Rates Of Necrotizing Enterocolitis Research Articles

Timing of Red Blood Cell Transfusions and Occurrence of Necrotizing Enterocolitis

Observational studies often report that anemia and red blood cell (RBC) transfusions are associated with a higher risk of necrotizing enterocolitis (NEC) among extremely low-birthweight (ELBW) infants. To evaluate whether there is a temporal association between 72-hour hazard periods of exposure to RBC transfusions and NEC among ELBW infants randomized to either higher or lower hemoglobin transfusion thresholds. This post hoc secondary analysis of 1690 ELBW infants who survived to postnatal day 10 enrolled in the Transfusion of Prematures (TOP) randomized multicenter trial between December 1, 2012, and April 12, 2017, was performed between June 2021 and July 2023. First, the distribution of RBC transfusions and the occurrence of NEC up to postnatal day 60 were examined. Second, 72-hour posttransfusion periods were categorized as hazard periods and the pretransfusion periods of variable duration as control periods. Then, the risk of NEC in posttransfusion hazard periods was compared with that in pretransfusion control periods, stratifying the risk based on randomization group (higher or lower hemoglobin transfusion threshold group). The primary outcome was incidence of NEC stage 2 or 3. Secondary outcomes included the incidence rates of NEC within five 10-day intervals, taking into account the number of days at risk. Of 1824 ELBW infants randomized during the TOP trial, 1690 were included in the present analysis (mean [SD] gestational age, 26.0 [1.5] weeks; 899 infants [53.2%] were female). After categorizing 4947 hazard periods and 5813 control periods, we identified 133 NEC cases. Fifty-nine of these cases (44.4%) occurred during hazard periods. Baseline and clinical characteristics of infants with NEC during hazard periods did not differ from those of infants with NEC during control periods. The risk of NEC was 11.9 per 1000 posttransfusion hazard periods and 12.7 per 1000 control periods (adjusted risk ratio, 0.95; 95% CI, 0.68-1.32; P = .74). This risk did not differ significantly between randomization groups, but the incidence rate of NEC per 1000 days peaked between postnatal days 20 and 29 in the lower hemoglobin transfusion threshold group. The findings of this post hoc analysis suggest that, among ELBW infants with the hemoglobin ranges occurring in the TOP trial, exposure to RBC transfusions was not temporally associated with a higher risk of NEC during 72-hour posttransfusion hazard periods. Given that the incidence rate of NEC peaked between postnatal days 20 and 29 among infants with lower hemoglobin values, a more in-depth examination of this at-risk period using larger data sets is warranted. ClinicalTrials.gov Identifier: NCT01702805.

No differences were observed in the prevention of necrotizing enterocolitis and late–onset sepsis among preterm infants who received either single–species or multi–species probiotics

BackgroundProbiotic prophylaxis has been suggested to reduce the incidence of necrotizing enterocolitis (NEC) and late–onset sepsis (LOS) in very preterm newborns. However, choosing the optimal probiotic is difficult due to variations in strain–specific effects and interactions facilitated by the use of combination species. AimsTo compare clinical outcomes of very preterm infants receiving multi or single–species probiotics. Study designRetrospective, single–center, cohort study. SubjectsVery preterm infants (<32 weeks' gestation) born between 2019 and 2022 at a tertiary perinatal center received either a multi–species (Lactobacillus rhamnosus 45 %, Lactobacillus casei 15 %, Lactobacillus acidophilus 15 %, Bifidobacterium infantis 15 %, Bifidobacterium bifidum 10 %; n = 228) or a single–species (Bifidobacterium breve BR03 and B632; n = 227) probiotic formulation. Main outcome measuresNEC, LOS, and mortality. ResultsThe overall incidence of NEC and LOS was 3.1 % and 13.8 %, respectively. There were no differences between the multi–species and single–species probiotic groups in the rate of NEC (3.5 % vs 2.6 %; p = 0.787), LOS (15.4 % vs 12.3 %; p = 0.416), mortality (0.9 % vs 1.8 %; p = 0.449), or composite outcome (NEC, LOS and/or death; 16.7 % vs 12.8 %; p = 0.290). ConclusionThe clinical outcomes of very preterm newborns receiving multi vs. single–species probiotic formulations were similar in our study. In view of the sample size and low baseline rate of NEC in our unit, further trials are warranted to investigate the effects of specific probiotics for prevention of serious neonatal morbidities.

