Perinatal outcome of maternal deaths at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa, January 2014 - June 2019

Background. Maternal death is a tragic event. Of maternal deaths worldwide, 99% occur in low- and middle-income countries. Perinatal outcome is related to maternal wellbeing. Maternal death has a negative impact on fetal and neonatal outcome in the short and long term. Objectives. To determine the perinatal outcomes of pregnancies that ended in a maternal death at Chris Hani Baragwanath Academic Hospital (CHBAH), Johannesburg, South Africa, over a 5-year period, to describe the causes of maternal death, and to determine the stillbirth rate (SBR) and early neonatal death (ENND) rate in this population. Methods. This was a retrospective cross-sectional study of maternal deaths in women with a viable pregnancy from January 2014 to June 2019 at CHBAH. All maternal deaths with gestation >26 weeks or fetal weight >500 g were included in the study. Information on demographics, booking status, antenatal care, pregnancy outcome, and fetal and neonatal outcome was extracted from maternal and neonatal files. Results. Of a total of 183 maternal deaths during the study period, 147 were included in the study. The institutional maternal mortality ratio was 135 deaths per 100 000 live births. Hypertension was the main direct cause of death (36.5%; n=27/74), followed by pregnancy related sepsis (27.4%; n=21/74) and obstetric haemorrhage (20.6%; n=15/74). Non-pregnancy-related infections, of which 91.4% were HIV and HIV-related complications, comprised 47.9% (n=35/73) of indirect causes of death, followed by medical and surgical disorders. Of a total of 151 babies, including two sets of twins and one set of triplets, 137 were delivered and 14 were undelivered at the time of maternal death. Ninety-one babies (61.9%) were born alive and 51 (34.6%) were stillbirths. Of the 91 liveborn infants, 6 (6.5%) had an ENND. Of the 51 stillbirths, 14 (27.5%) were undelivered and 11 (21.6%) were delivered by perimortem caesarean section. The SBR was 347 per 1 000 maternal deaths and the ENND rate 66 per 1 000 live births. The perinatal mortality rate (PMR) was 388 per 1 000 maternal deaths, which is 12 times higher than the PMR per 1 000 live births for the general population. Conclusion. Women who experience maternal death have babies with very poor perinatal outcomes, with a very high SBR, ENND rate and PMR. The health of the mother has a direct and significant effect on fetal and neonatal outcomes

Unraveling Specific Causes of Neonatal Mortality Using Minimally Invasive Tissue Sampling: An Observational Study

Background. Postmortem minimally invasive tissue sampling (MITS) is a potential alternative to the gold standard complete diagnostic autopsy for identifying specific causes of childhood deaths. We investigated the utility of MITS, interpreted with available clinical data, for attributing underlying and immediate causes of neonatal deaths. Methods. This prospective, observational pilot study enrolled neonatal deaths at Chris Hani Baragwanath Academic Hospital in Soweto, South Africa. The MITS included needle core-biopsy sampling for histopathology of brain, lung, and liver tissue. Microbiological culture and/or molecular tests were performed on lung, liver, blood, cerebrospinal fluid, and stool samples. The “underlying” and “immediate” causes of death (CoD) were determined for each case by an international panel of 12–15 medical specialists. Results. We enrolled 153 neonatal deaths, 106 aged 3–28 days. Leading underlying CoD included “complications of prematurity” (52.9%), “complications of intrapartum events” (15.0%), “congenital malformations” (13.1%), and “infection related” (9.8%). Overall, infections were the immediate or underlying CoD in 57.5% (n = 88) of all neonatal deaths, including the immediate CoD in 70.4% (58/81) of neonates with “complications of prematurity” as the underlying cause. Overall, 74.4% of 90 infection-related deaths were hospital acquired, mainly due to multidrug-resistant Acinetobacter baumannii (52.2%), Klebsiella pneumoniae (22.4%), and Staphylococcus aureus (20.9%). Streptococcus agalactiae was the most common pathogen (5/15 [33.3%]) among deaths with “infections” as the underlying cause. Conclusions. MITS has potential to address the knowledge gap on specific causes of neonatal mortality. In our setting, this included the hitherto underrecognized dominant role of hospital-acquired multidrug-resistant bacterial infections as the leading immediate cause of neonatal deaths

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)

Maintaining normal temperature immediately after birth in late preterm and term infants: A systematic review and meta-analysis

Aim: Prevention of hypothermia after birth is a global problem in late preterm and term neonates. The aim of this systematic review and meta-analysis was to evaluate delivery room strategies to maintain normothermia and improve survival in late preterm and term neonates (>= 34 weeks' gestation).Methods: Medline, Embase, CINAHL, CENTRAL and international clinical trial registries were searched. Randomized controlled trials (RCTs), quasi-RCTs and observational studies were eligible for inclusion. Risk of bias for each study and GRADE certainty of evidence for each outcome were assessed.Results: 25 RCTs and 10 non-RCTs were included. Room temperature of 23 degrees C compared to 20 degrees C improved normothermia [Risk Ratio (RR), 95% Confidence Interval (CI): 1.26, 1.11-1.42)] and body temperature [Mean Difference (MD), 95% CI: 0.30 degrees C, 0.23-0.37 degrees C), and decreased moderate hypothermia (RR, 95% CI: 0.26, 0.16-0.42). Skin to skin care (SSC) compared to no SSC increased body temperature (MD, 95% CI: 0.32, 0.10-0.52), reduced hypoglycemia (RR, 95% CI: 0.16, 0.05-0.53) and hospital admission (RR, 95% CI: 0.34, 0.14-0.83). Though plastic bag or wrap (PBW) alone or when combined with SSC compared to SSC alone improved temperatures, the risk-benefit balance is uncertain. Clinical benefit or harm could not be excluded for the primary outcome of survival for any of the interventions. Certainty of evidence was low to very low for all outcomes.Conclusions: Room temperature of 23 degrees C and SSC soon after birth may prevent hypothermia in late preterm and term neonates. Though PBW may be an effective adjunct intervention, the risk-benefit balance needs further investigation

