Multicentre external validation of the Neonatal Healthcare-associated infectiOn Prediction (NeoHoP) score: a retrospective case-control study.

BACKGROUND AND OBJECTIVES: Neonatal mortality due to severe bacterial infections is a pressing global issue, especially in low-middle-income countries (LMICs) with constrained healthcare resources. This study aims to validate the Neonatal Healthcare-associated infectiOn Prediction (NeoHoP) score, designed for LMICs, across diverse neonatal populations. METHODS: Prospective data from three South African neonatal units in the Neonatal Sepsis Observational (NeoOBS) study were analysed. The NeoHoP score, initially developed and validated internally in a South African hospital, was assessed using an external cohort of 573 sepsis episodes in 346 infants, focusing on different birth weight categories. Diagnostic metrics were evaluated, including sensitivity, specificity, positive predictive value and area under the receiver operating characteristic curve. RESULTS: The external validation cohort displayed higher median birth weight and gestational age compared with the internal validation cohort. A significant proportion were born before reaching healthcare facilities, resulting in increased sepsis evaluation, and diagnosed healthcare-associated infections (HAIs). Gram-negative infections predominated, with fungal infections more common in the external validation cohort.The NeoHoP score demonstrated robust diagnostic performance, with 92% specificity, 65% sensitivity and a positive likelihood ratio of 7.73. Subgroup analysis for very low birth weight infants produced similar results. The score's generalisability across diverse neonatal populations was evident, showing comparable performance across different birth weight categories. CONCLUSION: This multicentre validation confirms the NeoHoP score as a reliable 'rule-in' test for HAI in neonates, regardless of birth weight. Its potential as a valuable diagnostic tool in LMIC neonatal units addresses a critical gap in neonatal care in low-resource settings.

Neonatal encephalopathy due to suspected hypoxic ischemic encephalopathy: pathophysiology, current, and emerging treatments.

BACKGROUND: Neonatal encephalopathy (NE) due to suspected hypoxic-ischemic encephalopathy (HIE), referred to as NESHIE, is a clinical diagnosis in late preterm and term newborns. It occurs as a result of impaired cerebral blood flow and oxygen delivery during the peripartum period and is used until other causes of NE have been discounted and HIE is confirmed. Therapeutic hypothermia (TH) is the only evidence-based and clinically approved treatment modality for HIE. However, the limited efficacy and uncertain benefits of TH in some low- to middle-income countries (LMICs) and the associated need for intensive monitoring have prompted investigations into more accessible and effective stand-alone or additive treatment options. DATA SOURCES: This review describes the rationale and current evidence for alternative treatments in the context of the pathophysiology of HIE based on literatures from Pubmed and other online sources of published data. RESULTS: The underlining mechanisms of neurotoxic effect, current clinically approved treatment, various categories of emerging treatments and clinical trials for NE are summarized in this review. Melatonin, caffeine citrate, autologous cord blood stem cells, Epoetin alfa and Allopurinal are being tested as potential neuroprotective agents currently. CONCLUSION: This review describes the rationale and current evidence for alternative treatments in the context of the pathophysiology of HIE. Neuroprotective agents are currently only being investigated in high- and middle-income settings. Results from these trials will need to be interpreted and validated in LMIC settings. The focus of future research should therefore be on the development of inexpensive, accessible monotherapies and should include LMICs, where the highest burden of NESHIE exists.

A review of necrotising enterocolitis in very low birth weight babies in a tertiary hospital in Johannesburg.

Introduction: Necrotising enterocolitis (NEC) is the most common gastrointestinal complication in pre-mature infants. There are risk factors and modifying factors that have been identified and studied over the years, but not many studies have been conducted in middle-income countries. Aims and Objectives: This study aimed to describe the maternal, obstetric and neonatal characteristics in very low birth weight (VLBW) babies with NEC in a tertiary neonatal unit in South Africa. The survival to hospital discharge in VLBW babies with NEC was also determined. Materials and Methods: This study was a retrospective, cross-sectional, observational study of VLBW babies admitted to a tertiary neonatal unit between January 2013 and December 2017. The population comprised babies <1500 g and <37 weeks gestation. Maternal and neonatal risk factors of NEC were compared in infants with and without NEC. Results: In this study, 173 out of 2111 (8%) babies were diagnosed with NEC. HIV exposure, late-onset sepsis, respiratory support after initial resuscitation, administration of surfactant and blood transfusion were associated with NEC. Surgery was performed in 48/173 (27.7%) of babies with NEC. The mortality rate in babies with NEC was 49.1%. Death in babies with NEC was associated with surgery for NEC (P = 0.01), mechanical ventilation (P < 0.001) and late-onset sepsis (P = 0.018). Conclusion: Risk factors for NEC in our population are similar to other countries, with some variations such as HIV. Even though some prevention measures have been implemented, the mortality rate remains high.

