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Background. Respiratory syncytial virus (RSV) is the most common cause of severe bronchiolitis in children worldwide. Objectives. To describe clinical characteristics and outcomes of children hospitalised with bronchiolitis and to compare those with RSV bronchiolitis with children with other viral causes of bronchiolitis. Methods. A retrospective study of children admitted with virally screened bronchiolitis to Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) and Nelson Mandela Children's Hospital (NMCH) from 1 February to 31 August 2018 was conducted, where RSVpositive and -negative children were compared. These children were identified by the National Health Laboratory Service as having undergone respiratory viral multiplex molecular assay analysis and hospital charts were retrospectively reviewed. Results. A total of 131 children admitted with bronchiolitis from CMJAH and NMCH were compared in this study, 58 from CMJAH and 73 from NMCH. In the sample group, 65 (49.6%) children had RSV in comparison with 66 (50.4%) children without RSV. Children with RSV comprised 55 (42%) children with RSV only and 10 (7.6%) children with RSV in combination with another respiratory virus. Rhinovirus was the second most common virus detected in this cohort of children (n=17, 12.9%) followed by adenovirus (n=12, 9.2%) and coronavirus (n=9, 6.9%). A statistically significant risk factor noted in children requiring hospitalisation for RSV bronchiolitis was age less than six months (p<0.001). Conclusions. Bronchiolitis is a common disease in children. Respiratory syncytial virus is the most common cause of severe bronchiolitis in hospitalised infants less than six months of age. [ABSTRACT FROM AUTHOR]

Background. Necrotising enterocolitis (NEC) is an inflammatory disease almost exclusively affecting preterm infants. Previous research has presented a higher mortality rate in infants requiring surgical treatment compared with infants receiving medical treatment. However, the knowledge of mortality and morbidity of the disease in low- and middle-income countries is still limited. Objectives. To review infants with NEC admitted to the neonatal unit at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH), determine a potential difference in mortality between medically and surgically treated infants, and to identify characteristics and factors associated with mortality among these infants. Methods. This retrospective study described infants with NEC born between 1 January 2016 and 31 December 2018 who were admitted to the neonatal unit. The characteristics and survival of these infants were compared using univariate and multivariate analyses. Results. During the study period, 5 061 infants were admitted to the neonatal unit, of which 218 infants were diagnosed with NEC. The period prevalence of NEC was 4.3% among all neonatal infants and 11.0% among very-low-birthweight (VLBW) infants. Mortality was significantly higher among surgically treated infants with NEC compared with medically treated infants (p=0.025, odds ratio 1.888 (95% confidence interval 1.082 - 3.296)). Late-onset sepsis was significantly more common among VLBW infants with NEC (71.3%) compared with VLBW infants without NEC (27.1%). Among infants with late-onset sepsis, Gram-negative bacteria, multidrug-resistant bacteria and fungal sepsis was significantly more common in the group of infants with NEC. Conclusions. Infants with NEC treated surgically at CMJAH have an increased risk of dying compared with those receiving medical treatment, likely due to the severity of disease. Furthermore, this study emphasised the burden of sepsis among infants with NEC and may contribute to a better knowledge of NEC in South Africa. [ABSTRACT FROM AUTHOR]

Background. There is approximately one paediatric intensive care unit (PICU) bed per 22 800 children in SA, making PICU beds a very limited resource. Objectives. To determine the spectrum of medical conditions in children admitted to a PICU, their outcomes, and to compare the number and outcomes of HIV-exposed/infected children v. HIV-unexposed children. Methods. This was a retrospective chart review of children older than 28 days, admitted to Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) PICU for medical conditions from 1 January 2013 to 31 July 2014. Results. There were 883 admissions; 518 (59%) were neonates and 234 (26.5%) were surgical patients, leaving a final sample of 131 (14.8%) children with medical conditions. The median age of children admitted was 3.8 months. Out of 131 children, 44 (34%) were HIV-exposed and 16 (12.2%) had a positive HIV polymerase chain reaction (PCR) result. Lower respiratory tract infections (LRTIs) accounted for two-thirds of all admissions at 84 (64.1%) and were significantly more common in HIV-exposed children (p=0.0005); 32 (24.4%) patients died. HIV-exposed children stayed 3 days longer (p=0.015), were ventilated for 4 more days (p=0.012) and were three times more likely to require high-frequency oscillatory ventilation (p=0.0005) than HIV-unexposed children. Mortality was similar between these two groups. Children confirmed HIV PCR-positive had a significantly longer duration of ICU stay (p=0.03) and ventilation (p=0.006) than those who were exposed but uninfected. Conclusion. There were 883 children admitted in 19 months to CMJAH PICU. A total of 15% of admissions were for medical conditions, two-thirds of which were for LRTIs. One-third of the children were HIV-exposed and had similar outcomes to their unaffected counterparts, although their duration of ventilation and length of stay were longer. [ABSTRACT FROM AUTHOR]

