Background Early-onset Group B Streptococcus (EOGBS) leads to substantial morbidity and mortality in newborn infants. Intrapartum antibiotic prophylaxis (IAP) prevents EOGBS infection, but IAP strategies vary. The approach to the provision of IAP can be risk-based, universal or a combination of the two strategies. Previous systematic reviews reported that universal strategies might be most optimal in lowering EOGBS infection, but there is no consensus. Therefore, we aimed to provide up-to-date evidence on effectiveness of different strategies by comparing perinatal outcomes. Methods A systematic search for EOGBS prevention strategies was performed in MEDLINE, Embase and Web of Science. Studies were included if they reported on different strategies and outcomes of interest, including EOGBS infection, IAP administration and antimicrobial resistance. Summary data was extracted from published reports. Study quality was assessed using the ROBINS-I tool. Random-effects meta-analyses were used to determine risk ratios (RR) and 95%-confidence intervals. PROSPERO registration CRD42023411806. Findings A total of 6050 records were identified, of which 72 observational studies were included for synthesis with more than 10 million live births. Meta-analysis demonstrated that implementation of any strategy (n=34 studies, RR 0.46 (0.36-0.60)), risk-based strategies (n=11 studies, RR 0.65 (0.48-0.87)), or universal strategies (n=16 studies, RR 0.37 (0.25-0.55)) was associated with a reduced risk of EOGBS infection compared to no strategy. In direct comparison, universal strategies were associated with a reduced risk of EOGBS compared to a risk-based strategy (n=17 studies, RR 0.41 (0.30-0.55)), while the proportion of women receiving IAP did not differ between risk-based (16%) and universal (21%) strategies (n=9 studies, RR 1.29 (0.95-1.75)). There was no antimicrobial resistance of EOGBS isolates to penicillin or ampicillin (n=11 studies). Interpretation Any IAP strategy could reduce the risk of EOGBS infection without evidence of increasing antimicrobial resistance. Universal strategies give the largest reduction in the EOGBS burden, while not exposing a significantly higher proportion of pregnancies to IAP compared to risk-based strategies.

The authors have declared no competing interest.

UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction, a cosponsored programme executed by the World Health Organisation.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

MEDLINE, Web Of Science and Embase databases

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

All data were presented in the manuscript and supplementary files.