Prenatal and Peripartum Exposure to Antibiotics and Cesarean Section Delivery Are Associated with Differences in Diversity and Composition of the Infant Meconium Microbiome

Abstract

The meconium microbiome may provide insight into intrauterine and peripartum exposures and the very earliest intestinal pioneering microbes. Prenatal antibiotics have been associated with later obesity in children, which is thought to be driven by microbiome dependent mechanisms. However, there is little data regarding associations of prenatal or peripartum antibiotic exposure, with or without cesarean section (CS), with the features of the meconium microbiome. In this study, 16S ribosomal RNA gene sequencing was performed on bacterial DNA of meconium samples from 105 infants in a birth cohort study. After multivariable adjustment, delivery mode (p = 0.044), prenatal antibiotic use (p = 0.005) and peripartum antibiotic use (p < 0.001) were associated with beta diversity of the infant meconium microbiome. CS (vs. vaginal delivery) and peripartum antibiotics were also associated with greater alpha diversity of the meconium microbiome (Shannon and Simpson, p < 0.05). Meconium from infants born by CS (vs. vaginal delivery) had lower relative abundance of the genus Escherichia (p < 0.001). Prenatal antibiotic use and peripartum antibiotic use (both in the overall analytic sample and when restricting to vaginally delivered infants) were associated with differential abundance of several bacterial taxa in the meconium. Bacterial taxa in the meconium microbiome were also differentially associated with infant excess weight at 12 months of age, however, sample size was limited for this comparison. In conclusion, prenatal and peripartum antibiotic use along with CS delivery were associated with differences in the diversity and composition of the meconium microbiome. Whether or not these differences in the meconium microbiome portend risk for long-term health outcomes warrants further exploration.

Presence of distinctive microbiome in the first-pass meconium of newborn infants

“…Our results, however, showed that first-pass meconium likely harbors a distinct microbiota. We found that microbiomes of the meconium samples obtained after C-section delivery differ from those after vaginal delivery, which is analogous to the results of earlier studies 11 , 43 – 45 . This may indicate that meconium already shows the first steps of actual perinatal gut colonization.…”

“…In our study population, 100% of the mothers giving birth via C-section received intrapartum antibiotic treatment, whereas from vaginally delivering mothers only 22% received antibiotics. It has been previously shown that maternal antibiotic usage may affect the neonatal gut development 8 , 45 . It is possible that the antibiotic treatment has elevated the differences in meconium microbiota of C-sectionally delivered neonates.…”

Maternal anthropometric variables and clinical factors shape neonatal microbiome

“…For beta diversity, we observed a significant effect of delivery mode on both Jaccard and Bray–Curtis dissimilarities. This is in line with the results of Wong and colleagues 25 , a study based on a comparable sample size (n = 106) and with other smaller-sized studies 33 , 53 . However, such result is in contrast with other reports, some of which based on larger sample sizes 37 , 55 that however considered different beta diversity indexes, like phylogeny-based weighted and unweighted Unifrac distances- and other studies with smaller sample sizes 22 , 56 .…”

“…Nonetheless, some factors are thought to influence the microbiome during the prenatal period or during delivery, shaping the microbiome in terms of both abundance and composition 2 . Among these factors the most investigated are maternal diet 23 , maternal stress 24 , maternal antibiotic exposure during pregnancy 25 , 26 , delivery mode 11 and gestational age 27 . However, contrasting results have been observed in different studies, probably due to the small average sample size and to different statistical methods employed 28 .…”

Impact of Maternal Intrapartum Antibiotics, and Caesarean Section with and without Labour on Bifidobacterium and Other Infant Gut Microbiota

“…The original source of bifidobacterial species depletion in infancy was attributed to surgical interference of maternal microbiota transfer during birth [ 6 , 7 ]. Interestingly, bifidobacteria are minimally depleted immediately after birth in the meconium (first stool) of infants born by caesarean, with or without labour, compared to vaginal delivery [ 8 , 9 ].…”