Background. Nasal continuous positive airway pressure (NCPAP) is well established as a treatment for hyaline membrane disease (HMD) and other respiratory diagnoses in neonates. NCPAP is an affordable intervention that reduces the number of neonatal admissions to the intensive care unit (ICU) for ventilation. At the Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) we have been using NCPAP since April 2006. Objectives. To review the use of early NCPAP in our hospital setting. Methods. This was a retrospective, descriptive study of all neonates ≥750 g admitted to CMJAH between 1 January 2013 and 31 July 2014, who received NCPAP within 72 hours of birth. The characteristics and the survival of all infants who received NCPAP were described using univariate analysis. Results. The NCPAP group (n=481) of neonates <1 500 g was significantly associated with surfactant use (p<0.0005), bronchopulmonary dysplasia (p<0.0005) and late sepsis (p<0.0005). The survival to day 7 and to discharge of infants treated with NCPAP was significantly decreased (p<0.0005). NCPAP alone (without ventilation) improved the survival to discharge (p=0.001). The survival was 95.4% in the ≥1 500 g infants, compared with 87.6% in the very low birth weight infants and 55.2% in the extremely low birth weight infants. Conclusion. NCPAP is an effective intervention for HMD; it is both cost-effective and easy to use in a resource-limited setting, and reduces the morbidity and mortality associated with ICU admission. [ABSTRACT FROM AUTHOR]

Background. Perinatal asphyxia is a significant cause of death and disability. Objective. To determine the outcomes (survival to discharge and morbidity after discharge) of neonates with perinatal asphyxia at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH). Methods. this was a descriptive retrospective study. We reviewed information obtained from the computerised neonatal database on neonates born at CMJAH or admitted there within 24 hours of birth between 1 January 2006 and 31 December 2011, with a birth weight of <1 800 g and a 5-minute Apgar score >6. Results. Four hundred and fifty infants were included in the study; 185 (41.1%) were females, the mean birth weight (± standard deviation) was 3 034.8±484.9 g, and the mean gestational age was 39.1±2.2 weeks. Most of the infants were born at CMJAH (391/450, 86.9%) and by normal vaginal delivery (270/450, 60.0%). The overall survival rate was 86.7% (390/450). Forty-two infants were admitted to the intensive care unit (ICU). The ICU survival rate was 88.1% (37/42). Significant predictors of survival were place of birth (p=0.006), mode of delivery (p=0.007) and bag-mask ventilation at birth (p=0.040). Duration of hospital stay (p=0.000) was significantly longer in survivors than in non-survivors (6.5±6.6 days v. 2.8±9.8 days). The remaining factors, namely gender, antenatal care, chest compressions, diagnosis of meconium aspiration syndrome or persistant pulmonary hypertension, did not differ significantly between the two groups. The rate of perinatal asphyxia (5-minute Apgar score >6) was 4.7/1 000 live births, and there was evidence of hypoxic ischaemic encephalopathy (HIE) in 3.6/1 000 live births. Of the 390 babies discharged from CMJAH, 113 (29.0%) had follow-up records to a mean corrected age of 5.9±5.0 months. The majority (90/113, 79.6%) had normal development. Conclusions. (i) The high overall survival and survival after ICU admission provides a benchmark for further care; (ii) obtaining adequate data for long-term follow-up was not possible with the existing resources - surrogate early markers of outcome and/or more resources to ensure accurate follow-up are needed; and (iii) the high incidence of HIE suggests that a therapeutic hypothermia service, including a longterm follow-up component, would be beneficial. [ABSTRACT FROM AUTHOR]

