Incidence Of Necrotizing Enterocolitis Research Articles

Viral Infections and Neonatal Necrotizing Enterocolitis: A Meta-analysis.

Necrotizing enterocolitis (NEC) is a devastating intestinal disease affecting preterm infants. Studies implicate viral infections in etiopathogenesis. To summarize the association of viral infections with NEC by systematic review and meta-analysis. We searched Ovid-Medline, Embase, Web of Science, and Cochrane databases in November 2022. We included observational studies that examined the association between viral infections and NEC in newborn infants. We extracted data regarding the methodology, participant characteristics, and outcome measures. We included 29 and 24 studies in the qualitative review and meta-analysis, respectively. The meta-analysis demonstrated a significant association between viral infections and NEC (odds ratio [OR], 3.81, 95% confidence interval: 1.99-7.30, 24 studies). The association remained significant after excluding the outliers (OR, 2.89 [1.56-5.36], 22 studies) and studies with poor methodology (OR, 3.33 [1.73-6.43], 22 studies). In subgroup analysis based on participants' birth weight, studies including very low birth weight infants only (OR, 3.62 [1.63-8.03], 8 studies) and non-very low birth weight infants only (OR, 5.28 [1.69-16.54], 6 studies) showed a significant association. In subgroup analysis based on specific viruses, infection with rotavirus (OR, 3.96 [1.12-13.95], 10 studies), cytomegalovirus (OR, 3.50 [1.60-7.65], 5 studies), norovirus (OR, 11.95 [2.05-69.84], 2 studies), and astrovirus (OR, 6.32 [2.49-16.02], 2 studies) was significantly associated with NEC. Heterogeneity of the included studies. Viral infection is associated with an increased risk of NEC in newborn infants. We need methodologically sound prospective studies to assess the effect of preventing or treating viral infections on NEC incidence.

Stem cells as a therapeutic avenue for active and long-term complications of Necrotizing Enterocolitis

Necrotizing enterocolitis (NEC) is a devastating neonatal intestinal disease associated with significant morbidity and mortality. Although decades of research have been dedicated to understanding the pathogenesis of NEC and developing therapies, it remains the leading cause of death among neonatal gastrointestinal diseases. Mesenchymal stem cells (MSCs) have garnered significant interest recently as potential therapeutic agents for the treatment of NEC. They have been shown to rescue intestinal injury and reduce the incidence and severity of NEC in various preclinical animal studies. MSCs and MSC-derived organoids and tissue engineered small intestine (TESI) have shown potential for the treatment of long-term sequela of NEC such as short bowel syndrome, neurodevelopmental delay, and chronic lung disease. Although the advances made in the use of MSCs are promising, further research is needed prior to the widespread use of these cells for the treatment of NEC.

Probiotics and Human Milk Differentially Influence the Gut Microbiome and NEC Incidence in Preterm Pigs.

Necrotizing enterocolitis (NEC) is the leading cause of death caused by gastrointestinal disease in preterm infants. Major risk factors include prematurity, formula feeding, and gut microbial colonization. Microbes have been linked to NEC, yet there is no evidence of causal species, and select probiotics have been shown to reduce NEC incidence in infants. In this study, we evaluated the effect of the probiotic Bifidobacterium longum subsp. infantis (BL. infantis), alone and in combination with a human milk oligosaccharide (HMO)-sialylactose (3'SL)-on the microbiome, and the incidence of NEC in preterm piglets fed an infant formula diet. We studied 50 preterm piglets randomized between 5 treatments: (1) Preterm infant formula, (2) Donor human milk (DHM), (3) Infant formula + 3'SL, (4) Infant formula + BL. infantis, and (5) Infant formula and BL. infantis + 3'SL. NEC incidence and severity were assessed through the evaluation of tissue from all the segments of the GI tract. The gut microbiota composition was assessed both daily and terminally through 16S and whole-genome sequencing (WGS) of rectal stool samples and intestinal contents. Dietary BL. infantis and 3'SL supplementation had no effect, yet DHM significantly reduced the incidence of NEC. The abundance of BL. infantis in the gut contents negatively correlated with disease severity. Clostridium sensu stricto 1 and Clostridium perfringens were significantly more abundant in NEC and positively correlated with disease severity. Our results suggest that pre- and probiotics are not sufficient for protection from NEC in an exclusively formula-based diet. The results highlight the differences in microbial species positively associated with both diet and NEC incidence.

