Therapeutic hypothermia for neonatal hypoxic ischaemic encephalopathy should not be discontinued in low- and middle-income countries

Perinatal asphyxia is a major cause of death and disability in children. Therapeutic hypothermia (TH) has become a standard of care for newborn infants who have sustained hypoxic ischaemic encephalopathy (HIE) due to perinatal asphyxia. There is compelling evidence to support this approach. A Cochrane systematic review of 11 prospective randomised controlled trials including 1 505 newborns showed that TH started within 6 hours of birth in infants with HIE significantly decreased mortality and neurodevelopmental disability in survivors.http://www.samj.org.zadm2022ImmunologyPaediatrics and Child Healt

Patterns of antibiotic use, pathogens, and prediction of mortality in hospitalized neonates and young infants with sepsis: A global neonatal sepsis observational cohort study (NeoOBS)

BACKGROUND: There is limited data on antibiotic treatment in hospitalized neonates in low- and middle-income countries (LMICs). We aimed to describe patterns of antibiotic use, pathogens, and clinical outcomes, and to develop a severity score predicting mortality in neonatal sepsis to inform future clinical trial design. METHODS AND FINDINGS: Hospitalized infants <60 days with clinical sepsis were enrolled during 2018 to 2020 by 19 sites in 11 countries (mainly Asia and Africa). Prospective daily observational data was collected on clinical signs, supportive care, antibiotic treatment, microbiology, and 28-day mortality. Two prediction models were developed for (1) 28-day mortality from baseline variables (baseline NeoSep Severity Score); and (2) daily risk of death on IV antibiotics from daily updated assessments (NeoSep Recovery Score). Multivariable Cox regression models included a randomly selected 85% of infants, with 15% for validation. A total of 3,204 infants were enrolled, with median birth weight of 2,500 g (IQR 1,400 to 3,000) and postnatal age of 5 days (IQR 1 to 15). 206 different empiric antibiotic combinations were started in 3,141 infants, which were structured into 5 groups based on the World Health Organization (WHO) AWaRe classification. Approximately 25.9% (n = 814) of infants started WHO first line regimens (Group 1-Access) and 13.8% (n = 432) started WHO second-line cephalosporins (cefotaxime/ceftriaxone) (Group 2-"Low" Watch). The largest group (34.0%, n = 1,068) started a regimen providing partial extended-spectrum beta-lactamase (ESBL)/pseudomonal coverage (piperacillin-tazobactam, ceftazidime, or fluoroquinolone-based) (Group 3-"Medium" Watch), 18.0% (n = 566) started a carbapenem (Group 4-"High" Watch), and 1.8% (n = 57) a Reserve antibiotic (Group 5, largely colistin-based), and 728/2,880 (25.3%) of initial regimens in Groups 1 to 4 were escalated, mainly to carbapenems, usually for clinical deterioration (n = 480; 65.9%). A total of 564/3,195 infants (17.7%) were blood culture pathogen positive, of whom 62.9% (n = 355) had a gram-negative organism, predominantly Klebsiella pneumoniae (n = 132) or Acinetobacter spp. (n = 72). Both were commonly resistant to WHO-recommended regimens and to carbapenems in 43 (32.6%) and 50 (71.4%) of cases, respectively. MRSA accounted for 33 (61.1%) of 54 Staphylococcus aureus isolates. Overall, 350/3,204 infants died (11.3%; 95% CI 10.2% to 12.5%), 17.7% if blood cultures were positive for pathogens (95% CI 14.7% to 21.1%, n = 99/564). A baseline NeoSep Severity Score had a C-index of 0.76 (0.69 to 0.82) in the validation sample, with mortality of 1.6% (3/189; 95% CI: 0.5% to 4.6%), 11.0% (27/245; 7.7% to 15.6%), and 27.3% (12/44; 16.3% to 41.8%) in low (score 0 to 4), medium (5 to 8), and high (9 to 16) risk groups, respectively, with similar performance across subgroups. A related NeoSep Recovery Score had an area under the receiver operating curve for predicting death the next day between 0.8 and 0.9 over the first week. There was significant variation in outcomes between sites and external validation would strengthen score applicability. CONCLUSION: Antibiotic regimens used in neonatal sepsis commonly diverge from WHO guidelines, and trials of novel empiric regimens are urgently needed in the context of increasing antimicrobial resistance (AMR). The baseline NeoSep Severity Score identifies high mortality risk criteria for trial entry, while the NeoSep Recovery Score can help guide decisions on regimen change. NeoOBS data informed the NeoSep1 antibiotic trial (ISRCTN48721236), which aims to identify novel first- and second-line empiric antibiotic regimens for neonatal sepsis. TRIAL REGISTRATION: ClinicalTrials.gov, (NCT03721302)

