Transfusion-associated Necrotizing Enterocolitis Research Articles

RBC transfusion and necrotizing enterocolitis in very preterm infants: a multicenter observational study

The causal relationship between Packed red blood cell (RBC) transfusion and necrotizing enterocolitis (NEC) remains uncertain. This study aims to provide an exploration of transfusion and NEC in very preterm infants. Using data from the Chinese Neonatal Network cohort study between 2019 and 2021, the analysis focused on very preterm infants (with a birth weight of < 1500 g or a gestational age of < 32 weeks) who developed NEC after receiving transfusions. The time interval between the prior transfusion and NEC was analyzed. An uneven distribution of the time interval implies an association of transfusion and NEC. Additionally, multivariable logistic analysis was conducted to detect the prognosis of defined transfusion-associated NEC(TANEC). Of the 16,494 infants received RBC transfusions, NEC was noted in 1281 (7.7%) cases, including 409 occurred after transfusion. Notably, 36.4% (149/409) of post-transfusion NEC occurred within 2 days after transfusion. The time interval distribution showed a non-normal pattern (Shapiro–Wilk test, W = 0.513, P < 0.001), indicating a possible link between transfusion and NEC. TANEC was defined as NEC occurred within 2 days after transfusion. Infants with TANEC had a higher incidence of death (adjusted OR 1.69; 95% CI 1.08 to 2.64), severe bronchopulmonary dysplasia (adjusted OR 2.03; 95% CI 1.41 to 2.91) and late-onset sepsis (adjusted OR 2.06; 95% CI 1.37 to 3.09) compared with infants without NEC after transfusion. Unevenly high number of NEC cases after RBC transfusions implies transfusion is associated with NEC. TANEC is associated with a poor prognosis. Further research is warranted to enhance our understanding of TANEC.

Comparing two different Protocols in Withholding Feeds around time of Packed Red Cell Transfusion and Occurrence of TANEC (Transfusion Associated Necrotizing Enterocolitis) in Preterm Neonates

Background: Necrotizing enterocolitis (NEC) is a gastrointestinal disease characterized by pneumatosis intestinalis, pneumoperitoneum, or intestinal necrosis accompanied by signs or symptoms of shock. Our study aims to determine incidence of occurrence of NEC in preterm neonates after red blood cell transfusion with different feeding protocols and to assess the value of withholding feeds around the pRBCs transfusion in decreasing the incidence of transfusion associated necrotizing enterocolitis (TANEC). Methods: The study was done on 90 preterms who received packed red blood cells (pRBCs) during their admission in the neonatal intensive care unit (NICU). Theywere divided in two groups according to different feeding protocols; Group (A): 45 preterms where only one feed was withheld during pRBCs transfusion and Group (B): 45 preterms where feeds were withheld 4 hours before till 4 hours after pRBCs transfusion. Results: The incidence of transfusion related NEC (positive TANEC) in preterm neonates and other complications of prematurity such as (intracranial hemorrhage (ICH), bronchopulmonary dysplasia (BPD), patent ductus arteriosus (PDA), retinopathy of prematurity (ROP) and pneumothorax in group (A) were relatively higher than those of group (B). Conclusion: The modulation of feeding protocol and necessity of keeping nothing per oral (NPO) before, during and after blood transfusion. Significant risk factors for NEC occurrence are feeding preterm before and after pRBCS transfusion, low birth weight, low gestational age, low APGAR score.

Current Understanding of Transfusion-associated Necrotizing Enterocolitis: Review of Clinical and Experimental Studies and a Call for More Definitive Evidence