Administration colostrum in preventing mortality and morbidity in preterm infants

Background: Oropharyngeal administration of colostrum has found to play a role in preventing the Necrotizing Enterocolitis (NEC), thus reducing mortality and morbidity in preterm infants. We aimed to determine whether early oropharyngeal administration of mother’s own colostrum can reduce the rates of NEC and/or mortality in preterm infants. Methods: We conducted a randomized, placebo controlled, intervention study in Department of Neonatology, Bangabandhu Sheikh Mujib Medical University, Dhaka from 2019 to 2021. Total 92 infants were enrolled, 52 were randomized to oropharyngeal administration of colostrum group and 40 to placebo group. Oropharyngeal administration of colostrum group received maternal colostrum (0.2 ml), after 24 hours of postnatal life and were given every 3 hour for the next 3 days. Serum IgA was measured at 24 hrs and 7th day of postnatal age. Clinical data during hospitalization were collected. SPSS version 21 was used for statistical analysis. Results: Baseline characteristics were comparable and almost similar between the two groups. There was significant reduction in the incidence of NEC stage 2, 16 (30.7%) vs. 26, (65%); p = 0.001). There was significant reduction of age of achieving full enteral feeding (12.1±4.5 vs 19.5±7.5; p = 0.001), disseminated intravascular coagulation (DIC) 12 (23%) vs. 22 (55%); p=0.002, use of mechanical ventilators, 11 (21.1%) vs. 22 (55%); p = 0.001 and number of inotropes (1.2±0.3 vs. 1.61±0.4975; p = 0.002), duration of inotropes (19.7±14.2 vs. 36.5±17.5; p=0.002) in OAC group. However, there was no significant difference in probable sepsis, culture proven sepsis, survival rate and serum IgA level at 1st and 7th day in OAC group, compared to placebo. Conclusions: There was a positive effect in decreasing the incidence of NEC, but no significant effect was observed on survival rate. This intervention facilitates faster achievement of full enteral feeding, reducing the risk of DIC in preterm infants.

Association of Hospital Adoption of Probiotics With Outcomes Among Neonates With Very Low Birth Weight

For neonates with very low birth weight (VLBW), randomized clinical trials (RCTs) indicate that probiotic treatment decreases the risk of necrotizing enterocolitis (NEC), with smaller decreases in the risk of sepsis and death. There is little evidence on the rate of probiotic adoption in US neonatal intensive care units (NICUs) and whether the benefits seen in trials have materialized in practice. To estimate changes in probiotic use among neonates with VLBW and to test whether neonates with VLBW treated at NICUs adopting routine probiotic use experience better outcomes compared with neonates treated at nonadopting NICUs. This cohort study used Vermont Oxford Network data on neonates with VLBW in US NICUs from January 1, 2012, to December 31, 2019. Data were analyzed from January 2022 through February 2023. Probiotics adoption vs nonadoption. Adopting NICUs were defined as those that currently or previously treated at least 20% of neonates with VLBW with probiotics. The primary outcomes were rates of NEC, in-hospital mortality, and sepsis, defined as bacterial or fungal infection occurring after day 3 from birth. A difference-in-differences analysis compared changes in VLBW infant outcomes between adopting and nonadopting NICUs before and after hospital-level adoption of probiotics. Additional analyses used the proportion of neonates treated with probiotics in each neonate's birth NICU and year. The analysis included 307 905 neonates with VLBW (mean [SD] gestational age, 28.4 [2.9] weeks; 50.0% male) at 807 US hospitals. The rate of probiotic treatment of neonates with VLBW rose from 1572 of 38 296 neonates (4.1%) in 2012 to 4788 of 37 910 (12.6%) in 2019. Only 123 of 745 NICUs (16.5%) adopted probiotics by 2019, with 4591 of 6017 neonates with VLBW (76.3%) receiving probiotics in 2019 at adopting NICUs. Incidence of NEC declined by 18% at adopting NICUs (odds ratio [OR], 0.82; 95% CI, 0.70-0.95; P = .10) compared with nonadopting NICUs. Probiotic adoption was not associated with a significant reduction in sepsis (OR, 1.11; 95% CI, 0.98-1.25; P = .09) or mortality (OR, 0.93; 95% CI, 0.80-1.08; P = .33). In this cohort study, adoption of routine use of probiotics increased slowly in US NICUs and was associated with lower NEC risk but not with sepsis or mortality among neonates with VLBW. The findings for probiotic adoption and NEC, sepsis, and mortality were smaller than would have been predicted by the totality of RCT evidence but are consistent with a meta-analysis restricted to studies at low risk of bias.

