Obesity and overweight in children have rapidly become epidemic. One factor that may contribute to this phenomenon is infection, either changes in specific exposures or in colonizing flora, and use of antibiotics (ABX) may also play a role. The growth promoting effects of ABX in farm animals have been known since the 1940's. A similar effect of prolonged ABX use in humans seems increasingly plausible. A 1950's trial in army recruits showed that those treated with ABX gained more weight than did placebo controls. More recently, endocarditis patients receiving ABX had marked weight gain compared to matched controls without ABX. Investigators hypothesize that there is an association between obesity and gut microbiota and that ABX can affect weight also by altering gut microbiota. In young children, changes in gut microbiota by adding probiotics to formula have resulted in marked weight increase. Studying the role of ABX on weight is challenging because patients who take ABX are usually ill and then gain weight in the course of improving their health. Some relatively healthy subjects however, do receive ABX and this group is the focus of our study. HYPOTHESIS: Prolonged ABX use in healthy children and adolescents promotes weight gain that is greater from what would be expected based on their pre-ABX growth. OBJECTIVES:1. To study whether prolonged oral ABX in healthy children and adolescents results in greater weight gain than expected based on their normal growth. 2. To assess whether specific classes of ABX classes affect weight more than others. 3. To study the duration of such ABX effect. DESIGN: First, we will do a retrospective cohort study using data from the past 10 years, from patients in a large primary care setting. About 6,700 children and adolescents were prescribed prolonged oral ABX for e4 weeks (and had pharmacy fill data AND weights pre/post-ABX). In our primary analysis we will focus on adolescents with acne, the most healthy and homogeneous group. About 500 of those had weights AND heights pre/post- ABX. We will analyze also children, to study the effect of ABX on a broader spectrum of ages. In our primary analysis each patient will serve as his/her own control. We will measure the change between last pre-ABX BMI Z-score and first post-ABX (primary outcome) using standard t-test AND also the proportion that had a BMI Z-score change e0.5. In secondary analyses we will also capture the trajectory of data for each subject and explore the effect of additional variables on the studied association. Second, we will do a nested case-control study to compare adolescents with acne on oral ABX with a matched control group of acne patients only on topicals. With these analyses we will eliminate between-individuals variability, minimize within-individual variability and account for changes associated with normal growth. POTENTIAL IMPACT: Documentation of growth promoting effects of ABX will provide further empiric support for the role of gut microbiota and infection in childhood obesity and open new horizons for novel preventive strategies. We want to study whether prolonged ABX use in healthy children and adolescents has a growth promoting effect, whether this effect is specific to certain antibiotics and whether any weight gain is sustained after antibiotic cessation. Finding a link between antibiotics and weight may open new horizons for strategies to prevent childhood obesity.

Public Health Relevance

We want to study whether prolonged ABX use in healthy children and adolescents has a growth promoting effect, whether this effect is specific to certain antibiotics and whether any weight gain is sustained after antibiotic cessation. Finding a link between antibiotics and weight may open new horizons for strategies to prevent childhood obesity.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Small Research Grants (R03)
Project #
5R03HD072400-02
Application #
8511511
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Grave, Gilman D
Project Start
2012-07-20
Project End
2014-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
2
Fiscal Year
2013
Total Cost
$70,427
Indirect Cost
$17,738
Name
Palo Alto Medical Foundation Research Institute
Department
Type
DUNS #
622276137
City
Palo Alto
State
CA
Country
United States
Zip Code
94301