Introduction:The association between red blood cell (RBC) transfusions and necrotizing enterocolitis (NEC), so-called transfusion-associated NEC (ta-NEC), was first described in 1987. However, further work is needed to confirm a causal relationship, elucidate underlying mechanisms, and develop possible strategies for prevention. We performed an extensive literature search in the databases PubMed, EMBASE, and Scopus.Areas covered:Although multiple retrospective human studies have strongly suggested an association between blood transfusions and subsequent occurrence of NEC, meta-analyses of randomized controlled trials (RCTs) testing RBC transfusion thresholds or the use of recombinant erythropoiesis-stimulating growth factors did not confirm an association of anemia with ta-NEC. These conflicting data necessitated the development of an animal model to elucidate mechanisms and causal factors. Data from this recent mouse model of ta-NEC highlighted the importance of sequential exposure to severe anemia followed by transfusion for development of ta-NEC.Expert opinion:This review summarizes current human and experimental data, highlights open questions, and suggests avenues for further research aimed at preventing ta-NEC in preterm infants. Further studies are required to delineate whether there is a tipping point, in terms of the level and duration of anemia, and to develop an effective strategy for blood management and the quality of RBC transfusions.

Feeding Practices and Effects on Transfusion-Associated Necrotizing Enterocolitis in Premature Neonates.

Red blood cell (RBC) transfusions have been implicated in the development of necrotizing enterocolitis (NEC) in premature infants. Some evidence exists to support that withholding feedings during transfusion reduces the risk of subsequent NEC development. To review the most recent literature on this topic to determine best evidence-based practice regarding withholding or not withholding feedings during RBC transfusions. Four databases were searched using keywords and MeSH terms including "necrotizing enterocolitis," "NEC," "NPO," and "transfusion," with specifications limiting the search to articles published in the last 10 years and limiting the population to neonates. Four studies did not demonstrate a reduction in transfusion-associated necrotizing enterocolitis (TANEC) with the implementation of feeding protocols during packed red blood cell (PRBC) transfusions. One study concluded that it could not confirm the benefit of withholding feeds during transfusion to reduce the risk of TANEC. A 2020 randomized controlled trial (RCT) found no difference in splanchnic oxygenation when enteral feeds are withheld, continued, or restricted during a PRBC transfusion. Holding feedings during PRBC transfusions did not result in adverse nutritional outcomes. To determine best evidence-based practice surrounding feeding protocols during RBC transfusions in very low-birth-weight and premature infants less than 37 weeks' gestation. It is recommended that large, multicentered, adequately powered RCTs be conducted in this area. Individual institutions should standardize their practice to improve quality, safety, and patient outcomes.

Impact of a Care Bundle on the Incidence of Necrotizing Enterocolitis in the Neonatal Intensive Care Unit

Objective: Evaluate the impact of a care bundle on the incidence of necrotizing enterocolitis (NEC) in the neonatal intensive care unit. Study Design: Retrospective, single-center, population comparison of patients diagnosed with NEC before and after implementing an NEC care bundle utilizing standardized feeding protocol, donor milk program, transfusion protocol, early antibiotic protocol, and restricted indomethacin use. Result: Incidence of NEC fell from 1.92 to 0.83% (P &lt;0.0001). Incidence of NEC in the 23-27 weeks gestation group decreased from 14.21 to 6.09% (P = 0.0009). In the 28-30 weeks gestation group, NEC incidence decreased from 5.56 to 2.10% (P = 0.0096). Significant reduction of recurrent NEC and transfusion-associated NEC was observed. Conclusion: Implementation of an NEC care bundle reduced NEC incidence, with the greatest impact seen in the most vulnerable preterm and very preterm infants.

Analysis of risk factors for neonatal transfusion-associated necrotizing enterocolitis

