Short- and Long-Term Effects of Antibiotics on Childhood Growth

NCT ID: NCT02744846

Last Updated: 2019-12-20

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 681739 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2016-02-29
• Study Completion Date: 2018-12-31

Brief Summary

The objectives of the proposed study are to assess the effects of different types, timing, and amount of antibiotic use in the first two years of life with (Specific Aim 1) body mass index (BMI) and obesity at ages 5 and 10 years and (Specific Aim 2) growth trajectories to age 5 years. In Specific Aim 3, the investigators will address how big the effects of antibiotics on obesity are within subgroups of the population, such as different racial/ethnic groups and whether the child's mother got antibiotics while she was pregnant.

The data for this study will come from electronic medical records of about 600,000 children from 42 healthcare systems within 10 Clinical Data Research Networks (CDRNs) across the United States. The investigators will get information on antibiotic prescribing in the first two years of life, then "virtually" follow these children to ages 5 and 10 years to see what their BMIs are, and how many of them are obese by clinical standards (i.e., body mass index exceeding the 95th percentile for age and sex).

In the main analyses, the CDRNs will not send any individual data to a central site. Rather, using sophisticated computer programs, the study's coordinating center will send "questions to the data," thus protecting the privacy of patients' and the healthcare systems' records. In some analyses, to check how well this "distributed research network" approach works, we will work with individual records whose identifying information has been stripped off ("de-identified data").

In our Secondary Aim, the investigators will employ focus groups of parents and in-depth interviews with clinicians to explore how best to put the findings into everyday practice.

Throughout the study, in addition to employing privacy-protecting approaches to analyzing and sharing data, the investigators will adhere to principles of inclusion, patient-centeredness, stakeholder engagement, effective governance, and protection of human subjects. At the end of the two-year project, the investigators will propose avenues for dissemination of the scientific findings and other products.

Detailed Description

Antibiotics are among the most valuable medical discoveries. Recent research on understanding of how bacteria in our gut use energy, however, raises concerns about whether broad-spectrum antibiotics, which are over-prescribed for mild infections, prescribed in early infancy may cause obesity during childhood. Obesity is a very common and serious condition among US children, particularly children from disadvantaged populations. Past studies examining the link between antibiotic use and childhood obesity are too small and they lack diversity as well as modern scientific tools to gauge the extent to which prescribing antibiotics can lead to excess weight gain. PCORnet, the National Patient-Centered Clinical Research Network, comprising very large networks of data from electronic medical records, provides an ideal test bed to address this question. Further, it is not clear how caregivers and clinicians will use the results of earlier studies to decide which antibiotics to prescribe when faced with common infections like ear infections.

Specific Aim 1: To evaluate the comparative effects of different types, timing, and amount of antibiotics used during the first two years of life on body mass index and risk of obesity at ages 5 (primary outcome age) and 10 (secondary) years. Hypothesis: There will be a "dose-response" relationship between the number of antibiotic courses given during the first 2 years of life and both higher BMI and the probability of obesity at ages 5 and 10 years. This relationship will be strongest for broad-spectrum antibiotics prescribed in the first 6 months of life.

Specific Aim 2: To assess the comparative effects of different types, timing, and amount of antibiotics used during the first two years of life on the rates and patterns of childhood growth during the first 5 years of life. Hypothesis: There will be a "dose-response" relationship between the number of antibiotic courses given during the first 2 years of life and subsequent growth trajectories of children in a pattern that increases children's risk of later overweight and obesity. This relationship will be strongest for broad-spectrum antibiotics prescribed in the first 6 months of life.

Specific Aim 3: To explore how the effects of different types, timing, and amount of antibiotics on childhood BMI, obesity risk and growth (Aims 1 and 2) vary according to patient socio-demographic, clinical, and maternal characteristics, including: 1) socio-demographic (Child sex, Child race/ethnicity, Geography, based on location of clinical facility); 2) Clinical (Prescription of medications that also cause obesity, esp. corticosteroids, Low birth weight or macrosomia in term infants); 3) Maternal for the subset of data partners listed in section B above that have linked maternal and child records (BMI, Maternal receipt of antibiotics during pregnancy, Type of delivery, i.e., Cesarean v. vaginal). Hypotheses: The antibiotic effects will not vary by socio-demographic or maternal characteristics. Long-term corticosteroid use will potentiate the effect of antibiotics on childhood obesity.

