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In Utero Exposure to Antibiotics and Risk of Serious Infections in the First Year of Life

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Abstract

Introduction and Objective

Given the high prevalence of antibiotic prescription during pregnancy in France and previous studies suggesting an increased risk of infection in offspring with such exposures, our study aimed to investigate the association between prenatal exposure to systemic antibiotics and serious infections in full-term infants during their first year of life.

Methods

We conducted a retrospective population-based cohort study on singleton, full-term liveborn non-immunocompromised infants, using the French National Health Data System (SNDS) between 2012 and 2021. Systemic antibiotic dispensing in ambulatory care settings during pregnancy defined the exposure. Outcomes concerned serious infections (i.e., infections requiring hospitalization) in offspring identified between 3 and 12 months of life, hence excluding infections of maternal origin. Adjusted odds ratios (aORs) were estimated using logistic regression with multivariate models to control for potential confounders.

Results

Of 2,836,630 infants included, 39.6% were prenatally exposed to systemic antibiotics. Infants prenatally exposed to antibiotics had a higher incidence of serious infections compared with unexposed infants {aOR 1.12 [95% confidence interval (95% CI) 1.11–1.13]}. Similar associations were observed according to the timing of exposure during pregnancy, antibiotic class, and site of infections. The strongest association was observed when infants were prenatally exposed to three or more antibiotic courses during pregnancy [aOR 1.21 (95% CI 1.19–1.24)]. Limitations include residual confounders, such as genetic susceptibility to infections and the role of the underlying pathogen agent.

Conclusion

Prenatal exposure to systemic antibiotics is very common and is associated with a weak yet significant associations with subsequent serious infectious events during the first year of life. While our study revealed associations, it is important to note that causation cannot be established, given the acknowledged limitations, including potential confounding by indication.

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Authors and Affiliations

  1. Centre Régional de Pharmacovigilance, Service de Pharmacologie périnatale, pédiatrique et adulte, Hopital Cochin, Assistance Publique-Hopitaux de Paris (AP-HP), 27, rue du Faubourg Saint Jacques, 75014, Paris, France

    Mylène Tisseyre, Jean-Marc Treluyer & Laurent Chouchana

  2. EA7323, Evaluation thérapeutique et pharmacologie périnatale et pédiatrique, Université Paris Cité, Paris, France

    Mylène Tisseyre, Mathis Collier, Nathanaël Beeker, Florentia Kaguelidou, Jean-Marc Treluyer & Laurent Chouchana

  3. Unité de Recherche Clinique, Hopital Cochin, Assistance Publique-Hopitaux de Paris, Paris, France

    Mathis Collier, Nathanaël Beeker & Jean-Marc Treluyer

  4. Centre d’Investigations Cliniques, INSERM CIC1426, Hôpital Robert Debré, APHP.Nord, Paris, France

    Florentia Kaguelidou

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  1. Mylène Tisseyre
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Correspondence to Mylène Tisseyre.

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No funding was received for conducting this study.

Conflict of interest

All authors have no example conflicts of interest to disclose.

Availability of data and material

Data sharing is not applicable to this article, as the datasets used are based on pseudoanonymized data that are protected by agreements with the French Data Protection Commission (CNIL; Commission Nationale de l’Informatique et Liberté).

Ethics approval

This study was approved by the French Data Protection Commission (CNIL; Commission Nationale de l’Informatique et Liberté; agreement DE-2015-192) and the French Committee for the Protection of Healthcare Data (CERESS; Comité spécifique de Recherche sur les Données de Santé). In agreements with French regulations, observational studies conducted on anonymous medico-administrative data do not require an ethics committee approval.

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Code is available upon reasonable request to the authors.

Author contributions

M. Tisseyre conceptualized and designed the study, collected data, carried out the initial analyses, analyzed the results, drafted the initial manuscript, and critically revised the manuscript. M. Collier designed the data collection instruments, carried out the initial analyses, and critically reviewed the manuscript. N. Beeker designed the data collection instruments and critically reviewed the manuscript. F. Kaguelidou and JM. Treluyer reviewed the study design, analyzed the results, and critically reviewed the manuscript for important intellectual content. L. Chouchana conceptualized and designed the study, analyzed the results, drafted the initial manuscript, and critically reviewed and revised the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

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Tisseyre, M., Collier, M., Beeker, N. et al. In Utero Exposure to Antibiotics and Risk of Serious Infections in the First Year of Life. Drug Saf 47, 453–464 (2024). https://doi.org/10.1007/s40264-024-01401-z

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