Clinical trial NCT02744846: Short- and Long-Term Effects of Antibiotics on Childhood Growth
Official title: The Patient-Centered Outcomes Research Network (PCORnet) Obesity Observational Study: Short- and Long-Term Effects of Antibiotics on Childhood Growth
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Obesity
Keywords: antibiotics
children
pediatric
body mass index
Observational Study
Comparative Effectiveness Research
Obesity
Growth Trajectory
Cohort Study
Electronic Medical Record
Qualitative Research
Lead sponsor: Harvard Pilgrim Health Care
Sponsor class: OTHER
Collaborators: name: Patient-Centered Outcomes Research Institute
name: National Patient-Centered Clinical Research Network
name: ADVANCE CDRN
name: Chicago Area Patient-Centered Outcomes Research Network (CAPriCORN)
name: Greater Plains Collaborative Clinical Data Research Network
name: Mid-South Clinical Data Research Network
name: New York City Clinical Data Research Network
name: OneFlorida Clinical Research Consortium
name: PEDSnet: A Pediatric Learning Health System CDRN
name: PORTAL CDRN
name: Research Action for Health Network (REACHnet)
name: Scalable Collaborative Infrastructure for a Learning Healthcare System (SCILHS)
name: Genetic Alliance
name: StatLog
First posted: 2016-04-20
Enrollment: 681739
Sex: ALL
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study population will include children from age 0 to age 11 years. The population will be identified using data from participating sites formatted into the PCORnet Common Data Model (CDM).

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.

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

Primary outcomes:
measure: Body Mass Index Z-score Difference at 48-72 Months, Exposed vs. No Antibiotics Less Than 24 Months
timeFrame: 48-72 Months
measure: Body Mass Index Z-score Difference at 10 Years, Exposed vs. No Antibiotics Less Than 24 Months
timeFrame: 10 years
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Harvard Pilgrim Health Care Institute
name: Jason P Block, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital of Philadelphia
name: Christopher B Forrest, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Nationwide Children's Hospital
name: Douglas Lunsford
role: PRINCIPAL_INVESTIGATOR
References: