South African Children: A Matched Cohort Study of Neurodevelopmental Impairment in Survivors of Invasive Group B Streptococcus Disease Aged 5 to 8 Years

Abstract

Background Invasive Group B Streptococcus (iGBS) sepsis and meningitis are important causes of child mortality, but studies on neurodevelopmental impairment (NDI) after iGBS are limited. Using Griffiths Mental Development Scales-Extended Revised (GMDS-ER), we described NDI in iGBS survivors and non-iGBS children from South Africa, as part of a five-country study. Methods We identified children aged 5 -8 years with a history of iGBS and children with no history of iGBS between October 2019 - January 2021. Children were matched on sex, and birth data (month, year) (matched cohort study). Moderate-severe NDI was the primary outcome as a composite of GMDS-ER motor, GMDS-ER cognition, hearing and vision. Secondary outcomes included mild NDI, any emotional-behavioural problems, and GMDS-ER developmental quotients (DQ) calculated by dividing the age equivalent GMDS-ER score by the chronological age. Results 160 children (iGBS survivors, 43; non-iGBS, 117) were assessed. Amongst iGBS survivors 13 (30.2%) had meningitis and 30 (69.8%) had sepsis. Six (13.9%) iGBS survivors, and five (4.3%) non-iGBS children had moderate-severe NDI. iGBS exposure was associated with a 5.56 (95%CI: 1.07-28.93; p=0.041) adjusted odds of moderate-severe NDI at 5-8 years. Compared to the non-iGBS children, iGBS meningitis survivors had a significantly lower global median DQ (p < 0.05), as well as a lower median DQ for the language and performance GMDS-ER subscale (p<0.05). Conclusions Children surviving iGBS, particularly meningitis, are more likely to have NDI at 5 - 8 years compared to non-iGBS children. Further research is required to improve detection and care for at-risk newborns.

20 million pregnant women with group B streptococcus carriage: consequences, challenges, and opportunities for prevention

“…However, this pathogen is also associated with other health outcomes [2] (Fig. 1), including as a causative factor for stillbirths [3], and a risk factor for preterm births [4] and for long-term sequelae in survivors of acute disease [5,6 ▪▪ ,7,8,9 ▪ ,10 ▪▪ ]. It was estimated that 46,200 (95% posterior interval 20,300–111,300) stillbirths resulted from in utero GBS infection in 2020, and up to 518,100 (36,900–1142,300) preterm births might have been associated with GBS colonisation [1 ▪▪ ].…”

Neurodevelopmental and growth outcomes after invasive Group B Streptococcus in early infancy: A multi-country matched cohort study in South Africa, Mozambique, India, Kenya, and Argentina

“…In South Africa where HIV-exposure data was available, 29 iGBS survivorship was associated with increased NDI even after controlling for HIV-exposure. 13 Finally, we adjusted for prematurity as a potential confounder, 30 , 31 , 32 however we note that gestational age determination in our study was largely measured using last menstrual period, which is less accurate 33 and tends to overestimate prematurity. 34 Of note, complete case analysis, where only participants with information on gestational age variable were included, was performed and similar results were obtained (data not shown).…”

“…However, analysing key demographic and health history variables, there were no statistical difference between the South African children who enrolled in the study and those who were not reachable. 13 In Argentina, only a small number could to be contacted during the pandemic, and for this reason children from this site were not included in pooled analyses. We were unable to adjust for HIV-exposure or HIV status, which are risks for NDI 27 , 28 , due to limited data.…”

“…acute costs of care 11 ) or will be reported separately (e.g, long term economic outcomes). 12 Here, our focus is to (1) describe the risk of moderate/severe and mild NDI among iGBS survivors by site (South Africa, 13 Mozambique, 14 India, 15 combined with Kenya, Argentina), syndrome (meningitis, sepsis) and age; (2) estimate risk of multi-domain NDI and emotional-behavioural problems after iGBS exposure; (3) quantify domain-specific NDI and growth outcomes.…”

Bacterial and Host Determinants of Group B Streptococcal Infection of the Neonate and Infant

“…Invasive GBS infections in the neonate and infant are also associated with long-term sequelae related to brain injury. Meningitis is a major risk factor for neurodevelopmental impairment (NDI) with 1 in 5 survivors of infant GBS disease developing moderate to severe NDI over 18-months ( Kohli-Lynch et al, 2017 ; Harden et al, 2022 ). In Denmark and the Netherlands, any history of invasive GBS was associated with greater rates of neurodevelopmental injury versus unexposed newborns, as well as a higher risk of moderate and severe disability requiring educational support ( Horváth-Puhó et al, 2021 ).…”