Association of in utero antibiotic exposure on childhood ear infection trajectories: Results from a national birth cohort study

Aim Most prescribed medicines during pregnancy are antibiotics, with unknown effects on a fetus and on the infant's acquired microbiome. This study investigates associations between in utero antibiotic exposure and ear infection trajectories over the first decade of life, hypothesising effects on early or persistent, rather than later-developing, ear infections. Methods Design and participants: The Longitudinal Study of Australian Children birth cohort recruited a nationally-representative sample of 5107 infants in 2004. Measures Mothers reported antibiotic use in pregnancy when a child was 3-21 months old (wave 1), and ongoing problems with ear infection every 2 years spanning ages 0-1 to 10-11 years (waves 1-6). Analysis Latent class models identified ear infection trajectories, and univariable and multivariable multinomial logistic regression determined odds of adverse trajectories by antibiotic exposure. Results A total of 4500 (88.1% of original sample) children contributed (mean baseline age 0.7 years; 51.3% boys); 10.4% of mothers reported antibiotic use in pregnancy. Four probability trajectories for ear infection emerged: 'consistently low' (86.2%), 'moderate to low' (5.6%), 'low to moderate' (6.7%) and 'consistently high' (1.4%). Antibiotic use in pregnancy was associated with children following 'consistently high' (adjusted odds ratio 2.04, 95% confidence interval 1.08-3.88, P = 0.03) and 'moderate to low' (adjusted odds ratio 1.78, 95% confidence interval 1.25-2.53, P = 0.001) trajectories. Conclusions Antibiotic use in pregnancy is associated with an increased risk of persistent and early childhood ear infections. This highlights the wisdom of cautious antibiotic use during pregnancy, and the need for the study of potential mechanisms underlying these associations.