Neonatal Resuscitation Research Priorities in Low- and Middle-Income Countries

Several critical physiological changes occur during birth. Optimal and timely resuscitation is essential to avoid morbidity and mortality. The International Liaison Committee on Resuscitation (ILCOR) is a multinational committee that publishes evidence-based consensus and treatment recommendations for resuscitation in various scenarios including that for neonatal resuscitation. The majority of perinatal deaths occur in low- and middle-income countries (LMICs); however, there is limited research output from LMICs to generate evidence-based practice recommendations specific for LMICs. The current review identifies key areas of neonatal resuscitation-related research needed from LMICs to inform evidence-based resuscitation of neonates in LMICs.

Patterns, Predictors and Outcome of Time to Presentation Among Critically ill Paediatric Patients at Emergency Department of Muhimbili National Hospital, Dar es Salaam, Tanzania

Background: Mortality among under-five children in Tanzania remains high. While early presentation for treatment increases likelihood of survival, delays to care are common and factors causing delay to presentation among critically ill children are unknown.

Methodology: This was a prospective cohort study of critically ill children aged 28days to 14 years attending emergency department (ED) at Muhimbili National Hospital in Tanzania from September 2019 to January 2020. We documented demographics, time to ED presentation, ED interventions and 30-day outcome. The primary outcome was delay (>48 hours) from the onset of illness to ED presentation. Logistic regression and relative risk were calculated to measure the strength of the predictor and relationship between delay and mortality respectively.

Results: We enrolled 440 (59.1%) critically ill children, their median age was 12 [IQR =9-60] months and 63.9% were males. The median time to ED arrival was 3 days [IQR=1-5] and more than half (56.6%) of critically ill children presented to ED in > 48 hours where by being an infant, self-referral and belonging to poor family were independent predictors of delay. Infants and those referred from other facilities had 2.2 (95% CI 1.3-3.8) and 1.7 (95% CI 1.1-2.7) times increased odds of presenting late to the ED respectively. The overall 30-day in-hospital mortality was 26.5% in which those who presented late were 1.3 more likely to die than those who presented early (RR=1.3, CI: 0.9-1.9). Majority died >24 hours of ED arrival (P-value=0.021).

Conclusion: Delayed ED presentation of more than 48 hours from onset of illness was associated with in-hospital mortality. A larger study is needed to evaluate the care pathway of critically ill paediatric patients to identify preventable course of delay to tertiary care facility

Determinants of survival in children with cancer in Johannesburg, South Africa

Background: Childhood cancer, although rare, remains an important cause of death worldwide. The outcomes of children with all cancer types in South Africa are not well-documented.

Aim: The aim of the article was to determine local childhood cancer survival rates and establish determinants of survival.

Setting: The study was conducted at a state and a private hospital in South Africa.

Methods: This retrospective cohort study consecutively included all children with a proven malignancy from 01 January 2012 to 31 December 2016. Univariable and multivariable analyses were used to establish which factors significantly impacted overall survival (OS).

Results: Of a total of 677 study participants, 71% were black South Africans. The estimated 5-year overall survival (OS) was 57% (95% confidence interval [CI]: 53-61%) and significant determinants of OS on the multivariable analysis included: ethnicity, cancer-type and nutritional status. White and Indian patients had higher OS compared to black patients (hazard ration [HR] (95% CI) 0.46 (0.30-0.69) p = 0.0002 and HR (95%) 0.38 (0.19-0.78) p = 0.0087, respectively). Underweight patients had inferior survival (HR (95% CI) 1.78 (1.28-2.47)) p = 0.0006. Patients with neuroblastoma had an increased risk of dying compared to those with leukaemia (HR [95% CI] 1.78 [1.08-2.94]) p = 0.025. Progression of disease was the most common cause of death, followed by disease relapse.

Conclusion: The childhood cancer survival rate obtained in this study can be used as a baseline to facilitate improvement. Non-modifiable prognostic factors included ethnicity and cancer-type whilst modifiable risk factors included undernutrition. Undernutrition should be addressed on a national and local level to improve survival.

Wilms tumour

Wilms tumour (WT) is a childhood embryonal tumour that is paradigmatic of the intersection between disrupted organogenesis and tumorigenesis. Many WT genes play a critical (non-redundant) role in early nephrogenesis. Improving patient outcomes requires advances in understanding and targeting of the multiple genes and cellular control pathways now identified as active in WT development. Decades of clinical and basic research have helped to gradually optimize clinical care. Curative therapy is achievable in 90% of affected children, even those with disseminated disease, yet survival disparities within and between countries exist and deserve commitment to change. Updated epidemiological studies have also provided novel insights into global incidence variations. Introduction of biology-driven approaches to risk stratification and new drug development has been slower in WT than in other childhood tumours. Current prognostic classification for children with WT is grounded in clinical and pathological findings and in dedicated protocols on molecular alterations. Treatment includes conventional cytotoxic chemotherapy and surgery, and radiation therapy in some cases. Advanced imaging to capture tumour composition, optimizing irradiation techniques to reduce target volumes, and evaluation of newer surgical procedures are key areas for future research.

