Does the duration of empiric antibiotic treatment influence NEC incidence and severity relative to placental pathology?

Oral probiotics reduce the incidence and severity of necrotizing enterocolitis in very low birth weight infants

Probiotic Bacteria Induce Maturation of Intestinal Claudin 3 Expression and Barrier Function

Neonatal Necrotizing Enterocolitis: Possible Role of Probiotic Supplementation

Necrotizing enterocolitis (NEC) is an important contributor towardmortality in extremely premature infants and Very Low Birth Weight(VLBW) infants. The incidence of NEC was 9% in VLBW infants(birth weight 401 to 1,500 grams) in the Vermont Oxford Network(VON, 2006 to 2010, n = 188,703).1 The incidence of NEC was 7%in 1993, increased to 13% in 2008, and decreased to 9% in extremelypreterm infants (22 to 28 weeks gestation) in the Neonatal ResearchNetwork Centers (1993 to 2012).2 The incidence of surgically treatedNEC varies from 28 to 50% in all infants who develop NEC.3 SurgicalNEC occurred in 52% in the VON cohort.1 In this cohort, the odds ofsurgery decreased by 5% for each 100 gram increase in birth.The incidence of surgical NEC has not decreased in the pastdecade.4 The mortality from NEC is significantly higher in infantswho need surgery compared to those who did not (35% versus 21%).1The case fatality rate among patients with NEC is higher in thosesurgically treated (23 to 36%) compared to those medically treated (5to 24%).3 In addition to surgery, NEC mortality rates are influencedby gestational age, birth weight,1,2,5 assisted ventilation on the day ofdiagnosis of NEC, treatment with vasopressors at diagnosis of NEC,and black race.6,7Extremely preterm infants who survive NEC are at risk for severeneurodevelopmental disability and those with surgical NEC have asignificantly higher risk of such delays (38% surgical NEC versus 24%medical NEC).8 Diagnosis of necrotizing enterocolitis is challengingand it is usually suspected based on non-specific clinical signs. Bell’scriteria and Vermont-Oxford Network criteria help in the diagnosisof NEC.Bell’s criteria, commonly used for diagnosis, staging, and planningtreatment of NEC, were described in 1978 and modified in 1986.9,10Bell’s stage I signs are non-specific: temperature instability, lethargy,decreased perfusion, emesis or regurgitation of food, abdominal distension,recurrent apnea, and on occasion, increased support withmechanical ventilation. Abdominal distension and emesis are morecommon than bloody stools in very preterm infants compared to terminfants.7 Abdominal radiographic findings are an integral part of Bell’scriteria. Identification of Bell’s stage I NEC (early NEC) with abdominalradiograph is challenging, as the features on abdominal radiograph(normal gas pattern or mild ileus) are non-specific. With progressionof NEC to Bell Stage IIA, the symptoms (grossly bloody stools,prominent abdominal distension, absent bowel sounds) and featureson abdominal radiographs (one or more dilated loops and focal pneumatosis)are more specific.On the other hand, the Vermont Oxford Network criteria for NECconsist of at least one physical finding (bilious gastric aspirate oremesis, abdominal distension or occult/gross blood in the stool inthe absence of anal fissure) and at least one feature on abdominalradiograph (pneumatosis intestinalis, hepatobiliary gas, or pneumoperitoneum).1 These features correspond to Bell Stage IIA or StageIIB and are not features of early NEC. Thus relying solely on abdominalradiograph for diagnosis of early NEC, as is practiced currently,has significant drawbacks especially in extremely premature infants.7Ultrasound has been suggested to improve the percentage of infantsdiagnosed with early NEC.11 However, this imaging modality is notused routinely in the diagnosis or management of NEC.As the incidence of surgical NEC and mortality from NEC continuesto be high, the literature to demonstrate the shortcomings ofabdominal radiographs and promise of abdominal ultrasound in diagnosisof NEC is reviewed.