Determination of surgical intervention in pre-term infants with necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is the most common surgical disease in the neonatal period with a high mortality rate. To date, there is no consensus on the indications for surgery in the absence of pneumoperitoneum. This study aimed to determine the indications for surgery in pre-term infants with NEC and their mortality. We conducted a descriptive, observational, cross-sectional, and retrospective study including pre-term infants with NEC from two perinatal hospitals in Toluca, Mexico, between 2017 and 2022. Descriptive and inferential statistics and group comparisons were performed using Fisher and Kruskal-Wallis tests. Of 236 patients with NEC, 52 (22%) required surgery; we analyzed 42 cases with complete clinical records. The indications for surgery were divided into (a) clinical deterioration (33.3%); (b) radiographic findings (31%); (c) laboratory alterations (19%); and (d) positive paracentesis (16.7%). The group of radiographic findings underwent surgery later, up to 2 days after the other groups. The mortality rate of surgical NEC was 42.9%. The most common indication for surgery in pre-term infants with NEC was clinical worsening despite optimal medical management; radiographic findings were the indication associated with the highest mortality. Laboratory abnormalities and positive paracentesis were the indications with the best outcomes but the least used.

A prospective evaluation of the risk factors and utility of GutCheckNEC scoring system to predict necrotizing enterocolitis in preterm newborns, in a tertiary care centre in North India

Background: Necrotizing enterocolitis (NEC) is a serious gastrointestinal disease of neonate with high fatality. GutCheckNEC scoring system can be used in predicting NEC and decrease NEC rate. Aims: To assess risk factors and use scoring system GutCheckNEC in predicting necrotising enterocolitis. Methods: A prospective observational study with preterms, birth weight &lt;1500grams was done. Risk factor assessment was done using GutCheckNEC and serial scorings were done. Descriptive analyses of the various risk factors assessed were done. Results: 51 babies included, with gestational age 24 to 35 weeks (Median (IQR) 30+2 (27+2, 31+6), birth weight 500 to 1500 grams (Median (IQR) – 1105 (893, 1300). 9 NEC cases, 6(11.5%) confirmed NEC and 2(22%) were surgical NEC. Absence of ANS, HsPDA and late onset sepsis were risk factors. The median (IQR) scoring at 72 hrs., 86 hrs., 7 days, 14days, 21days and 28 days were 34 (31, 38), 34 (30, 39), 34 (26, 43), 31 (23, 35), 35 (23, 38), 35 (30, 40). The median risk for developing NEC was high (33-36) on all days except day 14, when it was moderate (20-32). The sensitivity and specificity for a cut off &gt;32 at 86hours was 85.7% and 48.5% (PPV – 26.1%, NPV – 94%) for medical NEC and 100% and 44.7% (PPV – 8.7%, NPV – 100%) respectively for surgical NEC. Conclusion: Hence we conclude that GUTCHECK can help in early prediction of NEC and prevention of NEC.

A Quality Improvement Initiative to Reduce Necrotizing Enterocolitis in Very Preterm Infants.

To reduce the incidence of necrotizing enterocolitis (NEC) among very preterm infants in the Calgary Health Region to ≤2% within 2 years. A multidisciplinary team developed key drivers for NEC. Targeted interventions included strategies to increase mothers' own milk (MOM), improve compliance with feeding regimens, standardize management of feeding intolerance, prevent intestinal microbial aberrations, and feed conservatively during blood transfusion and the treatment of patent ductus arteriosus. The outcome measure was NEC (≥ stage 2). Changes in NEC rates were examined among racial and ethnic groups. Process measures included MOM feeding at discharge, the difference between actual and expected time to reach full feeds, lowest hemoglobin, and the duration of empirical antibiotics. Growth, the rate of blood transfusion, and the duration of parenteral nutrition were balancing measures. The preintervention, intervention, and sustainment periods were January 2013 to June 2016, July 2016 to December 2018, and December 2018 to December 2021, respectively. We included 2787 infants born at ≤326/7 weeks' gestation (1105 preintervention, 763 during intervention, and 919 in sustainment). NEC decreased from 5.6% to 1.9%. Process measures indicated increased MOM feeding at discharge, improved compliance with feeding regimens, increased lowest hemoglobin levels, and shorter durations of empirical antibiotics. Balancing measures revealed improved weight Z-scores, shorter durations on parenteral nutrition, and increased rates of blood transfusion. Quality improvement initiatives to increase MOM, improve compliance with feeding regimens, feed conservatively during blood transfusion and treatment of patent ductus arteriosus, and prevent intestinal microbial aberrations were associated with reduced NEC.