Maintaining normothermia immediately after birth in preterm infants <34 weeks' gestation: A systematic review and meta-analysis

Aim: To evaluate delivery room (DR) interventions to prevent hypothermia and improve outcomes in preterm newborn infants <34 weeks' gestation. Methods: Medline, Embase, CINAHL and CENTRAL were searched till 22nd July 2022. Randomized controlled trials (RCTs), non-RCTs and quality improvement studies were considered. A random effects meta-analysis was performed, and the certainty of evidence was evaluated using GRADE guidelines. Results: DR temperature of ≥23 °C compared to standard care improved temperature outcomes without an increased risk of hyperthermia (low certainty), whereas radiant warmer in servo mode compared to manual mode decreased mean body temperature (MBT) (moderate certainty). Use of a plastic bag or wrap (PBW) improved normothermia (low certainty), but with an increased risk of hyperthermia (moderate certainty). Plastic cap improved normothermia (moderate certainty) and when combined with PBW improved MBT (low certainty). Use of a cloth cap decreased moderate hypothermia (low certainty). Though thermal mattress (TM) improved MBT, it increased risk of hyperthermia (low certainty). Heated-humidified gases (HHG) for resuscitation decreased the risk of moderate hypothermia and severe intraventricular hemorrhage (very low to low certainty). None of the interventions was shown to improve survival, but sample sizes were insufficient. Conclusions: DR temperature of ≥23 °C, radiant warmer in manual mode, use of a PBW and a head covering is suggested for preterm newborn infants <34 weeks' gestation. HHG and TM could be considered in addition to PBW provided resources allow, in settings where hypothermia incidence is high. Careful monitoring to avoid hyperthermia is needed

Unraveling Specific Causes of Neonatal Mortality Using Minimally Invasive Tissue Sampling: An Observational Study

Background. Postmortem minimally invasive tissue sampling (MITS) is a potential alternative to the gold standard complete diagnostic autopsy for identifying specific causes of childhood deaths. We investigated the utility of MITS, interpreted with available clinical data, for attributing underlying and immediate causes of neonatal deaths. Methods. This prospective, observational pilot study enrolled neonatal deaths at Chris Hani Baragwanath Academic Hospital in Soweto, South Africa. The MITS included needle core-biopsy sampling for histopathology of brain, lung, and liver tissue. Microbiological culture and/or molecular tests were performed on lung, liver, blood, cerebrospinal fluid, and stool samples. The “underlying” and “immediate” causes of death (CoD) were determined for each case by an international panel of 12–15 medical specialists. Results. We enrolled 153 neonatal deaths, 106 aged 3–28 days. Leading underlying CoD included “complications of prematurity” (52.9%), “complications of intrapartum events” (15.0%), “congenital malformations” (13.1%), and “infection related” (9.8%). Overall, infections were the immediate or underlying CoD in 57.5% (n = 88) of all neonatal deaths, including the immediate CoD in 70.4% (58/81) of neonates with “complications of prematurity” as the underlying cause. Overall, 74.4% of 90 infection-related deaths were hospital acquired, mainly due to multidrug-resistant Acinetobacter baumannii (52.2%), Klebsiella pneumoniae (22.4%), and Staphylococcus aureus (20.9%). Streptococcus agalactiae was the most common pathogen (5/15 [33.3%]) among deaths with “infections” as the underlying cause. Conclusions. MITS has potential to address the knowledge gap on specific causes of neonatal mortality. In our setting, this included the hitherto underrecognized dominant role of hospital-acquired multidrug-resistant bacterial infections as the leading immediate cause of neonatal deaths

UNITY:A low-field magnetic resonance neuroimaging initiative to characterize neurodevelopment in low and middle-income settings

Measures of physical growth, such as weight and height have long been the predominant outcomes for monitoring child health and evaluating interventional outcomes in public health studies, including those that may impact neurodevelopment. While physical growth generally reflects overall health and nutritional status, it lacks sensitivity and specificity to brain growth and developing cognitive skills and abilities. Psychometric tools, e.g., the Bayley Scales of Infant and Toddler Development, may afford more direct assessment of cognitive development but they require language translation, cultural adaptation, and population norming. Further, they are not always reliable predictors of future outcomes when assessed within the first 12–18 months of a child's life. Neuroimaging may provide more objective, sensitive, and predictive measures of neurodevelopment but tools such as magnetic resonance (MR) imaging are not readily available in many low and middle-income countries (LMICs). MRI systems that operate at lower magnetic fields (&lt; 100mT) may offer increased accessibility, but their use for global health studies remains nascent. The UNITY project is envisaged as a global partnership to advance neuroimaging in global health studies. Here we describe the UNITY project, its goals, methods, operating procedures, and expected outcomes in characterizing neurodevelopment in sub-Saharan Africa and South Asia.</p