Prognostic factors affecting survival in children and adolescents with HIV and Hodgkin lymphoma in South Africa.

South African children with Hodgkin lymphoma (HL) and human immunodeficiency virus (HIV) have low 5-year overall survival (OS) rates. In this retrospective multicenter study, 271 South African pediatric patients with HL were studied to determine OS and prognostic factors in those with HIV and HL. Univariate risk factor analysis was performed to analyze prognostic factors. The 29 HIV-infected patients were younger (p = .021), more likely to present with wasting (0.0573), stunting (0.0332), and Stage IV disease (p = .000) than HIV-uninfected patients. The 5- and 10-year OS of HIV-infected patients of 49% and 45% versus 84% and 79%, respectively for HIV-uninfected patients (p = .0001) appeared to be associated with hypoalbuminemia (<20 g/dL) and CD4 percentage of <15%. Causes of death in the HIV-infected group included disease progression (6/14), infection (4/14), unknown (3/14), and second malignancy (1/14). HIV-infected pediatric patients with HL experience increased mortality due to post-therapy opportunistic and nosocomial infections.

Towards understanding global patterns of antimicrobial use and resistance in neonatal sepsis: insights from the NeoAMR network.

OBJECTIVE: To gain an understanding of the variation in available resources and clinical practices between neonatal units (NNUs) in the low-income and middle-income country (LMIC) setting to inform the design of an observational study on the burden of unit-level antimicrobial resistance (AMR). DESIGN: A web-based survey using a REDCap database was circulated to NNUs participating in the Neonatal AMR research network. The survey included questions about NNU funding structure, size, admission rates, access to supportive therapies, empirical antimicrobial guidelines and period prevalence of neonatal blood culture isolates and their resistance patterns. SETTING: 39 NNUs from 12 countries. PATIENTS: Any neonate admitted to one of the participating NNUs. INTERVENTIONS: This was an observational cohort study. RESULTS: The number of live births per unit ranged from 513 to 27 700 over the 12-month study period, with the number of neonatal cots ranging from 12 to 110. The proportion of preterm admissions <32 weeks ranged from 0% to 19%, and the majority of units (26/39, 66%) use Essential Medicines List 'Access' antimicrobials as their first-line treatment in neonatal sepsis. Cephalosporin resistance rates in Gram-negative isolates ranged from 26% to 84%, and carbapenem resistance rates ranged from 0% to 81%. Glycopeptide resistance rates among Gram-positive isolates ranged from 0% to 45%. CONCLUSION: AMR is already a significant issue in NNUs worldwide. The apparent burden of AMR in a given NNU in the LMIC setting can be influenced by a range of factors which will vary substantially between NNUs. These variations must be considered when designing interventions to improve neonatal mortality globally.

Growth of extremely low birth weight infants at a tertiary hospital in a middle-income country.

BACKGROUND: Survival of extremely low birth weight (ELBW; birth weight less than 1000 g) infants has improved significantly since the 1990s. Consequently, growth monitoring in ELBW infants has gained more relevance. METHODS: We conducted this study to describe the growth of ELBW infants at a tertiary hospital, to audit macronutrient intake and explore the association of prematurity complications with growth. This was a retrospective study on 92 ELBW infants born at Charlotte Maxeke Johannesburg Academic Hospital. The association between good growth (regaining birth weight in 21 days or less and subsequent growth velocity > 15 g/kg/day) and complications of prematurity was explored. RESULTS: Only 11infants (13%) had a discharge weight above the 10th centile when the Fenton growth chart was used compared to 20 infants (22.4%) when the Intergrowth 21st Project growth standard was used. The mean weight velocity was 13.5 g/kg/day and the mean number of days to regain birth weight was 18.2 days. Factors associated with poor growth were late-onset sepsis, persistent patent ductus arteriosus, continuous positive airway pressure for more than 2 days, invasive ventilation, oxygen on day 28 and being kept nil per os. Protein and caloric intake correlate positively with growth velocity. Unlike the Fenton Growth Charts, use of the Intergrowth 21st Project growth standards revealed the association between neonatal factors and poor growth. CONCLUSION: Growth outcome in infants is poor at 36 weeks postmenstrual age at our institution. Intergrowth 21st Project growth standards were superior to Fenton Growth Charts, however a multicentre study is required before adoption.

