Stacks.cdc.gov



Supplementary material: Unravelling specific causes of neonatal mortality using minimal invasive tissue sampling: An observational pilot study.Methods supplementStudy site and populationAlthough categorized as a middle income country, wealth distribution is highly disparate in South Africa, with 19% of households surviving on less than $2 per day. The majority of Black Africans are among the lowest income categories, including the majority of the 40% unemployed workforce. Soweto is the largest urban settlement in South Africa, constituted almost exclusively of Black Africans, with a high unemployment rate but reasonable access to public health facilities. The population of Soweto is estimated at 1.2 million, including an under-5 population of 128,000 and annual birth cohort of 28,000. The majority (99%) of deliveries in Soweto occur at public health facilities, where health care is provided at no cost to all pregnant women and children by the State. Three quarters of all births in the public health sector in Soweto occur at Chris Hani Baragwanath Academic Hospital (CHBAH) and the others at one of 7 midwife operated units (MOUs). At the time of the study, CHBAH was the only public hospital in Soweto.Furthermore, there is a low threshold for referrals from the MOUs to the hospital if any signs of imminent obstetric complications are observed before or during labour, including women in preterm labour . Also, there is a low threshold for referring ill neonates from the surrounding primary health care clinics to CHBAH for further management. Facilities at CHBAH include a neonatal intensive care unit where invasive and non-invasive mechanical ventilator support is available. Due to resource constrains, the policy at CHBAH is to limit invasive mechanical ventilatory support to newborns weighing at least 1,000 grams at birth, whilst non-invasive mechanical ventilation such as continuous positive airway pressure is available to those weighing <1,000 grams if clinically indicated. The prevalence of HIV among pregnant women in Soweto has remained unchanged at 28-29% over the past decade, however, improved mother-to-child HIV prevention strategies have resulted in HIV transmission rates to HIV-exposed infants declining from 8% in 2004 to 1.1% by 2015 ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1097/INF.0000000000001840","ISBN":"0000000000","ISSN":"0891-3668","PMID":"29189609","abstract":"BACKGROUND:South Africa represents the first high-burden setting to introduce routine virological testing at birth within its early infant diagnosis program, implemented in June 2015. National HIV birth testing coverage, intra-uterine transmission rates and case rates for the first year since introduction of universal birth testing are reported.METHODS:HIV polymerase chain reaction (PCR) test data from June 2015 to May 2016 were extracted from the National Health Laboratory Service&apos;s central data repository by year, month, age, result and geographic location. Birth testing was defined as all HIV PCR tests performed at &lt;7 days of life; coverage as the proportion of all HIV-exposed neonates born who were tested at birth; estimated intra-uterine transmission rate as the percentage of HIV PCR positive tests in HIV-exposed neonates tested and case rates as the number of HIV PCR positive tests per 100 000 total live births.RESULTS:Between June 2015 to May 2016, the South African national monthly birth testing coverage increased from 39% (8 636 tests) to 93% (20 479 tests). During this period the number of positive tests at birth increased from 114 to 234 per month, equating to a national intra-uterine transmission rate of 1.1% and a birth case rate of 247 per 100 000 live births.CONCLUSION:Universal birth testing for all HIV-exposed neonates is rapidly being achieved in South Africa, facilitating earlier detection of intra-uterine infected neonates. However, the successful linkage into care of HIV-infected neonates