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. 2022 Apr 28:47:101358.
doi: 10.1016/j.eclinm.2022.101358. eCollection 2022 May.

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

Proma Paul  1   2 , Jaya Chandna  1   2 , Simon R Procter  1   2 , Ziyaad Dangor  3   4 , Shannon Leahy  4 , Sridhar Santhanam  5 , Hima B John  5 , Quique Bassat  6   7   8   9   10 , Justina Bramugy  6 , Azucena Bardají  6   7   10 , Amina Abubakar  11   12 , Carophine Nasambu  11 , Romina Libster  13 , Clara Sánchez Yanotti  13 , Farah Seedat  1   2 , Erzsébet Horváth-Puhó  14 , A K M Tanvir Hossain  15 , Qazi Sadeq-Ur Rahman  15 , Mark Jit  1 , Charles R Newton  11   16 , Kate Milner  17   18 , Bronner P Gonçalves  1   2 , Joy E Lawn  1   2 ; GBS long term outcomes LMIC collaborative group
Collaborators, Affiliations

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

Proma Paul et al. EClinicalMedicine. .

Abstract

Background: Data are limited regarding long-term consequences of invasive GBS (iGBS) disease in early infancy, especially from low- and middle-income countries (LMIC) where most cases occur. We aimed to estimate risk of neurodevelopmental impairment (NDI) in children with a history of iGBS disease.

Methods: A multi-country matched cohort study was undertaken in South Africa, India, Mozambique, Kenya, and Argentina from October 2019 to April 2021. The exposure of interest was defined as a history of iGBS disease (sepsis or meningitis) before 90 days of age, amongst children now aged 1·5-18 years. Age and sex-matched, children without history of GBS were also recruited. Age-appropriate, culturally-adapted assessments were used to define NDI across multiple domains (cognitive, motor, hearing, vision, emotional-behaviour, growth). Pooled NDI risk was meta-analysed across sites. Association of iGBS exposure and NDI outcome was estimated using modified Poisson regression with robust variance estimator.

Findings: Amongst 138 iGBS survivors and 390 non-iGBS children, 38·1% (95% confidence interval [CI]: 30·0% - 46·6%) of iGBS children had any NDI, compared to 21·7% (95% CI: 17·7% - 26·0%) of non- iGBS children, with notable between-site heterogeneity. Risk of moderate/severe NDI was 15·0% (95% CI: 3·4% - 30·8%) among GBS-meningitis, 5·6% (95% CI: 1·5% - 13·7%) for GBS-sepsis survivors. The adjusted risk ratio (aRR) for moderate/severe NDI among iGBS survivors was 1.27 (95% CI: 0.65, 2.45), when compared to non-GBS children. Mild impairment was more frequent in iGBS (27.6% (95% CI: 20.3 - 35.5%)) compared to non-GBS children (12.9% (95% CI: 9.7% - 16.4%)). The risk of emotional-behavioural problems was similar irrespective of iGBS exposure (aRR=0.98 (95% CI: 0.55, 1.77)).

Interpretation: Our findings suggest that iGBS disease is on average associated with a higher risk of moderate/severe NDI, however substantial variation in risk was observed between sites and data are consistent with a wide range of values. Our study underlines the importance of long-term follow-up for at-risk neonates and more feasible, standardised assessments to facilitate diagnosis in research and clinical practice.

Funding: This work was supported by a grant (INV-009018) from the Bill & Melinda Gates Foundation to the London School of Hygiene &Tropical Medicine.

Keywords: Disability; Group B streptococcus; Impairment; Infants; Meningitis; Neurodevelopment; Sepsis; children.

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Conflict of interest statement

SRP reports additional finding from Bill & Melinda Gates Foundation on Covid-19 related projects. ZD and SL report subawards from the London School of Hygiene & Tropical Medicine (LSHTM) to the Wits Health Consortium. SS and HBJ report subawards from LSHTM to Christian Medical College. QB and AB reports subawards from LSHTM to ISGlobal and Centro de Investigação em Saúde de Manhiça. AA and CN reports subawards from the LSHTM to the University of Oxford. CRN. reports subawards from LSHTM to Kenya Medical Research Institute, Kilifi, Kenya. CSY reports subawards from LSHTM to Fundación INFANT. RL reports subawards from LSHTM to Fundación INFANT. a grant from Program for Appropriate Technology in Health for a respiratory syncytial virus (RSV) costing study, grants to Fernando Polack from the Bill & Melinda Gates Foundation for estimating the RSV burden of disease, consulting fees and participating for serving on Pfizer’s GBS advisory board and Janssen’s RSV advisory board, payment or honoraria for Janssen’s RSV lecture and Merck’s human papillomavirus lecture, and stock or stock options from iTRIALS. FS reports non-financial support from The Federal University of São Paulo for submitted work and employment by the UK NSC hosted by the Department of Health, who developed the maternal GBS screening policy recommendation in the UK. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1:
Figure 1
Map of multi-country iGBS long-term follow-up studies: South Africa, Mozambique, Kenya, Argentina.
Figure 2:
Figure 2
Participant flow of iGBS cases and non-iGBS children recruited in multi-country study. Of the 159 iGBS survivors (43 South Africa, 39 Mozambique, 35 India, 29 Kenya, 13 Argentina) included in the country specific descriptive analyses (objective 1), 138 iGBS survivors were included to estimate pooled absolute and relative risk (43 South Africa, 33 Mozambique, 33 India, 29 Kenya).
Figure 3:
Figure 3
Multi-domain and domain specific impairment among non-iGBS children, any iGBS, GBS-sepsis, and GBS-meningitis, stratified by country. Proportion of children with different NDI outcomes in South Africa, Mozambique, India, Kenya, and Argentina for GBS exposed and unexposed children. (A) Overall impairment (moderate/severe and mild). (B) Motor impairment (moderate/severe and mild).(C) Cognitive impairment (moderate/severe and mild). (D) Emotional-behavioural problem (any problem in clinical range). (E) Hearing and vision impairment (any impairment). GBS=group B Streptococcus. GBS-M=GBS meningitis. GBS-S=GBS sepsis. NDI=neurodevelopmental impairment.
See this image and copyright information in PMC

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