Erythrocyte transfusions are associated with retinopathy of prematurity in extremely low gestational age newborns.

AIM: Retinopathy of prematurity (ROP) is a major morbidity in preterm infants causing visual impairment including blindness. Prevention and timely treatment are critical. We investigated the potential role of red blood cell (RBC) transfusions as risk factor for ROP development. METHODS: Retrospective cohort study of data from 68 tertiary level neonatal intensive care units in Germany. Preterm infants born at 22 + 0 to 28 + 6 weeks of gestation between January 2009 and December 2021 were enrolled. RESULTS: We included n = 12 565 infants. Prevalence of any ROP was 49.2% with most infants being diagnosed with stage 1 (21.5%) and 2 disease (17.2%). ROP stage 3 was present in 10.2%, stage 4 in 0.3%, and ROP requiring treatment in 6.6%. Infants with ROP had significantly more frequently a history of RBC transfusions. Adjusting for confounders, RBC transfusions were associated with increased odds of ROP (OR 1.4, p < 0.001), ROP progression (OR 2.1, p < 0.01) and ROP requiring treatment (OR 3.6, p < 0.001). Restrictive transfusion approaches correlated with decreased (OR 0.7, p < 0.001), liberal regimes with increased odds (OR 1.2, p = 0.001). CONCLUSION: The present study confirmed an association of RBC transfusions and ROP. Our findings emphasise the need for anaemia prevention and critical re-evaluation of transfusion practices in preterm infants.

Trial-related blood sampling and red blood cell transfusions in preterm infants.

AIM: To determine if trial-related blood sampling increases the risk of later red blood cell (RBC) transfusion in very preterm infants, we compared the volume of clinical- and trial-related blood samples, in a specific trial and correlated to subsequent RBC transfusion. METHODS: For 193 very preterm infants, participating in the FortiColos trial (NCT03537365), trial-related blood volume drawn was in accordance with ethical considerations established by the European Commission. Medical records were reviewed to assess the number and accumulated volume (mL/kg) of blood samples (both clinical- and trial-related). Data were compared with the need of RBC transfusions during the first 28 days of life. RESULTS: Mean (SD) gestational age and birth weight was 28 ± 1 weeks and 1168 ± 301 g. In total, 11% of total blood volume was drawn for sampling (8.1 ± 5.1 mL/kg) and trial-related sampling accounted for 1.6 ± 0.6 mL/kg. Trial-related blood sampling had no impact on RBC transfusion (p = 0.9). CONCLUSION: Clinical blood sampling in very preterm infants is associated with blood loss and subsequent need for RBC transfusions. In a specific trial requiring blood samples, we found no additional burden of trial-related blood sampling. The study suggests that trial-related sampling is safe if European criteria are followed.

Red Blood Cell Transfusion Thresholds for Anemia of Prematurity.

Anemia of prematurity affects the majority of preterm infants, particularly extremely low birthweight infants. Anemia of prematurity arises from both innate and iatrogenic causes and results in more than 80% of extremely preterm infants receiving red blood cell transfusions during the first month after birth. Multiple randomized controlled trials were conducted to evaluate the effect of using lower versus higher transfusion thresholds based on hemoglobin levels. These trials showed no difference in the primary outcome of neurodevelopmental impairment at 2 years of age between lower and higher thresholds. However, some uncertainties about transfusion thresholds remain. This review elaborates the following: 1) the etiology, prevention, and treatment of anemia of prematurity with a focus on red blood cell transfusions, 2) the history of randomized controlled trials on the treatment of anemia of prematurity, and 3) limitations of the evidence and remaining questions about thresholds for red blood cell transfusions in preterm infants.

Diagnosing Anemia in Neonates: An Evidence-Based Approach.

