Early exposure to antibiotic drugs and risk for psychiatric disorders: a population-based study

Abstract

Early life exposure to infection, anti-infectives and altered immune activity have been associated with elevated risk of some psychiatric disorders. However, the risk from exposure in fetal life has been proposed to be confounded by familial factors. The hypothesis of this study is that antibiotic drug exposure during the fetal period and the first two postnatal years is associated with risk for later development of psychiatric disorders in children. All births in Finland between 1996 and 2012, 1 million births, were studied for antibiotic drug exposure: mothers during pregnancy and the children the first two postnatal years. The children were followed up for a wide spectrum of psychiatric diagnoses and psychotropic drug treatment until 2014. Cox proportional hazards modeling was used to estimate effects of antibiotic drug exposure on offspring psychiatric disorders. Modestly (10-50%) increased risks were found on later childhood development of sleep disorders, ADHD, conduct disorder, mood and anxiety disorders, and other behavioral and emotional disorders with childhood onset (ICD-10 F98), supported by increased risks also for childhood psychotropic medication. The prenatal exposure effects detected were not explained by explored familial confounding, nor by registered maternal infections. To conclude, this longitudinal nation-wide study shows that early life antibiotic drug exposure is associated with an increased risk for childhood development of psychopathology. Given the high occurrence of early-life antibiotic exposure, these findings are of public health relevance. Whether the associations reflect effects of the antibiotic drug use or of the targeted infections remains to be explored further.

Fig. 1. Overview of adjusted Cox Hazard Ratios for (i) psychiatric diagnoses (ICD-10 F diagnoses), and (ii) psychotropic medication, in relation to exposure to any antibiotic drug prenatally (trimester 1–3) or in the first 2 years of life, among 990,098 births (1996–2012).

For prenatal exposure, outcomes after birth until 2014 were considered. For postnatal exposure (first 6 months, 6–11 month after birth, 1–2 years after birth), outcomes after 2 years of age until 2014 were considered. The following factors were adjusted for: maternal age, parity, maternal smoking during pregnancy [yes/no], mother unmarried [yes/no], mother born elsewhere than Finland [yes/no], cesarean section [yes/no], mother’s inpatient care due to mental health disorders [yes/no], mother’s purchase of psychotropic drugs (N05 or N06) during pregnancy [yes/no], mother’s diagnoses related to systemic inflammatory disorders [yes/no], multiple birth [yes/no], offspring sex, perinatal health problems (birth weight < 2500 grams, gestational age < 37 weeks or small for gestational age according to Finnish sex-specific standards) [yes/no]. For postnatal exposure we adjusted also for mother’s prescriptions for antibiotics during pregnancy [yes/no]. Error bars indicate 99% confidence interval. Reference: Births where the fetuses or offspring were not exposed to any antibiotic drug during the exposure period studied.

Fig. 2. Risk for any offspring psychiatric diagnosis by increasing number of mother’s antibiotic drug purchases during pregnancy (trimester 1–3).

All types of antibiotic drugs were considered. The covariates adjusted for are those listed in Fig. 1. Error bars indicate 99% confidence interval. Reference: Births where the mother had no antibiotic purchase during pregnancy.