Management of hypoxic-ischaemic encephalopathy (HIE) by therapeutic hypothermia (TH) is a major challenge in low- and middle-income countries (LMIC) because of the limited resources. Clinicians in ...

Sepsis and meningitis due to invasive group B Streptococcus (iGBS) disease during early infancy is a leading cause of child mortality. Recent systematic estimates of the worldwide burden of GBS suggested that there are 319,000 cases of infant iGBS disease each year, and an estimated 147,000 stillbirths and young-infant deaths, with the highest burden occurring in Sub-Saharan Africa. The following priority data gaps were highlighted: (1) long-term outcome data after infant iGBS, including mild disability, to calculate quality-adjusted life years (QALYs) or disability-adjusted life years (DALYs) and (2) economic burden for iGBS survivors and their families. Geographic data gaps were also noted with few studies from low- and middle- income countries (LMIC), where the GBS burden is estimated to be the highest. In this paper we present the protocol for a multi-country matched cohort study designed to estimate the risk of long-term neurodevelopmental impairment (NDI), socioemotional behaviors, and economic outcomes for children who survive invasive GBS disease in Argentina, India, Kenya, Mozambique, and South Africa. Children will be identified from health demographic surveillance systems, hospital records, and among participants of previous epidemiological studies. The children will be aged between 18 months to 17 years. A tablet-based custom-designed application will be used to capture data from direct assessment of the child and interviews with the main caregiver. In addition, a parallel sub-study will prospectively measure the acute costs of hospitalization due to neonatal sepsis or meningitis, irrespective of underlying etiology. In summary, these data are necessary to characterize the consequences of iGBS disease and enable the advancement of effective strategies for survivors to reach their developmental and economic potential. In particular, our study will inform the development of a full public health value proposition on maternal GBS immunization that is being coordinated by the World Health Organization.

Sepsis and meningitis due to invasive group B Streptococcus (iGBS) disease during early infancy is a leading cause of child mortality. Recent systematic estimates of the worldwide burden of GBS suggested that there are 319,000 cases of infant iGBS disease each year, and an estimated 147,000 stillbirths and young-infant deaths, with the highest burden occurring in Sub-Saharan Africa. The following priority data gaps were highlighted: (1) long-term outcome data after infant iGBS, including mild disability, to calculate quality-adjusted life years (QALYs) or disability-adjusted life years (DALYs) and (2) economic burden for iGBS survivors and their families. Geographic data gaps were also noted with few studies from low- and middle- income countries (LMIC), where the GBS burden is estimated to be the highest. In this paper we present the protocol for a multi-country matched cohort study designed to estimate the risk of long-term neurodevelopmental impairment (NDI), socioemotional behaviors, and economic outcomes for children who survive invasive GBS disease in Argentina, India, Kenya, Mozambique, and South Africa. Children will be identified from health demographic surveillance systems, hospital records, and among participants of previous epidemiological studies. The children will be aged between 18 months to 17 years. A tablet-based custom-designed application will be used to capture data from direct assessment of the child and interviews with the main caregiver. In addition, a parallel sub-study will prospectively measure the acute costs of hospitalization due to neonatal sepsis or meningitis, irrespective of underlying etiology. In summary, these data are necessary to characterize the consequences of iGBS disease and enable the advancement of effective strategies for survivors to reach their developmental and economic potential. In particular, our study will inform the development of a full public health value proposition on maternal GBS immunization that is being coordinated by the World Health Organization.

Background: Hypoxic ischaemic encephalopathy (HIE) is a common cause of neonatal death and severe neurological deficit in children, contributing to medico-legal litigation. Objectives: To describe the neurodevelopmental outcomes of infants with moderate and severe HIE at Chris Hani Baragwanath Academic Hospital and the proportions with neurodevelopmental impairment (NDI) and complications. To explore the effect of HIE severity and therapeutic hypothermia (TH) on neurodevelopmental outcome. Method: A retrospective, descriptive study at the Neonatal Neurodevelopmental Clinic included 239 infants with moderate and severe HIE, between 2015 and 2020. Neurodevelopmental outcomes were assessed by using the Griffiths Mental Developmental Scales at 1 year. General Quotient (GQ) scores defined NDI. Clinical and investigation criteria determined those with neurological complications. Results: Of the 239 infants, 211 (88.3%) and 28 (11.7%) had moderate HIE and severe HIE, respectively. Cerebral palsy (CP) was diagnosed in 9.2% and NDI in 17.1%. Severe HIE infants had significantly higher rates of NDI and CP, 50% (14) and 21.4% (6) respectively, as compared to those of moderate HIE infants, who had 12.7% (27) NDI and 7.6% (16) CP; 152(72%) moderate and 14 (50%) severe HIE infants received TH. Those who received TH were less likely to have NDI (p = 0.005), CP (p = 0.002), epilepsy and visual impairment. Conclusion: Developmental scores at 1 year of age were in the average range for the cohort, with equivalent profiles across domains. Those with severe HIE had the worst outcomes. Therapeutic hypothermia was associated with decreased CP and NDI in both groups. Contribution: This report supports the use of TH as a neuroprotective strategy in stage 2 and 3 HIE, highlighting the need for neurodevelopmental assessments at 2 years and beyond to determine longer-term outcomes and subtle deficits.