Objective To determine the difference in rate of weight gain from birth to 5 years based on exposure to maternal group B streptococcal (GBS) intrapartum antibiotic prophylaxis (IAP).

Design Retrospective cohort study of 13 804 infants.

Setting Two perinatal centres and a primary paediatric care network in Philadelphia.

Participants Term infants born 2007–2012, followed longitudinally from birth to 5 years of age.

Exposures GBS IAP defined as penicillin, ampicillin, cefazolin, clindamycin or vancomycin administered ≥4 hours prior to delivery to the mother. Reference infants were defined as born to mothers without (vaginal delivery) or with other (caesarean delivery) intrapartum antibiotic exposure.

Outcomes Difference in rate of weight change from birth to 5 years was assessed using longitudinal rate regression. Analysis was a priori stratified by delivery mode and adjusted for relevant covariates.

Results GBS IAP was administered to mothers of 2444/13 804 (17.7%) children. GBS IAP-exposed children had a significantly elevated rate of weight gain in the first 5 years among vaginally-born (adjusted rate difference 1.44% (95% CI 0.3% to 2.6%)) and caesarean-born (3.52% (95% CI 1.9% to 5.2%)) children. At 5 years, the rate differences equated to an additional 0.24 kg among vaginally-born children and 0.60 kg among caesarean-born children.

Conclusion GBS-specific IAP was associated with a modest increase in rate of early childhood weight gain. GBS IAP is an effective intervention to prevent perinatal GBS disease-associated morbidity and mortality. However, these findings highlight the need to better understand effects of intrapartum antibiotic exposure on childhood growth and support efforts to develop alternate prevention strategies.