# Early-life antibiotic exposure and type 1 diabetes risk: a systematic review and meta-analysis

## TL;DR

This study finds that preconception use of certain antibiotics may increase the risk of type 1 diabetes in offspring, suggesting a potential modifiable risk factor.

## Contribution

The study identifies specific antibiotic classes in the preconception period as potential risk factors for T1D, which could influence prescribing guidelines.

## Key findings

- Maternal preconception exposure to macrolide, sulfonamide/trimethoprim, or tetracycline antibiotics was linked to increased odds of T1D in offspring.
- Prenatal, neonatal, and postnatal antibiotic exposure did not show significant associations with T1D risk.
- The findings suggest preconception antibiotic use could be a modifiable risk factor for T1D.

## Abstract

Antibiotic exposure impacts the gut microbiome and potentially, in an infant, the developing immune system, with implications for the emergence of immune disorders such as type 1 diabetes (T1D). Reports of early-life antibiotic exposure on risk for T1D are inconsistent. We aimed to perform a systematic review and meta-analysis of the association between antibiotic exposure in early life and the development of T1D.

Observational studies were assembled that reported an association between early-life antibiotic exposure and the development of T1D. Four early-life periods were covered: 12 months preconception, prenatal (in pregnancy), neonatal and up to 24 months postnatal.

Medline, Embase, Web of Science Core Collection, and Scopus were searched from inception to August 28, 2024. All records were imported into Covidence for automated deduplication, abstract screening and full-text screening by two independent reviewers.

Data from 20 studies and 10, 960 T1D cases were extracted and analysed using a random effects meta-analysis. Pooled odds ratios (ORs) and hazard ratios (HRs) with associated 95% confidence intervals (CIs) were calculated.

In the preconception period, maternal exposure to macrolide (OR = 1.23 [95% CI: 1.02–1.48]), sulfonamide/trimethoprim (OR = 1.34 [95% CI: 1.07–1.69]) or tetracycline (OR = 1.26 [95% CI: 1.11–1.44]) antibiotics was associated with an increased odds of T1D. Prenatal, neonatal and postnatal antibiotic exposure was not significantly associated with T1D.

Preconception exposure to specific antibiotic classes may represent a modifiable maternal risk factor for T1D in the offspring. This would have implications for antibiotic prescribing guidelines but requires validation by the further study of defined antibiotic classes and their exact timing of preconception exposure.

The protocol was pre-registered on PROSPERO (CRD42024589374) and followed PRISMA guidelines.