Plant-Derived Substances for Prevention of Necrotising Enterocolitis: A Systematic Review of Animal Studies.

Inflammation, oxidative injury, and gut dysbiosis play an important role in the pathogenesis of necrotising enterocolitis (NEC). Plant-derived substances have historically been used as therapeutic agents due to their anti-inflammatory, antioxidant, and antimicrobial properties. We aimed to review pre-clinical evidence for plant-derived substances in the prevention and treatment of NEC. A systematic review was conducted using the following databases: PubMed, EMBASE, EMCARE, MEDLINE and Cochrane Library (PROSPERO CRD42022365477). Randomized controlled trials (RCTs) and quasi-RCTs that evaluated a plant-derived substance as an intervention for NEC in an animal model of the illness and compared pre-stated outcomes (e.g., clinical severity, severity of intestinal injury, mortality, laboratory markers of inflammation and oxidative injury) were included. Sixteen studies (n = 610) were included in the systematic review. Ten of the sixteen included RCTs (Preterm rat pups: 15, Mice: 1) reported mortality and all reported NEC-related histology. Meta-analysis showed decreased mortality [12/134 vs. 27/135; RR: 0.48 (95% CI: 0.26 to 0.87); p = 0.02, 10 RCTs] and decreased NEC in the experimental group [24/126 vs. 55/79; RR: 0.34 (95% CI: 0.22 to 0.52); p < 0.001, 6 RCTs]. Markers of inflammation (n = 11) and oxidative stress (n = 13) improved in all the studies that have reported this outcome. There was no significant publication bias for the outcome of mortality. Plant-derived substances have the potential to reduce the incidence and severity of histologically diagnosed NEC and mortality in rodent models. These findings are helpful in guiding further pre-clinical studies towards developing a food supplement for the prevention of NEC in preterm infants.

Young adult outcomes following premature birth: A Western Australian experience.

BACKGROUND: Childhood outcomes following preterm birth are widely published, however long-term adult outcomes are less well described. We aimed to determine the quality of life and burden of co-morbidities experienced by preterm-born young adults in Western Australia. METHODS: A retrospective observational study was conducted. Participants born at 23-33 weeks gestation cared for at King Edward Memorial Hospital during 1990 and 1991 were recruited from a historical birth cohort. Participants completed general, medical and reproductive health questionnaires. Results were compared with contemporaneous cohort data and/or population statistics. RESULTS: Questionnaires were received from 73 young adults aged 28 to 30 years. The majority of respondents completed high school (94.5 %), were employed fulltime (74.0 %) and had close friends and family relationships. Almost all the participants considered their health to be good (94.0 %) and participated in light exercise (90.0 %). Increased hypertension, hypercholesterolaemia, asthma, neuropsychiatric conditions and visual impairment were reported. Depression Anxiety and Stress Scale (DASS-21) scoring identified increased mild anxiety. Increased consultation with healthcare workers and use of prescription medications were reported. CONCLUSION: The group of preterm-born adults surveyed reported a good quality of life, supportive interpersonal relationships and they provided significant contributions to society. They did report increased medical and psychological conditions than the general population.

Causes of and Modifiable Factors Contributing to Neonatal Deaths at Dora Nginza Hospital in the Eastern Cape, South Africa.

Dora Nginza Hospital (DNH) has a neonatal mortality rate higher than global and national averages. In 2015 to 2016 the neonatal mortality rate in South Africa was 18.1/1000 live births compared with 31.3/1000 live births at DNH. A retrospective study was conducted including neonates less than 28 days of life with a birth weight ≥500 g that demised in DNH neonatal unit. The NMR for the study period was 17.7/1000 live births. There were 101 (70.6%) early and 42 (29.4%) late neonatal deaths. Causes of death included infection (n = 47; 32.9%), immaturity-related (n = 42; 29.4%), congenital abnormalities (n = 26; 18.2%), hypoxia (n = 24; 16.8%) and other (n = 4; 2.8%). There were significant associations between cause of death and administrative-related factors (P < .01), health-personnel related factors (P < .001) and patient-related factors (P = .01). Key strategies to be implemented include improving infection prevention and control, appropriate resource allocation, improved attendance and quality of antenatal care, ongoing skills training, and interventions to maintain normothermia.