The serum ferritin concentration was used as a screening test to identify the presence of iron overload in 599 Afrikaans subjects (300 males and 299 females) living in the South Western Cape, South Africa. Seventeen of the males with concentrations greater than 400 micrograms/l were reevaluated three and five years later. Serum ferritin concentrations were measured again and further diagnostic procedures were carried out. These included an assessment of alcohol intake and measurements of serum gamma glutamyltransferase, the percentage saturation of transferrin, and HLA-A,-B,-C, and -DR loci typing on the subjects as well as their families. Liver biopsies were performed on some affected subjects. Of the original 16 index subjects, four were diagnosed as homozygous for the HLA linked iron loading gene which is responsible for the clinical disease idiopathic haemochromatosis. Six appeared to be heterozygotes, three were heterozygotes who were also abusing alcohol, and two did not fit into any of the diagnostic groups. The calculated gene frequency was 0.082, with an expected heterozygote frequency of 0.148. The fact that no females were identified in the study suggested that the diagnostic criteria for homozygosity (serum ferritin greater than 400 micrograms/l and % saturation greater than 60%) were set too high. The data were therefore recalculated for the 300 males; when this was done the gene frequency was 0.115 and the heterozygote frequency 0.024. Two subjects were diagnosed as homozygotes in the study of family members and 37 as heterozygotes (33 definite and four probable). Both the homozygotes and nine of the heterozygotes showed mild to moderate disturbances of iron metabolism. There was considerable overlap between the phenotype expression in these nine heterozygotes and the homozygotes, probably as a result of setting the threshold for the serum ferritin concentrations at the relatively high value of 400 microgram/ml. By doing this a small subset of heterozygotes with biochemical abnormalities was identified. The results of the present pilot study suggest a high frequency of the HLA linked iron loading gene in the Afrikaner population of South Western Cape. [ABSTRACT FROM PUBLISHER]

Abstract Background Advances in neonatal care allow survival of extremely premature infants, who are at risk of handicap. Neurodevelopmental follow up of these infants is an essential part of ongoing evaluation of neonatal care. The neonatal care in resource limited developing countries is very different to that in first world settings. Follow up data from developing countries is essential; it is not appropriate to extrapolate data from units in developed countries. This study provides follow up data on a population of very low birth weight (VLBW) infants in Johannesburg, South Africa. Methods The study sample included all VLBW infants born between 01/06/2006 and 28/02/2007 and discharged from the neonatal unit at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH). Bayley Scales of Infant and Toddler Development Version 111 (BSID) 111 were done to assess development. Regression analysis was done to determine factors associated with poor outcome. Results 178 infants were discharged, 26 were not available for follow up, 9 of the remaining 152 (5.9%) died before an assessment was done; 106 of the remaining 143 (74.1%) had a BSID 111 assessment. These 106 patients form the study sample; mean birth weight and mean gestational age was 1182 grams (SD: 197.78) and 30.81 weeks (SD: 2.67) respectively. The BSID (111) was done at a median age of 16.48 months. The mean cognitive subscale was 88.6 (95% CI: 85.69 - 91.59), 9 (8.5%) were < 70, mean language subscale was 87.71 (95% CI: 84.85 - 90.56), 10 (9.4%) < 70, and mean motor subscale was 90.05 (95% CI: 87.0 - 93.11), 8 (7.6%) < 70. Approximately one third of infants were identified as being at risk (score between 70 and 85) on each subscale. Cerebral palsy was diagnosed in 4 (3.7%) of babies. Factors associated with poor outcome included cystic periventricular leukomalacia (PVL), resuscitation at birth, maternal parity, prolonged hospitalisation and duration of supplemental oxygen. PVL was associated with poor outcome on all three subscales. Birth weight and gestational age were not predictive of neurodevelopmental outcome. Conclusion Although the neurodevelopmental outcome of this group of VLBW infants was within the normal range, with a low incidence of cerebral palsy, these results may reflect the low survival of babies with a birth weight below 900 grams. In addition, mean subscale scores were low and one third of the babies were identified as "at risk", indicating that this group of babies warrants long-term follow up into school going age.

Abstract Background Little is known about the growth of VLBW infants in South Africa. The aim of this study was to assess the growth of a cohort of VLBW infants in Johannesburg. Methods A secondary analysis of a prospective cohort was conducted on 139 VLBW infants (birth weight ≤1500 g) admitted to Charlotte Maxeke Johannesburg Academic Hospital. Growth measurements were obtained from patient files and compared with the World Health Organization Child Growth Standards (WHO-CGS) and with a previous cohort of South African VLBW infants. The sample size per analysis ranged from 11 to 81 infants. Results Comparison with the WHO-CGS showed initial poor growth followed by gradual catch up growth with mean Z scores of 0.0 at 20 months postmenstrual age for weight, -0.8 at 20 months postmenstrual age for length and 0.0 at 3 months postmenstrual age for head circumference. Growth was comparable with that of a previous cohort of South African VLBW infants in all parameters. Conclusions Initial poor growth in the study sample was followed by gradual catch up growth but with persistent deficits in length for age at 20 months postmenstrual age relative to healthy term infants.