Mixed Feedings and Necrotizing Enterocolitis: The Proportion of Human Milk Matters.

Objectives: Impact of the proportion of human milk (HM) in mixed feeding on necrotizing enterocolitis (NEC) remains unknown. This study explores the influence of different proportions of HM on the risk of NEC. Materials and Methods: A retrospective cohort study was performed in infants with very low birth weight (VLBW). A spline smoothing curve was used to evaluate the dose-dependent association between HM and the risk of NEC. Univariate and multivariate analyses were performed to detect the association between the proportion of HM and NEC. Results: Twenty-four infants developed NEC, with 4 (1.9%) in the high HM group, 18 (28.1%) in the low HM group, and 2 (8.0%) in the exclusive formula group (p < 0.001). After adjusting for the relevant confounders, low HM (proportion of HM ≤54%) (OR 33.526, 95% confidential interval [CI] 7.183-156.475, p < 0.001) and exclusive formula feeding (OR 8.493, 95% CI 1.107-65.187, p = 0.040) significantly increased the incidence of NEC, compared with the high HM feeding (proportion of HM >54%). Similarly, low HM was independently associated with an increased risk of feeding intolerance compared with high HM feeding (OR 4.383, 95% CI 2.243-8.564, p < 0.001). Conclusion: A low ratio of HM (≤54%) significantly increased the risk of intestinal complications in VLBW infants. Mixed feeding should relate to the proportion of HM in premature infants.

Probiotics for Preventing Necrotizing Enterocolitis: A Meta-Analysis with Trial Sequential Analysis

What is Known and Objective. The role of probiotics, especially the different genera of probiotics, in managing necrotizing enterocolitis (NEC) is controversial. Thus, we performed a meta-analysis with trial sequential analysis (TSA) to determine the efficacy and safety of probiotics for preventing NEC. Methods. Medline, Embase, CENTRAL, WorldCat, TROVE, DART-Europe, and CBM were searched from inception to May 2022. Two investigators independently screened the literature, extracted data, and assessed the quality of the included studies. Meta-analysis was performed using RevMan 5.4, and TSA was conducted using TSA 0.9 beta. Results and Discussion. Fifty-five studies involving 12897 newborns were eligible. The use of probiotics for preventing NEC reduced the incidence of NEC (RR 0.48, 95% CI 0.41 to 0.57, and P &lt; 0.05) and sepsis (RR 0.77, 95% CI 0.64 to 0.94, and P &lt; 0.05), the risk of mortality (RR 0.69, 95% CI 0.58 to 0.84, and P &lt; 0.05), and shortened the average days of hospitalization (MD −3.12, 95% CI −4.98 to −1.26, and P &lt; 0.05). However, subgroup analysis revealed that different genera of probiotics gave rise to different outcomes. In addition, TSA indicated that the cumulative z-curve crossed the traditional and trial sequential monitoring boundaries for benefit, providing firm evidence that multiple strains and Lactobacillus species of probiotics decreased the incidence of NEC. However, the current evidence was inconclusive for Bifidobacterium and Saccharomyces species. What is New and Conclusions. Probiotics are effective in preventing NEC and sepsis and could provide added benefits, including decreasing mortality and the number of days of hospitalization. However, considering the heterogeneity of probiotics regimens and the risk of selective reporting of RCTs, more high-quality clinical trials targeting different genera of probiotics with suitable doses and timing to prophylactic use of probiotics are needed to avoid overestimating the role of probiotics in preterm infants.

Пробіотики, кишкова мікробіота та захворювання, пов’язані з незрілістю травного каналу, у значно недоношених немовлят

