Impact of delivery mode-associated gut microbiota dynamics on health in the first year of life

The early-life microbiome appears to be affected by mode of delivery, but this effect may depend on intrapartum antibiotic exposure. Here, we assess the effect of delivery mode on gut microbiota, independent of intrapartum antibiotics, by postponing routine antibiotic administration to mothers until after cord clamping in 74 vaginally delivered and 46 caesarean section born infants. The microbiota differs between caesarean section born and vaginally delivered infants over the first year of life, showing enrichment of Bifidobacterium spp., and reduction of Enterococcus and Klebsiella spp. in vaginally delivered infants. The microbiota composition at one week of life is associated with the number of respiratory infections over the first year. The taxa driving this association are more abundant in caesarean section born children, providing a possible link between mode of delivery and susceptibility to infectious outcomes.


Statistics
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MRI-based neuroimaging
The study had originally been powered based on the abundance and distribution of previously published microbiota data from infants, ensuring a power of 0.8 to detect at least significant differences in alpha and beta diversity between groups, as well as differences in abundance of the 25 most important operational taxonomical units (OTUs), taking into consideration OTUs with high and low variability and abundance and varying effect sizes. This power calculation was later verified by an online (HMP-based) tool. We initially aimed to enroll 88 infants, 44 infants per delivery mode group, allowing a drop-out of 10%. Due to uneven enrolment in both arms, approval was granted by the ethical committee to prolong enrolment to ensure sufficient caesarean section (CS) recruitment, simultaneously continuing the parallel enrolment of vaginally delivered (VD) infants to prevent seasonal/annual differences in microbiota development between the delivery mode groups. Eventually, 78 VD and 52 CS children were recruited; 10 (7.7%) dropped out after an average of 2 weeks of follow-up.
No data were excluded from the analyses.
We performed confirmatory shotgun sequencing on a subset of samples to validate the major 16S-rRNA-based sequencing results. We performed qPCR for a panel of biomarker species on a large set of samples, to validate our 16S-rRNA-based sequencing results on species level. We performed both parametric and non-parametric testing to validate our findings.
All women giving birth vaginally or by CS in the reasearch area were eligible for the study. Randomization was not applicable for this observational study.
Blinding of investigators was not performed, because this was not relevant to our observational study.