Study protocol for a population-based observational surveillance study of culture-confirmed neonatal bloodstream infections and meningitis in South Africa: Baby GERMS-SA.

INTRODUCTION: Worldwide, neonatal mortality remains high accounting for 47% of childhood deaths in 2019 and including an estimated 500 000 deaths from neonatal infections. While 42% of global neonatal deaths occur in sub-Saharan Africa, there is limited understanding of population-level burden and aetiology of neonatal infections outside tertiary-level institutions. METHODS AND ANALYSIS: We aim to implement the first population-level surveillance for bloodstream infections and meningitis among neonates aged <28 days in South Africa. Tier 1 will include national surveillance of culture-confirmed neonatal infections at all public-sector hospitals describing infection incidence risk, pathogen profile and antimicrobial susceptibility by institution, province and healthcare level (2014-2021). Tier 2 (nested within tier 1) will be conducted at six regional neonatal units over 12 months, will compare the clinical characteristics of neonates with early-onset and late-onset infections and identify potentially modifiable risk factors for mortality. Through tier 2, we will determine the antimicrobial susceptibility of neonatal pathogens, evaluate the appropriateness of empiric antibiotic prescribing and determine the genomic epidemiology of multidrug resistant bacterial and fungal pathogens. ETHICS AND DISSEMINATION: Ethics clearance was obtained from the Human Research Ethics Committee of the University of the Witwatersrand (M190320). Funding for the study was obtained through a grant from the Bill and Melinda Gates Foundation (OPP1208882). Baby GERMS-SA aims to impact on national policy, resource allocation and neonatal guidelines by describing the national burden of neonatal infections in South Africa. In addition, end-users in neonatal units will benefit from a facility-level dashboard displaying key indicators of the surveillance findings.

HIV exposure and neurodevelopmental outcome in very low birth weight infants in a low-middle income setting: a prospective cohort study.

Neurodevelopmental impairment is common in premature infants. We aimed to describe neurodevelopmental outcomes in very low birth weight (VLBW) infants at 12 months postmenstrual age (PMA) and correlated with maternal HIV status. A single-centre, prospective cohort study was conducted from 1 June 2017 to 31 January 2019 with follow-up to 12 months. In-born infants with birth weight <1500 g were enrolled. Follow-up care was provided to 12 months PMA. Participants provided informed consent and ethics approval was obtained. A total of 279 patients were enrolled of which 84 (30.1%) died before 12 months and 91 (32.6%) were lost to follow-up. Neurodevelopmental assessment was performed on 104 participants. Mean general development quotient was 106.8, 2 (2.0%) patients had moderate-to-severe impairment and 1 (1.0%) mild impairment. HIV exposure was associated with lower developmental scores (104.3 vs. 109.0; p=0.005), whilst antenatal treatment with magnesium sulphate (109.6 vs. 105.2; p=0.01) and breastfeeding (108.0 vs. 104.0; p = 0.03) were associated with higher developmental scores. Neurodevelopmental outcome at 12 months PMA correlated with maternal HIV status. HIV exposure in VLBW infants is associated with lower neurodevelopmental scores at 12 months PMA. Antenatal treatment with magnesium sulphate and breastfeeding are associated with improved outcomes.

IL-6 Predicts Poor Early Post-Natal Growth in Very Low-Birth-Weight Infants in a Low-Middle Income Setting.

