Results Summary and Professional Abstract

Results Summary

Results Summary

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What was the research about?

Antibiotics are medicines that help fight infections caused by bacteria. Antibiotics can cause side effects. One side effect may be weight gain. Weight gain may result when antibiotics kill good bacteria in the gut as well as the bacteria causing infection.

In this study, the research team wanted to learn how antibiotic use before age two affected weight and growth. The team reviewed children’s health records and looked at

• Body mass index, or BMI, at ages 5 and 10. BMI is a measure of a person’s body fat based on their height and weight.
• Risk of having overweight or obesity at ages 5 and 10.
• How fast children gained weight between ages 2 and 5.

The research team looked separately at children with and without long-term health problems.

What were the results?

Children with and without long-term health problems had similar results:

• At age 5, children who received an antibiotic prescription before age 2 had a slightly higher BMI and were a bit more likely to have overweight and obesity than those who didn’t receive one.
• At age 10, the children who received an antibiotic prescription before age 2 had a slightly higher BMI than those who didn’t have one. But they weren’t more likely to have overweight or obesity.
• Between ages 2 and 5, children who received a prescription for an antibiotic before age 2 gained weight at a slightly higher rate than those who didn’t receive one.

Who was in the study?

The study looked at health records between 2009 and 2016 for 362,550 children. These children were receiving care at 35 health systems across the United States. All children had at least three doctor’s visits where their height and weight were recorded. Of the children, 53 percent were white, 27 percent were black, and 2 percent were other or unknown race and ethnicity; 18 percent were Hispanic. Also, 52 percent were boys; 58 percent received a prescription for an antibiotic before age two.

What did the research team do?

The research team looked at health records for each child’s weight, height, and growth patterns. The team took into account other things that might affect weight gain such as

• Sex
• Race or ethnicity
• Premature birth
• Asthma
• Whether a child took steroids
• How often a child saw a doctor and had an infection before age two

Parents, caregivers, doctors, and people from health systems and community and advocacy groups provided input during the study.

What were the limits of the study?

The health records didn’t have data about whether children took the medicine as prescribed. The records also didn’t have some data, such as parents’ income, that may have affected the results. The study may have counted children twice if they saw doctors in more than one healthcare system.

Future research could explore how other medicines affect childhood weight and growth.

How can people use the results?

The relationship between antibiotics and weight was very small. Doctors and other health professionals can use the results when considering guidelines for prescribing antibiotics for children under age two.

How this project fits under PCORI’s Research Priorities This project is part of PCORnet®, the National Patient-Centered Clinical Research Network. PCORI provided funding for the development of PCORnet to improve the nation’s capacity to conduct patient-centered outcomes research. PCORnet is a network of networks. It brings together patients, clinicians, researchers, and healthcare systems to share information and participate in research.

Professional Abstract

Professional Abstract

Objective

To assess the effects of antibiotic use before age two on body mass index (BMI), risk of obesity, and growth trajectory

Study Design

Design Element	Description
Design	Observational: cohort study
Population	EHR data from 362,550 children receiving care at 35 healthcare systems across the United States
Interventions/ Comparators	Antibiotic use before 24 months of age No antibiotic use before 24 months of age
Outcomes	BMI and risk of overweight and obesity in children at 5 years of age, as measured after age 4 but before age 6; and at 10 years of age, as measured after age 9 but before age 11; growth trajectory from 2 to 5 years of age
Timeframe	5- and 10-year follow-up for study outcomes

This retrospective, observational cohort study examined the effects of antibiotic use before age two on 5- and 10-year weight outcomes and growth trajectories.

The study included electronic health record (EHR) data collected between 2009 and 2016 for 362,550 children receiving care at 35 US healthcare systems. All children had a same-day measurement for height and weight documented at least three times between birth and 72 months of age. Of the children, 53% were white, 27% were black, and 2% were other or unknown race and ethnicity; 18% were Hispanic. Also, 52% were male. For the exposure, 58% had a prescription for an antibiotic before age two.

Researchers stratified children with and without complex chronic conditions, defined as any medical condition involving multiple organ systems or requiring specialty care or hospitalization, excluding asthma but including hypothyroidism and pituitary disorders. Researchers controlled for sex, race, ethnicity, premature birth, asthma, infections, corticosteroid use, number of healthcare visits, and number of infections before age two. For growth trajectory, researchers examined differences in rates of weight change between children who had prescriptions and those who did not from ages two to five.

Parents, researchers, and representatives from community, health systems, and advocacy organizations provided input on the study design and analyses.

Results

At age five, children without chronic conditions who were prescribed antibiotics before age two had a slightly higher BMI z-score (95% confidence interval [CI]: 0.03, 0.05) and higher odds of being overweight and having obesity (odds ratio = 1.05; 95% CI: 1.03, 1.07) than those who were not prescribed antibiotics. At age 10, children without chronic conditions who were prescribed antibiotics before age two had a slightly higher BMI z-score (95% CI: 0.01, 0.06) but no increased odds of being overweight or having obesity compared with those who were not prescribed antibiotics. Results were similar for children with chronic conditions.