Malignant Extracranial Germ Cell Tumours: A First Report by the South African Children’s Cancer Study Group

OBJECTIVE To determine the overall survival (OS) and prognostic factors influencing outcomes in children and adolescents with malignant extracranial germ cell tumours (MEGCTs) in preparation for the development of a harmonised national treatment protocol. METHODS A retrospective folder review was undertaken at nine South African paediatric oncology units to document patient profiles, tumour and treatment-related data and outcomes. RESULTS Between 1 January 2000 and 31 December 2015, 218 patients were diagnosed with MEGCTs. Female sex (OR 2.26; p=0.037) and higher socio-economic status (SES) (HR 0.071; p=0.039) were associated with a significantly lower risk of death. Advanced clinical stage at diagnosis significantly affected 5-year OS: stage I -96%; stage II – 94.3%; stage III -75.5%; (p=0.017) and stage IV (60.1%; p<0.001). There was a significant association between earlier stage at presentation and higher SES (p=0.03). Patients with a serum AFP level of more than 33,000 ng/ml at diagnosis had significantly poorer outcomes (p=0.002). The use of chemotherapy significantly improved survival, irrespective of the regimen used (p33,000ng/ml were independently predictive of outcome. The relationship between SES and outcome is important as the implementation of a new national protocol aims to standardise care across the socio-economic divide.

An analysis of paediatric snakebites in north-eastern South Africa

Background: Snakebites are an underappreciated health concern in middle- and lower-income countries. The lack of national data vastly impacts funding for this health crisis, as well as strategies for treatment and prevention. Children are particularly vulnerable to snakebite and data in this group is limited.
Methods: This study included paediatric patients, aged 13 years old or younger, admitted to Ngwelezana Tertiary Hospital, Department of Surgery with a snakebite or snakebite related complication, from 1 September 2008 to 31 December 2013. Data captured included demographics, time of presentation, syndromic symptoms, blood results and patient management.
Results: A total of 274 patients were included in this study. The median age at presentation was 8 years, with approximately 70% of the patients aged between 6 and 13 years, with a male predominance (56%). The median time of presentation after sustaining a snakebite was 7 hours (interquartile range 4–13 hours). The majority of patients (71%) presented with cytotoxic manifestations. A total of 53 patients received antivenom of whom 25% suffered adverse reactions. Fifty-six patients underwent one or more procedures on their affected limbs. Three patients required admission to the intensive care unit; all were part of the cytotoxic group and received antivenom. There were no recorded mortalities.
Conclusion: The majority of snakebites are cytotoxic in nature. One-fifth of the paediatric population require antivenom and one-fifth require a surgical procedure post envenomation. Adverse effects post antivenom use are common but manageable. Prevention programmes are needed to help reduce this burden of disease and a nationwide snakebite registry is long overdu

Mobile Surgical Scouts Increase Surgical Access for Patients with Cleft Lip and Palate in Nepal

Background: In Nepal’s remote regions, challenging topography prevents patients with cleft lip and palate (CLP) from seeking care.

Objective: To measure the effect of a mobile surgical scout program on CLP surgical care in remote regions of Nepal.

Methods: Forty-four lay people were trained as mobile surgical scouts and over 5 months traversed remote districts of Nepal on foot to detect and refer CLP patients for surgical care. Surgical patients from remote districts were compared with matched time periods in the year before intervention. Diagnostic accuracy of the surgical scouts was assessed.

Findings: Mobile surgical scouts accurately diagnosed (90%) and referred (82%) patients for cleft surgery. Before the intervention, CLP surgeries from remote districts represented 3.5% of cleft surgeries performed. With mobile surgical scouting, patients from remote districts comprised 8.2% of all cleft surgeries (p = 0.007). When transportation and accompaniment was provided in addition to mobile surgical scouts, patients from remote districts represented 13.5% (p ≤ 0.001) of all cleft surgeries.

Conclusion: Task-shifting the surgical screening process to trained scouts resulted in accurate diagnoses, referrals, and increased access to cleft surgery in remote districts of Nepa

Clinical Profile and Predictors of Mortality in Neonates Born With Non-Immune Hydrops Fetalis: Experience From a Lower-Middle-Income Country

Introduction
Hydrops fetalis (HF) is a life-threatening condition in which a fetus has an abnormal collection of fluid in the tissue around the lungs, heart, abdomen, or under the skin. Based on its pathophysiology, it is classified into immune and non-immune types. With the widespread use of anti-D immunoglobulin, non-immune HF has become more common, with an incidence of one in 1,700-3,000 live births. A multitude of fetal diseases with various causes can lead to non-immune HF. Due to the recent advances in prenatal diagnostic and therapeutic interventions together with improved neonatal intensive care, the diagnosis and subsequent management of HF have been refined. However, HF is still associated with a high mortality rate. A recent assessment of the literature found that there is a lack of data on prognostic variables in neonates with HF from low- and middle-income countries. In light of this, we sought to establish the etiologic causes, predictors of mortality, and eventual fate of newborns born non-immune HF at the Aga Khan University Hospital, Karachi during the 10-year period spanning January 2009-December 2019 in this retrospective analysis.

