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, Jaya Chandna, Simon R. Procter, Ziyaad Dangor, Shannon Leahy, Sridhar Santhanam, Hima B. John, Quique Bassat, Justina Bramugy, Azucena Bardají, Amina Abubakar, Carophine Nasambu, Romina Libster, Clara Sánchez Yanotti, Farah Seedat, Erzsébet Horváth–Puhó, Ahmed Hossain, Qazi Sadeq-ur Rahman, Mark Jit, Charles R. Newton, Kate Milner, Bronner P. Gonçalves, Joy E Lawn, Shabir A. Madhi, Ziyaad Dangor, Shannon Leahy, Lois M. Harden, Azra Ghoor, Sibongile Mbatha, Sarah Lowick, Barbara Laughton, Tamara Jaye, Sanjay G. Lala, Pamela Sithole, Jacqueline Msayi, Ntombifuthi Kumalo, Tshepiso Msibi, Sridhar Santhanam, Hima B. John, Asha Arumugam, Nandhini Murugesan, Nandhini Rajendraprasad, Mohana Priya, Amina Abubakar, Carophine Nasambu, Adam Mabrouk Adan, Patrick V. Katana, Eva Mwangome, Charles R. Newton, Quique Bassat, Azucena Bardají, Justina Bramugy, Humberto Mucasse, Céline Aerts, Sérgio Massora, Romina Libster, Clara Sánchez Yanotti, Valeria Medina, Andrea Rojas, Daniel Miele Amado, Conrado J. Llapur, Ahmed Hossain, Qazi Sadeq-ur Rahman
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.