It is important for clinicians who render neonatal care to precisely and reproducibly diagnose anemia; however, confusion arises from various definitions. For the simplicity and consistency of detection, we advocate defining neonatal anemia as a hemoglobin level or hematocrit below the 5th percentile of the reference population, which is highly dependent on gestational and postnatal ages. Thus, a newborn infant delivered at 24 weeks' gestation will have anemia with a blood hemoglobin concentration much lower than a hemoglobin concentration defining anemia at term. Moreover, a hemoglobin concentration defining anemia at term birth is higher than that defining anemia in the same infant 60 days after birth. Diagnosing neonatal anemia can be evidence-based and consistent by using reference intervals derived from large neonatal databases. To do this, we advocate defining anemia as a hemoglobin level that plots below the 5th percentile lower reference interval, defining moderately severe anemia as a hemoglobin value between the 1st and 5th percentile, and defining severe anemia as a hemoglobin level that plots below the 1st percentile. The information provided in this review can easily be adopted by clinical laboratories and individual neonatal care units, thereby fostering application of these definitions for all infants whose hemoglobin levels are measured. Additional normative values included in this review describing various other erythrocyte metrics can likewise be easily adopted. Doing so will codify and standardize the diagnosis of neonatal anemia and will facilitate identifying the cause of the anemia, thus pointing the way to proper additional diagnostic testing and treatment.

Neonatal Anemia.

All neonates experience a downtrend in their hematocrit values immediately following the birth through normal falls in erythropoietin (Epo) production, transition to adult hemoglobin, and hemodilution with somatic growth. However, this drop is more pronounced in critically ill and preterm neonates and can lead to potentially pathologic anemia that impairs tissue oxygen delivery. In this review, we highlight the mechanisms underlying physiologic anemia and anemia of prematurity and briefly review the evidence for the treatment of anemia in the neonatal population, including the use of red blood cell transfusions, erythropoietic stimulating agents, and iron supplementation.

Red cell transfusion thresholds for preterm infants: finally some answers.

Extremely low birthweight infants become anaemic during their care in the neonatal intensive care unit because of the physiological anaemia experienced by all newborn infants compounded by early umbilical cord clamping, blood loss by phlebotomy for laboratory monitoring and delayed erythropoiesis. The majority of these infants receive transfusions of packed red blood cells, usually based on haemoglobin values below a certain threshold. The haemoglobin or haematocrit thresholds used to guide transfusion practices vary with infant status and among institutions and practitioners. Previous smaller studies have not given clear guidance with respect to the haemoglobin thresholds that should trigger transfusions or even if this is the best way to decide when to transfuse an infant. Two large clinical trials of similar design comparing higher and lower haemoglobin thresholds for transfusing extremely low birthweight infants were recently published, the ETTNO and TOP trials. These trials found reassuringly conclusive and concordant results. Within the range of haemoglobin transfusion thresholds studied, there was no difference in the primary outcome (which was the same in both studies), neurodevelopmental impairment at 2 years' corrected age or death before assessment, in either study. In addition, there was no difference in either study in either of the components of the primary outcome. In conclusion, haemoglobin transfusion thresholds within the ranges used in these trials, 11-13 g/dL for young critically ill or ventilated infants and 7-10 g/dL for stable infants not requiring significant respiratory support, can be safely used without expecting adverse consequences on survival or neurodevelopment.

Severe neonatal anemia affected by massive fetomaternal hemorrhage: a single-center retrospective observational study.