Complications and Outcomes of Nutritional Guidelines Implementation in Low Birth Weight Infants

Background: Necrotizing enterocolitis (NEC) is one of the most disastrous complications of premature infants. Using preterm feeding protocols can decrease NEC risk and improve feeding intolerance. Objective: To compare the rate of NEC and other comorbidities between low-birth-weight (LBW) infants that received a Bhumibol Adulyadej Hospital (BAH) standardized feeding protocol and those that underwent previous nutritional practice. Materials and Methods: A quasi-experimental study was conducted at neonatal intensive care unit (NICU) in BAH, Thailand. Participants were LBW newborns delivered at BAH between December 1, 2018 and March 31, 2020. The subjects were divided into the control group who underwent previous nutritional practice and the study group who were implemented with a new nutritional guideline. Primary outcome was NEC rate. Secondary outcomes were preterm complications such as neonatal sepsis, catheter-related bloodstream infection, parenteral nutrition-associated liver disease, osteopenia of prematurity, and intraventricular hemorrhage. Feeding achievement outcomes and growth outcome parameters were also evaluated. Results: Data were analyzed on 71 infants in the control group and 68 infants in the study group. The rate of NEC was not different between the two groups with 7% in the control versus 5.9% in the study (p=1.000). In addition, other preterm complications were not different between groups. However, the time to reaching full enteral feeding was shorter in the study group at 14 in the control versus 10 in the study (p&lt;0.001). Day of life when the fortification start was significantly earlier in the study group at 15.5 in the control versus 12 in the study (p=0.008). Other feeding achievement outcomes also improved, which was evidenced by fewer parenteral nutrition (PN) days at 11.55 in the control versus 7.0 in the study (p=0.004) and shorter duration of indwelling central line at 9.5 in the control versus 7 in the study (p=0.001). Conclusion: Initiation of the new nutritional guideline produced a lower rate of NEC as compared to previous practice. Furthermore, the time to full enteral feeding, PN days, and central line days were decreased without increasing other preterm complications. Keywords: Low birth weight; Nutrition; Complication; NEC

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.

Implementing an exclusive human milk diet for preterm infants: real-world experience in diverse NICUs

BackgroundHuman milk–based human milk fortifier (HMB-HMF) makes it possible to provide an exclusive human milk diet (EHMD) to very low birth weight (VLBW) infants in neonatal intensive care units (NICUs). Before the introduction of HMB-HMF in 2006, NICUs relied on bovine milk–based human milk fortifiers (BMB-HMFs) when mother's own milk (MOM) or pasteurized donor human milk (PDHM) could not provide adequate nutrition. Despite evidence supporting the clinical benefits of an EHMD (such as reducing the frequency of morbidities), barriers prevent its widespread adoption, including limited health economics and outcomes data, cost concerns, and lack of standardized feeding guidelines.MethodsNine experts from seven institutions gathered for a virtual roundtable discussion in October 2020 to discuss the benefits and challenges to implementing an EHMD program in the NICU environment. Each center provided a review of the process of starting their program and also presented data on various neonatal and financial metrics associated with the program. Data gathered were either from their own Vermont Oxford Network outcomes or an institutional clinical database. As each center utilizes their EHMD program in slightly different populations and over different time periods, data presented was center-specific. After all presentations, the experts discussed issues within the field of neonatology that need to be addressed with regards to the utilization of an EHMD in the NICU population.ResultsImplementation of an EHMD program faces many barriers, no matter the NICU size, patient population or geographic location. Successful implementation requires a team approach (including finance and IT support) with a NICU champion. Having pre-specified target populations as well as data tracking is also helpful. Real-world experiences of NICUs with established EHMD programs show reductions in comorbidities, regardless of the institution’s size or level of care. EHMD programs also proved to be cost effective. For the NICUs that had necrotizing enterocolitis (NEC) data available, EHMD programs resulted in either a decrease or change in total (medical + surgical) NEC rate and reductions in surgical NEC. Institutions that provided cost and complications data all reported a substantial cost avoidance after EHMD implementation, ranging between $515,113 and $3,369,515 annually per institution.ConclusionsThe data provided support the initiation of EHMD programs in NICUs for very preterm infants, but there are still methodologic issues to be addressed so that guidelines can be created and all NICUs, regardless of size, can provide standardized care that benefits VLBW infants.

