Long-Term Outcomes After Group B Streptococcal Disease in Infancy

Abstract

Source: Horváth-Puhó E, van Kassel MN, P Gonçalves BP, et al. Mortality, neurodevelopmental impairments, and economic outcomes after invasive group B streptococcal disease in early infancy in Denmark and the Netherlands: a national matched cohort study. Lancet Child Adolesc Health. 2021;5(6):398-407; doi: 10.1016/S2352-4642(21)00022-5Investigators from multiple institutions conducted a matched cohort study to assess the long-term health outcomes among infants with invasive group B streptococcal disease (iGBS). Data for this study were obtained from national registries in Denmark and the Netherlands. Data from Danish children born from 1997–2017 and Dutch children born 2000–2017 were included.Children with iGBS, defined as GBS sepsis, meningitis, or pneumonia by the age of 89 days, were identified using ICD-10 codes within Denmark’s Medical Birth and National Patient Registries and positive culture results within the Netherlands’ Reference Laboratory for Bacterial Meningitis. Age of iGBS onset was calculated using the first hospital admission date for iGBS disease and categorized as early (0-6 days) or late onset (7-89 days). Children without iGBS were randomly selected from similar administrative databases and matched 10:1 to each child with iGBS on sex, birth month and year, and gestational age.All children were followed from birth until death, emigration, or the end of the study period. Investigators computed the mortality risk during the first 3 months and 5 years of life using data from the Danish Civil Registration system and Dutch Municipal Personal Records Database. Five-year mortality rates were compared among children with and without iGBS disease. Among those who survived the first 3 months of life, investigators calculated the risk of neurodevelopment impairments (NDI) by age 10 years among children with and without iGBS disease using ICD-10 codes for mental, behavioral, and nervous system disorders in the Danish National Patient Registry and use of special educational support in national databases in the Netherlands.There were 2,258 children identified as having iGBS disease and 22,462 matched children without iGBS disease. Among children with iGBS disease, 86% of Danish children and 64% of Dutch children had early onset disease (EOD). Mortality risk in the first 3 months was 2.3% (95% Confidence Interval [C I], 1. 7, 3. 2) in Denmark and 7.6% (95% CI, 5.6, 9.5) in the Netherlands. The 5-year mortality risk was significantly higher in Dutch children with (vs without) iGBS disease (hazard ratio, 3.97; 95% CI, 2.89, 5.46). There was an overall increased risk of NDI by age 10 years in both Denmark (relative risk [RR], 1.77; 95% CI, 1.44, 2.18) and the Netherlands (RR, 2.28; 95% CI, 1.64, 3.17).The investigators conclude that iGBS disease in infancy is associated with increased mortality and higher risk of NDI in later childhood.Dr Brady has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Group B streptococci are estimated to cause more than 300,000 cases of neonatal disease annually, resulting in about 90,000 deaths worldwide.1 The current researchers are the first to quantify the long-term effects on survivors of iGBS disease in high-income countries that use intrapartum antibiotic prophylaxis (IAP) and have advanced neonatal care. The burden of iGBS disease is likely higher in low-income countries where these resources are not available.2The prevalence of EOD and late-onset disease (LOD) in Denmark and the Netherlands was stable over the study period and EOD predominated. In contrast, EOD has declined and now occurs less frequently than does LOD in the US. (See AAP Grand Rounds. 2019;41[5]:51.)3,4 It is not clear why a decline was not noted in these European countries. However, not all mothers are screened, and maternal GBS cultures may be falsely negative.3 As noted in the US study, almost 50% of EOD disease occurs in newborns without any known risk factors.3The World Health Organization has identified GBS as a high priority for the development of a vaccine.5 Developing a GBS vaccine has been challenging because its capsular polysaccharides are poorly immunogenic.6 However, Absalon et al7 recently reported that a novel hexavalent GBS conjugate vaccine was safe and elicited robust immune responses that persisted 6 months after vaccination in a randomized trial in healthy, non-pregnant adults. Additional studies in pregnant women to assess safety and passive antibody transfer to the neonate are needed.The burden of iGBS disease remains high despite IAP and advanced neonatal care. Further development and evaluation of GBS vaccines in pregnant women is a public health priority.