Interruption of the formation of gut microbiota in preterm infants increases the probability of necrotizing enterocolitis (NEC) and late-onset neonatal sepsis (LOS). The use of probiotics can reduce the corresponding risk. Purpose - to evaluate the clinical effectiveness of enteral administration of Lactobacillus reuteri DSM 17938 in reducing the incidence of NEC, LOS, and overall mortality in infants with gestational age (GA) ≤32 weeks, as well as the effect of the probiotic on the formation of the gut microbiota. Materials and methods. 100 newborns with GA ≤32 weeks and birth weight ≤1500 g were enrolled in the open randomized study. 50 infants in the probiotic group until reaching postmenstrual age (PMA) of 36 weeks received Lactobacillus reuteri DSM 17938 at a dose of 108 CFU/day with enteral feeding (EF), and 50 infants in the comparison group received standard treatment. The primary effectiveness criteria were the incidence of NEC, LOS, and overall mortality. As the secondary criteria, the duration of the period to reach the full EF, the number of episodes of feeding intolerance, duration of antibacterial therapy, weight at PMA of 36 weeks, and length of hospital stay were used. Results. The administration of Lactobacillus reuteri DSM 17938 at a dose of 108 CFU/day neither reduced the incidence of NEC and LOS nor overall mortality. This intervention, however, significantly reduced the length of hospital stay in infants with GA ≥28 weeks (56.0 (46.0-71.0) days vs 65.0 (60.0-87.9) days; р=0.03), and was associated with the earlier achievement of full enteral volume (23.0 (16.0-37.0) days vs 30.0 (18.0-37.0) days; р=0.26) and fewer episodes of feeding intolerance in infants with GA &lt;28 weeks (1.0 (1.0-3.0) vs 3.0 (3.0-4.0); р=0.19). No effect of the probiotic therapy on the gut colonization by Lactobacillus spp. and Bifidobacterium spp. was observed. Conclusions. Enteral administration of Lactobacillus reuteri DSM 17938 improves tolerance to EF and reduces the period to achieve full EF and the total length of hospital stay in preterm infants. The effect of this probiotic on the incidence of NEC and LOS, as well as the postnatal formation of the gut microbiota, requires further study. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of all participating institutions. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Effect of blood sampling management on reducing blood transfusions in very preterm infants.

Effect of blood sampling management on reducing blood transfusions in very preterm infants.

To feed or not to feed during therapeutic hypothermia in asphyxiated neonates: a systematic review and meta-analysis.

The practice of withholding feed during therapeutic hypothermia (TH) in neonates with hypoxemic ischemic encephalopathy (HIE) is based on conventions rather than evidence. Recent studies suggest that enteral feeding might be safe during TH. We systematically compared the benefits and harms of enteral feeding in infants undergoing TH for HIE. We searched electronic databases and trial registries (MEDLINE, CINAHL, Embase, Web of Science, and CENTRAL) until December 15, 2022, for studies comparing enteral feeding and non-feeding strategies. We performed a random-effects meta-analysis using RevMan 5.4 software. The primary outcome was the incidence of stage II/III necrotizing enterocolitis (NEC). Other outcomes included the incidence of any stage NEC, mortality, sepsis, feed intolerance, time to full enteral feeds, and hospital stay. Six studies ((two randomized controlled trials (RCTs) and four nonrandomized studies of intervention (NRSIs)) enrolling 3693 participants were included. The overall incidence of stage II/III NEC was very low (0.6%). There was no significant difference in the incidence of stage II/III NEC in RCTs (2 trials, 192 participants; RR, 1.20; 95% CI: 0.53 to 2.71, I2, 0%) and NRSIs (3 studies, no events in either group). In the NRSIs, infants in the enteral feeding group had significantly lower sepsis rates (four studies, 3500 participants, RR, 0.59; 95% CI: 0.51 to 0.67, I2-0%) and lower all-cause mortality (three studies, 3465 participants, RR: 0.43; 95% CI: 0.33 to 0.57, I2-0%) than the infants in the "no feeding" group. However, no significant difference in mortality was observed in RCTs (RR: 0.70; 95% CI: 0.28 to 1.74, I2-0%). Infants in the enteral feeding group achieved full enteral feeding earlier, had higher breastfeeding rates at discharge, received parenteral nutrition for a shorter duration, and had shorter hospital stays than the control group. Conclusion: In late preterm and term infants with HIE, enteral feeding appears safe and feasible during the cooling phase of TH. However, there is insufficient evidence to guide the timing of initiation, volume, and feed advancement. What is Known: • Many neonatal units withhold enteral feeding during therapeutic hypothermia, fearing an increased risk of complications (feed intolerance and necrotizing enterocolitis). • The overall risk of necrotizing enterocolitis in late-preterm and term infants is extremely low (< 1%). What is New: • Enteral feeding during therapeutic hypothermia is safe and does not increase the risk of necrotizing enterocolitis, hypoglycemia, or feed intolerance. It may reduce the incidence of sepsis and all-cause mortality until discharge.

Effects of prophylactic probiotics supplementation on infants born very preterm or very low birth weight.

