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

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 Bacteroides and Bifidobacterium 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.

Keywords: antibiotics; infant gut; intestinal microbiology; paediatric gastroenterology.

Figure 1

Consort diagram.

Figure 2

Mean Shannon diversity indices and taxonomic composition of the microbiota. (A) Mean Shannon diversity indices calculated from the taxonomic assignments (genus level) of the 16S rRNA gene sequence analyses of faecal samples collected at 1, 7 and 28 days postpartum from infants of mothers delivering via caesarean section who received prophylactic antibiotics either before skin incision (group A: antenatally antibiotic exposed infants) or after cord clamp (group B: antenatally antibiotic unexposed infants). Faecal samples were also collected from a third group of vaginally born infants (group C). Samples were analysed by 16S rRNA gene sequencing. At days 1 and 7 no significant difference was present between infants from all three groups. At day 7, mean Shannon diversity was 1.03 in group A and 1.36 in group B (p=0.23). At day 28 Shannon diversity index of vaginally born infants was significantly higher compared with both caesarean groups (p<0.001). (B and C) Left side dendrogram shows results of unsupervised cluster analysis of the taxonomic assignments (genus level) based on Bray-Curtis dissimilarity. Samples collected from vaginally born infant (group C) cluster to the exclusion of samples collected from caesarean section born infants (groups A and B). Right side; taxonomic composition of the microbiota demonstrated in a heat map of individual samples collected at day 7 (B) and day 28 (C) depicting the relative abundance (%) of the 15 most abundant bacterial families.