Objective To investigate the clinical relevant factors associated with transfusion associated necrotizing enterocolitis (TANEC) in order to reduce the incidence of neonatal necrotizing enterocolitis (NEC). Methods The clinical data of neonates admitted to the First Hospital of Lanzhou University and received blood transfusion therapy from January 2017 to June 2018 were collected, including perinatal factors, basic conditions of children, and comorbidities.According to the occurrence or absence of NEC within 48 hours after transfusion, the patients were divided into TANEC group and no-TANEC group.The clinical data of the two groups were compared. Results Univariate analysis showed that there were statistical differences (P<0.05) in the mode of delivery, gestational age, birth weight, neonatal sepsis, patent ductus arteriosus(PDA), neonatal respiratory distress syndrome (NRDS), and anemia.The logistic multivariate analysis revealed that gestational age(P<0.05, OR=0.772, 95%CI: 0.684-0.871), the birth weight(P<0.05, OR=0.236, 95%CI: 0.079-0.711)were protect fators of TANEC, the degree of anemia(mode 1: P<0.05, OR=3.129, 95%CI: 1.003-9.756; mode 2: P<0.05, OR=3.449, 95%CI: 1.024-11.609)and sepsis (mode 1: P<0.05, OR=6.327, 95%CI: 1.732-23.720; mode 2: P<0.05, OR=8.154, 95%CI: 2.122-31.336)were significant risk fators for TANEC. Conclusion The factors leading to the occurrence of TANEC are various.When transfused, the greater the gestational age, the higher the birth weight, the lower the risk of developing NEC.The more severe the combination of neonatal sepsis and anemia, the higher the risk of developing TANEC.Clinically, comprehensive measures should be taken to prevent neonatal anemia.According to the specific conditions of the children and the degree of anemia, a reasonable clinical strategy should be formulated to avoid blood transfusion to reduce the incidence of TANEC and improve the prognosis of the children. Key words: Neonate; Anemia; Blood transfusion; Transfusion-associated necrotizing enterocolitis; Sepsis

Risk of Necrotizing Enterocolitis Following Packed Red Blood Cell Transfusion in Very Low Birth Weight Infants.

To evaluate the association between red blood cell (RBC) transfusion leading to necrotizing enterocolitis (NEC) within 48h, known as transfusion-associated necrotizing enterocolitis (TANEC). A nested case-control study using historical data was conducted in the neonatal intensive care unit of Songklanagarind Hospital, Thailand. All very low birth weight (VLBW) infants delivered between November 2009 and July 2016 were enrolled. The infants were identified as RBC transfusion received and NEC developed. Logistic regression was used to evaluate risk factors for transfusion and the association between RBC transfusion and NEC. Four hundred and forty-four VLBW infants were enrolled in the study. The median (interquartile range) gestational age was 29 (27, 31) wk. The overall incidence of NEC was 13%. Three (5.2%) of the NEC infants had TANEC. The infants who received RBC transfusion had a lower gestational age [odds ratio, OR 0.64; 95% confidence interval (95%CI) 0.57, 0.73, p <0.001] and were more likely to have pneumonia (OR 9.86; 95%CI 5.02, 19.35, p < 0.001) or to have received H2 blocker (OR 2.92; 95%CI 1.73, 4.93, p <0.001). The ORs (95% CI) after adjusting for confounders, the association between RBC transfusion and NEC for transfusions ≤2 d, >2 to 4 d, and > 4 to 6 d prior to NEC were 1.83 (0.41, 8.16; p = 0.43), 1.7 (0.26, 11.16; p =0.58) and 1.19 (0.31, 4.62; p = 0.80) respectively. After controlling of confounders, no evidence of association was found between RBC transfusion and TANEC.

Retrospective case-control study of necrotizing enterocolitis and packed red blood cell transfusions in very low birth weight infants.

The study objective was to explore the relationship between necrotizing enterocolitis (NEC) and packed red blood cell (pRBC) transfusion in very low birth weight (VLBW) neonates (<1500 g). A six-year retrospective chart review of VLBW infants with NEC (Bell's Stage > II) and a pRBC transfusion within 48 hours of diagnosis. Prenatal data, postnatal course, transfusion history, and NEC outcomes were reviewed. The transfusion associated necrotizing enterocolitis (TANEC) cases were matched with controls (1:2) who were transfused but did not develop NEC as to proximity of birth date, gestational age, and receipt of transfusion. Of 1139 VLBW admissions, there were 73 cases of NEC and 30 cases of TANEC (annual NEC rate 6.4%). TANEC cases were matched with 60 controls who were transfused but never developed NEC. Neonatal profiles were similar between all 3 groups, except for a higher proportion of infants <10th percentile in the non-TANEC group. Days of antibiotics and frequency of patient ductus arteriosus (PDA) ligation were lower in controls compared to NEC cases. Lower feeding rate at diagnosis of NEC/match were more common in control infants compared to TANEC infants. However, feeding abstinence rates were similar between the two groups. The number of transfusions prior to diagnosis/match was similar in all groups. There was no significant difference in pre-transfusion hematocrit values between the groups. TANEC was common among NEC cases. PDA ligation was similar among TANEC and non-TANEC but lower in controls. Similar pre-transfusion hematocrits were found among TANEC and controls. Feeding abstinence rates were also similar between TANEC and controls.

