Childhood infection burden, recent antibiotic exposure and vascular phenotypes in preschool children

Angela Yu; Maria A C Jansen; Geertje W Dalmeijer; Patricia Bruijning-Verhagen; Cornelis K van der Ent; Diederick E Grobbee; David P Burgner; Cuno S P M Uiterwaal

doi:10.1371/journal.pone.0290633

Childhood infection burden, recent antibiotic exposure and vascular phenotypes in preschool children

PLoS One. 2023 Sep 15;18(9):e0290633. doi: 10.1371/journal.pone.0290633. eCollection 2023.

Authors

Angela Yu¹, Maria A C Jansen², Geertje W Dalmeijer², Patricia Bruijning-Verhagen², Cornelis K van der Ent³, Diederick E Grobbee², David P Burgner^{1

4

5}, Cuno S P M Uiterwaal²

Affiliations

¹ Department of Paediatrics, Monash University, Clayton, Australia.
² Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
³ Department of Pediatric Pulmonology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
⁴ Murdoch Children's Research Institute, Parkville, Australia.
⁵ Department of Paediatrics, Melbourne University, Parkville, Australia.

Abstract

Background: Severe childhood infection has a dose-dependent association with adult cardiovascular events and with adverse cardiometabolic phenotypes. The relationship between cardiovascular outcomes and less severe childhood infections is unclear.

Aim: To investigate the relationship between common, non-hospitalised infections, antibiotic exposure, and preclinical vascular phenotypes in young children.

Design: A Dutch prospective population-derived birth cohort study.

Methods: Participants were from the Wheezing-Illnesses-Study-Leidsche-Rijn (WHISTLER) birth cohort. We collected data from birth to 5 years on antibiotic prescriptions, general practitioner (GP)-diagnosed infections, and monthly parent-reported febrile illnesses (0-1 years). At 5 years, carotid intima-media thickness (CIMT), carotid artery distensibility, and blood pressure (BP) were measured. General linear regression models were adjusted for age, sex, smoke exposure, birth weight z-score, body mass index, and socioeconomic status.

Results: Recent antibiotic exposure was associated with adverse cardiovascular phenotypes; each antibiotic prescription in the 3 and 6 months prior to vascular assessment was associated with an 18.1 μm (95% confidence interval, 4.5-31.6, p = 0.01) and 10.7 μm (0.8-20.5, p = 0.03) increase in CIMT, respectively. Each additional antibiotic prescription in the preceding 6 months was associated with an 8.3 mPa-1 decrease in carotid distensibility (-15.6- -1.1, p = 0.02). Any parent-reported febrile episode (compared to none) showed weak evidence of association with diastolic BP (1.6 mmHg increase, 0.04-3.1, p = 0.04). GP-diagnosed infections were not associated with vascular phenotypes.

Conclusions: Recent antibiotics are associated with adverse vascular phenotypes in early childhood. Mechanistic studies may differentiate antibiotic-related from infection-related effects and inform preventative strategies.

Copyright: © 2023 Yu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Anti-Bacterial Agents* / adverse effects
Birth Cohort
Carotid Intima-Media Thickness*
Child, Preschool
Cohort Studies
Humans
Prospective Studies

Substances

Anti-Bacterial Agents

Grants and funding

The WHISTLER birth cohort was supported with a grant from the Netherlands Organization for Health Research and Development (grant nr 2001-1-1322) and by an unrestricted grant from Glaxo Smith Kline Netherlands. WHISTLER-Cardio was supported with an unrestricted strategic grant from the University Medical Center Utrecht (UMCU), The Netherlands. DB is supported by an Investigator Grant (Leadership level 1; GTN1175744) from the National Health and Medical Research Council (Australia). Research at the Murdoch Children's Research Institute is supported by the Victorian Government's Operational Infrastructure Program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.