Effect of oropharyngeal colostrum therapy on neonatal sepsis in preterm neonates: A systematic review and meta-analysis.

Various studies have shown that oropharyngeal colostrum application (OPCA) is beneficial to preterm neonates. We performed a systematic review and meta-analysis to assess whether OPCA reduces the incidence of culture-proven neonatal sepsis in preterm neonates. Randomized controlled trials comparing OPCA with placebo or standard care in preterm neonates were included. Medline, Embase, Web of Science, Cumulated Index to Nursing and Allied Health Literature, Scopus, and CENTRAL were searched for studies published up to June 15, 2023. We used the Cochrane Risk of Bias tool, version 2, for risk of bias assessment, the random-effects model (RevMan 5.4) for meta-analysis, and Gradepro software for assessing the certainty of evidence. Twenty-one studies involving 2393 participants were included in this meta-analysis. Four studies had a low risk of bias, whereas seven had a high risk. Oropharyngeal colostrum significantly reduced the incidence of culture-proven sepsis (18 studies, 1990 neonates, risk ratio [RR]: 0.78, 95% confidence interval [95% CI]: 0.65, 0.94), mortality (18 studies, 2117 neonates, RR: 0.73, 95% CI: 0.59, 0.90), necrotizing enterocolitis (NEC) (17 studies, 1692 neonates, RR: 0.59, 95% CI: 0.43, 0.82), feeding intolerance episodes (four studies, 445 neonates, RR: 0.59, 95% CI: 0.38, 0.92), and the time to full enteral feeding (19 studies, 2142 neonates, mean difference: -2 to 21 days, 95% CI: -3.44, -0.99 days). There was no reduction in intraventricular hemorrhage, retinopathy of prematurity, bronchopulmonary dysplasia, ventilator-associated pneumonia, neurodevelopmental abnormalities, hospital stay duration, time to full oral feeding, weight at discharge, pneumonia, and duration of antibiotic therapy. The certainty of the evidence was high for the outcomes of culture-positive sepsis and mortality, moderate for NEC, low for time to full enteral feeding, and very low for feeding intolerance. OPCA reduces culture-positive sepsis and mortality (high certainty), NEC (moderate certainty), and time to full enteral feeding (low certainty) in preterm neonates. However, scarcity of data from extremely premature infants limits the generalizability of these results to this population.

The Multi-Component Causes of Late Neonatal Sepsis-Can We Regulate Them?

Elucidating the mechanisms of bacterial translocation is crucial for the prevention and treatment of neonatal sepsis. In the present study, we aimed to evaluate the potential of lactoferrin to inhibit the development of late-onset blood infection in neonates. Our investigation evaluates the role of key stress factors leading to the translocation of intestinal bacteria into the bloodstream and, consequently, the development of life-threatening sepsis. Three stress factors, namely weaning, intraperitoneal administration of Gram-positive cocci and oral intake of Gram-negative rods, were found to act synergistically. We developed a novel model of rat pups sepsis induced by bacterial translocation and observed the inhibition of this process by supplementation of various forms of lactoferrin: iron-depleted (apolactoferrin), iron-saturated (hololactoferrin) and manganese-saturated lactoferrin. Additionally, lactoferrin saturated with manganese significantly increases the Lactobacillus bacterial population, which contributes to the fortification of the intestinal barrier and inhibits the translocation phenomenon. The acquired knowledge can be used to limit the development of sepsis in newborns in hospital neonatal intensive care units.

Berberine Attenuates Neonatal Sepsis in Mice By Inhibiting FOXA1 and NF-κB Signal Transduction Via the Induction of MiR-132-3p.

