Development and internal validation of a Neonatal Healthcare-associated infectiOn Prediction score (NeoHoP score) for very low birthweight infants in low-resource settings: a retrospective case-control study.

BACKGROUND AND OBJECTIVES: Early diagnosis of neonatal infection is essential to prevent serious complications and to avoid unnecessary use of antibiotics. The prevalence of healthcare-associated infections (HAIs) among very low birthweight (VLBW; <1500 g) infants is 20%; and the mortality in low-resource settings can be as high as 70%. This study aimed to develop an Infection Prediction Score to diagnose bacterial HAIs. METHODS: A retrospective cohort of VLBW infants investigated for HAI was randomised into two unmatched cohorts. The first cohort was used for development of the score, and the second cohort was used for the internal validation thereof. Potential predictors included risk factors, clinical features, interventions, and laboratory data. The model was developed based on logistic regression analysis. RESULTS: The study population of 655 VLBW infants with 1116 episodes of clinically suspected HAIs was used to develop the model. The model had five significant variables: capillary refill time >3 s, lethargy, abdominal distention, presence of a central venous catheter in the previous 48 hours and a C reactive protein ≥10 mg/L. The area below the receiver operating characteristic curve was 0.868. A score of ≥2 had a sensitivity of 54.2% and a specificity of 96.4%. CONCLUSION: A novel Infection Prediction Score for HAIs among VLBW infants may be an important tool for healthcare providers working in low-resource settings but external validation needs to be performed before widespread use can be recommended.

Impact of a multi-strain probiotic administration on peri-rectal colonization with drug-resistant Gram-negative bacteria in preterm neonates.

Background: Infections caused by drug resistant Gram-negative bacteria (DR-GNB) are a major health concern for hospitalized preterm neonates, globally. The aim of this study was to investigate the effect of a multi-strain probiotic on the incidence of rectal colonization with DR-GNB in preterm neonates. Methods: A double-blind, placebo-controlled, randomized clinical trial was conducted including 200 neonates, randomly allocated to a multi-strain probiotic (n = 100) or placebo (n = 100). Results: Fifteen percent of the neonates showed peri-rectal colonization with DR-GNB on the day of enrolment indicating probable maternal-to-neonate (vertical) bacterial transmission or environmental acquisition at time of delivery, with no difference between groups. Acquisition of further DR-GNB colonization was rapid, with an increase from 15% on the day enrolment to 77% by day 7 and 83% by day 14 of life. By day 7 (corresponding to early gut colonization), neonates in the probiotic group were 57% less likely to have peri-rectal DR-GNB colonization [OR: 0.43 (0.20-0.95); p = 0.04] and by day 14 (corresponding to late gut colonization), neonates in the probiotic group were 93% less likely to have peri-rectal DR-GNB colonization [OR: 0.07 (0.02-0.23); p < 0.001]. Conclusion: Hospitalized neonates showed substantial peri-rectal colonization with DR-GNB at enrolment and further rapid acquisition of DR-GNB in the first 2 weeks of life. The use of a multi-strain probiotic was effective in reducing early and late neonatal gut colonization with DR-GNB. Clinical Trial Registration: The trial was registered at the Pan African Clinical Trial Registry (PACTR202011513390736).

Effect of a Multi-Strain Probiotic on Growth and Time to Reach Full Feeds in Preterm Neonates.

Background: The main nutritional goal for premature neonates is to achieve a postnatal growth rate that the neonate would have experienced in utero. Postnatal growth failure is, however, very common in very and extremely low birth weight neonates. The use of probiotics shows promising results in reducing the time for full feeds, as well as in increased weight gain. The optimal probiotic strain has, however, not been elucidated. The aim of the present study was to evaluate the difference in the growth and time to reach full feeds between the two treatment arms, using LabinicTM as a multi-strain probiotic and a placebo. Methods: We conducted a double-blind, placebo-controlled, randomized clinical trial investigating the effect of a multi strain probiotic (LabinicTM) on various outcomes in preterm neonates. The results on the time to reach full feeds and the growth will be discussed in this paper. A probiotic or placebo was given once daily to the neonates for 28 days. Weight and feeding volume were measured daily, and length and head circumference were measured weekly. Results: The probiotic group reached full feeds earlier 8.7 days; ± 2.0 than the placebo group 9.7 days; ±4.3 (p = 0.04) and regained their birthweight earlier than the placebo group 11.5 days ± 6.3 vs. 13.3 days ± 6.3 (p = 0.06). From day 21 onwards, the probiotic group showed a significantly greater crude gain in weight (p < 0.001) than the placebo group (estimated difference between the two groups day 21: 56.7 g and at day 28: 83.7 g. There was a significant improvement observed in the weight Z-score change in the probiotic group over the 28-day period. Conclusion: The use of a multi-strain probiotic (LabinicTM) shows great potential as a low-cost, low-risk intervention in reducing the time to reach full feeds as well as shortening the time to regain birthweight. The probiotic had an additional beneficial impact on Z-score change in weight potentially decreasing post-natal growth restriction.