OBJECTIVES: Massive fetomaternal hemorrhage (FMH) is a rare but sometimes life-threatening event, and surviving neonates may suffer major neurological complications. Severe neonatal anemia (SNA) affected by massive FMH is less reported in the literature. This study aims to explore the clinical characteristics, laboratory diagnoses, treatments and outcomes of SNA affected by massive FMH. METHODS: Data were collected retrospectively from the hospital's electronic medical record system. All neonates born in the hospital and admitted to the neonatal unit diagnosed as SNA affected by massive FMH from 1 January 2013 to 31 June 2017 were included. RESULTS: A total of 8 cases of SNA affected by FMH were identified among 6825 neonates admitted to the neonatal unit. They all presented with pallor but without hydrops at birth. Median gestational age and birthweight were 375/7 (360/7‒401/7) weeks and 2,625 (2300‒3050) g, respectively. Median hemoglobin level was 39.5 (25‒53) g/L at birth and 109.5 (94-127) g/L at discharge. Median maternal serum alpha-fetoprotein (AFP) was 3958.5 (1606‒14,330) ng/mL, which was significantly increased. Three out of eight cases manifested as antenatal decreased fetal movement. Only 1 with the lowest initial hemoglobin 25 g/L manifested as characteristic sinusoidal fetal heart rate tracing and suffered severe neonatal asphyxia and hypovolemic shock. Having experienced resuscitation, he was admitted to the neonatal unit and received twice transfusion of cross-matched red blood cells there. Another case with the initial hemoglobin 45 g/L received positive pressure ventilation and once transfusion. All cases were successfully discharged with a median hospital stay of 8 (5-12) days. Follow-up was available for 6 (75%) of 8 neonates (age range 13 months to 50 months), and all infants were observed to be in good condition with normal neurological status. In our series of eight cases, there were no neonatal deaths. CONCLUSION: This study strengthens the idea that maternal AFP testing is valuable to confirm massive fetomaternal hemorrhage. Surviving neonates of massive FMH might have a good outcome despite severe anemia at birth.

Association of Blood Donor Sex and Age With Outcomes in Very Low-Birth-Weight Infants Receiving Blood Transfusion.

Importance: There are conflicting data on the association between blood donor characteristics and outcomes among patients receiving transfusions. Objective: To evaluate the association of blood donor sex and age with mortality or serious morbidity in very low-birth-weight (VLBW) infants receiving blood transfusions. Design, Setting, and Participants: This is a cohort study using data collected from 3 hospitals in Atlanta, Georgia. VLBW infants (≤1500 g) who received red blood cell (RBC) transfusion from exclusively male or female donors were enrolled from January 2010 to February 2014. Infants received follow-up until 90 days, hospital discharge, transfer to a non-study-affiliated hospital, or death. Data analysis was performed from July 2019 to December 2020. Exposures: Donor sex and mean donor age. Main Outcomes and Measures: The primary outcome was a composite outcome of death, necrotizing enterocolitis (Bell stage II or higher), retinopathy of prematurity (stage III or higher), or moderate-to-severe bronchopulmonary dysplasia. Modified Poisson regression, with consideration of covariate interactions, was used to estimate the association between donor sex and age with the primary outcome, with adjustment for the total number of transfusions and birth weight. Results: In total, 181 infants were evaluated, with a mean (SD) birth weight of 919 (253) g and mean (SD) gestational age of 27.0 (2.2) weeks; 56 infants (31%) received RBC transfusion from exclusively female donors. The mean (SD) donor age was 46.6 (13.7) years. The primary outcome incidence was 21% (12 of 56 infants) among infants receiving RBCs from exclusively female donors, compared with 45% (56 of 125 infants) among those receiving RBCs from exclusively male donors. Significant interactions were detected between female donor and donor age (P for interaction = .005) and between female donor and number of transfusions (P for interaction < .001). For the typical infant, who received a median (interquartile range) of 2 (1-3) transfusions, RBC transfusion from exclusively female donors, compared with male donors, was associated with a lower risk of the primary outcome (relative risk, 0.29; 95% CI, 0.16-0.54). The protective association between RBC transfusions from female donors, compared with male donors, and the primary outcome increased as the donor age increased, but decreased as the number of transfusions increased. Conclusions and Relevance: These findings suggest that RBC transfusion from female donors, particularly older female donors, is associated with a lower risk of death or serious morbidity in VLBW infants receiving transfusion. Larger studies confirming these findings and examining potential mechanisms are warranted.

Perinatal outcome of pregnancy complicated by twin anemia-polycythemia sequence: systematic review and meta-analysis.

