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

Abstract

Summary Background Group B Streptococcus (GBS) disease is a leading cause of neonatal death, but its long-term effects have not been studied after early childhood. The aim of this study was to assess long-term mortality, neurodevelopmental impairments (NDIs), and economic outcomes after infant invasive GBS (iGBS) disease up to adolescence in Denmark and the Netherlands. Methods For this cohort study, children with iGBS disease were identified in Denmark and the Netherlands using national medical and administrative databases and culture results that confirmed their diagnoses. Exposed children were defined as having a history of iGBS disease (sepsis, meningitis, or pneumonia) by the age of 89 days. For each exposed child, ten unexposed children were randomly selected and matched by sex, year and month of birth, and gestational age. Mortality data were analysed with the use of Cox proportional hazards models. NDI data up to adolescence were captured from discharge diagnoses in the National Patient Registry (Denmark) and special educational support records (the Netherlands). Health care use and household income were also compared between the exposed and unexposed cohorts. Findings 2258 children—1561 in Denmark (born from Jan 1, 1997 to Dec 31, 2017) and 697 in the Netherlands (born from Jan 1, 2000 to Dec 31, 2017)—were identified to have iGBS disease and followed up for a median of 14 years (IQR 7–18) in Denmark and 9 years (6–11) in the Netherlands. 366 children had meningitis, 1763 had sepsis, and 129 had pneumonia (in Denmark only). These children were matched with 22 462 children with no history of iGBS disease. iGBS meningitis was associated with an increased mortality at age 5 years (adjusted hazard ratio 4·08 [95% CI 1·78–9·35] for Denmark and 6·73 [3·76–12·06] for the Netherlands). Any iGBS disease was associated with an increased risk of NDI at 10 years of age, both in Denmark (risk ratio 1·77 [95% CI 1·44–2·18]) and the Netherlands (2·28 [1·64–3·17]). A history of iGBS disease was associated with more frequent outpatient clinic visits (incidence rate ratio 1·93 [95% CI 1·79–2·09], p<0·0001) and hospital admissions (1·33 [1·27–1·38], p<0·0001) in children 5 years or younger. No differences in household income were observed between the exposed and unexposed cohorts. Interpretation iGBS disease, especially meningitis, was associated with increased mortality and a higher risk of NDIs in later childhood. This previously unquantified burden underlines the case for a maternal GBS vaccine, and the need to track and provide care for affected survivors of iGBS disease. Funding The Bill & Melinda Gates Foundation. Translations For the Dutch and Danish translations of the abstract see Supplementary Materials section.

Complicated Streptococcus agalactiae Sepsis with/without Meningitis in Young Infants and Newborns: The Clinical and Molecular Characteristics and Outcomes

“…An obviously decreased GBS sepsis-attributable mortality rate has been reported in recent decades, from more than 20% in the 1980s to approximately 10.7% in recent studies [ 3 , 4 , 5 , 26 , 27 ]. The overall mortality rate in our cohort was compatible with recent studies [ 3 , 4 , 5 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ] and a reduction in mortality between 2012 and 2020 was observed in our cohort. As reported in recent studies, multiple factors may account for the reduced mortality rate, including widespread implementation of antibiotics in at-risk mothers and babies and advances in managing acutely ill neonates [ 33 , 34 ].…”

“…Therefore, we were unable to provide the incidence rate and trend of neonatal invasive diseases during the long study period. Compared with some nationwide surveillance or meta-analyses [ 2 , 3 , 4 , 31 , 41 ], the case number in this study was small. It is difficult to define the clinical importance of some GBS strains, including types III, V and VI.…”

“…Recent studies have found an increasing incidence of LOD [ 3 , 26 , 27 , 28 ], but most of them only enrolled cases of neonatal invasive GBS diseases until 2014 or 2015 [ 2 , 3 , 4 , 5 , 26 , 27 , 28 , 29 , 30 ]. Some updated information had data on GBS surveillance until 2017 or 2018 [ 31 , 32 , 33 ], while this report is one of the very few studies that enrolled neonatal invasive GBS diseases until 2020. We can conclude that the significant effects of general and universal GBS screening and IAP since 2012 in Taiwan have led to decreased invasive GBS diseases in neonates since 2018, in both EOD and LOD.…”

Invasive Group B Streptococcal Disease in Neonates and Infants, Italy, Years 2015–2019

“…In our study, 8.4% of infants who recovered from iGBS had brain lesions at hospital discharge. A national matched cohort study that was conducted in Netherlands and Denmark to assess long-term mortality, neurodevelopmental impairments and economic outcomes after iGBS through adolescence, pointed out that GBS meningitis was associated with increased mortality at age 5 and iGBS was associated with an increased risk of neurodevelopmental impairments at 10 years of age [48].…”

Neonatal early-onset infections: Comparing the sensitivity of the neonatal early-onset sepsis calculator to the Dutch and the updated NICE guidelines in an observational cohort of culture-positive cases

“…Neonatal early-onset sepsis and meningitis (early-onset disease; EOD) are important causes of neonatal death. 1 , 2 The predominant pathogen is Group B Streptococcus (GBS; Streptococcus agalactiae ), causing one-third to half of all EOD cases. 3 , 4 Survivors of invasive GBS disease are at increased risk of long-term neurodevelopmental impairment.…”