BackgroundTo explore the influences of prenatal antibiotic exposure, the intensity of prenatal and postnatal antibiotic exposure on gut microbiota of preterm infants and whether gut microbiota and drug resistant strains in the neonatal intensive care unit (NICU) over a defined period are related.MethodsAmong 28 preterm infants, there were two groups, the PAT (prenatal antibiotic therapy) group (12 cases), and the PAF (prenatal antibiotic free) group (12 cases). Fecal samples from both groups were collected on days 7 and 14. According to the time of prenatal and postnatal antibiotic exposure, cases were divided into two groups, H (high) group (11 cases) and L (low) group (11 cases), and fecal samples on day 14 were collected. Genomic DNA was extracted from the fecal samples and was subjected to high throughput 16S rRNA amplicon sequencing. Bioinformatics methods were used to analyze the sequencing results.ResultsPrenatal and postnatal antibiotic exposure exercised influence on the early establishment of intestinal microflora of preterm infants. Bacteroidetes decreased significantly in the PAT group (p < 0.05). The number of Bifidobacterium significantly decreased in the PAT group and H group (p < 0.05). The early gut microbiota of preterm infants with prenatal and postnatal antibiotic exposure was similar to resistant bacteria in NICU during the same period.ConclusionPrenatal and postnatal antibiotic exposure may affect the composition of early gut microbiota in preterm infants. Antibiotic-resistant bacteria in NICU may play a role in reshaping the early gut microbiota of preterm infants with prenatal and postnatal antibiotic exposure.

Necrotizing enterocolitis (NEC) is one of the most common gastrointestinal conditions affecting 6 to 10% of low-birth-weight infants and remains a leading cause of death. The risk factors associated with NEC are complex and multifactorial, including preterm birth and intrauterine exposure to inflammation and hypoxia. Chorioamnionitis has been associated with intestinal injury in animal and human clinical studies. This review presents current evidence about the clinical impact of the intrauterine environment on intestinal injury during pregnancy and postpregnancy. We present information from our own clinical and laboratory research in conjunction with information collected from an extensive search in the databases PubMed, EMBASE, and Scopus. Prospective multicenter studies, including accurate and precise clinical, maternal, and laboratory predictors (e.g., inflammatory biomarkers), will help identify the mechanisms associated with the placental pathology, the development of NEC, and the impact of in utero-triggered inflammation on the clinical outcomes. Filling the knowledge gap to link the inflammatory surge to postnatal life will aid in identifying at-risk infants for NEC in a timely manner and facilitate the development of novel immunomodulatory treatments or interventions to improve the outcomes of these vulnerable infants. KEY POINTS: · Placental inflammatory and vascular lesions are associated with NEC severity.. · Higher grade chorioamnionitis with a fetal response is associated with an increased risk of surgical NEC.. · There is a need for routine bedside utilization of placenta pathology in clinical decision-making..

BackgroundNecrotizing enterocolitis (NEC) and nosocomial sepsis are associated with increased morbidity and mortality in preterm infants. Through prevention of bacterial migration across the mucosa, competitive exclusion of pathogenic bacteria, and enhancing the immune responses of the host, prophylactic enteral probiotics (live microbial supplements) may play a role in reducing NEC and associated morbidity.ObjectivesTo compare the efficacy and safety of prophylactic enteral probiotics administration versus placebo or no treatment in the prevention of severe NEC and/or sepsis in preterm infants.Search methodsFor this update, searches were made of MEDLINE (1966 to October 2010), EMBASE (1980 to October 2010), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2010), and abstracts of annual meetings of the Society for Pediatric Research (1995 to 2010).Selection criteriaOnly randomized or quasi‐randomized controlled trials that enrolled preterm infants &lt; 37 weeks gestational age and/or &lt; 2500 g birth weight were considered. Trials were included if they involved enteral administration of any live microbial supplement (probiotics) and measured at least one prespecified clinical outcome.Data collection and analysisStandard methods of the Cochrane Collaboration and its Neonatal Group were used to assess the methodologic quality of the trials, data collection and analysis.Main resultsSixteen eligible trials randomizing 2842 infants were included. Included trials were highly variable with regard to enrollment criteria (i.e. birth weight and gestational age), baseline risk of NEC in the control groups, timing, dose, formulation of the probiotics, and feeding regimens. Data regarding extremely low birth weight infants (ELBW) could not be extrapolated. In a meta‐analysis of trial data, enteral probiotics supplementation significantly reduced the incidence of severe NEC (stage II or more) (typical RR 0.35, 95% CI 0.24 to 0.52) and mortality (typical RR 0.40, 95% CI 0.27 to 0.60). There was no evidence of significant reduction of nosocomial sepsis (typical RR 0.90, 95% CI 0.76 to 1.07). The included trials reported no systemic infection with the probiotics supplemental organism. The statistical test of heterogeneity for NEC, mortality and sepsis was insignificant.Authors' conclusionsEnteral supplementation of probiotics prevents severe NEC and all cause mortality in preterm infants. Our updated review of available evidence supports a change in practice. More studies are needed to assess efficacy in ELBW infants and assess the most effective formulation and dose to be utilized.Plain Language SummaryProbiotics for prevention of necrotizing enterocolitis in preterm infantsNecrotizing enterocolitis (NEC) is a serious disease that affects the bowel of premature infants in the first few weeks of life. Although the cause of NEC is not entirely known, milk feeding and bacterial growth play a role. Probiotics (dietary supplements containing potentially beneficial bacteria or yeast) have been used to prevent NEC. Our review of studies found that the use of probiotics reduces the occurrence of NEC and death in premature infants born less than 1500 grams. There is insufficient data with regard to the benefits and potential adverse effects in the most at risk infants less than 1000 grams at birth.