and their treatment outcomes remain to be assessed.","author":[{"dropping-particle":"","family":"Moyo","given":"Faith","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Haeri Mazanderani","given":"Ahmad","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Barron","given":"Peter","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bhardwaj","given":"Sanjana","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Goga","given":"Ameena Ebrahim","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pillay","given":"Yogan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sherman","given":"Gayle G.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"The Pediatric Infectious Disease Journal","id":"ITEM-1","issued":{"date-parts":[["2018"]]},"title":"Introduction of Routine HIV Birth Testing in the South African National Consolidated Guidelines","type":"article-journal"},"uris":[""]}],"mendeley":{"formattedCitation":"[1]","plainTextFormattedCitation":"[1]","previouslyFormattedCitation":"[1]"},"properties":{"noteIndex":0},"schema":""}[1]. The neonatal mortality rate in Soweto, based on a longitudinal cohort study from 2011 was estimated to be 22?per 1000 live births (unpublished data from Matflu study) ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1056/NEJMc1412050","ISSN":"0028-4793","author":[{"dropping-particle":"","family":"Madhi","given":"Shabir A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cutland","given":"Clare L.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kuwanda","given":"Locadiah","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Weinberg","given":"Adriana","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hugo","given":"Andrea","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Jones","given":"Stephanie","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"V.","family":"Adrian","given":"Peter","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"van","family":"Niekerk","given":"Nadia","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Treurnicht","given":"Florette","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ortiz","given":"Justin R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Venter","given":"Marietjie","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Violari","given":"Avy","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Neuzil","given":"Kathleen M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sim?es","given":"Eric A.F.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Klugman","given":"Keith P.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Nunes","given":"Marta C","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Team*","given":"for the Maternal Flu Trial (Matflu)","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"New England Journal of Medicine","id":"ITEM-1","issue":"24","issued":{"date-parts":[["2014","12","10"]]},"note":"doi: 10.1056/NEJMc1412050","page":"2340","publisher":"Massachusetts Medical Society","title":"Influenza Vaccination of Pregnant Women and Protection of Their Infants","type":"article-journal","volume":"371"},"uris":[""]}],"mendeley":{"formattedCitation":"[2]","plainTextFormattedCitation":"[2]","previouslyFormattedCitation":"[2]"},"properties":{"noteIndex":0},"schema":""}[2], which was higher than the national rate of 14 per 1000 live births estimated for South Africa in 2015 ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/S0140-6736(16)31593-8","ISBN":"1474-547X (Electronic) 0140-6736 (Linking)","ISSN":"1474547X","PMID":"25164069","abstract":"Background Despite remarkable progress in the improvement of child survival between 1990 and 2015, the Millennium Development Goal (MDG) 4 target of a two-thirds reduction of under-5 mortality rate (U5MR) was not achieved globally. In this paper, we updated our annual estimates of child mortality by cause to 2000–15 to reflect on progress toward the MDG 4 and consider implications for the Sustainable Development Goals (SDG) target for child