Is “transfusion‐associated necrotizing enterocolitis” an authentic pathogenic entity?

Christensen, Robert D.; Lambert, D K; Henry, Erick; Wiedmeier, Susan E.; Snow, Greg; Baer, Vickie L.; Gerday, Erick; Ilstrup, Sarah J.; Pysher, Theodore J.

doi:10.1111/j.1537-2995.2009.02542.x

Cited by 154 publications

(138 citation statements)

References 38 publications

(45 reference statements)

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“…Other studies have noted a similar 27,28 However, the nature of this association remains to be fully explored; it is unclear that this is truly a causative relationship. It is possible that patients who are beginning to manifest systemic signs of illness are more likely to have laboratory tests performed and perhaps a lowered transfusion threshold is applied.…”

Section: Discussionmentioning

confidence: 96%

Risk factors for necrotizing enterocolitis totalis: a case–control study

Thompson

Bizzarro

et al. 2011

J Perinatol

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Objective: The objective of this study was to compare demographic and clinical events in three groups of preterm neonates: those with necrotizing enterocolitis totalis (NEC-T), those with NEC non-totalis (NEC non-T) and in preterm patients without NEC.Study Design: This retrospective case-control study was conducted at Yale New Haven Children's Hospital using patient data from January 1991 to December 2007. Study patients were less than 36 weeks of gestational age (GA) at birth, without gastrointestinal (GI) malformations. Cases (NEC-T) were diagnosed at operation or at autopsy with observation of >80% necrosis of the GI tract. Two control groups were assigned: Group 1 or NEC non-T and Group II or Non-NEC. Two to four controls per case were matched to cases by GA at birth ± 2 weeks. Demographic and clinical data for the day of diagnosis and retrospectively up to 7 days preceding diagnosis were recorded for those with NEC-T and NEC. Group II controls were matched for date of birth and day of life, in addition to GA at birth.Result: A total of 14 075 patients were admitted to the Newborn Special Care Unit during the study interval. Overall 328 patients (2.3%) developed NECXBell's Stage II; 39 patients met inclusion criteria for NEC-T case status; 148 NEC non-T and 110 non-NEC controls were assigned. In the comparison of NEC T and NEC non-T neonates, use of breast milk was associated with decreased risk of NEC-T, adjusted odds ratio (OR) ¼ 0.26, 95% confidence interval (CI) of OR ¼ 0.08-0.085, P ¼ 0.03. When NEC T and non-NEC patients were compared, having reached full-enteral feeds before the date of diagnosis of the matched case (adjusted OR ¼ 28.5, 95% CI of OR ¼ 2.7-299, P ¼ 0.005) and use of breast milk (adjusted OR ¼ 0.09, 95% CI of OR ¼ 0.02-0.56, P ¼ 0.01) were significantly different between the two groups.Conclusion: Breast milk usage was significantly associated with decreased occurrence of NEC-T in our comparison of NEC-T, NEC non-T and non-NEC patients. Although there were some differences, the majority of demographic and clinical variables assessed were not shown to be significantly different between cases and controls. This highlights the need for more biological data in assessing risk of developing NEC-T.

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Section: Discussionmentioning

confidence: 96%

Risk factors for necrotizing enterocolitis totalis: a case–control study

Thompson

Bizzarro

et al. 2011

J Perinatol

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“…The association between RBC transfusion and the subsequent development of NEC is well documented. [20][21][22][23][24][25][26][27][28] Our current findings suggest that investigating eosinophils as participants in the pathogenesis of transfusionassociated NEC might be fruitful. We realize several weaknesses in our study, largely derivative of the retrospective methodology.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2011