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.

Inhaled Nitric Oxide and Higher Necrotizing Enterocolitis Rates in Congenital Heart Disease Patients

IntroductionCertain congenital cardiac lesions are at increased risk for the development of necrotizing enterocolitis (NEC). These patients are often reliant on pulmonary and systemic vasomodulators to maintain adequate perfusion and oxygenation. This study sought to determine whether pulmonary or systemic vasodilator treatment is protective against the development of NEC in this population. MethodsWe utilized International Classification of Diseases (ICD) codes to identify high risk congenital cardiac disease patients ≤6 mo of age, cared for at a tertiary children's hospital between January 2011 and January 2021. Cardiac anomalies were stratified into ductal dependent (pulmonary DD-P or systemic DD-S) or independent lesions. The rate of NEC development in those who received vasodilators (inhaled nitric oxide [iNO], pulmonary vasodilators, systemic vasodilators) was compared to controls in a multivariate analysis. ResultsOf the 352 patients, who met inclusion criteria, 77.6% had ductal dependent lesions (DD-S 41.9%, DD-P 35.7%), 19.5% received iNO, and 37.5% received other vasodilatory drugs. The overall NEC rate was 15.1%. On univariate analysis, DD-S, iNO use, and systemic vasodilators was associated with a significantly higher risk of NEC, while DD-P was associated with lower NEC risk. On multivariate analysis, only iNO (odds ratio 2.725, confidence interval [1.36-5.44]) and DD-S (odds ratio 2.279, confidence interval [1.02-5.11]) were independent risk factors for NEC. ConclusionsIn patients with at-risk congenital cardiac disease lesions, a ductus dependent systemic circulation or iNO treatment is associated with an increased risk of developing NEC. The presence of iNO or DD-S should be utilized as markers of increased risk both in the prevention and workup of suspected NEC.

Enteral supplementation with probiotics in preterm infants: A retrospective cohort study and 6-year follow-up.

The objective of this retrospective cohort study was to assess the impact of an enteral probiotics supplementation protocol on the incidence of necrotizing enterocolitis (NEC) in infants born <33 weeks gestational age (GA) or birth weight (BW) <1,500 g. In addition, a 6-year follow-up is presented after instigation of probiotic use. In October 2014, our NICU introduced an enteral probiotics supplementation protocol for infants born <33 weeks GA or BW <1,500 g. Infants received 0.5 g of Bifidobacterium breve HA-129, Lacticaseibacillus rhamnosus HA-111, Bifidobacterium bifidum HA-132, Bifidobacterium longum subsp. infantis HA-116, and Bifidobacterium longum subsp. longum HA-135 (FloraBABYⓇ) daily until discharge or transfer from hospital. The incidence of NEC was compared among infants for 2 years pre- and post implementation of the protocol then 6-years following continuous implementation of the probiotic use. In total, 370 infants not treated with probiotics between 2012 and 2014 were included with an incidence of NEC at 4.9%. In comparison, the 367 infants who received had a 67% reduction (4.9-1.6%, p = 0.01) in our Neonatal Intensive Care Unit (NICU). The results remained significant (aOR = 0.26; 95% CI: 0.09, 0.72; p < 0.01) after adjusting for GA, small for gestational age, and antenatal corticosteroid use. Data from the Canadian Neonatal Network not only showed a consistently high rate of NEC in October 2014, but also identified exceedingly high rates (8.7-15.6%) in some hospitals up to 2021, while our rates have been consistently low with using the probiotic as standard therapy for low BW premature babies, with no serious side effects reported. In conclusion, the introduction of a five-strain probiotic natural health product has coincided with a reduced incidence and complications of NEC in our NICU setting.