Neonatal sepsis (NS) is a severe syndrome in newborns that is induced by infections, and the initiation and development of NS are closely associated with the function of miRs. In the current study, the effects of berberine, which is a functional component in traditional Chinese medicine (TCM), against NS were assessed by focusing on the interaction of berberine with miR-132-3p-mediated signaling. An NS model was induced using cecal slurry (CS) in vivo and LPS in vitro, and berberine treatment was applies. The changes in survival rate, intestinal structure, and systemic inflammation in mice and the viability, apoptosis, and inflammatory response in intestinal cells were measured. At the molecular level, miR-132-3p levels and the activities of the FOXA1 and NF-κB pathways were analyzed. The data showed that berberine increased the survival rates of CS-induced mice. The intestinal injuries induced by CS were also attenuated by berberine, which was associated with inhibition of the production of systemic IL-6, IL-1ß, and TNF-α. At the molecular level, the expression of miR-132-3p was upregulated, suppressing the expression of FOXA1, p-IκBα, and p65 while inducing the expression of IκBα. The effects of berberine on NS-induced impairments were blocked by the injection of the miR-132-3p antagomir, which exacerbated intestinal injuries, induced systemic inflammation, and reactivated the FOXA1 and NF-κB pathways. The findings in the in vivo model were validated with in vitro assays. Collectively, the findings outlined in the current study indicated that berberine had solid protective effects against NS-induced symptoms in newborn mice, and the effects depended on the upregulation of miR-132-3p.

Advances in Management for Preterm Fetuses at Risk of Delivery.

Preterm birth accounts for only 11% of live births but contributes to up to 75% of neonatal mortality and more than half of long-term morbidity. Targeted interventions to reduce the most common causes of perinatal morbidity and mortality include intrapartum group B Streptococcus prophylaxis, magnesium sulfate for fetal neuroprotection, antenatal corticosteroids for fetal lung maturity, latency antibiotics for preterm premature rupture of membranes, and tocolysis to allow corticosteroid administration and transfer to a tertiary care center. This article reviews the evidence for interventions to improve outcomes for fetuses at risk for preterm delivery at different gestational ages.

Asociación entre la concentración de vitamina D y la sepsis neonatal extrahospitalaria de aparición tardía / Association between vitamin D level and community-acquired late-onset neonatal sepsis

Introducción. El objetivo fue determinar la relación entre la concentración materna e infantil de vitamina D y la sepsis de aparición tardía. Población y métodos. En este estudio se incluyó a los bebés nacidos con ≥ 37 semanas de gestación hospitalizados con diagnóstico de sepsis de aparición tardía. Se comparó la concentración de vitamina D de los niños y sus madres del grupo del estudio y del de referencia. Resultados. El grupo del estudio incluyó a 46 pacientes con sepsis de aparición tardía nacidos a término y el grupo de referencia, 46 pacientes con hiperbilirrubinemia. La suplementación con vitamina D durante el embarazo fue menor en las madres del grupo del estudio que en el de referencia (p = 0,001). La concentración sérica de 25-hidroxivitamina D [25(OH)D] de los niños y las madres del grupo del estudio fue significativamente menor que la del grupo de referencia (p < 0,001). Se observó una correlación positiva entre la 25(OH)D en las madres y los niños de ambos grupos (r: 0,38; p < 0,001). El valor de corte para la 25(OH)D, que determina el riesgo de sepsis neonatal de aparición tardía, se estableció en 15,45 ng/ml (sensibilidad: 91,3 %; especificidad: 71,7 %; área bajo la curva: 0,824; p < 0,001). Conclusiones. La concentración de 25(OH)D fue inferior en los bebés nacidos a término con sepsis de aparición tardía y sus madres en comparación con el grupo de referencia. La correlación entre la concentración sérica de 25(OH)D de los niños y sus madres fue positiva.