Characteristics and incidence of transfusion-associated necrotizing enterocolitis in the UK

Background and aims: The etiology of necrotizing enterocolitis (NEC) is unclear and postulated as being multifactorial. It has been suggested that one causative factor is the transfusion of packed red blood cells (PRBCs) leading to the disease entity commonly referred to as transfusion-associated NEC (TANEC). TANEC has been reported in North America but its incidence has not been formally investigated in the UK. Our aims were to identify the incidence of NEC and TANEC in tertiary-level UK neonatal units and to describe characteristics of TANEC cases.Materials and methods: Using strict case definitions for NEC and TANEC, we undertook a retrospective review to estimate the incidence of TANEC cases occurring in four UK tertiary-level centers during a 38-month period.Results: Of 8007 consecutive neonatal admissions of all gestations to the four centers, 68 babies went on to develop NEC and all affected infants were of very low birth weight (VLBW); 34 of these had previously received a transfusion of PRBCs but did not fit the diagnostic criteria for TANEC, whereas 15 (22%) of the 68 babies with NEC qualified as TANEC cases. UK cases occurred at an earlier postnatal age than cases reported in multiple large North American series and were of a lower birth weight.Conclusions: We have confirmed the presence of TANEC in the UK VLBW neonatal population. Its incidence lies within the wide range described in previous reports of this phenomenon globally, though with some local variation in characteristics. Further work is needed to clarify causation, pathophysiology, and possible mechanisms of prevention of TANEC.

Red Blood Cell Transfusions Affect Intestinal and Cerebral Oxygenation Differently in Preterm Infants with and without Subsequent Necrotizing Enterocolitis.

To assess intestinal and cerebral oxygenation during and after red blood cell (RBC) transfusions in preterms with or without subsequent transfusion-associated necrotizing enterocolitis (TANEC). In preterms of < 32 weeks' gestational age, we measured intestinal and cerebral regional tissue oxygen saturation (rintSO2, rcSO2) and their variabilities using near-infrared spectroscopy during and after transfusions. We compared eight infants who developed TANEC 6 to 48 hours after RBC transfusions with 16 controls. In TANEC infants, rcSO2 was lower during and after RBC transfusions than in controls, median (interquartile range) 55% (50-62) versus 72% (65-75), p < 0.01. There were no differences regarding rintSO2. Individual rintSO2 and rcSO2 ranges were smaller after transfusions in TANEC infants, 28% (9-36) versus 49% (40-65), p < 0.01, and 17% (14-33) versus 36% (26-57), p = 0.01, as was short-term rintSO2 variability. For each 10% higher rcSO2, the risk of developing TANEC decreased (odds ratio 0.09; 95% confidence interval 0.01-0.63). The smaller the rintSO2 range after transfusion, the higher the risk of developing TANEC. In preterm infants lower rcSO2, but not rintSO2, values during and after RBC transfusions are associated with TANEC. Lower rintSO2 and rcSO2 variabilities after RBC transfusions may represent a diminished capacity for vascular adaptation, possibly leading to TANEC.

Anemia, red blood cell transfusions, and necrotizing enterocolitis

In the past 15 years, multiple clinical studies have identified a temporal association between red blood cell (RBC) transfusions and necrotizing enterocolitis (NEC). With some variability, most of these studies indicate that up to one-third of all cases of NEC involving very low-birth weight infants may occur within 24–48h after receiving a RBC transfusion. There is also evidence that the risk of such transfusion-associated NEC may be higher in infants transfused with the greatest severity of anemia. In this article, we summarize the clinical evidence pertaining to these issues; specifically, the contribution of RBC transfusions, and the contribution of severity of underlying anemia, to the pathogenesis of a type of NEC potentially termed, “transfusion/anemia-associated NEC.”