OBJECTIVE: To report the perinatal outcome of monochorionic diamniotic (MCDA) twin pregnancies complicated by twin anemia-polycythemia sequence (TAPS), according to the type of TAPS (spontaneous or postlaser) and the management option adopted. METHODS: MEDLINE, EMBASE and The Cochrane Library databases were searched for studies reporting on the outcome of twin pregnancies complicated by TAPS. Inclusion criteria were non-anomalous MCDA twin pregnancies with a diagnosis of TAPS. The primary outcome was perinatal mortality; secondary outcomes were neonatal morbidity and preterm birth (PTB). The outcomes were stratified according to the type of TAPS (spontaneous or following laser treatment for twin-twin transfusion syndrome) and the management option adopted (expectant, laser surgery, intrauterine transfusion (IUT) or selective reduction (SR)). Random-effects meta-analysis of proportions was used to analyze the data. RESULTS: Perinatal outcome was assessed according to whether TAPS occurred spontaneously or after laser treatment in 506 pregnancies (38 studies). Intrauterine death (IUD) occurred in 5.2% (95% CI, 3.6-7.1%) of twins with spontaneous TAPS and in 10.2% (95% CI, 7.4-13.3%) of those with postlaser TAPS, while the corresponding rates of neonatal death were 4.0% (95% CI, 2.6-5.7%) and 9.2% (95% CI, 6.6-12.3%), respectively. Severe neonatal morbidity occurred in 29.3% (95% CI, 25.6-33.1%) of twins after spontaneous TAPS and in 33.3% (95% CI, 17.4-51.8%) after postlaser TAPS, while the corresponding rates of severe neurological morbidity were 4.0% (95% CI, 3.5-5.7%) and 11.1% (95% CI, 6.2-17.2%), respectively. PTB complicated 86.3% (95% CI, 77.2-93.3%) of pregnancies with spontaneous TAPS and all cases with postlaser TAPS (100% (95% CI, 84.3-100%)). Iatrogenic PTB was more frequent than spontaneous PTB in both groups. Perinatal outcome was assessed according to the management option adopted in 417 pregnancies (21 studies). IUD occurred in 9.8% (95% CI, 4.3-17.1%) of twins managed expectantly and in 13.1% (95% CI, 9.2-17.6%), 12.1% (95% CI, 7.7-17.3%) and 7.6% (95% CI, 1.3-18.5%) of those treated with laser surgery, IUT and SR, respectively. Severe neonatal morbidity affected 27.3% (95% CI, 13.6-43.6%) of twins in the expectant-management group, 28.7% (95% CI, 22.7-35.1%) of those in the laser-surgery group, 38.2% (95% CI, 18.3-60.5%) of those in the IUT group and 23.3% (95% CI, 10.5-39.2%) of those in the SR group. PTB complicated 80.4% (95% CI, 59.8-94.8%), 73.4% (95% CI, 48.1-92.3%), 100% (95% CI, 76.5-100%) and 100% (95% CI, 39.8-100%) of pregnancies after expectant management, laser surgery, IUT and SR, respectively. CONCLUSIONS: The present meta-analysis provides pooled estimates of the risks of perinatal mortality, neonatal morbidity and PTB in twin pregnancies complicated by TAPS, stratified by the type of TAPS and the management option adopted. Although a direct comparison could not be performed, the results from this systematic review suggest that spontaneous TAPS may have a better prognosis than postlaser TAPS. No differences in terms of mortality and morbidity were observed when comparing different management options for TAPS, although these findings should be interpreted with caution in view of the limitations of the included studies. Individualized prenatal management, taking into account the severity of TAPS and gestational age, is currently the recommended strategy. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Anemia of Prematurity and Oral Feeding Milestones in Premature Infants.

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.

Hemodynamics of different volumes of red blood cell transfusion in preterm infants.

BACKGROUND: Although many controversies exist regarding the risk of red blood cell (RBC) transfusions, half of preterm infants born at <32 weeks of gestational age receive such transfusions because of anemia of prematurity. Because of the costs and risks associated with multiple transfusions, it has been suggested that a large transfusion volume reduces the number of transfusions. However, there have been persistent concerns that RBC transfusion might lead to volume overload. METHODS: We examined the impacts of large (20 mL/kg) compared to standard volume (15 mL/kg) transfusions on the hemodynamic variables of stable, electively transfused, preterm infants, by serially measuring echocardiographic parameters and plasma B-type natriuretic peptide levels. RESULTS: A total of 39 infants born at <34 weeks of gestation and aged >2 weeks at the time of enrollment were randomly allocated to either a standard volume (15 mL/kg) or a large volume (20 mL/kg) group. Significant reductions in cardiac output and transient increases in plasma B-type natriuretic peptide levels were found after RBC transfusion in both the standard and large volume (20 mL/kg) groups. However, these changes were not significantly different between the two groups. CONCLUSIONS: Large-volume transfusions could be tolerable in stable preterm infants with anemia.

