Analysis of the Efficacy of Red Blood Cell Transfusion in Very Low Birth Weight Infants and Construction of a Prediction Model

Timing of Caffeine Therapy in Very Low Birth Weight Infants

Anemia in very low birth weight (VLBW) infants is common and frequently managed with red blood cell (RBC) transfusions. We utilized a linked vein-to-vein database to assess the role of blood donors and component factors on measures of RBC transfusion effectiveness in VLBW infants. We linked blood donor and component manufacturing data with VLBW infants transfused RBCs between January 1, 2013 and December 31, 2016 in the Recipient Epidemiology Donor Evaluation Study-III (REDS III) database. Using multivariable regression, hemoglobin increments and subsequent transfusion events following single-unit RBC transfusion episodes were examined with consideration of donor, component, and recipient factors. Data on VLBW infants (n = 254) who received one or more single-unit RBC transfusions (n = 567 units) were linked to donor demographic and component manufacturing characteristics for analysis. Reduced post-transfusion hemoglobin increments were associated with RBC units donated by female donors (-0.24 g/dL [95% confidence interval (CI) -0.57, -0.02]; p = .04) and donors <25 years old (-0.57 g/dL [95% CI -1.02, -0.11]; p = .02). For RBC units donated by male donors, reduced donor hemoglobin levels were associated with an increased need for subsequent recipient RBC transfusion (odds ratio 3.0 [95% CI 1.3, 6.7]; p < .01). In contrast, component characteristics, storage duration, and time from irradiation to transfusion were not associated with post-transfusion hemoglobin increments. Donor sex, age, and hemoglobin levels were associated with measures of RBC transfusion effectiveness in VLBW infants. Mechanistic studies are needed to better understand the role of these potential donor factors on other clinical outcomes in VLBW infants.

Changing patterns of red blood cell transfusion in very low birth weight infants

To estimate the risk of iron overload in very low birthweight (VLBW) infants who receive more than two red blood cell (RBC) transfusions, in comparison with those who receive two or less during their hospital stay. Prospective open cohort study in VLBW infants with >2 (exposed) and ≤2 (non-exposed) RBC transfusions. Ferritin, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured at birth and after each RBC transfusion. The incidence of iron overload was determined. Risk factors were analysed using a logistic regression model. RBC transfusion volume correlations with ferritin, ALT and AST were calculated with Spearman's rank correlation coefficient, as well as correlations between ferritin and aminotransferases. A total of 63 patients were enrolled, 18 of which were exposed and 45 non-exposed. Twelve patients developed severe iron overload, eight exposed (44·5%) vs. four (8·8%) non-exposed (RR: 5, 95% CI: 1·7-14·6). Multivariate analysis showed that the number of transfusions increased the risk of iron overload (OR: 2·07, 95% CI: 1·36-2·14) while a higher one-minute Apgar score was associated with a lower risk (OR: 0·56, 95% CI: 0·32-0·99). Severe iron overload mainly occurred with a transfusion volume higher than 120 ml/kg. There was a positive correlation between ferritin and transfusion (r = 0·53; P < 0·001). There was a higher risk of iron overload in exposed infants in comparison with non-exposed infants. Severe iron overload in VLBW infants may occur with a total transfusion volume >120 ml/kg.

