Severe Anemia Is Associated with Intestinal Injury in Preterm Neonates

Özcan, Beyza; Aydemir, Özge; Işık, Dilek Ulubaş; Baş, Ahmet Yağmur; Demirel, Nihal

doi:10.1055/s-0039-1683982

Cited by 14 publications

(15 citation statements)

References 18 publications

(24 reference statements)

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“…Recent concerns regarding the association between RBC transfusions and the development of necrotizing enterocolitis (NEC) may have further restricted transfusion policies in preterm infants. 5 However, anemia itself resulting in tissue hypoxia may also cause intestinal injury, 6 – 8 as is also supported by the results of two preclinical studies. 9 , 10 It remains unclear, whether this increased risk of NEC is related mainly to the transfusion or to the anemia itself.…”

Section: Introductionmentioning

confidence: 77%

Neonatal anemia relates to intestinal injury in preterm infants

Kalteren

Bos

Oeveren³

et al. 2021

Pediatr Res

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Background Anemia is associated with decreased tissue oxygenation in preterm infants and may contribute to developing necrotizing enterocolitis (NEC). We aimed to investigate whether hemoglobin level is associated with intestinal injury, by comparing anemic infants 10 days prior to red blood cell (RBC) transfusion with non-anemic controls. Methods A nested case–control study in which we matched anemic preterms (gestational age (GA) < 32 weeks) with non-anemic controls (1:1), based on GA, birth weight (BW), and postnatal age. We measured urinary intestinal fatty acid-binding protein, I-FABP, marker for intestinal injury, twice weekly. Simultaneously, we assessed splanchnic oxygen saturation (r s SO 2 ) and r s SO 2 variability. Results Thirty-six cases and 36 controls were included (median GA 27.6 weeks, BW 1020 grams). Median I-FABP level was higher in cases from 6 days to 24-h before transfusion (median ranging: 4749–8064 pg/ml versus 2194–3751 pg/ml). R s SO 2 and r s SO 2 variability were lower in cases than controls shortly before transfusion. Hemoglobin levels correlated negatively with r s SO 2 and r s SO 2 variability in cases, and negatively with I-FABP in cases and controls together. Conclusions Urinary I-FABP levels were higher in anemic infants before RBC transfusion than in non-anemic matched controls, suggesting intestinal injury associated with anemia. This may predispose to NEC in some anemic preterm infants. Impact Anemia is a common comorbidity in preterm infants and may lead to impaired splanchnic oxygen saturation and intestinal tissue hypoxia, a proposed mechanism for NEC. Lower hemoglobin level is associated with higher urinary I-FABP levels, a marker for intestinal injury, both in anemic preterm infants and in cases and controls together. Lower splanchnic oxygen saturation and reduction of its variability are associated with higher urinary I-FABP levels in anemic preterm infants before their first RBC transfusion. These results support the hypothesis that anemia in very preterm infants results in intestinal cell injury, which may precede NEC development in some.

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Section: Introductionmentioning

confidence: 77%

Neonatal anemia relates to intestinal injury in preterm infants

Kalteren

Bos

Oeveren³

et al. 2021

Pediatr Res

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“…Our previous clinical trial found that the improvement of severe anemia reduced the incidence of NEC in preterm infants, which also suggested the impact of anemia on the development of NEC [19]. A prospective cohort study showed that anemia was associated with intestinal injury [33]. The possible mechanism is that anemia can reduce tight junction protein ZO-1 expression, increase intestinal barrier permeability, and increase intestinal inflammation through altered macrophage function, leading to intestinal injury that may increase the risk of NEC [20,21].…”

Section: Discussionmentioning

confidence: 94%

The association of severe anemia, red blood cell transfusion and necrotizing enterocolitis in neonates

Shi

Dong

et al. 2021

PLoS ONE

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Background The relationship between severe anemia, red blood cell transfusion and Neonatal necrotizing enterocolitis (NEC) remains controversial. The purpose of this study was to determine the association of severe anemia and RBC transfusion with NEC in neonates. Methods The clinical characteristics of NEC were observed in 467 infants with different birth weights from January 2012 to July 2020. A 1:1 ratio case-control study was performed in very low birth weight (VLBW) infants. Severe anemia, RBC transfusion, and confounding factors, including maternal and perinatal complications, feeding, and antibiotics administration were collected in both groups. Univariate and multivariate analyses were used to investigate effects on the risk of NEC. Results The day of NEC onset and mortality were inversely associated with birth weight. In VLBW infants, adjusting for other factors, severe anemia within 72 h [OR = 2.404, P = 0.016], RBC transfusion within 24 h [OR = 4.905, P = 0.016], within 48 h [OR = 5.587, P = 0.008], and within 72 h [OR = 2.858, P = 0.011] increased the risk of NEC. Conclusion Both severe anemia and RBC transfusion appears to increase the risk of NEC in VLBW infants. The early prevention and treatment of anemia, strict evaluation of the indications for transfusion and enhanced monitoring after transfusion is encouraged in the NICU.

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“…Similarly, the critical value for abdominal tissue desaturation is noted when the HCT is less than 24%, predisposing premature infants for necrotizing enterocolitis and intestinal injury. [23][24][25] AOP also reported to be associated with increased incidence of intermittent hypoxic episodes in premature infants, especially after the first month of life, and RBC transfusions has been associated with reduction in apnea frequency in the short term. 26,27 In our study, premature infants with severe AOP during initial PO were more premature at birth, compared with controls.…”

Section: Discussionmentioning

confidence: 97%

Anemia of Prematurity and Oral Feeding Milestones in Premature Infants

Viswanathan

Jadcherla

2019

Am J Perinatol

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Objective Anemia of prematurity (AOP) and oral feeding problems are common in premature infants. This study aimed to determine the influence of AOP on aerodigestive outcomes and the duration to full Per Oral (PO). Study Design Prospectively collected data on premature infants who initiated oral feeds at ≤ 34 weeks' postmenstrual age were examined. Infants were categorized into “AOP+” and “AOP−” based on hematocrit at initial PO, that is, < 29 or ≥ 29%. Results Forty-four infants in AOP+ compared with 74 in AOP−. AOP+ infants had lower birth gestation and weight (p < 0.001). The anthropometrics at initial PO were similar. AOP+ had lower mean hematocrit and higher oxygen need at initial PO, and at full PO (p < 0.05). AOP+ reached full PO at a later gestation and took longer days from initial PO to full PO (p < 0.01). BPD, intraventricular hemorrhage (IVH ≤ 2), and hospital stay were greater in the AOP+ (p < 0.05). After adjusting for covariates, initial PO hematocrit was not predictive of time to full PO [hazard ratio 1.3 (CI 0.88–2.0), p = 0.18]. Conclusion AOP is not independently associated with the duration to full PO. Supplemental oxygen for associated comorbidities may have compensated for the underlying anemia.

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Severe Anemia Is Associated with Intestinal Injury in Preterm Neonates

Cited by 14 publications

References 18 publications

Neonatal anemia relates to intestinal injury in preterm infants

Neonatal anemia relates to intestinal injury in preterm infants

The association of severe anemia, red blood cell transfusion and necrotizing enterocolitis in neonates

Anemia of Prematurity and Oral Feeding Milestones in Premature Infants

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