Red blood cell transfusions can induce proinflammatory cytokines in preterm infants.

The risk of developing red blood cell (RBC) transfusion-associated necrotizing enterocolitis (TANEC) in preterm infants has recently been emphasized. Our aim was to assess changes in cytokine serum levels after RBC transfusions in a cohort of very preterm infants to evaluate their possible proinflammatory effect. We carried out a prospective observational study. One transfusion event was studied in infants less than 32 weeks' gestation and more than 7 days old (n = 20) admitted to a tertiary neonatal intensive care unit. Interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α, interferon-γ (IFN-γ), IL-17, monocyte chemoattractant protein-1 (MCP-1), interferon-γ-induced protein 10 (IP-10), intracellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule serum levels were measured in enrolled patients within 120 minutes before (T0 ) the RBC transfusion and then within 120 minutes (T1 ), 12 ± 3 hours (T2 ), 24 ± 6 hours (T3 ), and 48 ± 6 hours (T4 ) after the end of RBC transfusion. Infants received 19.8 ± 3.0 mL of RBCs at the mean age of 50 ± 18 days. Their hematocrit level increased from 24.1 ± 1.2% to 39.4 ± 2.9%. IL-1β, IL-8, IFN-γ, IL-17, MCP-1, IP-10, and ICAM-1 increased significantly after RBC transfusions. Proinflammatory cytokines are increased after RBC transfusion. These findings may contribute to explaining the pathogenesis of TANEC and suggest the opportunity of adopting wise transfusion guidelines that would help to avoid detrimental risks of transfusion-related immunomodulation and of undertransfusion.

Transfusion-associated necrotizing enterocolitis (TANEC) – early post-transfusion complication in neonates with extremely low birth weight (ELBW) or one of the risk factor necrotizing enterocolitis (NEC)? One centre’s experience

Introduction. Necrotising enterocolitis (NEC) is a disease developing in neonates. In extreme cases, the septic necrosis of the intestine wall can cover the entire thickness of its wall and result in intestine perforation and, in consequence, to peritonitis. Transfusion of packed red blood cells (RBCs) is indicated as a NEC onset predisposing factor, possibly resulting in development of the disease unit referred to as TANEC (transfusion-associated NEC) in 48 hours upon transfusion. The noted TANEC cases caused a more serious course than in case of NEC and in most cases they required a lifesaving surgical intervention and were connected with high death rate. Neonates with TANEC are more probable to undergo a lifesaving surgical intervention than neonates with NEC in whom no RBCs were transfused. Aim. Gathering data from the literature and our own experience associated with NEC and analysis, whether TANEC can be considered as a new early post-transfusion complications that occurs in premature infants with ELBW. Material and methods. The analysis covered medical documentation and laboratory test results in order to explain the reasons for post-transfusion complications in a 3-months old female neonate. Results. Based on the data from literature and upon analysis of the described case, one can pose the following question: can TANEC be deemed the new early post-transfusion reaction in preemies with ELBW? Conclusions. TANEC can be deemed the new early post-transfusion reaction in preemies with ELBW. Determination of such a cause and effect relation requires performance of further research and clinical analysis on a greater number of patients.

79: Withholding Feeds During Blood Transfusion and Risk of Transfusion Associated Necrotizing Enterocolitis (TANEC)

79: Withholding Feeds During Blood Transfusion and Risk of Transfusion Associated Necrotizing Enterocolitis (TANEC)

Surgical Findings in Transfusion-Associated Necrotizing Enterocolitis.

