Improving the Treatment of Neonatal Sepsis in Resource-Limited Settings: Gaps and Recommendations.

Neonatal sepsis causes significant global morbidity and mortality, with the highest burden in resource-limited settings where 99% of neonatal deaths occur. There are multiple challenges to achieving successful treatment of neonates in this setting. Firstly, reliable and low-cost strategies for risk identification are urgently needed to facilitate treatment as early as possible. Improved laboratory capacity to allow identification of causative organisms would support antimicrobial stewardship. Antibiotic treatment is still hampered by availability, but also increasingly by antimicrobial resistance - making surveillance of organisms and judicious antibiotic use a priority. Finally, supportive care is key in the management of the neonate with sepsis and has been underrecognized as a priority in resource-limited settings. This includes fluid balance and nutritional support in the acute phase, and follow-up care in order to mitigate complications and optimise long-term outcomes. There is much more work to be done in identifying the holistic needs of neonates and their families to provide effective family-integrated interventions and complete the package of neonatal sepsis management in resource-limited settings.

Early care and support for young children with developmental disabilities and their caregivers in Uganda: The Baby Ubuntu feasibility trial.

Background: Early care and support provision for young children with developmental disabilities is frequently lacking, yet has potential to improve child and family outcomes, and is crucial for promoting access to healthcare and early education. We evaluated the feasibility, acceptability, early evidence of impact and provider costs of the Baby Ubuntu participatory, peer-facilitated, group program for young children with developmental disabilities and their caregivers in Uganda. Materials and methods: A feasibility trial, with two parallel groups, compared Baby Ubuntu with standard care. Caregivers and children, aged 6-11 months with moderate-severe neurodevelopmental impairment, were recruited and followed for 12 months. Quantitative and qualitative methods captured information on feasibility (ability to recruit), acceptability (satisfactory attendance), preliminary evidence of impact (family quality of life) and provider costs. Results: One hundred twenty-six infants (median developmental quotient, 28.7) were recruited and randomized (63 per arm) over 9 months, demonstrating feasibility; 101 (80%) completed the 12-month follow-up assessment (9 died, 12 were lost to follow up, 4 withdrew). Of 63 randomized to the intervention, 59 survived (93%); of these, 51 (86%) attended ≥6 modules meeting acceptability criteria, and 49 (83%) completed the 12 month follow-up assessment. Qualitatively, Baby Ubuntu was feasible and acceptable to caregivers and facilitators. Enabling factors included community sensitization by local champions, positive and caring attitudes of facilitators toward children with disability, peer support, and the participatory approach to learning. Among 101 (86%) surviving children seen at 12 months, mixed methods evaluation provided qualitative evidence of impact on family knowledge, skills, and attitudes, however impact on a scored family quality of life tool was inconclusive. Barriers included stigma and exclusion, poverty, and the need to manage expectations around the child's progress. Total provider cost for delivering the program per participant was USD 232. Conclusion: A pilot feasibility trial of the Baby Ubuntu program found it to be feasible and acceptable to children, caregivers and healthcare workers in Uganda. A mixed methods evaluation provided rich programmatic learning including qualitative, but not quantitative, evidence of impact. The cost estimate represents a feasible intervention for this vulnerable group, encouraging financial sustainability at scale. Clinical trial registration: [https://doi.org/10.1186/ISRCTN44380971], identifier [ISRCTN44380971].

Protocol for the Birth Asphyxia in African Newborns (Baby BRAiN) Study: a Neonatal Encephalopathy Feasibility Cohort Study.

BACKGROUND: Neonatal encephalopathy (NE) is a leading cause of child mortality worldwide and contributes substantially to stillbirths and long-term disability. Ninety-nine percent of deaths from NE occur in low-and-middle-income countries (LMICs). Whilst therapeutic hypothermia significantly improves outcomes in high-income countries, its safety and effectiveness in diverse LMIC contexts remains debated. Important differences in the aetiology, nature and timing of neonatal brain injury likely influence the effectiveness of postnatal interventions, including therapeutic hypothermia. METHODS: This is a prospective pilot feasibility cohort study of neonates with NE conducted at Kawempe National Referral Hospital, Kampala, Uganda. Neurological investigations include continuous video electroencephalography (EEG) (days 1-4), serial cranial ultrasound imaging, and neonatal brain Magnetic Resonance Imaging and Spectroscopy (MRI/ MRS) (day 10-14). Neurodevelopmental follow-up will be continued to 18-24 months of age including Prechtl's Assessment of General Movements, Bayley Scales of Infant Development, and a formal scored neurological examination. The primary outcome will be death and moderate-severe neurodevelopmental impairment at 18-24 months. Findings will be used to inform explorative science and larger trials, aiming to develop urgently needed neuroprotective and neurorestorative interventions for NE applicable for use in diverse settings. DISCUSSION: The primary aims of the study are to assess the feasibility of establishing a facility-based cohort of children with NE in Uganda, to enhance our understanding of NE in a low-resource sub-Saharan African setting and provide infrastructure to conduct high-quality research on neuroprotective/ neurorestorative strategies to reduce death and disability from NE. Specific objectives are to establish a NE cohort, in order to 1) investigate the clinical course, aetiology, nature and timing of perinatal brain injury; 2) describe electrographic activity and quantify seizure burden and the relationship with adverse outcomes, and; 3) develop capacity for neonatal brain MRI/S and examine associations with early neurodevelopmental outcomes.