Secondary Aim: Through focus groups and in-depth interviews, to explore how parents and other caregivers and their providers assess information related to current and future benefits and risks, particularly for treatments such as antibiotics in early childhood, which can have substantial near-term benefits along with moderate long-term risks. The investigators will also explore how clinicians, health care organizations, and policy makers should best present study findings to help parents understand its strengths and limitations in the context of shared clinical decision-making.

Conditions

Obesity

Keywords

antibiotics; children; pediatric; body mass index; Observational Study; Comparative Effectiveness Research; Obesity; Growth Trajectory; Cohort Study; Electronic Medical Record; Qualitative Research

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

Children from birth to 5 years

Children from birth to 5 years where:

1. 1 or more encounters with length and weight measured in the following age interval: 0-12 m, 12-30 m, and

2. > 1 encounter with height and weight measured in either or both of the following age intervals: 4.0 to 5.9 y ("age 5 years"), or eligible to be followed to these ages for use in multiple imputation to account for missing data

Antibiotics exposure

Intervention Type: DRUG

Children from birth to 10 years

Children from birth to 10 years where:

1. 1 or more encounters with length and weight measured in each of the following age intervals: 0-12 m, 12-30 m, and

2. > 1 encounter with height and weight measured in the following age interval: 9.0 to 10.9 y ("age 10 years"), or eligible to be followed to these ages for use in multiple imputation to account for missing data.

Antibiotics exposure

Intervention Type: DRUG

Interventions

Antibiotics exposure

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. 1 or more encounters with length and weight measured in each of the following age intervals: 0-12 months, 12-30 months, and

2. 1 or more encounters with height and weight measured after 24 months of age (need 1 or more measure at 4.0-5.9 years for the 5 year outcome and 1 or more measure at 9.0 to 10.9 years for the 10 year outcome), or eligible to be followed to these ages using multiple imputation to account for missing data.

Exclusion Criteria

1. Biologically implausible length/height or weight measurements

• Maximum Eligible Age: 11 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Patient-Centered Outcomes Research Institute

OTHER

Sponsor Role: collaborator

National Patient-Centered Clinical Research Network

OTHER

Sponsor Role: collaborator

ADVANCE CDRN

UNKNOWN

Sponsor Role: collaborator

Chicago Area Patient-Centered Outcomes Research Network (CAPriCORN)

OTHER

Sponsor Role: collaborator

Greater Plains Collaborative Clinical Data Research Network

OTHER

Sponsor Role: collaborator

Mid-South Clinical Data Research Network

OTHER

Sponsor Role: collaborator

New York City Clinical Data Research Network

OTHER

Sponsor Role: collaborator

OneFlorida Clinical Research Consortium

OTHER

Sponsor Role: collaborator

PEDSnet: A Pediatric Learning Health System CDRN

UNKNOWN

Sponsor Role: collaborator

PORTAL CDRN

UNKNOWN

Sponsor Role: collaborator

Research Action for Health Network (REACHnet)

OTHER

Sponsor Role: collaborator

Scalable Collaborative Infrastructure for a Learning Healthcare System (SCILHS)

UNKNOWN

Sponsor Role: collaborator

Genetic Alliance

OTHER

Sponsor Role: collaborator

StatLog

UNKNOWN

Sponsor Role: collaborator

Harvard Pilgrim Health Care

OTHER

Sponsor Role: lead

Responsible Party

Jason Block

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jason P Block, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Harvard Pilgrim Health Care Institute

Christopher B Forrest, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Douglas Lunsford

Role: PRINCIPAL_INVESTIGATOR

Nationwide Children's Hospital

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

OBS-1505-30699

Identifier Type: -

Identifier Source: org_study_id