For growth trajectories between ages two and five, children with and without chronic conditions who were prescribed an antibiotic gained weight at a slightly higher rate than those who were not prescribed an antibiotic (95% CI: 0.5, 0.9).

Limitations

EHR data did not document whether the pharmacy dispensed the prescription or if children took the antibiotic as prescribed; children in either group may not have actually received or taken the antibiotics. Data that were not available in the EHRs, such as socioeconomic status, may have influenced the results. Because researchers were unable to link EHR data across organizations, children that visited more than one institution would have been counted twice.

Conclusions and Relevance

This study showed that being prescribed an antibiotic before age two had small effects on body weight. This result is not likely to influence clinician decision making but could be important at the population level.

Future Research Needs

Future research could examine the effects of medicines other than antibiotics on childhood weight gain and growth.

How this project fits under PCORI’s Research Priorities This project is part of PCORnet®, the National Patient-Centered Clinical Research Network. PCORI provided funding for the development of PCORnet to improve the nation’s capacity to conduct patient-centered outcomes research. PCORnet is a network of networks. It brings together patients, clinicians, researchers, and healthcare systems to share information and participate in research.

More on this Project  

Peer-Review Summary

Peer review of PCORI-funded research helps make sure the report presents complete, balanced, and useful information about the research. It also assesses how the project addressed PCORI’s Methodology Standards. During peer review, experts read a draft report of the research and provide comments about the report. These experts may include a scientist focused on the research topic, a specialist in research methods, a patient or caregiver, and a healthcare professional. These reviewers cannot have conflicts of interest with the study.

The peer reviewers point out where the draft report may need revision. For example, they may suggest ways to improve descriptions of the conduct of the study or to clarify the connection between results and conclusions. Sometimes, awardees revise their draft reports twice or more to address all of the reviewers’ comments. 

Peer reviewers commented and the researchers made changes or provided responses. Those comments and responses included the following:

• The reviewers asked why the researchers did not use statistical methods to estimate missing data, such as multiple imputation, or to try to account for co-occurring variables that might have affected outcomes using propensity scores. The researchers explained that they decided against using propensity scores because the data presented a small number of covariates to use, resulting in limited utility for the propensity scores. They said this was particularly true because they were already stratifying analyses using the most important difference between children: the presence or absence of a complex chronic condition. The researchers said they decided against using multiple imputation because the most likely missing variable would be antibiotic use, the exposure condition. For the outcome of body mass index (BMI), the researchers restricted their sample to the children who had a measure to include. This was because they would not be able to easily sort out whether missing BMI data were due to incomplete reporting or due to the child being too young to have BMI recorded.
• The reviewers questioned the researchers’ approach to heterogeneity of treatment effects (HTE) analyses in aim 3 of the study. The researchers added text to their methods section that they completed HTE analyses on fewer potential confounding variables than originally planned, focusing only on those variables hypothesized to present different outcomes from children’s antibiotic use. The reviewers also noted that these analyses focused only on changes in outcomes within each stratum but did not present interaction analyses demonstrating the effects of the strata on the relationship between antibiotic use and outcomes. The researchers explained that they had initially left some of this information out because the results were not clinically meaningful. They also did not test for interaction effects of complex chronic conditions on antibiotic use because they chose to stratify the analyses by this potential confounder throughout the study.
• The reviewers asked about potential misclassification of children’s antibiotic exposure, commenting that the report suggests that only 58 percent of prescribed antibiotics were filled at a pharmacy. The researchers clarified that past research showed that 58 percent of children 0-24 months of age received antibiotic prescriptions. Based on past literature, the researchers expected that a large proportion of those prescriptions are filled. They noted that in additional analyses they found prescription fill rates exceeded 90 percent. 

Conflict of Interest Disclosures

View the COI disclosure form.

Project Details

Principal Investigator

Jason Block, MD, MPH^

Project Status

Completed; PCORI Public and Professional Abstracts Posted

Project Title

Understanding How Antibiotic Use Affects Childhood Obesity and Growth

Board Approval Date

August 2015

Project End Date

March 2020

Organization

Harvard Pilgrim Health Care, Inc.

Year Awarded

2015

State

Massachusetts

Year Completed

2020

Project Type

Research Project

Health Conditions  

Gastrointestinal Disorders

Infectious Diseases

Nutritional and Metabolic Disorders

Obesity

Reproductive and Perinatal Health

Pregnancy and Birth Outcomes

Respiratory Diseases

Asthma

Respiratory Infections

Urinary Disorders

Urinary Tract Infections

Populations

Children -- 18 and under

Funding Announcement

Obesity Observational Research Initiative

Project Budget

$4,553,788

Study Registration Information

HSRP20162181

NCT02744846