Allogeneic cord blood transfusions prevent fetal haemoglobin depletion in preterm neonates. Results of the CB-TrIP study.

Repeated red blood cell (RBC) transfusions in preterm neonates are associated with poor outcome and increased risk for prematurity-associated diseases. RBC transfusions cause the progressive replacement of fetal haemoglobin (HbF) by adult haemoglobin (HbA). We monitored HbF levels in 25 preterm neonates until 36 weeks of post-menstrual age (PMA); patients received RBC units from allogeneic cord blood (cord-RBCs) or from adult donors (adult-RBCs), depending on whether cord-RBCs were available. Primary outcome was HbF level at PMA of 32 weeks. Twenty-three neonates survived until this age: 14 received no transfusions, two only cord-RBCs, three only adult-RBCs and four both RBC types. HbF levels in neonates transfused with cord-RBCs were significantly higher than in neonates receiving adult-RBCs (P < 0·0001) or both RBC types (P < 0·0001). Superimposable results were obtained at PMA of 36 weeks. Every adult-RBCs transfusion increased the risk for an HbF in the lowest quartile by about 10-fold, whereas this effect was not evident if combined adult- and cord-RBCs were evaluated. Overall, these data show that transfusing cord-RBCs can limit the HbF depletion caused by conventional RBC transfusions. Transfusing cord blood warrants investigation in randomised trials as a strategy to mitigate the severity of retinopathy of prematurity (NCT03764813).

Are single-donor red blood cell transfusions still relevant for preterm infants?

OBJECTIVE: To explore the worth of a single-donor program for preterm infants through the recipient profile and the impact on donor exposure, red blood cell (RBC) pack waste, storage duration, and transfusion performance. STUDY DESIGN: Patients and transfusion characteristics were collected for 3 years (2015-2017) in preterm infants according to single-donor program prescription in a unit not practicing placental transfusion or erythropoietin supplementation. RESULTS: Among 1048 eligible preterm infants, 161 met the inclusion criteria, and 51 received single-donor packs. Our single-donor program induced a donor number reduction (34% less than the transfusion number) and an extension of storage duration (median: 9 versus 7 days, p < 0.0001) without altering the transfusion performance. However, 41% of small packs were not used. CONCLUSION: A single-donor program partially reduced donor exposure but led to drastic RBC pack waste. Optimization of transfusion alternatives may increase this phenomenon, calling into question the rationale of this practice.

Impacto del volumen de sangre extraído por flebotomía sobre el requerimiento transfusional en prematuros menores de 1500 g. Estudio cuasiexperimental / Impact of the volume of blood collected by phlebotomy on transfusion requirements in preterm infants with birth weight of less than 1500 g. A quasi-experimental study

Introducción. La anemia es una complicación para los recién nacidos de muy bajo peso al nacer, y los exámenes de laboratorio son un factor de riesgo preponderante. Más del 50 % recibe, al menos, una transfusión de glóbulos rojos. Estas se han asociado a mayor riesgo de infecciones, hemorragia intracraneal, enterocolitis necrotizante y displasia broncopulmonar. En 2012, se implementó, en el Hospital Italiano de Buenos Aires, una estrategia de menor volumen de extracción de sangre por flebotomía. El objetivo del presente estudio fue evaluar su asociación con el número detransfusiones.Métodos. Estudio cuasiexperimental del tipo antes/después. Se comparó el número de transfusiones entre dos grupos de prematuros de muy bajo peso con diferente volumen de extracción. Se evaluó la correlación entre el volumen extraído y el número de transfusiones estimando el coeficiente de Spearman. Para ajustar por confundidores, se realizó un modelo de regresión logística.Resultados. Se incluyeron en el estudio 178 pacientes con edad gestacional media de 29,4 semanas (desvío estándar: 2,7) y peso al nacer de 1145 gramos (875-1345). El perfil de la serie roja inicial fue similar entre ambos grupos. El número de transfusiones (p = 0,017) y el volumen transfundido (p = 0,048) disminuyeron significativamente. El coeficiente de correlación resultó de 0,83. En el análisis multivariado, volumen de extracción y peso al nacer se asociaron a un requerimiento mayor de 3 transfusiones.Conclusión. Un menor volumen de extracción de sangre en prematuros de muy bajo peso está asociado de manera independiente a menor requerimiento transfusional.