Methodology
For this study, we collected data from the computerized database and patient record files at the hospital on all infants with non-immune HF. Demographic data, postnatal interventions, clinical and laboratory findings, outcomes, and the results of comparison between HF patients who died and those who survived were analyzed.

Results
The incidence of non-immune HF at our hospital was 0.62/1,000 live births during the period under study, with 33 newborn babies diagnosed with non-immune HF from a total of 53,033 live-born deliveries. An etiologic factor was discovered in 17 (51.5%) neonates with non-immune HF while 16 (48.4%) were classified as those with unidentified etiology. The most common causes were cardiovascular and genetic syndromes, which resulted in 100% mortality. The overall mortality rate was 67%. The need for mechanical ventilation, surfactant therapy, and prolonged hospitalization were identified as independent risk factors of mortality.

Conclusion
Our study proves that the need for mechanical ventilation [moderate to severe hypoxic respiratory failure (HRF)] and prolonged hospitalization are strong predictors of poor outcomes in neonates with non-immune HF. Therefore, severe hydrops causing significant mortality can be anticipated based on the patients’ respiratory status and the need for escalated oxygen support.

Treating Children With Advanced Rheumatic Heart Disease in Sub-Saharan Africa: The NGO EMERGENCY’s Project at the Salam Centre for Cardiac Surgery in Sudan

Rheumatic heart disease is endemic in Sub-Saharan Africa and while efforts are under way to boost prophylaxis and early diagnosis, access to cardiac surgery is rarely affordable. In this article, we report on a humanitarian project by the NGO EMERGENCY, to build and run the Salam Centre for Cardiac Surgery in Sudan. This hospital is a center of excellence offering free-of-charge, high-quality treatment to patients needing open-heart surgery for advanced rheumatic and congenital heart disease. Since it opened in 2007, more than 8,000 patients have undergone surgery there; most of them Sudanese, but ~20% were admitted from other countries, an example of inter-African cooperation. The program is not limited to surgical procedures. It guarantees long-term follow-up and anticoagulant treatment, where necessary. By way of example, we report clinical features and outcome data for the pediatric cohort: 1,318 children under the age of 15, operated on for advanced rheumatic heart disease between 2007 and 2019. The overall 5-year survival rate was 85.0% (95% CI 82.7–87.3). The outcomes for patients with mitral valves repaired and with mitral valves replaced are not statistically different. Nevertheless, observing the trend of patients undergoing valve repair, a better outcome for this category might be assumed. RHD in children is an indicator of poor socio-economic conditions and an inadequate health system, which clearly will not be cured by cardiac surgery alone. Nevertheless, the results achieved by EMERGENCY, with the crucial involvement and participation of the Sudanese government over the years, show that building a hospital, introducing free cardiac surgery, and offering long-term post-operative care may help spread belief in positive change in the future.

Task-sharing to support paediatric and child health service delivery in low- and middle-income countries: current practice and a scoping review of emerging opportunities

Background
Demographic and epidemiological changes have prompted thinking on the need to broaden the child health agenda to include care for complex and chronic conditions in the 0–19 years (paediatric) age range. Providing such services will be undermined by general and skilled paediatric workforce shortages especially in low- and middle-income countries (LMICs). In this paper, we aim to understand existing, sanctioned forms of task-sharing to support the delivery of care for more complex and chronic paediatric and child health conditions in LMICs and emerging opportunities for task-sharing. We specifically focus on conditions other than acute infectious diseases and malnutrition that are historically shifted.

Methods
We (1) reviewed the Global Burden of Diseases study to understand which conditions may need to be prioritized; (2) investigated training opportunities and national policies related to task-sharing (current practice) in five purposefully selected African countries (Kenya, Uganda, Tanzania, Malawi and South Africa); and (3) summarized reported experience of task-sharing and paediatric and child health service delivery through a scoping review of research literature in LMICs published between 1990 and 2019 using MEDLINE, Embase, Global Health, PsycINFO, CINAHL and the Cochrane Library.

Results
We found that while some training opportunities nominally support emerging roles for non-physician clinicians and nurses, formal scopes of practices often remain rather restricted and neither training nor policy seems well aligned with probable needs from high-burden complex and chronic conditions. From 83 studies in 24 LMICs, and aside from the historically shifted conditions, we found some evidence examining task-sharing for a small set of specific conditions (circumcision, some complex surgery, rheumatic heart diseases, epilepsy, mental health).

Conclusion
As child health strategies are further redesigned to address the previously unmet needs careful strategic thinking on the development of an appropriate paediatric workforce is needed. To achieve coverage at scale countries may need to transform their paediatric workforce including possible new roles for non-physician cadres to support safe, accessible and high-quality care.