survival. Methods We increased the estimation input data for causes of deaths by 43% among neonates and 23% among 1–59-month-olds, respectively. We used adequate vital registration (VR) data where available, and modelled cause-specific mortality fractions applying multinomial logistic regressions using adequate VR for low U5MR countries and verbal autopsy data for high U5MR countries. We updated the estimation to use Plasmodium falciparum parasite rate in place of malaria index in the modelling of malaria deaths; to use adjusted empirical estimates instead of modelled estimates for China; and to consider the effects of pneumococcal conjugate vaccine and rotavirus vaccine in the estimation. Findings In 2015, among the 5·9 million under-5 deaths, 2·7 million occurred in the neonatal period. The leading under-5 causes were preterm birth complications (1·055 million [95% uncertainty range (UR) 0·935–1·179]), pneumonia (0·921 million [0·812 ?1·117]), and intrapartum-related events (0·691 million [0·598 ?0·778]). In the two MDG regions with the most under-5 deaths, the leading cause was pneumonia in sub-Saharan Africa and preterm birth complications in southern Asia. Reductions in mortality rates for pneumonia, diarrhoea, neonatal intrapartum-related events, malaria, and measles were responsible for 61% of the total reduction of 35 per 1000 livebirths in U5MR in 2000–15. Stratified by U5MR, pneumonia was the leading cause in countries with very high U5MR. Preterm birth complications and pneumonia were both important in high, medium high, and medium child mortality countries; whereas congenital abnormalities was the most important cause in countries with low and very low U5MR. Interpretation In the SDG era, countries are advised to prioritise child survival policy and programmes based on their child cause-of-death composition. Continued and enhanced efforts to scale up proven life-saving interventions are needed to achieve the SDG child survival target. Funding Bill & Melinda Gates Foundation, WHO.","author":[{"dropping-particle":"","family":"Liu","given":"Li","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Oza","given":"Shefali","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hogan","given":"Dan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Chu","given":"Yue","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Perin","given":"Jamie","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zhu","given":"Jun","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lawn","given":"Joy E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cousens","given":"Simon","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mathers","given":"Colin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Black","given":"Robert E.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"The Lancet","id":"ITEM-1","issued":{"date-parts":[["2016"]]},"title":"Global, regional, and national causes of under-5 mortality in 2000–15: an updated systematic analysis with implications for the Sustainable Development Goals","type":"article-journal"},"uris":[""]}],"mendeley":{"formattedCitation":"[3]","plainTextFormattedCitation":"[3]","previouslyFormattedCitation":"[3]"},"properties":{"noteIndex":0},"schema":""}[3].Minimal invasive tissue sampling (MITS) procedures:The MITS was undertaken either by a medical doctor or professional nurse assisted by research assistants. Study staff observed standardised procedures, including use of personal protective equipment, and other precautionary measures to avoid contamination of samples. The corpse was first washed using water, then disinfected using 70% ethanol to mitigate contamination of the samples obtained. Using the Bard Monopty 14-gauge disposable core biopsy needles (Bard Peripheral Vascular Inc, Temple, USA), the chest wall was punctured through the 6th intercostal space posteriorly and angling the needle towards the different lung zones. Lung tissue was collected from the upper, middle and lower