Introduction. Anemia is a complication in very low birth weight (VLBW) infants, and lab tests are a predominant risk factor. At least one red blood cell transfusion is given in more than 50 % of cases. Transfusions are associated with a higher risk for infections, intracranial hemorrhage, necrotizing enterocolitis, and bronchopulmonary dysplasia. In 2012, Hospital Italiano de Buenos Aires implemented a strategy to collect a lower blood volume by phlebotomy. The objective of this study was to assess its association with the number of transfusions.Methods. Before-and-after, quasi-experimental study. The number of transfusions was compared between two groups of VLBW preterm infants with different blood collection volumes. The correlation between the collection volume and the number of transfusions was assessed estimating Spearman's coefficient. A logistic regression model was used to adjust for confounders.Results. The study included 178 patients with a mean gestational age of 29.4 weeks (standard deviation: 2.7) and a birth weight of 1145 g (875-1345). The baseline red series profile was similar between both groups. The number of transfusions (p = 0.017) and the transfusion volume (p = 0.048) decreased significantly. The correlation coefficient was 0.83. In the multivariate analysis, collection volume and birth weight were associated with a requirement of more than three transfusions.Conclusion. A lower blood collection volume in VLBW preterm infants is independently associated with fewer transfusion requirements.

Association of Bolus Feeding With Splanchnic and Cerebral Oxygen Utilization Efficiency Among Premature Infants With Anemia and After Blood Transfusion.

Importance: The pathogenesis of transfusion-associated necrotizing enterocolitis remains elusive. Splanchnic hypoperfusion associated with packed red blood cell transfusion (PRBCT) and feeding has been implicated, but studies of splanchnic tissue oxygenation with respect to feeding plus PRBCT are lacking. Objective: To investigate the oxygen utilization efficiency of preterm gut and brain challenged with bolus feeding during anemia and after transfusion using near-infrared spectroscopy. Design, Setting, and Participants: This prospective cohort study conducted from September 1, 2014, to November 30, 2016, at a tertiary neonatal intensive care unit included 25 hemodynamically stable infants with gestational age less than 32 weeks, birth weight less than 1500 g, and postmenstrual age younger than 37 weeks. Data analysis was performed from August 1, 2017, to October 31, 2018. Exposures: Infants received PRBCT (15 mL/kg for 4 hours) and at least 120 mL/kg daily of second hourly bolus feedings. Main Outcomes and Measures: Splanchnic fractional tissue oxygen extraction (FTOEs) and cerebral fractional tissue oxygen extraction (FTOEc) measures were made during 75-minute feeding cycles that comprised a 15-minute preprandial feeding phase (FP0) and 4 contiguous 15-minute postprandial feeding phases (FP1, FP2, FP3, and FP4; each 15 minutes long). The intraindividual comparisons of feeding-related changes were evaluated during the pretransfusion epoch (TE0: 4 hours before onset of transfusion) and 3 TEs after transfusion (TE1: first 8 hours after PRBCT completion; TE2: 9-16 hours after PRBCT completion; and TE3: 17-24 hours after PRBCT completion). Results: Of 25 enrolled infants (13 [52%] female; median birth weight, 949 g [interquartile range {IQR}, 780-1100 g]; median gestational age, 26.9 weeks [IQR, 25.9-28.6 weeks]; median enrollment weight, 1670 g [IQR, 1357-1937 g]; and median postmenstrual age, 34 weeks [IQR, 32.9-35 weeks]), 1 infant was excluded because of corrupted near-infrared spectroscopy data. No overall association was found between FTOEs and FPs in a multivariable repeated-measures model that accounted for transfusion epochs (primary analysis approach) (FP0: mean estimate, 11.64; 95% CI, 9.55-13.73; FP1: mean estimate, 12.02; 95% CI, 9.92-14.11; FP2: mean estimate, 12.77; 95% CI, 10.68-14.87; FP3: mean estimate, 12.54; 95% CI, 10.45-14.64; FP4: mean estimate, 12.98; 95% CI, 10.89-15.08; P = .16 for the FP association). However exploratory analyses of postprandial changes in FTOEs undertaken for each transfusion epoch separately found evidence of increased postprandial FTOEs during TE1 (mean [SD] FTOEs, 10.55 [5.5] at FP0 vs 13.21 [5.96] at FP4, P = .046). The primary and exploratory analyses found no association between FTOEc and feeding phases, suggesting that cerebral oxygenation may be protected. Conclusions and Relevance: The findings suggest that enteral feeding may be associated with gut ischemia and potentially transfusion-associated necrotizing enterocolitis. The postprandial changes in FTOEs appear to warrant further investigation in larger randomized studies.