Surviving and Thriving: Early Intervention for Neonatal Survivors With Developmental Disability in Uganda.

Global attention on early child development, inclusive of those with disability, has the potential to translate into improved action for the millions of children with developmental disability living in low- and middle-income countries. Nurturing care is crucial for all children, arguably even more so for children with developmental disability. A high proportion of survivors of neonatal conditions such as prematurity and neonatal encephalopathy are affected by early child developmental disability. The first thousand days of life is a critical period for neuroplasticity and an important window of opportunity for interventions, which maximize developmental potential and other outcomes. Since 2010, our group has been examining predictors, outcomes, and experiences of neonatal encephalopathy in Uganda. The need for an early child intervention program to maximize participation and improve the quality of life for children and families became apparent. In response, the "ABAaNA early intervention program," (now re-branding as 'Baby Ubuntu') a group participatory early intervention program for young children with developmental disability and their families, was developed and piloted. Piloting has provided early evidence of feasibility, acceptability, and impact and a feasibility trial is underway. Future research aims to develop programmatic capacity across diverse settings and evaluate its impact at scale.

Randomised controlled pilot feasibility trial of an early intervention programme for young infants with neurodevelopmental impairment in Uganda: a study protocol.

INTRODUCTION: Early intervention programmes (EIPs) for infants with neurodevelopmental impairment have been poorly studied especially in low-income settings. We aim to evaluate the feasibility and acceptability of a group participatory EIP, the 'ABAaNA EIP', for young children with neurodevelopmental impairment in Uganda. METHODS AND ANALYSIS: We will conduct a pilot feasibility, single-blinded, randomised controlled trial comparing the EIP with standard care across two study sites (one urban, one rural) in central Uganda. Eligible infants (n=126, age 6-11 completed months) with neurodevelopmental impairment (defined as a developmental quotient <70 on Griffiths Scales of Mental Development, and, or Hammersmith Infant Neurological Examination score <60) will be recruited and randomised to the intervention or standard care arm. Intervention arm families will receive the 10-modular, peer-facilitated, participatory, community-based programme over 6 months. Recruited families will be followed up at 6 and 12 months after recruitment, and assessors will be blinded to the trial allocation. The primary hypothesis is that the ABAaNA EIP is feasible and acceptable when compared with standard care. Primary outcomes of interest are feasibility (number recruited and randomised at baseline) and acceptability (protocol violation of arm allocation and number of sessions attended) and family and child quality of life. Guided by the study aim, the qualitative data analysis will use a data-led thematic framework approach. The findings will inform scalability and sustainability of the programme. ETHICS AND DISSEMINATION: The trial protocol has been approved by the relevant Ugandan and UK ethics committees. Recruited families will give written informed consent and we will follow international codes for ethics and good clinical practice. Dissemination will be through peer-reviewed publications, conference presentations and public engagement. TRIAL REGISTRATION NUMBER: ISRCTN44380971; protocol version 3.0, 19th February 2018.

Neonatal Encephalopathy With Group B Streptococcal Disease Worldwide: Systematic Review, Investigator Group Datasets, and Meta-analysis.

BACKGROUND: Neonatal encephalopathy (NE) is a leading cause of child mortality and longer-term impairment. Infection can sensitize the newborn brain to injury; however, the role of group B streptococcal (GBS) disease has not been reviewed. This paper is the ninth in an 11-article series estimating the burden of GBS disease; here we aim to assess the proportion of GBS in NE cases. METHODS: We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus) and sought unpublished data from investigator groups reporting GBS-associated NE. Meta-analyses estimated the proportion of GBS disease in NE and mortality risk. UK population-level data estimated the incidence of GBS-associated NE. RESULTS: Four published and 25 unpublished datasets were identified from 13 countries (N = 10436). The proportion of NE associated with GBS was 0.58% (95% confidence interval [CI], 0.18%-.98%). Mortality was significantly increased in GBS-associated NE vs NE alone (risk ratio, 2.07 [95% CI, 1.47-2.91]). This equates to a UK incidence of GBS-associated NE of 0.019 per 1000 live births. CONCLUSIONS: The consistent increased proportion of GBS disease in NE and significant increased risk of mortality provides evidence that GBS infection contributes to NE. Increased information regarding this and other organisms is important to inform interventions, especially in low- and middle-resource contexts.