To evaluate the effects of guideline-driven prophylactic supplementation of a multi-strain neonatal intensive care unit-specific probiotic product on infants born very preterm (VP) or very low birth weight (VLBW). A prospective cohort of 125 infants born in one year after implementation who received probiotics were compared to a retrospective cohort of eligible 126 VP or VLBW infants who did not receive probiotics. The primary outcome of interest was necrotizing enterocolitis (NEC). The incidence of NEC decreased from 6.3 to 1.6%. After adjusting for multiple variables, there were no significant differences in primary or other outcomes of interest; odds ratio (95% confidence interval) NEC 0.27 (0.05-1.33), death 0.76 (0.26-2.21) and late-onset sepsis 0.54 (0.18-1.63). No adverse effects related to probiotics supplementation were observed. Although nonsignificant, prophylactic probiotics supplementation in infants born VP or VLBW was associated with reduction of NEC.

Impact of probiotic administration on the incidence of necrotising enterocolitis: A single-centre cohort study.

To examine the effect of probiotic administration on the incidence of necrotising enterocolitis (NEC) in preterm infants. We conducted a retrospective study examining the incidence of NEC in a cohort of infants that received probiotics compared to those that had not, over an 18-year period in a single centre. Infants were included if they were born <32 weeks' gestation with birthweight <1500 g and survived beyond 72 h. Infants in the probiotic group received either ABC Dophilus or Infloran. The primary outcome was the rate of NEC. The main secondary outcomes were late-onset sepsis and mortality. Differences in these outcomes between cohorts were examined in univariate and multivariate analyses, taking account of confounding variables, reporting adjusted odds ratios (aORs) with 95% confidence intervals (CIs). 805 infants were included in the study. Infants receiving probiotics had a lower risk of developing NEC compared with those that did not (32/419 (7.6%) vs. 14/386 (3.6%); aOR 0.37 (95% CI 0.18-0.74)). There was also a reduction in the late-onset sepsis rate (22.4% vs. 14.2%, aOR 0.52, 95% CI 0.35-0.77) and mortality rate (9.5% vs. 4.6%, aOR 0.35, 95% CI 0.17-0.73). The administration of a multi-organism probiotic formulation, including Bifidobacteria, to very preterm infants in our unit was associated with a reduced incidence of NEC, late-onset sepsis and mortality.

Inhaled nitric oxide in premature infants for preventing bronchopulmonary dysplasia: a meta-analysis

BackgroundThe effectiveness of nitric oxide (NO) in reducing the risk of bronchopulmonary dysplasia (BPD) remains debatable. In this study, we performed a meta-analysis to guide clinical decision-making regarding the significance of inhaled NO (iNO) on the potential occurrence and outcomes of BPD in premature infants.MethodsData from clinical randomized controlled trials (RCTs) published in PubMed, Embase, Cochrane Library, Wanfang, China National Knowledge Infrastructure (CNKI) and Chinese Scientific Journal Database VIP databases for premature infants were searched from inception to March 2022. Review Manager 5.3 statistical software was used for heterogeneity analysis.ResultsOf the 905 studies retrieved, 11 RCTs met the screening criteria of this study. Our analysis showed that the iNO group was associated with a significantly lower incidence of BPD than the control group (relative risk [RR] = 0.91, 95% confidence interval (CI) 0.85-0.97, P = 0.006). We also observed no significant difference in the incidence of BPD between the two groups at the initial dose of 5 ppm (ppm) (P = 0.09) but those treated with 10 ppm iNO had a significantly lower incidence of BPD (RR = 0.90, 95%CI 0.81-0.99, P = 0.03). However, it should be noted that although the iNO group had an increased risk for necrotizing enterocolitis (NEC) (RR = 1.33, 95%CI 1.04-1.71, P = 0.03), cases treated with an initial dose of 10 ppm revealed no significant difference in the incidence of NEC compared with the control group (P = 0.41), while those treated with an initial dosage of 5 ppm of iNO had a significantly greater NEC rates than the control group (RR = 1.41, 95%CI 1.03-1.91, P = 0.03). Further, we observed no statistically significant differences in the incidence of in-hospital mortality, intraventricular hemorrhage (IVH) (Grade 3/4) or periventricular leukomalacia (PVL) and pulmonary hemorrhage (PH) between the two treatment groups.ConclusionsThis meta-analysis of RCTs showed that iNO at an initial dosage of 10 ppm seemed more effective in reducing the risk of BPD than conventional treatment and iNO at an initial dosage of 5 ppm in preterm infants at a gestational age of ≤34 weeks who required respiratory support. However, the incidence of in-hospital mortality and adverse events between the overall iNO group and Control were similar.