Abstract Background Audit of disease and mortality patterns provides essential information for health budgeting and planning, as well as a benchmark for comparison. Neonatal mortality accounts for about 1/3 of deaths < 5 years of age and very low birth weight (VLBW) mortality for approximately 1/3 of neonatal mortality. Intervention programs must be based on reliable statistics applicable to the local setting; First World data cannot be used in a Third World setting. Many neonatal units participate in the Vermont Oxford Network (VON); limited resources prevent a significant number of large neonatal units from developing countries taking part, hence data from such units is lacking. The purpose of this study was to provide reliable, recent statistics relevant to a developing African country, useful for guiding neonatal interventions in that setting. Methods This was a retrospective chart review of 474 VLBW infants admitted within 24 hours of birth, between 1 July 2006 and 30 June 2007, to the neonatal unit of Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) in Johannesburg, South Africa. Binary outcome logistic regression on individual variables and multiple logistic regression was done to identify those factors determining survival. Results Overall survival was 70.5%. Survival of infants below 1001 grams birth weight was 34.9% compared to 85.8% for those between 1001 and 1500 grams at birth. The main determinant of survival was birth weight with an adjusted survival odds ratio of 23.44 (95% CI: 11.22 - 49.00) for babies weighing between 1001 and 1500 grams compared to those weighing below 1001 grams. Other predictors of survival were gender (OR 3. 21; 95% CI 1.6 - 6.3), birth before arrival at the hospital (BBA) (OR 0.23; 95% CI: 0.08 - 0.69), necrotising enterocolitis (NEC) (OR 0.06; 95% CI: 0.02 - 0.20), hypotension (OR 0.05; 95% CI 0.01 - 0.21) and nasal continuous positive airways pressure (NCPAP) (OR 4.58; 95% CI 1.58 - 13.31). Conclusions Survival rates compare favourably with other developing countries, but can be improved; especially in infants < 1001 grams birth weight. Resources need to be allocated to preventing the birth of VLBW babies outside hospital, early neonatal resuscitation, provision of NCPAP and prevention of NEC.

Gram-negative bacteria (GNB) are a major cause of neonatal sepsis in low- and middle-income countries (LMICs). Although the World Health Organization (WHO) reports that over 80% of these sepsis deaths could be prevented through improved treatment, the efficacy of the currently recommended first- and second-line treatment regimens for this condition is increasingly affected by high rates of drug resistance. Here we assess three well known antibiotics, fosfomycin, flomoxef and amikacin, in combination as potential antibiotic treatment regimens by investigating the drug resistance and genetic profiles of commonly isolated GNB causing neonatal sepsis in LMICs. The five most prevalent bacterial isolates in the NeoOBS study (NCT03721302) are Klebsiella pneumoniae, Acinetobacter baumannii, E. coli, Serratia marcescens and Enterobacter cloacae complex. Among these isolates, high levels of ESBL and carbapenemase encoding genes are detected along with resistance to ampicillin, gentamicin and cefotaxime, the current WHO recommended empiric regimens. The three new combinations show excellent in vitro activity against ESBL-producing K. pneumoniae and E. coli isolates. Our data should further inform and support the clinical evaluation of these three antibiotic combinations for the treatment of neonatal sepsis in areas with high rates of multidrug-resistant Gram-negative bacteria., (© 2024. The Author(s).)

Background: An estimated 2.4 million babies died within the first 28 days of life in 2020. The third leading cause of neonatal death continues to be neonatal sepsis. Sepsis-causing bacterial pathogens vary temporally and geographically and, with a rise in multidrug-resistant organisms (MDROs), pose a threat to the neonatal population., Methods: This was a single-center, retrospective study of very low birth weight (VLBW) infants with late-onset sepsis (LOS) admitted to a neonatal unit in South Africa. We aimed to calculate the prevalence of multidrug-resistant (MDR) infections in this population. The data collected included demographic and clinical characteristics, length of hospital stay, risk factors for MDRO and mortality, and microbiology results. Logistic regression was used to assess the association between prespecified risk factors with MDR infections and mortality., Results: Of 2570 VLBW infants admitted, 34% had LOS, of which 33% was caused by MDROs. Infection with Acinetobacter spp., Pseudomonas spp., extended-spectrum beta-lactamase Klebsiella spp., or Escherichia coli was associated with the highest mortality in the LOS cohort. Infants with congenital infections (adjusted odds ratio [aOR], 5.13; 95% CI, 1.19-22.02; P = .028) or a history of necrotizing enterocolitis (aOR, 2.17; 95% CI, 1.05-4.49; P = .037) were at significantly higher risk for MDR infections., Conclusions: More than one-third of LOS cases in VLBW infants were caused by MDROs in this study. MDR infections cause substantial neonatal mortality. Antimicrobial stewardship programs, infection control protocols, and ongoing surveillance are needed to prevent further emergence and spread of MDR infections worldwide., Competing Interests: Potential conflicts of interest. All authors: no reported conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)