BACKGROUND: Extra-uterine growth restriction (EUGR) is common in preterms and may be associated with elevated pro-inflammatory cytokines. OBJECTIVE: Describe postnatal growth in a cohort of very low-birth-weight (VLBW) infants and determine the association of interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-α) in umbilical cord blood with growth at 40 weeks and 12 months postmenstrual age (PMA). METHODS: Single-centre, prospective cohort study conducted from 1 June 2017 to 31 January 2019 with follow-up to 31 March 2020. Infants <1500 g at birth were enrolled, cord blood collected for IL-6 and TNF-α assays and postnatal care, including anthropometry, provided to 12 months PMA. Informed consent and ethics approval were obtained. RESULTS: In total, 279 patients were enrolled; 84 (30.1%) died before 12 months and 91 (32.6%) lost to follow-up. Anthropometry was available for 151 infants at 40 weeks and 105 at 12 months. Z-Scores at 40 weeks for males and females combined were -2.5, -2.1 and -1.2 for weight, length and head circumference. EUGR occurred in 103/113 (91.2%), 98/107 (91.6%) and 70/109 (64.2%) participants for weight, length and head circumference. Elevated IL-6 was associated with restricted weight (56.0 vs. 14.5 pg/ml, p = 0.02) and length (60.4 vs. 7.3 pg/ml, p = 0.01) at 40 weeks. There was no difference in IL-6 at 12 months and no difference in TNF-α at 40 weeks or 12 months. CONCLUSION: The study reports significant EUGR. Elevated IL-6 was associated with growth restriction at 40 weeks but not 12 months PMA.

Umbilical cord interleukin-6 predicts outcome in very low birthweight infants in a high HIV-burden setting: a prospective cohort study.

OBJECTIVES: South Africa has a double burden of high neonatal mortality and maternal HIV prevalence. Common to both is a proinflammatory in utero and perinatal milieu. The aim of this study was to determine cytokine profiles in HIV exposed (HE) and HIV unexposed (HU) very low birthweight (VLBW) infants and to determine whether these were associated with predischarge outcomes. DESIGN: Single-centre, prospective cohort study conducted from 1 June 2017 to 31 January 2019. PATIENTS: Inborn infants with birth weight of <1500 g were enrolled and cord blood was collected for interleukin (IL)-6 and tumour necrosis factor alpha (TNF-α) assays. Participants provided informed consent and ethics approval was obtained. OUTCOME MEASURES: The primary outcome was umbilical cord cytokine levels according to maternal HIV status. Secondary outcomes included death and/or serious neonatal infection, necrotising enterocolitis, intraventricular haemorrhage, periventricular leucomalacia, chronic lung disease and haemodynamically significant patent ductus arteriosus before discharge. RESULTS: A total of 279 cases were included with 269 cytokine assays performed on 122 HEs and 147 HUs. Median IL-6 levels were 53.0 pg/mL in HEs and 21.0 pg/mL in HUs (p=0.07). Median TNF-α levels were 7.2 pg/mL in HEs and 6.5 pg/mL in HUs (p=0.6). There was significantly more late-onset sepsis in the HE group compared with the HU group (41.2% vs 27.9%) (p=0.03). IL-6 levels were significantly higher for those with any adverse outcome (p=0.006) and death and/or any adverse outcome (p=0.0001). TNF-α levels did not differ according to predischarge outcomes. CONCLUSION: There is no significant difference in IL-6 and TNF-α levels in cord blood of HE compared with HU VLBWs. However, IL-6 levels are significantly higher in VLBWs with adverse predischarge outcomes, and VLBW HEs are at increased risk of adverse predischarge outcomes compared with HUs, particularly late-onset sepsis.

Usefulness of a Computerized Reminder System to Improve Inferior Vena Cava Filter Retrieval and Complications.

Inferior vena cava filters (IVCF) are associated with complications which may be due to delayed retrieval. Initiation of an automated reminder system may improve retrieval rates and reduce complications. A computerized reminder system, which provides interactive email reminders after implantation while collecting IVCF use data, was implemented. IVCF retrieval was compared before ("reminder not provided" group) and after ("reminder provided" group) implementation. Data regarding implantation, retrieval, and complications were collected. The primary efficacy outcome was retrieval rate, and the primary safety outcome was indwelling complication rate. Secondary outcomes were time to retrieval and a composite adverse outcome defined as IVCF thrombosis, deep venous thrombosis (DVT), pulmonary embolism, and death. A total of 1,070 IVCF insertions were included, 715 in the "reminder not provided" group and 355 in the "reminder provided" group. Patient age (61 vs 64 years, p = 0.95) and gender (42% vs 40% female, p = 0.55) were similar in the "reminder not provided" and "reminder provided" groups, respectively. In the "reminder provided" group, the retrieval rate was higher (148/297 [49.8%] vs 223/715 [31.2%], p = 0.0001), the indwelling complication rate was lower (30/319 [9.4%] vs 115/715 [16.1%], p = 0.005), and the time to retrieval was shorter (112 days vs 146 days, p = 0.02). The composite adverse outcome occurred less frequently in the "reminder provided" group: (85/355 [23.9%] vs 297/715 [41.5%], p = 0.0001). The system was associated with increased odds of IVCF retrieval (odds ratio 2.56; 95% confidence interval: 1.82 to 3.59; p <0.0001) and reduced odds of the composite adverse outcome (odds ratio 0.72; 95% confidence interval: 0.60 to 0.80; p <0.0001). In conclusion, implementing a computerized email reminder system was associated with higher IVCF retrieval rates, fewer indwelling complications, and shorter dwell times.