Introduction The extent of intestinal damage in transfusion-associated necrotizing enterocolitis (TNEC) has been scarcely studied. The aim of this investigation was to study surgical findings in TNEC and determine their severity considering the extent of the disease and risk of bowel perforation. Materials and Methods Neonates who required surgical treatment for necrotizing enterocolitis (NEC) were studied retrospectively. Patients who developed NEC within 48 hours after a red blood cell transfusion (RBCT) formed group TR48 and patients who did not receive a RBCT 48 hours before the diagnosis of NEC became group CN (conventional NEC). Both groups were compared: main outcomes were the extent of the disease (isolated, multifocal, or panintestinal), the existence of perforated NEC, and mortality. Categorical variables were analyzed with the chi-square test and continuous variables with the Mann-Whitney u-test. The relationship between RBCTs 48 hours before the diagnosis and the extent of intestinal disease was evaluated by ordinal logistic regression. Results Forty-seven patients were included in the study: 16 patients in TR48 and 31 in CN. The odds ratio of multifocal or panintestinal NEC for patients in TR48 was 0.5 (95% CI: 0.148-1.68). Neonates in TR48 had a relative risk (RR) of perforated NEC of 1.2 (95% CI: 0.76-1.85). The RR of death was 1.55 (95% CI: 0.76-3.14) in group TR48. Conclusion No differences in surgical findings between TR48 and CN could be demonstrated in this investigation; therefore, the hypothesis that intestinal damage might be more severe in TNEC was not confirmed.

Feeding practices and other risk factors for developing transfusion-associated necrotizing enterocolitis

AimsThe objective of this study is to determine the incidence of and risk factors for necrotizing enterocolitis (NEC) and transfusion-associated NEC (TANEC) in very-low-birth-weight (VLBW) infants pre/post implementation of a peri-transfusion feeding protocol. Study designA retrospective cohort study was conducted including all inborn VLBW infants admitted to the Duke intensive care nursery from 2002 to 2010. We defined NEC using Bell's modified criteria IIA and higher and TANEC as NEC occurring within 48h of a packed red blood cell (pRBC) transfusion. We compared demographic and laboratory data for TANEC vs. other NEC infants and the incidence of TANEC pre/post implementation of our peri-transfusion feeding protocol. We also assessed the relationship between pre-transfusion hematocrit and pRBC unit age with TANEC. ResultsA total of 148/1380 (10.7%) infants developed NEC. Incidence of NEC decreased after initiating our peri-transfusion feeding protocol: 126/939 (12%) to 22/293 (7%), P=0.01. The proportion of TANEC did not change: 51/126 (41%) vs. 9/22 (41%), P>0.99. TANEC infants were smaller, more likely to develop surgical NEC, and had lower mean pre-transfusion hematocrits prior to their TANEC transfusions compared with all other transfusions before their NEC episode: 28% vs. 33%, P<0.001. Risk of TANEC was inversely related to pre-transfusion hematocrit: odds ratio 0.87 (0.79–0.95). ConclusionsPre-transfusion hematocrit is inversely related to risk of TANEC, which suggests that temporally maintaining a higher baseline hemoglobin in infants most at risk of NEC may be protective. The lack of difference in TANEC pre-/post-implementation of our peri-transfusion feeding protocol, despite an overall temporal decrease in NEC, suggests that other unmeasured interventions may account for the observed decreased incidence of NEC.

Changes in hematocrit following a blood transfusion does not influence the risk for necrotizing enterocolitis: A case-control study.

Transfusion Associated Necrotizing Enterocolitis (TANEC) is defined as the onset of necrotizing enterocolitis (NEC) within 48 hours of receiving a blood transfusion in preterm neonates. We wanted to determine if hematocrit changes following blood transfusions were associated with disease development. This is a case-control analysis of inborn neonates ≤32 weeks' gestational age, from January 1, 2007 and December 31, 2010, who were diagnosed with Bell stage II or greater NEC. Those meeting TANEC criteria were identified and an analysis completed to determine if beginning or ending hematocrit values were associated with an increased risk for disease development. Nineteen of forty-nine (39%) infants with NEC met the criteria for TANEC. We found no differences in gestational age at birth or birth weight in our experimental groups. The degree of illness including PDA, IVH, central line use, and respiratory support 48 hours prior to disease onset was also similar between groups. Those with TANEC had higher modified Bell staging of NEC and were more likely to be receiving full enteric feeds at the time of NEC onset. No statistically significant differences were found in hematocrit levels prior to or following the blood transfusion closest to NEC onset in the TANEC group, as compared to classic NEC (CNEC) or control infants. The onset of NEC following transfusion occurs with a frequency that invites investigation regarding causation. Our data indicates no association between the beginning and ending hematocrit values and TANEC in our patient population.

