Pathways of atopic disease and neurodevelopmental impairment: assessing the evidence for infant antibiotics

ABSTRACT

Introduction

Epidemiologic studies are starting to report associations between antibiotic use in early life and neurodevelopmental disorders. Through mechanisms within the gut microbiota-brain axis, indeed, it is plausible that infant antibiotic treatment plays a role in the development of atopic disease and neurodevelopmental disorders.

Areas covered

This narrative review summarizes and interprets published evidence on infant antibiotic use in future outcomes of atopic disease, and neurodevelopmental delay and disorders, including attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). To this end, we critically assess study bias from two main confounding factors, maternal/infant infection and infant feeding status. We also discuss common mechanisms that link atopy and neurodevelopment, and propose hypotheses related to immune activation and the gut microbiome.

Expert opinion

Atopic disease and neurodevelopmental disorders share many risk factors and biological pathways. Infant antibiotic use has been linked to both disorders and is likely a marker for prenatal or infant infection. The mediating role of breastfeeding can also not be discounted. The exploration of causal pathways along the gut-brain axis leading toward neurodevelopmental impairment is evolving and of future interest.

KEYWORDS:

• atopy
• breastfeeding
• infant
• infection
• inflammation
• neurodevelopment
• microbiome
• antibiotics
• gut-brain axis

Article highlights

• Atopic disease and neurodevelopmental disorders share many risk factors, including infant antibiotic use.

• A large body of literature points to an association between infant antibiotic use, and atopic phenotypes of asthma or atopic dermatitis, but not sensitization to food or inhaled allergens. Causal pathways for the former, more severe atopy phenotypes through gut microbial dysbiosis are likely.

• In the emerging literature on neurodevelopment, associations between infant antibiotic use and: i) low neurodevelopmental scores are solely seen with antibiotic use for documented infection, ii) ADHD is likely confounded by underlying infection and not evident in rigorous twin and family-based analyses, and iii) ASD association is not statistically significant.

• Prenatal and/or postnatal infection and gut dysbiosis may contribute to atopic disease and neurodevelopmental impairment. Maternal intrapartum or infant antibiotic use is a marker for infection, and causes infant gut microbial dysbiosis that can be further compounded by lack of breastfeeding.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.