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.
Highlights
Certain parasite, viral and severe bacterial infections mainly in hospitalized cases have been shown to increase the risk for psychotic disorders and mood disorders[1,2,3]
The diagnosis-groups indicated by the following International Classification of Diseases (ICD)–10 codes were studied: F20–39, F92 (Mood disorders), F40–43, F93 (Anxiety disorders), F50 (Eating disorders), F51 (Non-organic sleeping disorders), F84, F90–F91 (ADHD and Conduct disorders) and F98 (Other behavioral and emotional disorders with onset usually occurring in childhood and adolescence) (Supplementary Table S1)
Our findings indicate that exposure to antibiotic drugs, in utero and the first two postnatal years, is associated with a modestly increased risk for pediatric psychiatric disorders, including sleep disorders, Attention Deficit Hyperactivity Disorder (ADHD) and conduct disorder, mood and anxiety disorders, as well as the diagnosis group of other behavioral and emotional disorders with onset usually occurring in childhood and adolescence
Summary
Viral and severe bacterial infections mainly in hospitalized cases have been shown to increase the risk for psychotic disorders and mood disorders[1,2,3]. A few cross-sectional studies in adults have reported that certain non-hospitalized infection events were associated with an overrepresentation of psychotic, mood or anxiety disorders[4,5,6]. Nation-wide populationbased registry studies in Denmark reported elevated risks for a spectrum of mental disorders after infections and anti-infective drug exposures, especially antibiotics, in childhood/adolescence[7,8]. Maternal infections and inflammation during pregnancy have been reported to affect the fetal brain, increasing the risk of offspring mental disorder with a focus mainly on psychotic disorders[3,12,13,14].
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