Transfusion-Associated Necrotizing Enterocolitis

Transfusion-associated necrotizing enterocolitis (TANEC) has been described as necrotizing enterocolitis (NEC) that arises within 48 hours of a blood transfusion. It has been shown to be associated with 25% to 35% of NEC cases in recent studies. Evidence related to TANEC is limited to observational, retrospective studies. Infants who develop TANEC tend to be smaller, born preterm, more severely ill, and develop NEC after 30 days of age. Evidence in 2 studies support holding feedings during transfusion to protect the preterm gut from the cascade of events that lead to NEC, but higher quality research, including prospective randomized controlled trials, is needed to evaluate the effect of feeding on TANEC.

Neonates presenting with bloody stools and eosinophilia can progress to two different types of necrotizing enterocolitis

We hypothesized that neonates with bloody stools and concomitant eosinophilia are likely to have atopic enteropathy rather than necrotizing enterocolitis (NEC). This was a retrospective cross-sectional study using electronic medical records and paper charts. Records of neonates admitted to any Intermountain Healthcare NICU between 1 January 2005 and 30 June 2010 were eligible if 'bloody stools' were listed in any archive. Qualifying records were divided into two groups depending on whether or not within 72 h of passing bloody stool eosinophil counts were above the 95th percentile reference range limit for age. Bloody stools were identified in 275 predominantly Caucasian neonates. Fifty-four of these had eosinophilia and 221 had normal eosinophil counts. Those with eosinophilia were born at a slightly younger gestational age (31.3 ± 4.6 vs 32.6 ± 4.0 weeks, mean ± s.d., P=0.032). Contrary to our hypothesis, those with eosinophilia did not have a lower rate of pneumatosis or bowel resection, or death ascribed to NEC. Eosinophilia was more common among those who had a red blood cell (RBC) transfusion within 48 h before passing bloody stools (P<0.001). Those with a recent RBC transfusion were the only neonates to have NEC surgery or to die from NEC. Preceding the bloody stools, those with no antecedent transfusion had been fed a larger volume (P=0.014), and had trends toward receiving calorically enriched feedings (P=0.055) and recent addition of human milk fortifier (P=0.060). Eosinophil counts following RBC transfusion tended to increase for 3-6 days, but when bloody stools were not preceded by transfusion the eosinophil counts were more static over that period. In this predominantly Caucasian group of neonates with bloody stools, the presence of eosinophilia did not identify a benign condition distinct from NEC. A total of 44% of these neonates had transfusion-associated NEC. Eosinophils could have a previously unrecognized role in the pathogenesis of this NEC subtype.

Red blood cell transfusion, feeding and necrotizing enterocolitis in preterm infants

Preliminary studies suggested an association between red blood cell (RBC) transfusion and necrotizing enterocolitis (NEC) in premature neonates. An advantageous effect of withholding feeds during transfusion has never been studied. We aimed, first, to determine whether preterm infants who developed NEC were more likely to be transfused in the 48 to 72 h before the diagnosis of NEC; second, to test if a strict policy of withholding feeds during transfusion would decrease the incidence of transfusion-associated NEC. The study was conducted in two phases. Phase 1: a retrospective case-control study of premature low-birth weight (<32 weeks and <2500 g) infants who developed NEC over a 6-year period. Phase 2: a comparison study of the incidence of NEC during the 18-months preceding, and the 18 months following the change of practice to withholding feeds during RBC transfusion. In the case-control study (25 infants with NEC and 25 controls), more infants in the NEC group received transfusions in the 48 and 72 h preceding diagnosis (56 vs 20% within 48 h, P=0.019; and 64 vs 24% within 72 h, P=0.01). The total number of transfusions and age of RBCs were not different between the two groups. Implementing the policy of withholding feeds during transfusion was associated with a decrease in the incidence of NEC from 5.3 to 1.3% (P=0.047). Infants who developed NEC frequently received RBC transfusions in the 48 and 72 h preceding presentation of NEC. A strict policy of withholding feeds during transfusion may have a protective effect from NEC.