Age at first exposure to antibiotics and neurodevelopmental outcomes in childhood

RATIONALE: Viral illnesses in children are common and are frequently treated with antibiotic medication. Antibiotics reduce the diversity and composition of the gut microbiota, leading to poor developmental outcomes. OBJECTIVES: To investigate the relationship between age at first exposure to antibiotics and cognitive and behavioural development at 4.5 years while controlling for multiple confounders, including otitis media. METHODS: Study participants were 5589 children enrolled in the broadly generalisable Growing Up in New Zealand cohort study, with antibiotic exposure data, maternal antenatal information, and age 4.5-year behaviour and cognitive outcome data. Children were categorised as first exposed to antibiotics according to the following mutually exclusive ages: 0–2 months; 3–5 months; 6–8 months; 9–11 months; 12–54 months or not exposed by 54 months. Developmental outcome measures included the Strengths and Difficulties Questionnaire, Luria hand clap task, and the Peabody Picture Vocabulary Test-III. RESULTS: In univariate analysis, there was an evident dose–response relationship where earlier exposure to antibiotics in the first year of life was associated with behavioural difficulties, lower executive function scores, and lower receptive language ability. After adjusting for confounders, pairwise comparisons showed that first antibiotic exposure between birth and 3 months or between 6 and 9 months was associated with lower receptive vocabulary. Antibiotic exposure at any age prior to 12 months was associated with increases in behavioural difficulties scores at 4.5 years. CONCLUSIONS: Following adjustment for socioeconomic factors and otitis media, there is evidence that antibiotic exposure during potentially sensitive windows of development is associated with receptive language and behaviour later in childhood.