Anticoagulation Is Associated with Decreased Inferior Vena Cava Filter-Related Complications in Patients with Metastatic Carcinoma.

OBJECTIVES: Patients with metastatic carcinoma and venous thromboembolism commonly have contraindications to anticoagulation that prompt the use of retrievable inferior vena cava filters. The aim of this study was to compare the pattern of inferior vena cava filter use, anticoagulation management, and development of inferior vena cava filter-related complications in patients with localized versus metastatic carcinoma. METHODS: We conducted a retrospective cohort study of inferior vena cava filter use at a tertiary referral hospital between January 1, 2009, and December 31, 2011. Including only patients with cancer and carcinomas, both metastatic and localized, we recorded the indications for inferior vena cava filter, postfilter practices including anticoagulation use, filter retrieval rates, and filter-related complications. RESULTS: Overall, 154 patients with carcinoma underwent inferior vena cava filter placement. Basic demographics and indication for filter placement were similar between the metastatic and localized groups. Metastatic patients had more filter-related complications (25% vs 11%, P = .03) and underwent filter retrieval less often (31% vs 58%, P = .01). Time to reinitiating anticoagulation was longer in metastatic patients (5.5 vs 2 days, P = .05). In multivariate analysis, metastatic disease was associated with reduced inferior vena cava filter retrieval (odds ratio, 0.3; P = .003). Anticoagulation use was associated with a lower rate of filter-related complications (odds ratio, 0.3; P = .005). CONCLUSIONS: Patients with metastatic carcinoma with an indwelling inferior vena cava filter had a higher rate of filter-related complications, a lower filter retrieval rate, and a greater median time to initiating anticoagulation. When possible, early reinitiation of anticoagulation may reduce inferior vena cava filter-related complications.

Comparison of Inferior Vena Cava Filters Placed at the Bedside via Intravenous Ultrasound Guidance Versus Fluoroscopic Guidance.

BACKGROUND: IVCFs are usually placed under fluoroscopic guidance in dedicated angiography suites. Bedside placement of inferior vena cava filters (IVCF) is possible in patients not suitable for transportation, but data regarding their use are limited. The objective of this study is to compare utilization, procedural outcomes, complications, and long-term patient outcomes associated with bedside placement of IVCFs using intravascular ultrasound (IVUS) and fluoroscopic placement of IVCF. METHODS: All patients receiving IVCF between January 2009 and December 2011 at a tertiary care institution were retrospectively identified. Data regarding patient characteristics, IVCF indications, complications, and outcomes were collected, and comparisons were made between patients receiving fluoroscopic-guided and IVUS-guided bedside IVCF. RESULTS: There were 117 bedside and 571 fluoroscopic-guided IVCF placed during this period. Patients receiving bedside IVCF were younger (50.8 vs. 60.7 years, P < 0.001), less often had malignancy (22.2% vs. 42.6%, P < 0.001), and received prophylactic filters more commonly (59.9% vs. 29.9%, P < 0.001). Placement-related complications occurred in 4.3% and 0.6%, respectively (bedside IVCF: 4 malpositions, 1 severe tilt; fluoroscopic-guided IVCF: 1 malposition, 1 severe tilt, P = 0.01). Indwelling IVCF-related complications occurred equally during median follow-up of 463 and 488 days, respectively (deep vein thrombosis: 13.7% vs. 13.3%, P = 0.92; pulmonary embolism: 5.1% vs. 4.0%, P = 0.61; filter thrombosis: 3.4% vs. 3.9%, P = 0.82). Time to indwelling complication was similar between groups (74 vs. 127 days, P = 0.29). CONCLUSIONS: Bedside placement of IVUS-guided IVCF is safe, but with higher procedural complications when compared with fluoroscopic placement. Long-term indwelling complications are similar between IVCF placed via bedside IVUS guidance and fluoroscopic approach.