Introduction. The objective was to determine the relationship between mother and infant vitamin D levels and late onset sepsis. Population and methods.Infants born ≥37 weeks of gestational age who were hospitalized with the diagnosis of late-onset sepsis were enrolled to this prospective case control study. VitaminD levels of the infants and their mothers in the study and a control group were compared. Results. Fourty six term patients with lateonset sepsis composed the study group, 46 patients with hyperbilirubinemia as the control group. Vitamin D supplementation during pregnancy was lower in mothers of study group compared to the control group (p = 0.001). Serum 25-hydroxyvitamin D levels of infants and mothers in the study group were significantly lower than the control group (p < 0.001). There was a positive correlation between 25-hydroxyvitaminD levels of mothers and infants in both groups (r: 0.38, p < 0.001). The best cut off value of 25-hydroxyvitamin D, which determines the risk of late-onset sepsis in neonates, was detected as 15.45 ng/ml (sensitivity: 91.3 %, specificity: 71.7 %, area under the curve: 0.824, p < 0.001). Conclusions.In this study, 25-hydroxyvitaminD levels were found to be lower in term infants with late-onset sepsis and among their mothers compared to the control group. Positive correlation was found between serum 25(OH)D levels of infants and their mothers. Key words: newborn infant, sepsis,

Efficacy of zinc supplementation for neonatal sepsis: a systematic review and meta-analysis.

Background: Zinc supplementation has some potential in treating neonatal sepsis. We conduct a systematic review and meta-analysis to explore the efficacy of zinc supplementation for neonatal sepsis. Methods: PubMed, Embase, Web of science, EBSCO, and Cochrane Library databases are systematically searched. Randomized controlled trials (RCTs) assessing the efficacy of zinc supplementation in neonatal sepsis are included. Two investigators independently search articles, extract the data, and assessed the quality of included studies. Meta-analysis is performed using the random-effect model. Results: Four RCTs involving 986 patients are included in the meta-analysis. Overall, compared with control intervention in neonatal sepsis, zinc supplementation is able to significantly reduce mortality rate (risk ratio (RR) = 0.48; 95% confidence intervals (CIs) = 0.25-0.94; p = .03) and improve serum zinc (mean difference (MD) = 81.97; 95% CI = 34.57-129.37; p = .0007), but has no remarkable influence on hospital stay (MD = -4.51; 95% CI = -15.08 to 6.05; p = .40) and the number of expired patients (RR = 0.63; 95% CI = 0.24-1.65; p = .35). Conclusions: Zinc supplementation may significantly reduce mortality rate and improve serum zinc in neonatal sepsis, but has no substantial influence on hospital stay and the number of expired patients.

Ceftriaxone Absorption Enhancement for Noninvasive Administration as an Alternative to Injectable Solutions.

Neonatal sepsis is a major cause of infant mortality in developing countries because of delayed injectable treatment, making it urgent to develop noninjectable formulations that can reduce treatment delays in resource-limited settings. Ceftriaxone, available only for injection, needs absorption enhancers to achieve adequate bioavailability via nonparenteral administration. This article presents all available data on the nonparenteral absorption of ceftriaxone in humans and animals, including unpublished work carried out by F. Hoffmann-La Roche (Roche) in the 1980s and new data from preclinical studies with rabbits, and discusses the importance of these data for the development of noninjectable formulations for noninvasive treatment. The combined results indicate that the rectal absorption of ceftriaxone is feasible and likely to lead to a bioavailable formulation that can reduce treatment delays in neonatal sepsis. A bile salt, chenodeoxycholate sodium salt (Na-CDC), used as an absorption enhancer at a 125-mg dose, together with a 500-mg dose of ceftriaxone provided 24% rectal absorption of ceftriaxone and a maximal plasma concentration of 21 µg/ml with good tolerance in human subjects. The rabbit model developed can also be used to screen for the bioavailability of other formulations before assessment in humans.

Effect of probiotics on C-reactive protein levels in preterm infants: Secondary analysis of a randomized controlled trial.