An audit of neonates admitted to the general ward at Charlotte Maxeke Johannesburg academic hospital

dissertation submitted to the Faculty of Health Sciences for the degree of Masters in Medicine in the University of the Witwatersrand, Johannesburg. August ,2013South Africa is one of the countries in which neonatal mortality has either remained the same or decreased marginally over the past 20 years (1). Resource constraints result in early discharge of well newborns and curtailment of follow up home visits by nurses. This potentially high-risk group of infants may contribute to these neonatal deaths post hospital discharge. In addition, once a neonate has been home, they are no longer admitted to the neonatal unit but to the general paediatric wards that may lack specialized neonatal care. Numerous programs, algorithms, education drives and protocols have been devised in an attempt to improve the quality of healthcare offered to the newborn. These have led to a perceptible decline in the neonatal mortality and morbidity rates respectively. The neonatal mortality and morbidity rates remain unacceptably high however, particularly in resource poor settings. Aim: The aim was to determine the profile and outcome of neonates admitted to the general paediatric wards at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH). Methodology: Audit of all newborns (<28days) admitted to the general wards from 1 January 2011 to 30 April 2011. Patients transferred from other tertiary hospitals were excluded. Patients with incomplete records were also excluded Results: There were a total of 73 neonates admitted with a mean weight of 3.2kg (SD 0.65). The median age for 0-7 days was 4 days and for 8-28 days was 17 days. The majority of neonates 41/73 (56.2%) were male and 21/73 (28.8%) were HIV exposed. In the HIV exposed group only 16/21 (76%) were on HIV prophylaxis. Although antenatal care (ANC) was received by 76.7% of mothers, this is lower than ANC received by the general population. Lack of ANC could possibly be a risk factor for admission of neonates. Possible risk factors for serious illness included 8 (11%) were ex premature infants and 11 (15.1%) had a low birth weight (<2.5 kg). Individual indicators for severity of illness by World Health Organization (WHO) Integrated Management of Childhood and Neonate Illness (IMCNI) were used. The most frequent indicators were tachypnoea (RR>60) 34 (46.6%), jaundice 30 (41.1%) and only 1 (1%) presented with convulsions. Respiratory distress was very sensitive (100%) and relatively specific (76%) for detecting bronchopneumonia (BRPN) with a LR of 3.98. The other clinical indicators were neither specific nor sensitive in detecting serious illness. Most 45 (61%) were referred from the local clinic. The commonest diagnoses were bronchopneumonia (BRPN) 20 (27.4%), neonatal sepsis (NNS) 22 (30.1%) and jaundice 22 (30.1%). Two patients died (2.7%). Their diagnoses were NNS and BRPN Conclusions: There are a significant number of newborns admitted to the general paediatric wards, although the mortality rate in this group was low. IMCNI guidelines remain the most sensitive indicator of the need for admission, and “routine” blood investigations are often non-contributory Community based care and education programmes as well as targeted neonatal care in hospitals for this group is warranted