Association between Abnormal Antenatal Doppler Characteristics and Gastrointestinal Outcomes in Preterm Infants

Antenatal Doppler disturbances are associated with fetal hypoxia and may induce a brain-sparing vascular redistribution at the expense of splanchnic circulation, possibly predisposing to gut complications. We aimed to compare several gastrointestinal outcomes among very-low-birthweight (VLBW) preterm infants with different antenatal Doppler features. VLBW infants born between 2010-2022 were retrospectively included and stratified into the following clusters based on antenatal Doppler characteristics: normal Doppler (controls); absent or reversed end-diastolic flow in the umbilical artery (UA-AREDF) alone or also in the ductus venosus (UA+DV-AREDF); and abnormal Doppler with or without brain-sparing redistribution. The following outcomes were evaluated: time to reach full enteral feeds (FEF), feeding intolerance (FI), necrotizing enterocolitis (NEC), and spontaneous intestinal perforation (SIP). Overall, 570 infants were included. Infants born following UA+DV-AREDF had significantly higher FI, NEC, and SIP rates and achieved FEF later compared to controls. Increased FI prevalence and a longer time to FEF compared to controls were also observed among UA-AREDF infants and in the presence of brain-sparing redistribution, which also increased NEC rates. Antenatal Doppler abnormalities exacerbate the gastrointestinal risks of preterm infants. Detailed knowledge of Doppler features can aid in identifying those at highest risk of intestinal complications who may benefit from tailored enteral feeding management.

25 Paracetamol versus Indomethacin for management of Patent Ductus Arteriosus in Premature Infants- A Systematic Review and Meta-Analysis

Abstract Background Premature infants with hemodynamically significant patent ductus arteriosus (HsPDA) have high rates of morbidity and mortality in neonatal units. Indomethacin has been the most common agent used for pharmacological closure of the PDA. Recently, paracetamol has gained interest in the neonatal community for its use for management of HsPDA. Objectives To conduct a systematic review of randomized controlled trials (RCTs) comparing the efficacy and safety of paracetamol with indomethacin for HsPDA management in preterm infants. Design/Methods We searched PROSPERO, OVID Medline, OVID EMBASE, Wiley Cochrane Library (CDSR and Central), EBSCO CINAHL, and SCOPUS using controlled vocabulary and key words representing the concepts "preterm neonates" and "acetaminophen" and "indomethacin". Databases were searched from inception to June 15, 2021. Bibliographies of identified studies were searched for additional references. Studies were included if they enrolled preterm infants with HsPDA (diagnosed on echocardiogram), and randomised them for treatment with paracetamol or indomethacin for the primary outcome of HsPDA closure. Discrepancies among reviewers for study selection, RoB assessments, and data extraction were resolved by consensus. Data were analyzed with the help of Review Manager (RevMan) Version 5.3. Results Four RCTs were identified, enrolling a total of 380 subjects. There was no difference between the two interventions for the rates of PDA closure either after one course (4 studies; RR 1.04 [95% CIs: 0.84, 1.29], p-value 0.70) or after two courses of treatment (2 studies; RR 1.01 [95% CIs: 0.92, 1.12], p-value 0.77), and for PDA ligation (3 studies; RR 1.56 [95% CIs: 0.48, 5.12], p-value 0.46). However, the patients who received paracetamol had lower rates of necrotizing enterocolitis (NEC) (3 studies; RR 0.37 [95% CIs: 0.14, 0.95], p-value 0.04). There were no significant differences noted in the other important secondary outcomes, i.e., Intraventricular hemorrhage, bronchopulmonary dysplasia, retinopathy of prematurity requiring treatment, and death. Two studies reported baseline and post-treatment serum markers for renal and hepatic injury; there was significant post-treatment elevation of serum creatinine and blood urea noted with the indomethacin use in each of these studies, as compared to no change noted with paracetamol use. Conclusion The efficacy of paracetamol is comparable to indomethacin for the outcome of PDA closure, with lesser rate of NEC and post-treatment azotemia noted with the paracetamol use. Paracetamol should be preferred over indomethacin for HsPDA management in premature infants.

