Sex differences in long-term outcomes after Group B streptococcal infections during infancy in Denmark and the Netherlands: national cohort studies of neurodevelopmental impairments and mortality.

BACKGROUND Higher incidences of invasive GBS disease (iGBS) have been described in male, compared to female, infants, however data on sex differences in mortality and long-term outcomes after iGBS are lacking. We therefore assessed whether a child´s sex influences the effect of iGBS on mortality and risk of neurodevelopmental impairments (NDI). METHODS We used Danish and Dutch medical and administrative registry data to conduct a nationwide cohort study of infants with a history of iGBS. A comparison cohort, children without history of iGBS, was randomly selected and matched on relevant factors. Effect modification by sex was assessed on additive and multiplicative scales. RESULTS Our analyses included data from children with a history of iGBS in Denmark (period 1997-2017; n=1,432) and the Netherlands (2000-2017; n=697), and from 21,172 children without iGBS. There was no clear evidence of between-sex heterogeneity in iGBS-associated mortality. In both countries, boys had a higher of risk of NDI, with evidence for effect modification on additive scale at the age of 5 years for any NDI (relative excess risk due to interaction=1.28 [95% confidence interval: -0.53-3.09] in Denmark and 1.14 [-5.13-7.41] in the Netherlands). A similar pattern was observed for moderate/severe NDI at age of 5 in Denmark and age of 10 in the Netherlands. CONCLUSION Boys are at higher risk of NDI, and our results suggest this is disproportionally increased in those who develop iGBS. Future studies should investigate mechanisms of this effect modification by sex.