zones. The left and the right lung tissue samples were processed separately. Liver tissue from the left and right lobes was collected through a puncture in the 10th intercostal space mid-axillary line and angled towards the xiphoid process to reach the left lobe. Brain tissue was collected using the Bard Max-core 18-gauge disposable biopsy needle (Bard Peripheral Vascular Inc, Temple, USA) through either a transnasal approach (through the cribriform plate of the roof of the nose) or through the anterior fontanelle. Tissue samples for culture were placed in sterile normal saline containing jars, and those for histology in 10% neutral buffered formalin containing jars. In all instances, the first tissue biopsy sample was sent for culture, the second for molecular test (lung only) and subsequent six core samples obtained were sent for histopathology examination. Bacterial culture and antibiotic susceptibility testing methodsBlood was collected following decontamination of the skin surface using alcohol solution and through cardiac puncture or by supraclavicular approach into the left subclavian vessel and was placed into an EDTA tube and then 0.5-5 ml inoculated into Bact/ALERT PF Plus bottle and evaluated using the BacT/Alert microbial system (BioMerieux, Marcy l’Etoile, France) at the National Health Laboratory Services (NHLS) at CHBAH. All positive cultures from the various sample types were Gram stained and further identified using standard manual methods. Cerebrospinal fluid was collected through a puncture into the cisterna magna posteriorly and placed in sterile tube and cultured using culture plates. Gram staining, culture identification and antibiotic susceptibility testing were done according to clinical laboratory standard institute (CLSI) guidelines following culture.Molecular diagnostic testingLiver and lung tissues for molecular testing were collected in the Qiagen lysis buffer. The biopsies were macerated in 600?L of sterile saline and subsequently mixed with a 25mg/mL proteinase K in 20mM Tris-HCl, pH 8.3, stock solution in a 1:1 ratio. The biopsy containing solution was incubated at 55oC for 15 minutes and vortexed every 5 minutes. Total nucleic acids were extracted from 400?L of the lung biopsy solution and from 200?L of the whole blood and cerebral spinal fluid samples using the NucleiSens EasyMag extraction system as per manufactures instructions (BioMerieux, Marcy l'Etoile, France) using the Specific B off-board extraction protocol. Whereas, nucleic acids were extracted from 400?L of stool samples using the NucleiSens EasyMag extraction system as per manufactures instructions (BioMerieux, Marcy l'Etoile, France) using the standard on-board extraction protocol.The total nucleic acid specimens were evaluated with FTD multiplexed real-time PCR assays according to manufactures instructions. RT-PCR for all FTD kits were performed using the Applied Biosystems 7500? instruments (Applied Biosystems, Foster City, CA) using the following cycling conditions: 50oC for 15 minutes, 95oC for 10 minutes followed by 40 cycles of 95oC for 8 seconds and then 60oC for 34 seconds. The kits used for testing of different samples and the target organism probes included in the individual kits is outlined in Supplementary Table 1. Each assay included template and non-template controls as well as external and internal controls supplied with the kits. A cycle threshold (Ct) cut-off above 35 Ct was implemented for all FTD kits and only those with Ct<35 were considered as “positive” provided the run passed the controls quality criteria.Determination of Cause of Death (DeCoDE) processThe DeCoDE panel convened from 26th March to 5th April 2017 in South Africa and reviewed each individual case. Following a summarised presentation of each case by either SAM or RC, the panel under the Chair of either CW or SD attributed the CoD. All the MITS results and hospital medical records were made available to the DeCoDE panel. The CoD