Premature infants receiving delayed cord clamping with and without cord milking: a randomized control trial

BackgroundPreterm infants often have long hospital stays and frequent blood tests; they often develop anemia requiring multiple blood transfusions. Placental transfusion via delayed cord clamping (DCC) or umbilical cord milking (UCM) helps increase blood volume. We hypothesized umbilical cord milking (UCM), together with DCC, would be superior in reducing blood transfusions.ObjectivesTo compare the effects of DCC and DCC combined with UCM on hematologic outcomes among preterm infants.MethodsOne hundred twenty singleton preterm infants born at 280/7- 336/7 weeks of gestation at Thammasat University Hospital were enrolled in an open-label, randomized, controlled trial. They were placed into three groups (1:1:1) by a block-of-three randomization: DCC for 45 s, DCC with UCM performed before clamping (DCM-B), and DCC with UCM performed after clamping (DCM-A). The primary outcomes were hematocrit levels and number of infants receiving blood transfusions during the first 28 days of life. Intraventricular hemorrhage (IVH) and necrotizing enterocolitis (NEC) were secondary outcomes. Analyses were performed with an intent-to-treat approach.ResultsOne hundred twenty preterm infants were randomized. There was no statistically significant difference in neonatal outcomes; hematocrit on admission 54.0 ± 5.5, 53.3 ± 6.0, and 54.3 ± 5.8 (p = 0.88), receiving blood transfusions 25%, 20%, and 12.5% (p = 0.24), incidence of NEC 7.5, 0 and 10% (p = 0.78) in the DCC, DCM-B and DCM-A groups, respectively. There were no preterm infants with severe IVH, polycythemia, maternal or neonatal death.ConclusionThe placental transfusion techniques utilized, DCC and DCC combined with UCM, provided the same benefits for preterm infants born at GA 28 and 33 weeks in terms of reducing the need for RBC transfusions, severities of IVH and incidence of NEC without increasing comorbidity.Trial registrationTCTR20190131002. Registered 31 January 2019—Retrospectively registered.

Bovine colostrum as a fortifier to human milk in very preterm infants – A randomized controlled trial (FortiColos)

Human milk for very preterm infants need fortification for optimal growth and development but the optimal fortification product remains to be identified. To investigate feasibility, safety and preliminary efficacy on growth and blood biochemistry when using intact bovine colostrum (BC) as a fortifier to human milk in very preterm infants. In an open-label, multicenter, randomized controlled pilot trial (infants 26-31 weeks' gestation), mother's own milk or donor human milk was fortified with powdered BC (n=115) or a conventional fortifier (CF, bovine-milk-based, n=117) until 35 weeks' postmenstrual age. Fortifiers and additional micronutrients were added to human milk according to local guidelines to achieve optimal growth (additional protein up to+1.4g protein/100mL human milk). Anthropometry was recorded weekly. Clinical morbidities including necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) were recorded. Clinical biochemistry included plasma amino acid (AA) levels to assess protein metabolic responses to the new fortifier. A total of 232 infants, gestational age (GA) 28.5±1.4 (weeks+days), fulfilled inclusion criteria. Birthweight, GA and delta Z scores from birth to end of intervention on weight, length or head circumference did not differ between groups, nor between the subgroups of small for gestational age infants. Likewise, incidence of NEC (BC: 3/115 vs. CF: 5/117, p=0.72, unadjusted values), LOS (BC: 23/113 vs. CF: 14/116, p=0.08) and other morbidities did not differ. BC infants received more protein than CF infants (+10%, p<0.05) and showed several elevated AA levels (+10-40%, p<0.05). Infants fortified with BC showed similar growth but received more protein and showed a moderate increase in plasma AA-levels, compared with CF. Adjustments in protein composition and micronutrients in BC-based fortifiers may be required to fully suit the needs for very preterm infants.

