P2305Repeated antibiotic exposure up to age 4 years is related to higher body mass at age 4.5 years: longitudinal findings from the growing up in New Zealand cohort

Abstract

Background: New Zealand has the third highest prevalence of obesity among OECD countries. Childhood overweight/obesity increases the risk of adult obesity and related health problems (e.g. cardiovascular diseases). Exposures in early life (such as, antibiotic use) can change the bacterial composition of the intestine (microbiome), potentially increasing the risk of obesity. Purpose: To determine whether antibiotic exposure up to age 4 years is associated with an increased risk of obesity at age 4.5 years. Methods: This research was undertaken within a longitudinal study in New Zealand which recruited 6853 children. The parents completed computer assisted personal interviews antenatally and when their children were approximately ages 9, 24 and 54 months. At the 54 month follow-up, 5734/6156 children (93%) had both weight and height data. BMI-for-age z-scores were derived using the World Health Organization (WHO) reference standards. The study obtained community antibiotic dispensing from the New Zealand Pharmaceutical Collection database for children whose parents consented to external data linkage (n=5666). Variables measuring exposure to any antibiotics and to four broad groups (penicillins, macrolides, cephalosporins/cephamycins, co-trimoxazole) were quantified. The study included children with both BMI and prescription data (n=5546) and excluded 418 children (twins/triplets, gestational age <28 weeks or missing data, birthweight data missing, or congenital anomalies). Multivariable generalised linear models (n=4546) examined the relationship between BMI-for-age z-score and antibiotic exposure variables, adjusting for the following child factors: gender; birthweight; mode of delivery; season of birth; dispensings for anti-reflux medication by age 48 months; sleep duration at age 24 months; time spent (last weekday) watching TV/DVD/video at age 24 months; duration of exclusive breastfeeding; dietary intake at age 24 months. The models also accounted for maternal age, ethnicity and socioeconomic deprivation. Results: The adjusted mean BMI-for-age z-score was significantly higher among children with any exposure to antibiotics (1.02 vs. 0.85; p=0.028). It also increased significantly (p<0.001) with the number of antibiotic dispensings as follows: none=0.82, 1-2=0.86, 3-4=0.91, 5-6=1.03, 7-8=1.03, 9-11=1.02, 12- 16=1.02, >16=1.16. Stratified by gender, the dose-response relationship was only apparent among girls. The adjusted mean BMI-for-age z-score was significantly higher in the exposed compared to unexposed groups for macrolides (1.09 vs. 0.98; p=0.003), cephalosporins/cephamycins (1.05 vs. 0.98; p=0.043) and co- trimoxazole (1.08 vs. 0.96; p=0.001), but not for penicillins (1.02 vs. 0.93; p=0.178). Conclusion: Children with repeated antibiotic exposure by age 4 years are more likely to have a higher body mass at age 4.5 years. Repeated antibiotic exposure is a potentially modifiable risk factor for obesity.