Influence of timing of maternal antibiotic administration during caesarean section on infant microbial colonisation: a randomised controlled trial.

Thomas Dierikx, Daniel Berkhout, Anat Eck, Sebastian Tims, Johan van Limbergen, Douwe Visser, Marjon de Boer, Nanne de Boer, Daan Touw, Marc Benninga, Nine Schierbeek, Laura Visser, Jan Knol, Guus Roeselers, Johanna de Vries, Tim de Meij

Journal: Gut 2022;71(9):1803-1811

PMID: 34803023

Plain Language Summary

plain language summary logo

Early-life microbiome acquisition and development can be compromised by external perturbations such as delivery via caesarean section (CS), formula feeding and antibiotics. Currently, based on revised international guidelines, all infants born by CS are exposed to broad-spectrum antibiotics via the umbilical cord. Even though there was not an increase in the incidence of neonatal sepsis, the effects on the gut microbiota colonisation and long-term health consequences remain largely unknown. The hypothesis for this study was that exposure to antibiotics in children delivered by CS, related to the revised international guidelines, influences the microbial colonisation process and may impact health outcome. This study is a randomised controlled trial on the microbiome and health state of infants up to 3 years of age. The study enrolled women delivering via CS who received antibiotics prior to skin incision (n=20) or after umbilical cord clamping (n=20) and women who had a vaginal delivery (n=23). Results show that CS delivery in general leads to a profound impact on the initial microbial colonisation. Furthermore, maternal antibiotic administration prior to CS does not lead to a ‘second hit’ on the already compromised microbiome in CS born infants. Authors conclude that early-life microbiome development is strongly affected by mode of delivery.

Abstract

OBJECTIVE

Revised guidelines for caesarean section (CS) advise maternal antibiotic administration prior to skin incision instead of after umbilical cord clamping, unintentionally exposing the infant to antibiotics antenatally. We aimed to investigate if timing of intrapartum antibiotics contributes to the impairment of microbiota colonisation in CS born infants.

DESIGN

In this randomised controlled trial, women delivering via CS received antibiotics prior to skin incision (n=20) or after umbilical cord clamping (n=20). A third control group of vaginally delivering women (n=23) was included. Faecal microbiota was determined from all infants at 1, 7 and 28 days after birth and at 3 years by 16S rRNA gene sequencing and whole-metagenome shotgun sequencing.

RESULTS

Compared with vaginally born infants, profound differences were found in microbial diversity and composition in both CS groups in the first month of life. A decreased abundance in species belonging to the genera and was found with a concurrent increase in members belonging to the phylum Proteobacteria. These differences could not be observed at 3 years of age. No statistically significant differences were observed in taxonomic and functional composition of the microbiome between both CS groups at any of the time points.

CONCLUSION

We confirmed that microbiome colonisation is strongly affected by CS delivery. Our findings suggest that maternal antibiotic administration prior to CS does not result in a second hit on the compromised microbiome. Future, larger studies should confirm that antenatal antibiotic exposure in CS born infants does not aggravate colonisation impairment and impact long-term health.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Address: Department of Paediatric Gastroenterology, Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands [email protected].; Department of Paediatric Gastroenterology, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands.; Department of Paediatric Gastroenterology, Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands.; Nutricia Research Center, Utrecht, The Netherlands.; Department of Paediatrics, Dalhousie University, Halifax, Nova Scotia, Canada.; Department of Neonatology, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands.; Department of Obstetrics and Gynaecology, Reproduction and Development, Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands.; Department of Gastroenterology and Hepatology, Amsterdam University Medical Centres, Amsterdam, The Netherlands.; Department of Pharmaceutical Analysis, University of Groningen Groningen Research Institute of Pharmacy, Groningen, The Netherlands.; Department of Clinical Pharmacy and Pharmacology, University Medical Centre Groningen, Groningen, The Netherlands.; Laboratory of Microbiology, Wageningen University & Research, Wageningen, The Netherlands.
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