Specific class of intrapartum antibiotics relates to maturation of the infant gut microbiota: a prospective cohort study

Abstract

Objective: To evaluate the potential impact of intrapartum antibiotics, and their specific classes, on the infant gut microbiota in the first year of life.

Design: Prospective study of infants in the New Hampshire Birth Cohort Study (NHBCS).

Settings: Rural New Hampshire, USA.

Population or sample: Two hundred and sixty-six full-term infants from the NHBCS.

Methods: Intrapartum antibiotic use during labour and delivery was abstracted from medical records. Faecal samples collected at 6 weeks and 1 year of age were characterised by 16S rRNA sequencing, and metagenomics analysis in a subset of samples.

Exposures: Maternal exposure to antibiotics during labour and delivery.

Main outcome measure: Taxonomic and functional profiles of faecal samples.

Results: Infant exposure to intrapartum antibiotics, particularly to two or more antibiotic classes, was independently associated with lower microbial diversity scores as well as a unique bacterial community at 6 weeks (GUnifrac, P = 0.02). At 1 year, infants in the penicillin-only group had significantly lower α diversity scores than infants not exposed to intrapartum antibiotics. Within the first year of life, intrapartum exposure to penicillins was related to a significantly lower increase in several taxa including Bacteroides, use of cephalosporins was associated with a significantly lower rise over time in Bifidobacterium and infants in the multi-class group experienced a significantly higher increase in Veillonella dispar.

Conclusions: Our findings suggest that intrapartum antibiotics alter the developmental trajectory of the infant gut microbiome, and specific antibiotic types may impact community composition, diversity and keystone immune training taxa.

Tweetable abstract: Class of intrapartum antibiotics administered during delivery relates to maturation of infant gut microbiota.

Keywords: Gut; infant; intestinal microbiota; intrapartum antibiotics; neonate.

Figure 1.

Infant gut microbial α diversity by specific class of maternal intrapartum antibiotic administered. Box plots of the α diversity scores (Shannon and Simpson). Significance values from linear models adjusted for infant birthweight, feeding mode, prenatal antibiotic use and infant postpartum antibiotic use: 6 weeks (n = 266), 1 year (n = 152). **P < 0.01; *P < 0.05; ^■P < 0.1.

Figure 2.

(A–D) Bacterial community composition at 6 weeks and 1 year. Generalized UniFrac principle components analysis plots illustrating that although samples from the infant gut microbiome at 6 weeks and 1 year overlap based on specific class of intrapartum antibiotic administered, there was some visual separation at 6 weeks that was not evident at 1 year. The association between intrapartum antibiotic use and microbiome community profiles at (A) 6 weeks (and (B) 1 year. The association between specific classes of intrapartum antibiotic use and microbiome community profiles at (C) 6 weeks and (D) 1 year. Values of P were derived from multivariable PERMANOVA models (adjusted for antibiotic use during pregnancy and infancy, feeding mode, duration of breastfeeding and infant antibiotic use).

Figure 3.

Taxa that are significantly associated with maternal antibiotic exposure (unexposed infants as the reference group). Heatmap highlights results from the MZILN model. Using the log-scale changes in absolute abundance, the MZILN coefficients identify taxa that were associated with specific classes of maternal antibiotic exposure for 6-week samples and 1-year samples. **Additionally, abundance data from both time-points were used to examine taxa that significantly differed in the change over time from 6 weeks to 1 year (temporal changes) comparing infants exposed to maternal intrapartum antibiotics with those who were not.