Effect of a Multi-Strain Probiotic on the Incidence and Severity of Necrotizing Enterocolitis and Feeding Intolerances in Preterm Neonates.

Background: Necrotizing enterocolitis (NEC) is a multifactorial disease, causing inflammation of the bowel. The exact root of NEC is still unknown, but a low weight and gestational age at birth are known causes. Furthermore, antibiotic use and abnormal bacterial colonization of the premature gut are possible causes. Premature neonates often experience feeding intolerances that disrupts the nutritional intake, leading to poor growth and neurodevelopmental impairment. Methods: We conducted a double-blind, placebo-controlled, randomized clinical trial to investigate the effect of a multi-strain probiotic formulation (LabinicTM) on the incidence and severity of NEC and feeding intolerances in preterm neonates. Results: There were five neonates in the placebo group who developed NEC (Stage 1A−3B), compared to no neonates in the probiotic group. Further, the use of probiotics showed a statistically significant reduction in the development of feeding intolerances, p < 0.001. Conclusion: A multi-strain probiotic is a safe and cost-effective way of preventing NEC and feeding intolerances in premature neonates.

Amniotic Fluid: A Perspective on Promising Advances in the Prevention and Treatment of Necrotizing Enterocolitis.

Necrotizing enterocolitis (NEC) is a common and potentially fatal disease that typically affects preterm (PIs) and very low birth weight infants (VLBWIs). Although NEC has been extensively studied, the current therapeutic approaches are unsatisfactory. Due to the similarities in the composition between human amniotic fluid (AF) and human breast milk (BM), which plays a protective role in the development of NEC in PIs and VLBWIs, it has been postulated that AF has similar effects on the outcome of NEC and potential therapeutic implications. AF has been long used for its diagnostic purposes and is often discarded after birth as "biological waste". However, researchers have started to elucidate its therapeutic potential. Experimental studies in animal models have shown that diseases of various organ systems can possibly benefit from AF-based therapy. Hence, we have identified three approaches which show promising results for future clinical application in the prevention and/or treatment of NEC: (1) administration of processed AF (PAF) isolated from donor mothers, (2) administration of AF stem cells (AFSCs), and (3) administration of simulated AF (SAF) formulated to mimic the composition of physiological AF. We have highlighted the most important aspects that should be taken into account to guide further research on the clinical application of AF-based therapy. We hope that this review can provide a framework to identify the challenges of AF-based therapy and help to design future studies to better evaluate AF-based approaches for the treatment and/or prevention of NEC in PIs and VLBWIs.

Performance Comparison of Infection Prediction Scores in a South African Neonatal Unit: A Retrospective Case-Control Study.

Background and objectives: Infection prediction scores are useful ancillary tests in determining the likelihood of neonatal hospital-acquired infection (HAI), particularly in very low birth weight (VLBW; <1,500 g) infants who are most vulnerable to HAI and have high antibiotic utilization rates. None of the existing infection prediction scores were developed for or evaluated in South African VLBW neonates. Methods: We identified existing infection prediction scores through literature searches and assessed each score for suitability and feasibility of use in resource-limited settings. Performance of suitable scores were compared using a retrospective dataset of VLBW infants (2016-2017) from a tertiary hospital neonatal unit in Cape Town, South Africa. Sensitivity, specificity, predictive values, and likelihood ratios were calculated for each score. Results: Eleven infection prediction scores were identified, but only five were suitable for use in resource-limited settings (NOSEP1, Singh, Rosenberg, and Bekhof scores). The five selected scores were evaluated using data from 841 episodes of HAI in 659 VLBW infants. The sensitivity for the scores ranged between 3% (NOSEP1 ≥14; proven and presumed infection), to a maximum of 74% (Singh score ≥1; proven infection). The specificity of these scores ranged from 31% (Singh score ≥1; proven and presumed infection) to 100% (NOSEP1 ≥11 and ≥14, NOSEP-NEW-1 ≥11; proven and presumed infection). Conclusion: Existing infection prediction scores did not achieve comparable predictive performance in South African VLBW infants and should therefore only be used as an adjunct to clinical judgment in antimicrobial decision making. Future studies should develop infection prediction scores that have high diagnostic accuracy and are feasible to implement in resource-limited neonatal units.