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.