In order to know the response of the skin microcirculation to local warming, we determined changes in the skin blood volume (Vol), velocity (Vel) and flow (F) by using a new laser Doppler device on newborns. The study subjects were 39 infants whose gestational age was 34.1 +/- 2.8 weeks and birth weight was 2189 +/- 572 g. The study was performed from 8 h postnatally to 28 postnatal days. We measured skin blood volume, velocity and flow at 36 degrees C (Vol36, Vel36, F36), and each value at 5 min (Vol44-5, Vel44-5, F44-5) and 10 min (Vol44-10, Vel44-10, F44-10) after local warming was applied at 44 degrees C and the response curve of each parameter was obtained. Subsequently, serial changes in the response of skin microcirculation to local warming were investigated in nine very low birth weight (VLBW) infants (28.3 +/- 0.9 weeks, 1150 +/- 148 g) and 12 low birth weight (LBW) infants (32.8 +/- 1.3 weeks, 1971 +/- 292 g). The F36, the increment rate of blood volume (delta Vol) and the increment rate of blood velocity (delta Vel) were obtained within 24 h, from day 1 to day 7 and from day 8 to day 30 in both VLBW and LBW infants and from day 31 to day 60 and at more than 61 days in VLBW infants. The F36, delta Vol and delta Vel were compared during the study periods in VLBW and LBW infants. All results were expressed as mean +/- SD. The results showed that F36/F44-10 and F44-5/F44-10, Vol36/Vol44-10 and Vol44-5/Vol44-10, Vel36/Vel44-10 and Vel44-5/Vel44-10 were 0.25 +/- 0.09 and 0.74 +/- 0.17, 0.58 +/- 0.14 and 0.94 +/- 0.08, 0.42 +/- 0.12 and 0.79 +/- 0.15, respectively. Different modes of delivery did not have a significant effect on this response. The F36 in VLBW infants was high during the early neonatal period and gradually decreased with postnatal age. The delta Vol was low in VLBW infants during the neonatal period and gradually increased. The F36 in VLBW1-7 was significantly higher than in LBW1-7 (P < 0.01) and full-term controls (P < 0.001). The delta Vol in VLBW1-7 was 0.26 +/- 0.23, which is significantly lower than in LBW1-7 (0.57 +/- 0.17, P < 0.001) and full-term controls (0.77 +/- 0.21, P < 0.001). The delta Vel in VLBW1-7 and LBW1-7 was significantly higher than in controls (P < 0.05). The skin blood flow increased continuously when local warming was applied at 44 degrees C. This high blood flow and limited potential of vasodilatation are the characteristics of the skin microcirculation in VLBW infants during the neonatal period.

Background: In order to know the response of the skin microcirculation to local warming, we determined changes in the skin blood volume (Vol), velocity (Vel) and flow (F) by using a new laser Doppler device on newborns. Methods: The study subjects were 39 infants whose gestational age was 34.1~2.8 weeks and birth weight was 2189~572 g. The study was performed from 8 h postnatally to 28 postnatal days. We measured skin blood volume, velocity and flow at 36°C (Vol36, Vel36, F36), and each value at 5 min (Vol44–5, Vel44–5, F44–5) and 10 min (Vol44–10, Vel44–10, F44–10) after local warming was applied at 44°C and the response curve of each parameter was obtained. Subsequently, serial changes in the response of skin microcirculation to local warming were investigated in nine very low birth weight (VLBW) infants (28.3~0.9 weeks, 1150~148 g) and 12 low birth weight (LBW) infants (32.8~1.3 weeks, 1971~292 g). The F36, the increment rate of blood volume (ΔVol) and the increment rate of blood velocity (ΔVel) were obtained within 24 h, from day 1 to day 7 and from day 8 to day 30 in both VLBW and LBW infants and from day 31 to day 60 and at more than 61 days in VLBW infants. The F36, ΔVol and ΔVel were compared during the study periods in VLBW and LBW infants. All results were expressed as mean~SD. Results: The results showed that F36/F44–10 and F44–5/F44–10, Vol36/Vol44–10 and Vol44–5/Vol44-10, Vel36/Vel44-10 and Vel44–5/Vel44–10 were 0.25~0.09 and 0.74~0.17, 0.58~0.14 and 0.94~0.08, 0.42~0.12 and 0.79~0.15, respectively. Different modes of delivery did not have a significant effect on this response. The F36 in VLBW infants was high during the early neonatal period and gradually decreased with postnatal age. The ΔVol was low in VLBW infants during the neonatal period and gradually increased. The F36 in VLBW1–7 was significantly higher than in LBW1–7 (P<0.01) and full-term controls (P<0.001). The ΔVol in VLBW1–7 was 0.26~0.23, which is significantly lower than in LBW1–7 (0.57~0.17, P<0.001) and full-term controls (0.77~0.21, P<0.001). The ΔVel in VLBW1–7 and LBW1–7 was significantly higher than in controls (P<0.05). Conclusions: The skin blood flow increased continuously when local warming was applied at 44°C. This high blood flow and limited potential of vasodilatation are the characteristics of the skin microcirculation in VLBW infants during the neonatal period.

