The effect of intrapartum antibiotic prophylaxis on the neonatal gut microbiome: a systematic review

Background: Intrapartum antibiotic prophylaxis (IAP) is an established preventative method for early onset neonatal sepsis. Despite the benefits, the long-term adverse effects remain unclear. This systematic review updates a 2017 review with recent evidence on the impact of IAP on the neonatal gut microbiome and the associated clinical consequences.
Methodology: A search was conducted in MEDLINE, EMBASE, CAB Abstracts, MIDRIS, CENTRAL and LILCACS from 16/10/2016 to 16/10/2020. Papers citing the 2017 review were identified using SCOPUS and reference lists of citing articles were hand searched. Studies were included if they were primary studies reporting on the impact on neonates born to women exposed to IAP for any prophylactic purpose, compared to an unexposed group. Quality appraisal was completed by two reviewers using the Cochrane Risk of bias tool, ROBINS-I tool and Newcastle Ottawa scale.
Results: 1195 unique references were identified, 14 were included. Data investigating the microbiome in 1592 infants, including 3003 faecal samples, showed that infants exposed to IAP had a lower microbial diversity, lower levels of Actinobacteria, especially Bifidobacteria, and higher levels of Proteobacteria. Results for Bacteroidetes and Firmicutes were conflicting. Microbial changes were not followed to clinical outcomes. Of the five long-term adverse effects investigated in 193540 mother-infant dyads, evidence found IAP-exposed infants were more susceptible to colic only. However, studies were inconsistent and at risk of bias.
Conclusion: There is consistent evidence that IAP has a negative impact on the neonatal gut microbiome up to one year of age. Links between the microbial signatures of IAP-related gut dysbiosis and pathogenesis of disease should be developed further.