Inferior vena cava filter usage, complications, and retrieval rate in cancer patients.

BACKGROUND: Venous thromboembolism contributes significantly to morbidity and mortality in cancer patients. Because cancer patients frequently have contraindications to anticoagulation, inferior vena cava filters are commonly placed. The use, safety, and retrieval of retrievable inferior vena cava filters in cancer patients have not been well studied. METHODS: A retrospective review of retrievable inferior vena cava filter use at a tertiary referral hospital was conducted between January 1, 2009 and December 31, 2011. Indications for inferior vena cava filter placement, anticoagulation practices, complications, filter retrieval, and patient outcomes were analyzed for patients with and without active cancer and for cancer subtypes, including localized and metastatic cases. RESULTS: Of 666 patients receiving retrievable inferior vena cava filters during this time period, 247 (37.1%) had active cancer. Of these, 151 (22.7%) had carcinoma, 92 (13.8%) had sarcoma, and 115 (17.3%) had metastatic disease. Overall, follow-up was available for a median of 401.0 (interquartile range: 107.5-786.5) days. Indwelling filter-related complications occurred in 19.8% of patients without cancer and 17.7% with an active cancer (P = .50). Patients with cancer were less likely to have the filter retrieved (28.0% vs 42.0%, P < .001). In multivariable analysis, cancer was not associated with filter-related complications but was associated with a lower rate of filter retrieval. CONCLUSIONS: In a modern cohort of patients undergoing retrievable inferior vena cava filter placement, active diagnosis of cancer is not associated with a significant increase in filter-related complications, but is associated with a reduced rate of filter retrieval.

Effect of delayed inferior vena cava filter retrieval after early initiation of anticoagulation.

Retrievable inferior vena cava filters (IVCFs) were designed to provide temporary protection from pulmonary embolism in high-risk situations. However, little is known about their effectiveness, and many remain permanently implanted, leading to potential complications. The aim of this study was to determine patient characteristics, indications for IVCF placement, retrieval rates, complications, and post-IVCF anticoagulation (AC) practices in patients who have received IVCFs. A retrospective review of IVCF use by 3 specialty groups from January 1, 2009, to December 31, 2011, was conducted at a tertiary referral center. Indications for IVCF, procedural success and complications, post-IVCF AC practices, and patient outcomes were assessed. Seven hundred fifty-eight IVCFs were placed. Follow-up was available for 688 patients (90.7%) at a median of 342.0 days (interquartile range 81.5 to 758.0). Indications for IVCF placement included contraindication to AC in the presence of acute venous thromboembolism (n = 287 [41.7%]) and prophylaxis (n = 235 [34.2%]). Insertion-related complications occurred in 28 patients (4.1%). After IVCF placement, adequate AC was initiated in 454 patients (66.0%) <3.0 days (interquartile range 0 to 13.0) after insertion, but the overall retrieval rate was only 252 of 688 (36.6%) within a median of 134.0 days (interquartile range 72.50 to 205.8). Significant IVCF-related complications occurred in 122 patients (17.7%) within 32 days (interquartile range 13.0 to 116.8). The most common complication (72 of 131 [55.0%]) was deep vein thrombosis. In conclusion, in a large, modern cohort of patients receiving retrievable IVCFs for a variety of indications by various specialties, IVCF insertion remains safe. However, many patients have IVCF-related complications, and often, even when IVCFs are retrieved, there is a delay between AC and retrieval. Quality improvement initiatives that facilitate the expeditious retrieval of IVCF are needed.

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.

Growth of a cohort of very low birth weight infants in Johannesburg, South Africa.

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.