Lutein and zeaxanthin are nutrients with antioxidant properties found in the macula of the eye and brain tissue. They have been reported to play a role in reducing oxidative damage, especially in the eyes and possibly in other organ systems. Oxygen free radicals are one of the agents postulated to cause tissue damage in preterm infants, which leads to morbidities such as retinopathy of prematurity (ROP), intraventricular haemorrhage (IVH), and necrotising enterocolitis (NEC). Supplementation with lutein and zeaxanthin may reduce oxidative damage, hence reducing morbidity and mortality in preterm infants. To assess the effectiveness of lutein and zeaxanthin supplementation in reducing morbidity and mortality in preterm infants. We conducted searches up to 17 December 2024 in CENTRAL, MEDLINE, Embase, and two trial registries. We also searched the reference lists of included studies, and related reviews and studies. We included randomised controlled trials (RCTs), cluster-RCT, cross-over trials, and quasi-RCTs that compared lutein and zeaxanthin supplementation against placebo or no supplementation for preterm infants less than 37 completed weeks' postmenstrual age. We used standard Cochrane methods. Our primary outcomes were the incidence of any stage of ROP, incidence of ROP stage 3 and above, incidence of visual impairment, and mortality assessed throughout the neonatal intensive care unit (NICU) stay. Secondary outcomes included the incidence of IVH, incidence of NEC, and any reported adverse effects. We used GRADE to assess the certainty of the evidence. We included five studies (666 preterm infants) that compared lutein and zeaxanthin supplementation versus control (placebo or no supplementation). All five studies were conducted in high-income countries (Italy and the USA). We did not find any studies comparing lutein or zeaxanthin separately versus placebo or no supplementation. Most of the studies had a low risk of bias in most key domains, such as allocation concealment and blinding. The evidence suggests that lutein and zeaxanthin supplementation probably has little or no effect on ROP (any stage) when comparing infants who received lutein and zeaxanthin supplementation with those who did not (risk ratio (RR) 0.90, 95% confidence interval (CI) 0.66 to 1.24; P = 0.53; I2 = 0%; 4 studies, 532 infants; moderate-certainty evidence). Lutein and zeaxanthin supplementation probably reduces the incidence of ROP stage 3 and above (RR 0.49, 95% CI 0.29 to 0.81; P = 0.005; I2 = 0%; 4 studies, 532 infants; moderate-certainty evidence). No studies assessed the incidence of visual impairment. Lutein and zeaxanthin supplementation may have little or no effect on mortality assessed throughout the NICU stay (RR 0.95, 95% CI 0.42 to 2.17; P = 0.91; I2 = 0%; 4 studies, 470 infants; low-certainty evidence), incidence of IVH (all grades) (RR 0.87, 95% CI 0.44 to 1.75; P = 0.70; I2 = 0%; 4 studies, 483 infants; low-certainty evidence), and incidence of NEC: Bell's stage II or greater (RR 0.87, 95% CI 0.43 to 1.76; P = 0.71; I2 = 0%; 5 studies, 666 infants; low-certainty evidence). No adverse effects were reported in either group. While supplementation with lutein and zeaxanthin from day one of life in preterm infants until discharge probably reduces the incidence of ROP stage 3 and above, it may have little or no effect on the incidence of ROP at any stage, IVH or NEC, or mortality assessed throughout the NICU stay. However, the pooled estimates for these outcomes may change with further rigorously conducted trials. There were no adverse effects reported.