attribution was based on the WHO International Classification of Diseases, 10th revision (ICD-10) for deaths during the perinatal period (ICD-PM) ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1038/321326a0","ISBN":"9789241549752","ISSN":"0028-0836","URL":"","abstract":"The Giotto space probe's neutral mass spectrometer experiment has determined the abundances and the chemical, elemental and isotopic compositions of gases and low energy ions in the coma of comet Halley. Preliminary results show water predominating, at about 80 percent by volume, with a density of 4.7 x 10 to the 7th molecules/cu cm at 1000 km and a photodestruction scale length of 39,000 km. Limits on the abundances of CO2, NH3 and CH4 relative to H2O are also obtained. An ion temperature change observation indicates a contact surface location at 47,000 + or - 200 km.","accessed":{"date-parts":[["2018","8","29"]]},"author":[{"dropping-particle":"","family":"World Health Organization","given":"","non-dropping-particle":"","parse-names":false,"suffix":""}],"id":"ITEM-1","issued":{"date-parts":[["2016"]]},"page":"1-88","title":"The WHO application of ICD-10 to deaths during the perinatal period","type":"webpage"},"uris":[""]}],"mendeley":{"formattedCitation":"[4]","plainTextFormattedCitation":"[4]","previouslyFormattedCitation":"[4]"},"properties":{"noteIndex":0},"schema":""}[4], using a modified standard CoD reporting template; Supplementary Table 2. This included recording the “underlying condition” considered to have initiated the chain of events which led to or predisposed to the death. Furthermore, antecedentg conditions and the ultimate event which led to death (“immediate cause”) were also evaluated for. The perinatal deaths per ICD-10 guidelines are classified in a 3-stage process: 1) Firstly, neonatal deaths are grouped according to timing (early neonatal: up to day 7 of postnatal life; or late neonatal: days 8–28 of postnatal life), 2) The main cause of perinatal death is assigned and grouped according to the ICD-PM groupings. 3. The main maternal condition at the time of perinatal death is assigned and grouped according to the ICD-PM groupings, if applicable. Maternal data were unavailable for analyses in our study.As an example, a prematurely born neonate who died following a hospital-acquired infection, would have “prematurity and its complications” attributed as the “underlying” CoD and nosocomial sepsis as the “immediate” CoD. In contrast, a prematurely born baby dying from invasive bacterial infection on Day 0 of life, could have the underlying (and immediate) CoD attributed to the invasive bacterial disease if the infection was considered to have possibly precipitated the preterm birth. The ultimate decision regarding the underlying and immediate causes in cases that were not straightforward, was taken by consensus of the panel members after discussion of each individual case.The DeCoDE panel agreed to listing up to two “immediate” (i.e. co-immediate) CoD if there were similar levels of evidence for different diseases having contributed to the death, including infectious causes in which the individual role of different pathogens could not be prioritised. An example of this is a two-day-old neonate with co-immediate CoD attributed to histologically confirmed cytomegalovirus (CMV) pneumonitis and nosocomial methicillin resistant Staphylococcus aureus (MRSA) with the underlying CoD attributed to “LBW/prematurity complications”. In the event that the panel determined a single pathogen to be the CoD, despite multiple putative pathogens being identified, the other pathogens were listed either as antecedent causes or as a possible “contributing” factors but not directly implicated in the causal pathway of the death. The final CoD forms were ICD-10 coded by a medical doctor (FS). Consensus was reached for all cases on the CoD by the DeCoDe panel.Results supplement Supplementary table 1: Type of post-mortem specimen collected, location of