Background and Objective: Necrotizing enterocolitis (NEC) remains an important cause of mortality in preterm neonates. There are many risk factors for NEC; however, probably the most controversial one is red blood cell transfusions (RBCT). The data concerning the link between NEC and RBCT has been conflicting. Therefore, we aimed to analyze the association between NEC and RBCT in Neonatal Intensive Care Unit (NICU) at the Hospital of Lithuanian University of Health Sciences. Materials and Methods: We used the Very Low Birth Weight (VLBW) Infants database to match all infants with ≥2a Bell’s stage NEC admitted between 1 January 2005 and 31 December 2014 (n = 54) with a control group (n = 54) of similar gestational age and birth weight and without NEC. We analyzed the charts of these infants and performed statistical analysis on 20 clinical variables including RBCT. Results: The main clinical and demographic characteristics did not differ between the two groups. All variables associated with RBCT (receipt of any RBCT, the number of transfusions and the volume transfused in total) were significantly higher in the NEC group both before the onset of NEC and throughout the hospitalization. RBCT increased the odds of NEC even after adjustment for confounding factors. In addition, we found that congenital infection was more abundant in the NEC group and increased the odds of NEC 2.7 times (95% confidence interval CI (1.1, 6.3), p = 0.024). Conclusions: A higher number and the total volume of RBCT are associated with an increased risk of NEC in VLBW infants. The presence of congenital infection might identify the infants at risk.

Magnesium metabolism in preterm infants: Effects of calcium, magnesium, and phosphorus, and of postnatal and gestational age

A systematic review was conducted to examine the effects of restrictive versus liberal red blood cell (RBC) transfusion thresholds on clinically important outcomes in very low birth weight (VLBW) infants. Randomised controlled trials (RCTs) of varying RBC transfusion thresholds in VLBW infants were identified by searching MEDLINE, EMBASE, CINAHL, all of the Cochrane Library and other supplementary sources. Selected studies included one of the following outcomes: total number of red blood cell transfusions, donor exposure rate, cranial ultrasonographically diagnosed brain injury, retinopathy of prematurity, bronchopulmonary dysplasia, necrotising enterocolitis or death. Studies to be included were selected by two reviewers who also assessed the risk of bias of each trial. Data extraction and analyses were independently performed by two reviewers. All data were analysed using RevMan 5. Six RCTs were identified. One trial did not meet the inclusion criteria, while two had inadequate methodological quality. Pooled analysis of two trials showed that the restrictive transfusion group received a significantly lower mean number of transfusions per infant (mean difference (MD) -1.35, 95% confidence interval (CI) [-2.61, -0.09]) and donor exposure rate (MD -0.54, 95% CI [-0.93, -0.15]). No other statistically significant differences were observed. Restrictive RBC transfusion thresholds in VLBW infants may be utilised without incurring clinically important increases in the risk of death or major short-term neonatal morbidities.

Delayed cord clamping (DCC) for 30 to 60 seconds after birth facilitates placental transfusion, increases blood volume, and decreases red blood cell (RBC) transfusion in preterm infants. Study objective was to determine (1) RBC transfusion burden over a 5-year period, (2) impact of DCC practice on RBC transfusions, and (3) association of RBC transfusion on outcomes in very low birthweight (VLBW) preterm infants. A retrospective medical chart review was performed in 787 VLBW infants between 2016 and 2020. Demographic factors, DCC status, number of RBC transfusions, and neonatal outcomes were determined in eligible infants. Adjusted association between DCC, RBC transfusion, and outcomes were determined using logistic and linear regression methods. Of the 538 eligible VLBW infants, 62% (N = 332) received RBC transfusions. Proportion receiving RBC transfusion were significantly higher for infants <1,000 g (N = 217, 65.4%) and gestational age (GA) <29 weeks (N = 256, 77.1%) than larger (1,001-1,250 g, N = 77, 23.2% and 1,251-1,500 g, N = 38, 11.4%) and older GA ≥ 29 weeks' infants (N = 76, 22.9%, p < 0.05). Of the 81/538 (15.1%) who received DCC, 48 (59.2%) received no RBC transfusion (p < 0.001). In multivariable logistic regression analysis, preterm infants with DCC were 55% less likely to receive RBC transfusions as compared with infants with no DCC. At any given GA, the number of RBC transfusions in preterm infants with DCC was 25% lower as compared with infants without DCC (p < 0.05). Transfusion was associated with 8-fold increased odds for bronchopulmonary dysplasia and 4-fold increased odds for medical and surgically treated patent ductus arteriosus compared with no transfusion. There was no significant association of transfusion with neonatal sepsis, laser treated retinopathy of prematurity, necrotizing enterocolitis, and intraventricular hemorrhage. DCC was significantly associated with reduced RBC transfusion, but fewer preterm infants received DCC. Further research is needed to explore the feasibility of providing neonatal resuscitation during DCC in preterm infants. · Delayed cord clamping significantly reduced the need for RBC transfusions.. · Fewer very preterm infants received DCC.. · Future research is needed to explore feasibility of neonatal resuscitation during DCC..