The relationship between early antibiotic exposure, necrotizing enterocolitis (NEC), and growth faltering (GF) in extremely preterm infants is unknown. We evaluated the association between peripartum and postnatal antibiotic exposure in the first week after birth with NEC and GF in this secondary analysis of Preterm Erythropoietin Neuroprotection Trial subjects. NEC was defined as Bell's stage ≥ IIA; GF was defined as decreased weight, length, or head circumference (HC) z-score from birth to discharge of < -0.8. Multivariable analyses were adjusted with maternal and infant factors. A total of 891 infants survived the first week and were included in the NEC analyses, while 828 infants survived to discharge and were included in the growth analyses. For every 1-day increase in infant antibiotic exposure during the first week after birth, there was a significantly increased adjusted hazard of NEC (aHR/day 1.14 [1.01-1.28], p = 0.034). Antibiotics for 3-4 days and 5-7 days total in the first week were associated with increased odds of weight GF (aOR 1.90 [1.21-2.99], aOR 2.32 [1.44-3.74]), length GF (aOR 1.76 [1.22-2.59], aOR 1.88 [1.26-2.80]), and HC GF (aOR 1.75 [1.08-2.84], aOR 1.87 [1.14-3.08]). Increased antibiotic exposure in the first week after birth was associated with NEC and GF risk. In this post-hoc analysis of a large multi-site trial, we found infant antibiotic exposure in the first week after birth was associated with an increased hazard of necrotizing enterocolitis in the extremely preterm infant after adjusting for maternal and infant factors. First week antibiotic exposure in the extremely preterm infant was associated with an increased odds of weight, linear, and head circumference growth faltering after adjusting for maternal and infant factors. These findings encourage the judicious use of early antibiotics in extremely preterm infants.

Placing a small volume of colostrum directly onto the buccal mucosa of preterm infants during the early neonatal period may provide immunological and growth factors that stimulate the immune system and enhance intestinal growth. These benefits could potentially reduce the risk of infection and necrotising enterocolitis (NEC) and improve survival and long-term outcome. To determine if early (within the first 48 hours of life) oropharyngeal administration of mother's own fresh or frozen/thawed colostrum can reduce rates of NEC, late-onset invasive infection, and/or mortality in preterm infants compared with controls. To assess trials for evidence of safety and harm (e.g. aspiration pneumonia). To compare effects of early oropharyngeal colostrum (OPC) versus no OPC, placebo, late OPC, and nasogastric colostrum. We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 8), MEDLINE via PubMed (1966 to August 2017), Embase (1980 to August 2017), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to August 2017). We also searched clinical trials registries for ongoing and recently completed trials (clinicaltrials.gov; the World Health Organization International Trials Registry (www.whoint/ictrp/search/en/), and the ISRCTN Registry), conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. We performed the last search in August 2017. We contacted trial investigators regarding unpublished studies and data. We searched for published and unpublished randomised controlled trials comparing early administration of oropharyngeal colostrum (OPC) versus sham administration of water, oral formula, or donor breast milk, or versus no intervention. We also searched for studies comparing early OPC versus early nasogastric or nasojejunal administration of colostrum. We considered only trials that included preterm infants at < 37 weeks' gestation. We did not limit the review to any particular region or language. Two review authors independently screened retrieved articles for inclusion and independently conducted data extraction, data analysis, and assessments of 'Risk of bias' and quality of evidence. We graded evidence quality using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We contacted study authors for additional information or clarification when necessary. We included six studies that compared early oropharyngeal colostrum versus water, saline, placebo, or donor, or versus no intervention, enrolling 335 preterm infants with gestational ages ranging from 25 to 32 weeks' gestation and birth weights of 410 to 2500 grams. Researchers found no significant differences between OPC and control for primary outcomes - incidence of NEC (typical risk ratio (RR) 1.42, 95% confidence interval (CI) 0.50 to 4.02; six studies, 335 infants; P = 0.51; I² = 0%; very low-quality evidence), incidence of late-onset infection (typical RR 0.86, 95% CI 0.56 to 1.33; six studies, 335 infants; P = 0.50; I² = 0%; very low-quality evidence), and death before hospital discharge (typical RR 0.76, 95% CI 0.34 to 1.71; six studies, 335 infants; P = 0.51; I² = 0%; very low-quality evidence). Similarly, meta-analysis showed no difference in length of hospital stay between OPC and control groups (mean difference (MD) 0.81, 95% CI -5.87 to 7.5; four studies, 293 infants; P = 0.65; I² = 49%). Days to full enteral feeds were reduced in the OPC group with MD of -2.58 days (95% CI -4.01 to -1.14; six studies, 335 infants; P = 0.0004; I² = 28%; very low-quality evidence).The effect of OPC was uncertain because of small sample sizes and imprecision in study results (very low-quality evidence).No adverse effects were associated with OPC; however, data on adverse effects were insufficient, and no numerical data were available from the included studies.Overall the quality of included studies was low to very low across all outcomes. We downgraded GRADE outcomes because of concerns about allocation concealment and blinding, reporting bias, small sample sizes with few events, and wide confidence intervals. Large, well-designed trials would be required to evaluate more precisely and reliably the effects of oropharyngeal colostrum on important outcomes for preterm infants.

