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: Male infants have a higher incidence of invasive group B Streptococcus disease (iGBS) compared with female infants; however, data on sex differences in mortality and long-term outcomes after iGBS are lacking. We assessed whether a child's sex influences the effects of iGBS on mortality and risk of neurodevelopmental impairments (NDIs). Methods: We used Danish and Dutch registry data to conduct a nationwide cohort study of infants with a history of iGBS. A comparison cohort, children without a 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 = 1432) 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. Boys had a higher 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 [CI], -0.53 to 3.09 in Denmark and 1.14; 95% CI, -5.13 to 7.41 in the Netherlands). A similar pattern was observed for moderate/severe NDI at age 5 years in Denmark and age 10 years in the Netherlands. Conclusion: Boys are at higher risk of NDI; our results suggest this is disproportionally increased in those who develop iGBS. Future studies should investigate mechanisms of this effect modification by sex.