testing and the type of testing undertaken on the collected tissuesSpecimen typeLabEarly Neonatal deaths (<72hours age)Late Neonatal deaths(3 -28 days age)BloodNHLS-Micro1MC&S4MC&SRMPRU2 FTD5 -Sepsis kit6FTD Sepsis kitCerebrospinal fluidNHLS-MicroMC&SMC&SRMPRUFTD Neuro-97 and Sepsis kitFTD Neuro-9 and Sepsis kitLung tissueNHLS-MicroMC&SMC&SNHLS-Histo3HistologyHistologyRMPRUFTD Neuro-9 and Sepsis kitFTD Neuro-9, Sepsis and Resp-338 panel kitLiver tissueNHLS-MicroMC&SMC&SNHLS-HistoHistologyHistologyRMPRUArchiveArchiveBrain tissueNHLS-MicroMC&SMC&SNHLS-HistoHistologyHistologyRMPRUArchiveArchiveRectal swabRMPRUFTD-Gastro kit9FTD-Gastro kit1NHLS-micro: National Health Laboratory Service microbiology department. 2RMPRU: Respiratory and Meningeal Pathogens Research Unit laboratory. 3NHLS-Histo: National Health Laboratory Service, Anatomical Pathology department. 4MC&S= Microscopy, culture and antibiotic susceptibility testing5FTD=Fast Track Diagnostics multiple PCR kits. 6FTD sepsis kit PCR probes for Cytomegalovirus, Group B streptococcus (Streptococcus agalactiae), Listeria monocytogenes, Escherichia coli, Staphylococcus aureus, Chlamydia trachomatis and Ureaplasma urealyticum/parvum7FTD Neuro-9 PCR probes for: cytomegalovirus (CMV), Epstein-Barr Virus, Adenovirus, herpes simplex virus 1 and 2, varicella-zoster virus, enterovirus, parechovirus, human herpes virus 6 and 7 and parvovirus B19.8FTD Resp-33 PCR panel probes for: cytomegalovirus, influenza C, influenza A, influenza B, rhinovirus, coronavirus NL63, 229E, OC43, HKU1, parainfluenza 1, 2, 3, 4, human metapneumovirus A/B, bocavirus, respiratory syncytial virus A/B (RSV), adenovirus, enterovirus, parechovirus, Mycoplasma pneumoniae Chlamydia pneumoniae, Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenza, Pneumocystis jirovecii, Haemophilus influenzae type B, Bordetella spp. (except Bordetella parapertussis), Moraxella catarrhalis, Klebsiella pneumoniae, Legionella spp. and Salmonella spp.9FTD-Gastro kit: Probes for Enterohemorrhagic verotoxin producing E. coli; Norovirus G1 and G2; Adenovirus; Astrovirus; Sapovirus; Campylobacter; Salmonella sp.; Yersinia enterocolitica; Cryptosporidium spp, Rotavirus, Clostridium difficile, Shigella/Enteroinvasive E.coli, Entamoeba histolytica, Giardia lambliaSupplementary Table 2: Template of cause of death form completed by the Determination of Cause of Death (DeCoDe) panel.center-46482000left-46418500Supplementary Table 3: Sample adequacy for histological evaluationSampleAdequateAutolysedInadequateSuboptimalSumLiver137 (90.7)2 (1.3)8 (5.3)4 (2.6)151 (100)Left lung96 (64)1 (0.7)35 (23.3)18 (12)150 (100)Right lung104 (68.4)1 (0.7)28 (18.4)19 (12.5)152 (100)Brain127 (84.1)0 (0)14 (9.3)10 (6.6)151 (100)Total464 (76.8)4 (0.6)85 (14.1)51 (8,4)604 (100)Supplementary Table 4a: Level of certainty for underlying cause of death attribution by the DeCoDe panelUnderlying Cause of Death (ICD-PM)aNLevel of CertaintyLevel 1(Confident)Level 2(Probable)Level 3(Uncertain)Congenital malformations, deformations and chromosomal disorder (N1)2017 (85.0%)2 (10.0%)1 (5.0%)Complications of intrapartum events (N4)2319 (82.6%)4 (17.4%)0 (0.0%)Convulsions and disorders of cerebral status (N5)10 (0.0%)1 (100%)0 (0.0%)Infection (N6)159 (60.0%)5 (33.3%)1 (6.7%)Respiratory and cardiovascular disorders (N7)55 (100%)0 (0.0%)0 (0.0%)Other neonatal conditions (N8)74 (57.1%)3 (42.9%)0 (0.0%)Low birth weight/prematurity complications (N9)8181 (100.0%)0 (0.0%)0 (0.0%)Neonatal death of unspecified cause (N11)10 (0.0%)0 (0.0%)1 (100%)Total153135 (88.2%)15 (9.8%)3 (2.0%)a WHO ICD10 Perinatal Mortality (ICD-PM)Supplementary Table 4b: Level of certainty for immediate cause of death attribution by the DeCoDe panel.Immediate Cause of DeathNLevel of CertaintyLevel 1Level 2Level 3Communicable (Infections)MeningitisCommunity-acquired31 (33.3%)1 (33.3%)1 (33.3%)Nosocomial-acquired55 (100%)0 (0.0%)0 (0.0%)PneumoniaCommunity-acquired 55 (100%)0 (0.0%)0 (0.0%)Nosocomial-acquired 