The preterm infants are at risk of cerebellar injury and the risk factors for necrotizing enterocolitis (NEC) associated cerebellar injury are not fully understood. Determine the risk factors of cerebellar injury in infants with surgical necrotizing enterocolitis (NEC). Retrospective study compared clinical/pathological information between surgical NEC infants with and those without cerebellar injury detected on brain MRI obtained at term equivalent age. Cerebellar Injury patterns that we identified on MRI brain were cerebellar hemorrhage, siderosis and/or cerebellar volume loss. Cerebellar injury (21/65, 32.3%) in preterm infants with NEC was associated with patent ductus arteriosus (PDA) (18/21(85.7%) vs. 25/44(56.8%); p = 0.021), blood culture positive sepsis (13/21 (61.9%) vs. 11/44 (25%); p = 0.004) following NEC, predominantly grew gram positive bacteria (9/21(42.9%) vs. 4/44(9.1%); p = 0.001), greater red cell transfusion, higher rates of cholestasis following NEC and differences in intestinal histopathology (more hemorrhagic and reparative lesions) on univariate analysis. Those with cerebellar injury had higher grade white matter injury (14/21 (66.7%) vs. 4/44(9.1%) p = 0.0005) and higher-grade ROP (70.6% vs. 38.5%; p = 0.027) than those without cerebellar injury.On multilogistic regression, the positive blood culture sepsis (OR 3.9, CI 1.1-13.7, p = 0.03), PDA (OR 4.5, CI 1.0-19.9, p = 0.04) and severe intestinal pathological hemorrhage (grade 3-4) (OR 16.9, CI 2.1-135.5, p = 0.007) were independently associated with higher risk of cerebellar injury. Preterm infants with surgical NEC with positive blood culture sepsis, PDA, and severe intestinal hemorrhagic lesions (grade 3-4) appear at greater risk for cerebellar injury.

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.