Inhaled Nitric Oxide Treatment Is Associated with Higher Rates of Necrotizing Enterocolitis in At-risk Congenital Cardiac Disease Patients

INTRODUCTION: Certain congenital cardiac lesions are at increased risk for the development of necrotizing enterocolitis (NEC). These patients with these lesions are often reliant on pulmonary and systemic vasomodulators to maintain adequate perfusion and oxygenation. This study sought to determine whether pulmonary or systemic vasodilator treatment is protective against the development of NEC in this population. METHODS: We used ICD codes to identify high-risk congenital cardiac disease patients ≤6 months of age, cared for at a tertiary children’s hospital between January 2011 and January 2021. Cardiac anomalies were stratified into ductal-dependent (pulmonary DD-P or systemic DD-S) or independent lesions. The rate of NEC development in those who received vasodilators (inhaled nitric oxide [iNO], pulmonary vasodilators, systemic vasodilators) was compared with controls in a multivariate analysis. RESULTS: Of the 353 patients who met inclusion criteria, 77.6% had ductal-dependent lesions (DD-S 41.9%, DD-P 35.7%), 19.5% received iNO, and 51.8% received other vasodilatory drugs. The overall NEC rate was 15.3%. On univariate analysis, DD-S, iNO use, and systemic vasodilators had a significantly higher risk of NEC, and DD-P was associated with lower NEC risk (Figure). On multivariate analysis, only iNO (odds ratio 2.725 [CI 1.36 to 5.44]) and DD-S (odds ratio 2.279 [CI 1.02 to 5.11]) were independent risk factors for NEC.FigureCONCLUSION: In patients with at-risk congenital cardiac disease lesions, a ductus-dependent systemic circulation and/or iNO treatment increases the risk of developing NEC. The presence of iNO or DD-S should be used as a marker of increased risk both in the prevention and workup of suspected NEC.

Effects of Probiotics on Gut Microbiomes of Extremely Preterm Infants in the Neonatal Intensive Care Unit: A Prospective Cohort Study

Background: Probiotics have been previously reported to reduce the incidence of necrotizing enterocolitis (NEC) in extremely preterm infants, but the mechanisms by which the probiotics work remain unknown. We aimed to investigate the effects of probiotics on the gut microbiota of extremely preterm infants. Methods: A prospective cohort study was conducted on 120 extremely preterm neonates (gestational age ≤ 28 weeks) between August 2019 and December 2021. All neonates were divided into the study (receiving probiotics) and the control (no probiotics) groups. Multivariate logistic regression analysis was performed to investigate the significantly different compositions of gut microbiota between these two groups. The effects of probiotics on the occurrence of NEC and late-onset sepsis were also investigated. Results: An increased abundance of Lactobacillus was noted in neonates who received the probiotics (AOR 4.33; 95% CI, 1.89–9.96, p = 0.009) when compared with the control group. Subjects in the probiotic group had significantly fewer days of total parenteral nutrition (median [interquartile range, IQR]) 29.0 (26.8–35.0) versus 35.5 (27.8–45.0), p = 0.004) than those in the control group. The probiotic group had a significantly lower rate of late-onset sepsis than the control group (47.1% versus 70.0%, p = 0.015), but the rate of NEC, duration of hospitalization and the final in-hospital mortality rates were comparable between these two groups. Conclusions: Probiotic supplementation of extremely preterm infants soon after the initiation of feeding increased the abundance of Lactobacillus. Probiotics may reduce the risk of late-onset sepsis, but further randomized controlled trials are warranted in the future.

Analysis of clinical features of neonates with congenital heart disease who develop necrotizing enterocolitis: a retrospective case-control study.