BACKGROUND: Excessive inflammation is associated with adverse outcomes in preterm infants. C- reactive protein (CRP) is a marker of inflammation/infection. Probiotics have anti-inflammatory properties. Randomized controlled trials (RCTs) in preterm infants have not reported effect of probiotics on CRP. AIM: To evaluate effect of probiotics on CRP in preterm infants who had participated in a RCT of Bifidobacterium breve (B. breve) m-16v. METHODS: Data on all infants (GA <33 weeks, n = 159) enrolled in the RCT was analyzed. For study purpose, CRP <15 mg/L and ≤10 mg/L was considered normal for the first week, and thereafter respectively. Mixed logistic regression modelling was used to assess probiotic effect on CRP levels. RESULTS: There were 1579 CRP measurements (Probiotic: 851 vs. Placebo: 728). Baseline characteristics and number [Median (IQR)] of CRP estimations per infant [l0 (5, 20) vs. 10 (6, 17), p = 0.861] were comparable between probiotic vs. placebo group. There was no significant difference in the proportion of infants with high CRP over time (treatment by weekly time points interaction, p = 0.187), and across all time points between probiotic and placebo group (adjusted OR: 1.62, 95% CI: 0.91-2.88, p = 0.102)CONCLUSION:B. breve m-16v did not decrease CRP levels in preterm infants born <33 weeks.

Reduction in necrotizing enterocolitis and improved outcomes in preterm infants following routine supplementation with Lactobacillus GG in combination with bovine lactoferrin.

BACKGROUND: Preterm infants remain at high risk of adverse outcomes following necrotizing enterocolitis (NEC) and late onset sepsis (LOS). Meta-analysis of randomized trials has indicated a reduction in severe NEC following use of probiotics and bovine lactoferrin (LF). Overall, however, uncertainty remains over which probiotic, or combination to use. The aim of this study was to compare the incidence of severe NEC and LOS before and after routine supplementation with Lactobacillus GG (LGG) and LF. METHODS: In this retrospective cohort study, infants <32 weeks or <1500 g routinely received LGG and 100 mg lactoferrin daily from 2011 -2015 were compared with similar infants born from 2004-2008. Cases of NEC were Bell stage 2 or greater and LOS was blood or spinal fluid culture positive after 48 hrs of age. RESULTS: We noted a marked decline in the incidence of NEC from 3% to 1% with a RR of 0.29 (CI 0.1-0.9) and a number needed to benefit of 50. The cost of preventing one case of NEC was estimated to be NZ $2800, considerably lower than the cost of treatment. LOS rates were not significantly different. There was a decrease in retinopathy treatment rates. During the period there was one case of LGG sepsis in a 23 week gestation infant with abdominal pathology and one infant developed NEC after stopping prophylaxis. CONCLUSION: The rates of severe NEC was markedly reduced following prophylaxis. The case of LGG sepsis indicates caution is required in extremely preterm infants.

Probiotics Prevent Candida Colonization and Invasive Fungal Sepsis in Preterm Neonates: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

To investigate whether probiotic supplementation could reduce the risk of fungal infection in preterm neonates in neonatal intensive care units (NICUs), we systematically searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials databases for randomized controlled trials (RCTs) focusing on the effect of probiotics on fungal infection in preterm neonates. The outcomes of interest were Candida colonization and invasive fungal sepsis. Seven trials involving 1371 preterm neonates were included. Meta-analysis (fixed-effects model) showed that probiotic supplementation was significantly associated with a lower risk of Candida colonization (2 RCTs, n = 329; relative risk (RR), 0.43; 95% confidence interval (CI), 0.27-0.67; p = 0.0002; I2 = 0%), and invasive fungal sepsis (7 RCTs, n = 1371; RR, 0.64; 95% CI, 0.46-0.88; p = 0.006; I2 = 13%). After excluding one study with a high baseline incidence (75%) of fungal sepsis, the effect of probiotics on invasive fungal sepsis became statistically insignificant (RR, 0.88; 95% CI, 0.44-1.78; p = 0.72; I2 = 15%). When using the random-effects model, the effect of probiotics remained favorable for Candida colonization (RR, 0.43; 95% CI 0.27-0.68; p = 0.0002; I2 = 0%) but not for fungal sepsis (RR, 0.64; 95% CI 0.38-1.08; p = 0.10; I2 = 13%). Current evidence indicates that probiotics can reduce the risk of Candida colonization in preterm neonates in NICUs. Limited data support that probiotic supplementation prevents invasive fungal sepsis in preterm neonates. High-quality and adequately powered RCTs are warranted.