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.

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.

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.

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.