2827 (96.4%)1 (3.4%)0 (0.0%)SepsisCommunity-acquired118 (72.7%)3 (27.3%)0 (0.0%)Nosocomial-acquired3230 (96.8%)1 (3.1%)1 (3.1%)Pulmonary mucormycosis11 (100%)0 (0.0%)0 (0.0%)Non-communicableAcute kidney failure11 (100%)0 (0.0%)0 (0.0%)Acquire hydrocephalus of the newborn11 (100%)0 (0.0%)0 (0.0%)Birth asphyxia33 (100%)0 (0.0%)0 (0.0%)Congenital malformations77 (100%)0 (0.0%)0 (0.0%)Hyaline membrane disease1413 (92.9%)1 (7.1%)0 (0.0%)Hypoxic ischaemic encephalopathy1814 (77.8%)4 (22.2%)0 (0.0%)Intrauterine hypoxia65 (83.3%)1 (16.7%)0 (0.0%)Intraventricular Haemorrhage44 (100%)0 (0.0%)0 (0.0%)Kernicterus32 (66.7%)1 (33.3%)0 (0.0%)Necrotising Enterocolitis22 (100%)0 (0.0%)0 (0.0%)Persistent foetal circulation43 (75.0%)1 (25.0%)0 (0.0%)Pneumothorax11 (100%)0 (0.0%)0 (0.0%)Pulmonary haemorrhage11 (100%)0 (0.0%)0 (0.0%)Shock11 (100%)0 (0.0%)0 (0.0%)Subarachnoid haemorrhage11 (100%)0 (0.0%)0 (0.0%)Vascular disorders of intestines11 (100%)0 (0.0%)0 (0.0%)Total153137 (89.5%)14 (9.2%)2 (1.3%)Supplementary Table 5: Prevalence of antibiotic resistance of bacteria cultured post-mortem attributed to be either the immediate or underlying cause of deathAntimicrobialAcinetobacter baumanniiEscherichia coliStreptococcus agalactiaeKlebsiella pneumoniaeStaphylococcus aureusEnterobacter cloacaeEnterococcus faecalis/faeciumAmikacin37/43 (86.0%)0/8 (0.0%)ND1/25 (4.0%)ND0/6 (0.0%)NDAmoxicillin.clavulanic.acidND2/8 (25.0%)ND21/25 (84.0%)ND7/8 (87.5%)NDAmpicillin.amoxicillinND8/8 (100%)ND25/25 (100%)ND8/8 (100%)7/14 (50.0%)CefazolinND1/8 (12.5%)ND21/26 (80.8%)ND7/8 (87.5%)NDCefepime41/47 (87.2%)0/8 (0.0%)ND19/26 (73.1%)ND2/7 (28.6%)NDCefotaxime, ceftriaxoneND0/8 (0.0%)0/3 (0.0%)17/23 (73.9%)ND3/8 (37.5%)NDCefoxitinND0/8 (0.0%)ND1/25 (4.0%)ND7/8 (87.5%)NDCeftazidime42/47 (89.4%)10/8 (0.0%)ND20/26 (76.9%)ND3/8 (37.5%)NDCefuroxime, parenteralND0/8 (0.0%)ND21/26 (80.8%)ND4/8 (50.0%)NDChloramphenicolND0/8 (0.0%)0/3 (0.0%)8/26 (30.8%)13/15 (86.7%)2/7 (28.6%)NDCiprofloxacin46/47 (97.9%)24/8 (50.0%)ND4/24 (16.7%)111/14 (78.6%)0/8 (0.0%)NDClindamycinNDND0/3 (0.0%)ND2/15 (13.3%)NDNDCloxacillinNDNDNDND13/15 (86.7%)NDNDColistin0/47 (0%)NDNDNDNDNDNDErtapenemND0/8 (0.0%)ND0/26 (0.0%)ND0/8 (0.0%)NDErythromycin.azithromycinNDND0/3 (0.0%)ND13/15 (86.7%)NDNDFusidic_acidNDNDNDND0/15 (0.0%)NDNDGentamicin47/47 (100%)4/8 (50.0%)ND22/26 (84.6%)13/15 (86.7%)3/7 (42.9%)NDGentamicin, high.level.resistanceNDNDNDNDNDND7/15 (46.7%)Imipenem46/46 (100%)0/8 (0.0%)ND0/26 (0.0%)ND0/8 (0.0%)NDLinezolidNDND0/3 (0.0%)ND1/15 (6.7%)ND0/15 (0.0%)Meropenem46/46 (100%)0/8 (0.0%)ND0/25 (0.0%)ND0/8 (0.0%)NDNalidixic acidND5/8 (62.5%)ND3/26 (11.5%)ND1/8 (12.5%)NDPenicillin.ampicillinNDND0/3 (0.0%)ND15/15 (100%)NDSNDPiperacillin.tazobactam45/45 (100%)0/8 (0.0%)ND8/26 (30.8%)3ND0/8 (0.0%)NDRifampicinNDNDNDND0/15 (0.0%)NDNDStreptomycin, high.level.resistanceNDNDNDNDNDND2/15 (13.3%)Tobramycin39/46 (84.8%)13/8 (37.5%)ND18/26 (69.2%)ND2/8 (25.0%)NDTrimethoprim.sulfamethoxazole46/46 (100%)6/8 (75.0%)ND22/26 (84.6%)13/15 (86.7%)3/8 (37.5%)NDVancomycinNDND0/3 (0.0%)ND0/15 (0.0%)ND0/16 (0.0%)1One intermediate resistance. 2Two intermediate resistance. 3Four intermediate resistance. ND= not doneReferencesADDIN Mendeley Bibliography CSL_BIBLIOGRAPHY 1. Moyo F, Haeri Mazanderani A, Barron P, et al. Introduction of Routine HIV Birth Testing in the South African National Consolidated Guidelines. Pediatr Infect Dis J 2018; 2. Madhi SA, Cutland CL, Kuwanda L, et al. Influenza Vaccination of Pregnant Women and Protection of Their Infants. N Engl J Med 2014; 371:2340. Available at: . Liu L, Oza S, Hogan D, et al. Global, regional, and national causes of under-5 mortality in 2000–15: an updated systematic analysis with implications for the Sustainable Development Goals. Lancet 2016; 4. World Health Organization. The WHO application of ICD-10 to deaths during the perinatal period. 2016: 1–88. Available at: . Accessed 29 August 2018. ................
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