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Objective: We hypothesized that neonates with bloody stools and concomitant eosinophilia are likely to have atopic enteropathy rather than necrotizing enterocolitis (NEC).Study Design: 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.Result: 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 ¼ 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 ¼ 0.014), and had trends toward receiving calorically enriched feedings (P ¼ 0.055) and recent addition of human milk fortifier (P ¼ 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. Conclusion: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. Keywords: necrotizing enterocolitis; bloody stools; eosinophilia; RBC transfusion; transfusion-associated NEC; atopic enteropathy Introduction Eosinophilia is diagnosed when the concentration of eosinophils in the blood exceeds the upper reference range limit. 1 Until recently, this upper limit was not well defined for neonates, allowing imprecision in defining eosinophilia and in identifying associations between it and various clinical conditions. Using laboratory values from over 63 000 neonates we recently reported the 5th and 95th percentile values for blood eosinophil concentrations at various gestational and postnatal ages. 2 The 95th percentile upper limit ranges from 1180 eosinophils ml À1 in the first week to about 1560 ml À1 after 3 weeks. 2 Given this more precise definition of neonatal eosinophilia, we commenced the present study of the association between bloody stools and eosinophilia.When bloody stools are observed in a neonate, the possibility of necrotizing enterocolitis (NEC) enters the ...

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“…or percent. of necrotizing enterocolitis 26 and transfusion-associated graft versus host disease. 27 Another unwanted effect of late transfusions in this population is their suppressive effect on erythropoietin production and therefore on erythropoiesis.…”

Section: Discussionmentioning

confidence: 99%

Very low birth weight infants qualifying for a ‘late’ erythrocyte transfusion: Does giving darbepoetin along with the transfusion counteract the transfusion's erythropoietic suppression?

et al. 2011

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Objective: Red blood cell (RBC) transfusions can suppress erythropoiesis. On this basis, RBC transfusions administered to very low birth weight (VLBW) neonates potentially render them more likely to qualify for a subsequent transfusion.Study Design: We hypothesized that 'late' (>14 days after birth) RBC transfusions given to VLBW neonates result in a decrease in reticulocyte count persisting for at least 7 to 10 days. We also hypothesized that a single dose of darbepoetin given along with the transfusion would have the opposite effect, increasing the reticulocyte count for at least 7 to 10 days. To test this, we conducted a single-centered randomized trial with 20 VLBW neonates who, according to our transfusion guidelines, qualified for a late transfusion.Result: VLBW infants about to receive a late RBC transfusion were randomized (1:1) to also receive vs not receive (controls) a single subcutaneous dose of darbepoetin (10 mg kg À1 ). Reticulocyte counts diminished significantly in the controls (a drop of 85±62 Â 10 3 ml À1 (mean ± s.d.) at 7 to 10 days), but increased significantly in the darbepoetin recipients (an increase of 177±120 Â 10 3 ml À1 at 7 to 10 days, P<0.0001). At 7 to 10 days after the transfusion, hematocrits of the controls were 8.1±4.9 points above their pre-transfusion values and of the darbepoetin group were 12.4 ± 2.7 points above their pre-transfusion values (P ¼ 0.033). Conclusion:This was a limited-scope, single-centered, randomized trial intended to pilot-test a new concept in neonatal transfusion practice. Namely, we tested whether a late RBC transfusion suppressed reticulocytosis and whether a concomitant single dose of darbepoetin counteracted that suppression. Using the pilot data presented in this study, larger trials can now be designed to address meaningful clinical outcomes such as transfusion avoidance using this approach.

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Is “transfusion‐associated necrotizing enterocolitis” an authentic pathogenic entity?

Abstract: Approximately one-third of surgical NEC cases in our system occurred after a transfusion. We speculate that a target area for reducing the prevalence of posttransfusion NEC involves feeding practices immediately before and during RBC transfusion.

Cited by 154 publications

References 38 publications

Risk factors for necrotizing enterocolitis totalis: a case–control study

Risk factors for necrotizing enterocolitis totalis: a case–control study

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

Very low birth weight infants qualifying for a ‘late’ erythrocyte transfusion: Does giving darbepoetin along with the transfusion counteract the transfusion's erythropoietic suppression?

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