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

Abstract 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

Neurodevelopmental outcome of late preterm infants in Johannesburg, South Africa

Abstract Background Late preterm infants, previously considered low risk, have been identified to be at risk of developmental problems in infancy and early childhood. There is limited information on the outcome of these infants in low and middle income countries. Methods Bayley scales of infant and toddler development, version III, were done on a group of late preterm infants in Johannesburg, South Africa. The mean composite cognitive, language and motor sub-scales were compared to those obtained from a group of typically developed control infants. Infants were considered to be “at risk” if the composite subscale score was below 85 and “disabled” if the composite subscale score was below 70. Infants identified with cerebral palsy were also reported. Results 56 of 73 (76.7%) late preterm infants enrolled in the study had at least one Bayley assessment at a mean age of 16.5 months (95% CI 15.2–17.6). The mean birth weight was 1.9 kg (95%CI 1.8–2.0) and mean gestational age 33.0 weeks (95% CI 32.56–33.51). There was no difference in the mean cognitive subscales between late preterm infants and controls (95.4 9, 95% CI 91.2–99.5 vs 91.9.95% CI 87.7–96.0). There was similarly no difference in mean language subscales (94.5, 95% CI 91.3–97.7 vs 95.9, 95% CI 92.9–99.0) or motor subscales (96.2, 95% CI 91.8–100.7 vs 97.6, 95% CI 94.7–100.5). There were four late preterm infants who were classified as disabled, two of whom had cerebral palsy. None of the control group was disabled. Conclusions This study demonstrates that overall developmental outcome, as assessed by the Bayley scales of infant and toddler development, was not different between late preterm infants and a group of normal controls. However, 7.1% of the late preterm infants, had evidence of developmental disability. Thus late preterm infants in low and middle income countries require long term follow up to monitor developmental outcome. In a resource limited setting, this may best be achieved by including a parental screening questionnaire, such as the Ages and Stages Questionnaire, in the routine well baby clinic visits

A review of delivery room resuscitation in very low birth weight infants in a middle income country

Abstract Background Advanced levels of delivery room resuscitation in very low birth weight infants are reported to be associated with death and complications of prematurity. In resource limited settings, the need for delivery room resuscitation is often used as a reason to limit care in these infants. Methods This was a review of delivery room resuscitation in very low birth weight infants born in a tertiary hospital in South Africa between 01 January 2013 and 30 June 2016. Outcomes included death and serious complications of prematurity. Advanced delivery room resuscitation was defined as the need for intubation, chest compressions or the administration of adrenaline. Results A total of 1511 very low birth weight infants were included in the study. The majority (1332/1511 (88.2%) required oxygen in the delivery room. Face mask ventilation was needed in 45.2% (683/1511). Advanced delivery room resuscitation was only required in 10.6% (160/1511). More than half the infants who required advanced delivery room resuscitation died (89/160; 55.6%). Advanced delivery room resuscitation was required in significantly more infants 1000 grams (83/539 (15.4%) vs 77/972 (7.9%) p < 0.001). Advanced delivery room resuscitation was significantly associated with a 5 minute Apgar score < 6 (OR 13.8 (95%CI 8.6–22.0), supplemental oxygen at day 28 (OR 2.2 (95% CI 1.4–3.9), metabolic acidosis (OR 2.3 (95% CI 1.1–4.8) and death (OR 1.9 95% CI 1.1–3.3). Other serious complications of prematurity were not associated with advanced delivery room resuscitation. Mortality was increased in infants with a low admission temperature (35.1 °C (SD 0.92) vs 36.1 °C (SD 1.4) (p < 0.001). Conclusion There was a high mortality rate associated with advanced delivery room resuscitation; however complications of prematurity were not increased in survivors..The need for advanced delivery room resuscitation alone should not be used as a predictor of poor outcome in very low birth weight infants. Survivors of advanced delivery room resuscitation should be afforded ventilatory support if required. Special care must be taken to avoid hypothermia in very low birth weight infants requiring resuscitation at birth

Demographic characteristics of infants with invasive Group B <i>Streptococcal</i> (GBS) disease.

<p>¹EOD-Early-onset disease.</p><p>²LOD-Late-onset disease.</p><p>³OR(95%CI)-calculated odds ratio with 95% confidence comparing EOD to LOD.</p><p>⁴p-value-using Chi-squared, Fischer exact or Wilcoxon rank-sum (Mann-Whitney) test.</p><p>⁵CSF-Cerebrospinal fluid.</p><p>Demographic characteristics of infants with invasive Group B <i>Streptococcal</i> (GBS) disease.</p

Predictors of mortality from invasive Group B streptococcus (GBS) disease.

<p>¹OR(95%CI)-calculated odds ratio with 95% confidence comparing infants that demised versus survivors of GBS disease using Chi-squared or Fischer exact test.</p><p>² Multivariate-OR(95%CI)-calculated odds ratio with 95% confidence using logistic regression (adjusted for timing of disease, HIV-exposure, prematurity (<34 weeks), ventilation, inotropic support, apnea, seizures).</p><p>³WCC-White cell count.</p><p>⁴CRP-C-reactive protein.</p><p>Predictors of mortality from invasive Group B streptococcus (GBS) disease.</p