A comparison between raw and predicted mortality in a paediatric intensive care unit in South Africa.

OBJECTIVE: Paediatric intensive care resources are limited in sub-Saharan Africa. The mortality rate in a combined Paediatric/Neonatal Intensive Care Unit in Johannesburg, South Africa was almost double that in a dedicated paediatric intensive care unit in the same country. This study aimed to compare the raw mortality rate with that predicted with the Paediatric Index of Mortality (version 3), by doing a retrospective analysis of an existing database. RESULTS: A total of 530 patients admitted to the intensive care unit between 1 January 2015 and 31 December 2017 were included. The raw mortality rate was 27.1% and the predicted mortality rate was 27.0% (p = 0.971). Cardiac arrest during ICU admission (p < 0.001), non-reactive pupils (0.035), inotropic support (p < 0.001) and renal disease (p = 0.002) were all associated with an increased risk of mortality. These findings indicate that the high mortality rate is due to the severity of illness in the patients that are admitted. It also indicates that the quality of care delivered is acceptable.

Assessment of developmental outcome in very low birth weight infants in Southern Africa using the Bayley Scales of Infant Development (III).

OBJECTIVES: The study aimed to compare the developmental outcome of very low birth weight infants with a group of normal-term controls in a tertiary hospital in sub-Saharan Africa. DESIGN: A group of 105 very low birth weight infants were assessed at a mean age of 17.6 months (95% CI 16.7 to 18.6) using the Bayley Scales of Infant Development, Third Edition, and compared with a group of normal-term controls at the same mean age. RESULTS: Seven of the study infants (7%) had developmental delay (a score below 70), compared with none in the control group (p=0.04). Three of the seven study infants were delayed on all three subscales, one of whom had cerebral palsy. A further 34% of the study infants were 'at risk' of developmental delay (a score below 85). There was no difference in the mean composite score between the study group and controls for the cognitive (p=0.56), motor (p=0.57) or language (p=0.66) subscales. There was no difference in mean composite scores on all subscales between infants who were appropriate for gestational age and those who were small for gestational age. Cognitive and motor scores remained stable in paired assessments of study infants before and after 1 year of age; language scores decreased significantly (p<0.001). Mechanical ventilation was the only risk factor significantly associated with a cognitive score below 85 in study infants. CONCLUSION: Very low birth weight infants in sub-Saharan Africa are at risk of developmental delay and require long-term neurodevelopmental follow-up.

Serum 1,3-ßD-Glucan assay in the diagnosis of invasive fungal disease in neonates.

Invasive fungal disease is a significant cause of morbidity and mortality in the neonate. The current study aims to assess the 1, 3-ßD-Glucan (BG) assay in a prospective analysis in neonates with suspected fungaemia. A multicentre, prospective cohort study was conducted in Johannesburg, South Africa. The study included 72 neonates with clinically suspected late onset sepsis who were at high risk of fungaemia. A BG assay was performed on each patient and correlated with a sepsis classification based on the full blood count, C-reactive protein and blood culture results as no fungaemia, possible fungaemia, probable fungaemia or definite fungaemia. Sensitivity and specificity of the BG assay at levels of 60 pg/mL are 73.2% and 71.0% respectively and at levels of 80 pg/mL are 70.7% and 77.4% respectively. Positive and negative predictive values at 60 pg/mL are 76.9% and 66.7% respectively and at 80 pg/mL are 80.6% and 66.7% respectively. The area under the receiver operating curve is 0.753. The BG assay is a useful adjunct to the diagnosis of invasive fungal disease in neonates. It does, however, need to be considered in the context of the clinical picture and supplementary laboratory investigations.