This study aims to explore the primary risk factors for necrotizing enterocolitis (NEC) in very low birth weight (VLBW) infants through meta-analysis, providing scientific evidence for clinical prevention and treatment. A systematic search was conducted in PubMed, Embase, Cochrane Library, and Web of Science databases for studies investigating risk factors for NEC in VLBW infants, covering the period from database inception to October 10, 2025. Eligible studies included case-control studies, cohort studies, and cross-sectional studies meeting the inclusion criteria. Quality assessment was performed using the NOS and AHRQ scores. Data were pooled using Stata 15 software with a random-effects model. a total of 16 research articles involving 179,289 patients included, meta-analysis results suggest that Small Gestational Age [OR = 1.35, 95% CI (1.14, 1.60)], red blood cells transfusion [OR = 1.75, 95% CI (1.26, 2.43)], maternal hypertensive disorders [OR = 1.27, 95% CI (1.03, 1.57)], patent ductus arteriosus [OR = 1.56, 95% CI (1.30, 1.88)], sepsis [OR = 1.87, 95% CI (1.22, 2.87)] were associated with NEC in very low birth weight infants. This systematic meta-analysis consolidates and confirms previously reported associations between several clinical factors and the risk of necrotizing enterocolitis in very low birth weight infants. The findings support the association of small gestational age, red blood cell transfusion, maternal hypertensive disorders, patent ductus arteriosus, and sepsis with an increased risk of NEC. PROSPERO CRD420251149565.

BackgroundProlonged storage of transfused red blood cells (RBCs) is associated with hemolysis in healthy adults and inflammation in animal models. We aimed to determine whether storage duration affects markers of hemolysis (e.g., serum bilirubin, iron, and non-transferrin-bound iron (NTBI)) and inflammation (e.g., interleukin (IL)-8 and monocyte chemoattractant protein (MCP)-1) in transfused very low birth weight (VLBW) infants.MethodsBlood samples from 23 independent transfusion events were collected by heel stick before and 2–6h after transfusion.ResultsSerum iron, total bilirubin, NTBI, and MCP-1 levels were significantly increased after transfusion of RBCs (P<0.05 for each comparison). The storage age of transfused RBCs positively correlated with increases in NTBI following transfusion (P<0.001; R2 = 0.44). No associations between storage duration and changes in the other analytes were observed.ConclusionsTransfusion of RBCs into VLBW infants is associated with increased markers of hemolysis and the inflammatory chemokine MCP-1. RBC storage duration only correlated with increases in NTBI levels following transfusion. NTBI was only observed in healthy adults following 35 days of storage; however, this study suggests that VLBW infants are potentially more susceptible to producing this pathological form of iron, with increased levels observed after transfusion of only 20-day old RBCs.

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.

Background The aim of this study was to evaluate the association between red blood cell (RBC) transfusions on the risk of death, retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), and necrotizing enterocolitis (NEC) in very low birth weight (VLBW) infants. Study Design and Methods This is an observational study. Data were entered prospectively into the study database at the time of the first transfusion. Clinical characteristics, adverse events, and outcomes of the patients transfused in the first 28 days of life were compared with the population of VLBW infants not transfused during the same period. The association among birth weight, gestational age, comorbidities, and the number of transfusions was estimated with a Poisson regression model. The association between the composite outcome and the occurrence of death, ROP, or BPD separately considered and a set of covariates was estimated with a logistic regression model. Results We enrolled 641 VLBW infants, 42% of whom were transfused. Transfusions were associated with the risk of developing the composite outcome, independently from other conditions; this risk correlated with several transfusions ≥ 3 (odds ratio: 5.88, 95% confidence interval: 2.74-12.6). ROP and BPD were associated with several transfusions ≥ 3. Conclusion We observed an association between RBC transfusions and the composite risk of death or ROP, BPD, and NEC.

Role of Intervention Strategies for At-risk Preterm Infants