesity at age 4 years.

Methods

We performed a retrospective cohort study of 21,714 children in The Health Improvement Network—a population-representative dataset of >10 million individuals derived from electronic medical records from 1995 through 2013 in the United Kingdom. Eligible subjects were registered within 3 months of birth with complete follow-up and height and weight were recorded within 12 months of their 4th birthday. Antibiotic exposure was assessed before age 2 years, and classified based on anti-anaerobic activity. The primary outcome was obesity at age 4 years. We performed logistic regression analyses, adjusting for maternal and sibling obesity, maternal diabetes, mode of delivery, socioeconomic status, year and country of birth, and urban dwelling.

Results

In the cohort, 1306 of the children (6.4%) were obese at 4 years of age. Antibiotic exposure was associated with an increased risk of obesity at 4 years (odds ratio [OR] = 1.21; 95% confidence interval [CI]: 1.07–1.38). ORs increased with repeated exposures: for 1–2 prescriptions, OR = 1.07 (95% CI, 0.91–1.23); for 3–5 prescriptions, OR = 1.41 (95% CI, 1.20–1.65); and for 6 or more prescriptions, OR = 1.47 (95% CI, 1.19–1.82). Antifungal agents were not associated with obesity (OR = 0.81; 95% CI, 0.59–1.11).

Conclusions

Administration of 3 or more courses of antibiotics before children reach an age of 2 years is associated with an increased risk of early childhood obesity.

Section snippets

Study Design

We performed a retrospective cohort study using data collected prospectively in the scope of routine care from 1995 to 2013 within The Health Improvement Network (THIN). THIN data are derived from general practitioners’ electronic medical records (EMR). THIN represents approximately 6% of the UK population,¹³ includes information on age, sex, socioeconomic status, medication use, and has been validated for multiple medical diagnoses.14, 15, 16, 17, 18 Height and weight data are recorded during

Results

Among 533,238 children identified in THIN within 3 months of birth, 253,157 had 4 years of follow-up. 21,714 children with complete follow-up for 4 years met the inclusion and exclusion criteria (Figure 1); 64.1% were prescribed antibiotics before age 2 years. Median time from birth to cohort entry was 37 days (interquartile range, 25–51 days) and 1306 (6.4%) were obese at age 4 years. Obesity at age 4 years was observed in 5.2% of children without antibiotic exposure and 6.4% of those with

Discussion

With rising rates of childhood obesity worldwide, it is important to identify modifiable contributing factors.32, 33, 34, 35 Antibiotics are prescribed during an estimated 49 million pediatric outpatient visits per year in the United States; the majority are broad-spectrum agents.⁶ Between 2006 and 2008, >10 million antibiotic prescriptions were written annually for children without clear indication, despite increased awareness of the societal risks of antibiotic resistance.36, 37 This study

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: Conflicts of interest The authors disclose no conflicts.

: Funding This research was supported in part by grants K08-DK095951 (Frank I. Scott), K24-DK078228 (James D. Lewis), and K08-DK098272 (David S. Goldberg) from the National Institute of Diabetes and Digestive and Kidney Diseases, as well as grants K23-CA187185 (Ronac Mamtani) from the National Cancer Institute and F32-AR066461 (Daniel B. Horton) from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and by the University of Pennsylvania’s Center for Pharmacoepidemiology Research and Training and the Penn-CHOP Microbiome Program.

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Original ResearchFull Report: Clinical—Alimentary TractAdministration of Antibiotics to Children Before Age 2 Years Increases Risk for Childhood Obesity

Background & Aims

Methods

Results

Conclusions

Section snippets

Study Design

Results

Discussion

J Dairy Sci

Prev Med

Adv Nutr

PM R

Lancet

J Biol Chem

J Biol Chem

Cell

Antibiotics in animal feeds and animal production

Bioscience

Antibiotics as growth promotants: mode of action

Animal Biotechnol

A comparison of the growth of chicks in the Gustafsson germ-free apparatus and in a conventional environment, with and without dietary supplements of penicillin

Br J Nutr

Antibiotic prescribing in ambulatory pediatrics in the United States

Pediatrics

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)

Infant antibiotic exposures and early-life body mass

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Antibiotic treatment during infancy and increased body mass index in boys: an international cross-sectional study

Int J Obes (Lond)

Association of antibiotics in infancy with early childhood obesity

JAMA Pediatr

Infant antibiotic exposure and the development of childhood overweight and central adiposity

Int J Obes (Lond)

Antibiotic use and childhood body mass index trajectory

Int J Obes (Lond)

Generalisability of The Health Improvement Network (THIN) database: demographics, chronic disease prevalence and mortality rates

Inform Prim Care

Validity and completeness of the General Practice Research Database for studies of inflammatory bowel disease

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Validation of ischemic cerebrovascular diagnoses in the health improvement network (THIN)

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Validity of The Health Improvement Network (THIN) for epidemiologic studies of hepatitis C virus infection

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Cancer incidence in The Health Improvement Network

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Association between perinatal depression in mothers and the risk of childhood infections in offspring: a population-based cohort study

BMC Public Health

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Original Research
Full Report: Clinical—Alimentary Tract
Administration of Antibiotics to Children Before Age 2 Years Increases Risk for Childhood Obesity