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

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.

Inclusion criteria

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

• Biologically implausible length/height or weight measurements