Background. Damage to the intestine culminating in NEC may occur by reduced mesenteric blood flow, bacterial overgrowth, enteral feeding or a combination of these factors. Antenatal steroids, human milk, lower pH formula, enteral IgA and antibiotics have each been reported to lower the incidence of NEC. In this study, the inclusion of EPL in a PT formula led to an apparent reduction in the incidence of NEC but not other diseases in hospitalized PT infants. Methods. In a randomized, double-masked trial, PT infants (725-1375 g birth weight, n=119) were fed either a control formula (CF) or an egg phospholipid-supplemented formula (EPLF) made by replacing some coconut oil in CF with EPL (75% phosphatidylcholine, 20% phosphatidylethanolamine, 5% other PL). PT and T versions of CF and EPLF were fed from -3 mo to 2 mo and 2 mo to 12 mo, respectively (40 wks gestation = 0 mo). EPLF, but not CF, contained ARA (0.4%) and DHA (0.13%, total fatty acids). Infants were assigned to one of three treatments that were balanced for gender in three stratified weight ranges (725-925 g; 926-1150 g; 1151-1375 g): Control (CF from -3 mo to 12 mo, n=41); Late Supplementation (CF from -3 mo to -1 mo; EPLF from -1 mo to 12 mo, n=44); and Early Supplementation (EPLF from -3 mo to 12 mo, n=34). Subjects lost before 4 mo corrected age were replaced to ensure study of at least 30 infants/group through that age. Infants fed CF and EPLF had similar neonatal, perinatal and demographic characteristics. Results. Fifteen of 85 infants (17.6%) fed CF in hospital (Control and Late Supplementation) and 1 of 34 (2.9%) fed EPLF (Early Supplementation) developed NEC stage II or III (p<0.05). Diet had no apparent effect on other diseases including sepsis (CF, 28.2%; EPLF, 26.5%), BPD (CF,23.4%; EPLF, 23.5%), and ROP (CF,40.0; EPLF,38.2%). The incidence of NEC was higher among male than female infants (11/60 vs 5/59, p,<0.05). All 11 males who developed NEC were fed CF (11/43, 25.6%) (p<0.01 vs males fed EPLF). Summary. EPLF appeared to decrease the incidence of NEC but not other common diseases of PT infants. Conclusion. We speculate that EPL or some component of EPL (e.g., ARA, DHA or choline) protected the immature intestine by one of several plausible mechanisms. A prospective randomized trial to test the effect of EPLF on NEC seems warranted, because NEC remains a major cause of morbidity and mortality among PT infants.

Introduction: The management of neonates with congenital heart disease (CHD) may be complicated by necrotizing enterocolitis (NEC), however, there is limited multicenter data describing the incidence and outcomes of NEC in the CHD population. Objective: We aimed to assess the incidence and risk factors for the development of NEC in neonates with major CHD and the impact on survival. Methods: A retrospective cohort study of neonates with CHD was performed for all index hospitalizations of neonates (&lt;28 days) with major CHD between 2004 and 2014 using the Pediatric Health Information System database. The diagnosis of NEC was determined by the presence of ICD-9 code 777.5x. The incidence of NEC was determined as were risk factors for the development of NEC. Mortality was the primary outcome measure. Results: Of 38770 neonates with major CHD, 1448 (3.6%) were diagnosed with NEC. The rate of NEC varied between 0-8% by hospital and was not associated with hospital volume (p=0.4). Among neonates with a single, major CHD diagnosis, the rate of NEC was 6% in hypoplastic left heart syndrome (HLHS), 6% in truncus arteriosus (TA) , 4% in tetralogy of Fallot (TOF), 3% in aortic arch obstruction (AO), and 2% in transposition of the great arteries (TGA); these diagnoses accounted for 47% of all NEC. Prematurity and chromosomal anomalies were independently associated with the diagnosis of NEC (p≤0.01 for both). Unadjusted mortality among neonates with NEC was 24% compared to 12% in neonates without NEC (OR 2.4, 95%CI 2.1-2.7). When evaluating changes in adjusted mortality associated with NEC by CHD diagnosis, TOF mortality increased from 8% to 16% (p&lt;.01), TGA increased from 5% to 21% (p&lt;0.01), AO increased from 6% to 20% (p&lt;0.01), HLHS increased from 22% to 28% (p=.07), and TA decreased from 13% to 12% (p=0.7). Median LOS was higher in neonates with NEC than without NEC (54d [IQR 31-93] vs. 18d [IQR 9-34], p&lt;0.01) as was median hospital charge ($600k [IQR 310k-1.1m] vs. $220k [IQR 100k-430k], p&lt;0.01). Conclusions: The incidence of NEC among neonates with major CHD is highest in HLHS and TA. NEC is associated with significantly higher hospital mortality, LOS, and charges. Determining modifiable factors associated with NEC may allow for interventions to reduce morbidity in this population.

The Impact of Maternal Antibiotics on Neonatal Disease