TO STUDY THE ROLE OF PROBIOTICS IN PREVENTING NECROTIZING ENTEROCOLITIS IN PRETERM AND LOW BIRTH WEIGHT NEONATES

Introduction: Necrotising Enterocolitis (NEC) is the most common gastrointestinal emergency in NICU, it is a life-threatening disease that occurs primarily in premature infants.1 Probiotics are the live microbial dietary supplements that when administered in adequate amount promotes health.2 In premature infants they are thought to improve the positive balance of colonizing bacteria that facilitate development of mucosal immunity and prevent the excessive inammation associated with NEC.3 Methods and Materials: The present study is a Prospective Observational study conducted in the NICU at Prathima Institute Of Medical Sciences, Karimnagar,Telangana. During the period of 2 years between December 2020 and November 2022. Neonates of &lt;37 weeks of gestation and with birth weight &lt;1500 gms admitted into NICU are included in the study. The selected neonates would be administered probiotic 2 million spores of Bacillus clausii ampules per day along with expressed mother's own milk daily till they reach full feeds (150ml/kg/day). These neonates were observed clinically, investigated and studied during their period of admission in NICU for the development of Necrotising Enterocolitis and also the morbidity and mortality of such neonates was studied. Results: In the present study, out of 50 neonates, 11 (22%) preterms developed NEC while 39 (78%) of them did not. This was found to be statistically signicant (p=0.01). Out of the 11 preterms, 1 (2%) belonged to ELBW while 10 (90%) belonged to VLBW. Out of the 11 preterms who developed developed NEC, 4 (8%) developed stage I NEC, 5 (10%) developed stage II NEC and 2 (4%) developed stage III NEC. This was statistically signicant (p= 0.001) In our present study, 4 (8%) of the preterms developed with sepsis while 46 (92%) did not develop sepsis. This was statistically signicant (p=0.001) Conclusion: Necrotizing Enterocolitis is a worldwide problem in Preterms Low Birth Weight neonates. The present study has found that Probiotic supplementation has reduced both the 4 incidence and severity of NEC in such neonates. Probiotic supplementation has also reduced the incidence of culture proven 5 sepsis in preterm and Low Birth Weight neonates.

Probiotics to prevent necrotizing enterocolitis in very low birth weight infants: A network meta-analysis.

This study aims to review the evidence for the optimal regimen of probiotics for the prevention of necrotizing enterocolitis (NEC) in very low birth weight infants. Through searching PubMed, EMBASE, Cochrane Library, and Web of Science till September 30, 2022, only randomized controlled trials were included to evaluate the optimal regimen of probiotics for the prevention of NEC in very low birth weight infants. The methodological quality of the included studies was assessed by the Cochrane risk of bias assessment tool (RoB 2), and the collected data were analyzed accordingly using Stata software. Twenty-seven RCTs were included, and the total sample size used in the study was 529. The results of the network meta-analysis showed that Bovine lactoferrin + Lactobacillus rhamnosus GG (RR 0.03; 95% CI 0.00-0.35), Lactobacillus rhamnosus + Lactobacillus plantarum + Lactobacillus casei + Bifidobacterium lactis (RR 0.06; 95% CI 0.00-0.70), Bifidobacterium lactis + inulin (RR 0.16; 95% CI 0.03-0.91) were superior to the control group (Bifidobacterium lactis + Bifidobacterium longum) in reducing the incidence of NEC. The reduction in the incidence of NEC were as follows: Bovine lactoferrin + Lactobacillus rhamnosus GG (SUCRA 95.7%) > Lactobacillus rhamnosus + Lactobacillus plantarum + Lactobacillus casei + Bifidobacterium lactis (SUCRA 89.4%) > Bifidobacterium lactis + inulin (SUCRA 77.8%). This network meta-analysis suggests that Lactobacillus rhamnosus GG combined with bovine lactoferrin maybe the most recommended regimen for the prevention of NEC in very low birth weight infants.

Human Bone Marrow-Derived Mesenchymal Stromal Cells Reduce the Severity of Experimental Necrotizing Enterocolitis in a Concentration-Dependent Manner.

Necrotizing enterocolitis (NEC) is a devastating gut disease in preterm neonates. In NEC animal models, mesenchymal stromal cells (MSCs) administration has reduced the incidence and severity of NEC. We developed and characterized a novel mouse model of NEC to evaluate the effect of human bone marrow-derived MSCs (hBM-MSCs) in tissue regeneration and epithelial gut repair. NEC was induced in C57BL/6 mouse pups at postnatal days (PND) 3-6 by (A) gavage feeding term infant formula, (B) hypoxia/hypothermia, and (C) lipopolysaccharide. Intraperitoneal injections of PBS or two hBM-MSCs doses (0.5 × 106 or 1 × 106) were given on PND2. At PND 6, we harvested intestine samples from all groups. The NEC group showed an incidence of NEC of 50% compared with controls (p < 0.001). Severity of bowel damage was reduced by hBM-MSCs compared to the PBS-treated NEC group in a concentration-dependent manner, with hBM-MSCs (1 × 106) inducing a NEC incidence reduction of up to 0% (p < 0.001). We showed that hBM-MSCs enhanced intestinal cell survival, preserving intestinal barrier integrity and decreasing mucosal inflammation and apoptosis. In conclusion, we established a novel NEC animal model and demonstrated that hBM-MSCs administration reduced the NEC incidence and severity in a concentration-dependent manner, enhancing intestinal barrier integrity.

