Aberrant Growth in 5-Year-Old Children After Antibiotics in the First Week of Life

Abstract

AIM: We examined the relationship between early-life antibiotics, different regimens, and growth until age five years. METHODS: Data from two parallel birth cohorts were analysed: 128 healthy term-born children and 147 term-born children who received antibiotics for suspected neonatal sepsis, randomised across three regimens: Amoxicillin+Cefotaxime, Augmentin+Gentamicin, Penicillin+Gentamicin. Until age five years, growth, environmental exposures, diet, and physical activity data were collected. Primary outcomes were weight-for-age, height-for-age, and weight-for-height z-scores with early-life antibiotic exposure and the regimen as determinants of interest. RESULTS: The median antibiotic exposure duration was 3 days (interquartile range 2.4-5.5 days). Children exposed to early-life antibiotics had on average 0.26 lower weight-for-height z-scores over the first five years compared to unexposed controls (p = 0.014). Especially children treated with Augmentin+Gentamicin showed lower weight-for-height z-scores, compared to unexposed controls (coefficient = 0.36; p = 0.013). Additionally, at age five years, higher birth weight percentiles were associated with higher weight-for-age, height-for-age and weight-for-height and weekly lemonade consumption was associated with higher weight-for-age z-scores. CONCLUSION: Antibiotics in the first week of life are associated with lower weight-for-height up to age five years, with effects varying by treatment type. To explain these effects, further examination of antimicrobial-induced early-life microbiome perturbations and subsequent growth is needed. TRIAL REGISTRATION: International Clinical Trial Registry Platform (https://trialsearch.who.int/): NL4882 and NL3821.