BackgroundInfants with congenital heart disease (CHD) are known to have higher rates of necrotizing enterocolitis (NEC). Although the etiology is recognized as distinct from the premature neonatal population, there is not a universal consensus regarding etiology or specific risk factors. To analyze the clinical features of neonates with CHD who develop NEC.MethodsA retrospective study of neonates with CHD in the cardiac intensive care unit (ICU) between 2015 and 2018 was performed, and modified Bell’s criteria were used to diagnose NEC. Patients were divided into 2 groups according to ductal-dependent (DD) lesions, and were further stratified by Risk Adjustment for Congenital Heart Surgery-1 (RACHS-1) score and Aristotle score, to compare the differences.ResultsAmong 412 patients with CHD, 69 (16%) developed NEC. The incidence of NEC was notably higher among DD patients than among non-DD (nDD) patients (18.7% vs. 11.1%; P=0.04). Patients with RACHS-1 >2 also had a higher rate of NEC than did those with RACHS-1 ≤2 (19.49% vs. 9.29%; P=0.01). nDD patients who developed NEC were younger, had a lower gestational age (36.25±1.88 vs. 38.10±1.28 weeks; P=0.00), a lower weight (2.86±0.85 vs. 3.33±0.55 kg; P=0.01), and a lower birth weight (2.79±0.79 vs. 3.26±0.55; P=0.01) compared to the DD group. All nDD patients developed NEC after congenital heart surgery, while only 38 cases (76%), NEC occurred after heart surgery in the DD group. Four patients needed surgery for NEC in the DD group and RACHS-1 >2 group. Presence of NEC was not associated with an increased risk of mortality in any group.ConclusionsNEC is a common complication in neonates with CHD and can occur both before and after CHD operations. Likely there are varying mechanism for NEC in different forms of CHD. While NEC is more common in patients with DD CHD and those with more complex forms of CHD, there was no significant difference observed in weight-for-age Z-score (WAZ) between the DD group during follow-up.

A quality improvement initiative to reduce necrotizing enterocolitis in high-risk neonates.

Prompted by an acute increase in necrotizing enterocolitis (NEC) rates, we aimed to decrease the rate of stage 2 or greater NEC in infants born at <1500 grams or <30 weeks gestational age from 19.5% to less than 9.7% (a 50% reduction) within 18 months, without adversely affecting central line-associated bloodstream infection (CLABSI) rates. We utilized Define, Measure, Analyze, Improve, and Control (DMAIC) as our improvement model. Informed by our key driver diagram and root cause analyses, six Plan-Do-Study-Act cycles were completed. 147 infants in the QI initiative had a median gestational age of 28.1 weeks and a median birthweight of 1070 grams. NEC rates decreased from the QI baseline of 19.5% to 6% (p = 0.03). Oral care administration increased, and maximal gavage tube dwell time decreased. NEC rates decreased during this QI initiative through a combination of multidisciplinary interventions aimed at reducing dysbiosis.

Is Early Preventive Caffeine Safe and Effective in Premature Neonates? A Clinical Trial.

Background Advantages of caffeine for the treatment of apnea of prematurity (AOP) have prompted clinicians to use it as a preventive drug even before the occurrence of apnea. Objective To compare the effect of early preventive caffeine therapy with routine late preventive caffeine on the occurrence rate of apnea of prematurity, bronchopulmonary dysplasia (BPD) and related radiographic changes, necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), and patent ductus arteriosus (PDA), the need for mechanical ventilation, the length of mechanical ventilation, and the length of hospitalization. Materials and Methods In this open randomized clinical trial study, 90 preterm neonates with the gestational age of 25-35 weeks were divided into 2 groups: group A received caffeine during the first two days of life (early preventive caffeine), while group B received caffeine during the third to the tenth day of life (late preventive caffeine). The occurrence rate of AOP and other outcomes were the primary outcomes. The adverse effects of caffeine in each group were the secondary outcomes. Results The total occurrence rate of AOP was significantly higher (32.6%) in the late group versus (6.8%) in the early group (p = 0.002). The total occurrence rate of BPD was also significantly higher (37%) in the late group versus (18.2%) in the early group (p = 0.047). On the other hand, we found a lower need for mechanical ventilation, shorter length of mechanical ventilation, shorter length of hospitalization, and a lower occurrence rate of PDA, NEC, and IVH in the early group that was not significant. No adverse effect of caffeine was observed in each group. Conclusions Early preventive caffeine administration was associated with a significantly lower occurrence rate of AOP, BPD, and BPD radiologic changes. As other outcomes occurred lesser in the early group that were not significant, future studies with more participants are recommended. This study has been registered at the Iranian Registry of Clinical Trials (IRCT20160827029535N8).