Probiotics to prevent necrotizing enterocolitis and reduce mortality in neonates: A meta-analysis.

Probiotics are gradually being used as a supplementation to prevent necrotizing enterocolitis (NEC) and reduce mortality in neonates. We performed an updated meta-analysis to systematically evaluate the efficacy and safety of prophylactic probiotic supplementation for preventing NEC. The databases including PubMed, Embase, Scopus, Web of Science, and China National Knowledge Infrastructure were used to search the relevant articles. The latest retrieval date was up to December 2021. The meta-analysis was performed using Stata version 10.0. Finally, a total of 70 studies containing 8319 cases and 9283 controls were included. The strength of the association between the supplementation of probiotics and NEC was measured by risk ratios (RRs) with 95% confidence intervals (CIs). Pooled effect sizes across studies were performed by a random effect model. The results showed that the probiotics could significantly reduce the incidence of NEC (stage II or more) (RR = 0.436, 95% CI = 0.357-0.531, P < .001), the overall mortality (RR = 0.651, 95% CI = 0.506-0.836, P < .001), and NEC-related mortality (RR = 0.639, 95% CI = 0.423-0.966, P = .034). Due to the lack of sufficient sample size, we did not perform the subgroup analysis by types of probiotic strain. This meta-analysis indicates that the use of probiotics can effectively reduce the occurrence of NEC and mortality in neonates.

ПРЕДИКТОРЫ НЕКРОТИЗИРУЮЩЕГО ЭНТЕРОКОЛИТА У НЕДОНОШЕННЫХ НОВОРОЖДЕННЫХ С ГЕСТАЦИОННЫМ ВОЗРАСТОМ МЕНЕЕ 32 НЕДЕЛЬ

Necrotizing enterocolitis (NEC) is a serious gastrointestinal problem in premature newborns that can often lead to a poor outcome. Physicians’ knowledge of the earliest predictors of NEC will reduce the likelihood of its development. The purpose of the research was to seek for the earliest predictors of NEC development in the neonatal period in surviving premature newborns with the gestational age (GA) at birth of less than 32 weeks. Materials and methods used: a single-center retrospective cohort study. The analysis of 167 medical records in the Moscow Oblast Regional Perinatal Center (MOPC, located in Balashikha, Moscow Oblast, Russia) was carried out. Inclusion criteria: 1) newborns with GA of less than 32 weeks; 2) information corresponding to the primary variables of this research in the patient's medical records; 3) patients were treated during the period from Apr. 22 to Dec. 24, 2021. Exclusion criteria: 1) lethal outcome, 2) congenital malformations affecting the outcome, 3) chromosomal and/or genetic abnormalities. Two groups: G1 (“NEC”) of 35 patients with NEC; G2 (“without NEC”) of 132 without NEC. Results: NEC incidence was 8.3% (35/167). Prenatal factors that are statistically significantly more common in the NEC group: an increase in the level of C-reactive protein (CRP) in the mother's blood prior to the delivery (p=0.003), an increase in pathogenic microflora during pregnancy (p=0.010), detection of Enterococcus faecalis during pregnancy (p=0.016), delivery by the C-section (p=0.028) and the C-section due to fetal deterioration (p=0.001). In premature newborns from the NEC group, a decrease in serum albumin (SA) concentration was statistically significantly more common in the first 30 hours of life (p&lt;0.001). The use of dexamethasone in the first 168 hours of life (p=0.003) and for the prevention of bronchopulmonary dysplasia (p=0.010) was statistically significantly more common in patients with NEC. Conclusion: the earliest prenatal predictors of NEC in surviving premature newborns with the GA at birth of less than 32 weeks are as follows: an increase in the level of CRP in the mother's blood prior to the delivery, the growth of pathogenic microflora during pregnancy, esp. of the fecal Enterococcus, the C-section, esp. due to the deterioration of the fetus; and the postnatal predictors of NEC are as follows: lower concentration of SA in premature infants in the first 30 hours of life, the use of dexamethasone in the neonatal period.