Gestational age modifies associations between Group B Streptococcus genomic characteristics and postnatal age at disease onset.

Prematurity is a major risk factor for invasive Group B Streptococcus (iGBS) disease in infancy. Whether gestational age (GA) modifies the association between GBS genomic characteristics and postnatal age at disease onset remains unclear. We analyze isolates from infants with iGBS disease in Denmark between 2000 and 2023 using whole-genome sequencing to identify clonal complexes and genes encoding alpha-like surface proteins and capsular serotypes. Isolates are classified into clones based on shared genomic characteristics.Among 510 infants, 356 (70%) are term, 66 (13%) moderate preterm, and 88 (17%) very preterm. Approximately half of term and moderate preterm infants develop iGBS during days 1-3 of life, compared with 9% of very preterm infants. GBS clone distributions differ by GA and postnatal age, particularly for disease onset at 4-89 days. Term and moderate preterm infants are predominantly infected with CC17/Rib/III (71%), whereas very preterm infants show greater clonal diversity, with a lower prevalence of CC17/Rib/III (31%) and higher prevalences of CC23/Alp1/Ia (27%) and CC12/AlphaC/Ib-II (19%). These findings show that GA modifies associations between GBS genomic characteristics and postnatal age at disease onset, highlighting the importance of GA- and postnatal age-stratified GBS surveillance to inform preventive strategies and maternal vaccine implementation.