Iron Nutrition, Erythrocytes, and Erythropoietin in the NICU: Erythropoietic and Neuroprotective Effects.

Prematurity, maternal diabetes, maternal smoking, being medically underserved, and small size for gestational age are common characteristics of neonates in the NICU and can predispose them to develop congenital iron deficiency. Iron is critical for organ development. In the fetus and newborn, iron is prioritized for red blood cell production, sometimes at the expense of other tissues, including the brain. It is critical to optimize iron levels in newborns to support erythropoiesis, growth, and brain development. Available studies support improved neurodevelopmental outcomes with either iron supplementation or delayed umbilical cord clamping at birth. Erythropoietic doses of erythropoietin/erythrocyte-stimulating agents may also improve neurocognitive outcomes. However, the literature on the effect of liberal red blood cell transfusions on long-term neurodevelopment is mixed. Understanding age-specific normal values and monitoring of iron indices can help individualize and optimize the iron status of patients in the NICU.

Infantile Pyknocytosis: An Uncommon Cause of Newborn Hemolytic Anemia.

Infantile pyknocytosis is a rare cause of neonatal hemolytic anemia, which presents in the first few weeks of life. We report a classic case of infantile pyknocytosis that presented to our institution with rebound hyperbilirubinemia after receiving phototherapy. The infant was found to have a hemoglobin of 5.8 g/dL, requiring a total of 15 mL/kg of red blood cells (in 2 separate transfusions) before discharge. The diagnosis was ultimately made by a review of the peripheral blood smear. We review the literature and suggest pediatricians consider infantile pyknocytosis on their differential when hemolytic anemia presents in the newborn period.

The role of recombinant Human erythropoietin in neonatal anemia.

AIM: To estimate the blood level of Erythropoietin(EPO) in neonates with anemia of prematurity (APO) and in late hypo-regenerative anemia and to clarify role of EPO in correction of anemia and reducing the number of blood transfusions. METHODS: This study was carried out on 60 neonates divided into; group I (30 preterm neonates) with AOP received EPO (250 IU/kg/dose subcutaneously 3 times weekly for 4 weeks), compared to group II (30 neonates) with AOP treated only with blood transfusion. CBC parameters and transfusion requirements were followed during therapy. Serum level of EPO was measured by ELISA technique. RESULTS: By the end of the 4th week of therapy, there was significant increase in group I post r-Hu EPO compared to group II regarding reticulocyte counts (P < 0.001) leading to rise of the Hb (P < 0.001), Hct levels (P < 0.001) with subsequent reduction in the overall number of blood transfusions (P < 0.001). CONCLUSION: EPO therapy in conjunction with iron, vitamin E and folic acid, stimulated erythropoiesis and significantly reduced the need for blood transfusion in AOP.

7 Is the New 8: Improving Adherence to Restrictive PRBC Transfusions in the Pediatric ICU.

Up to 30%-40% of children admitted to the pediatric intensive care unit (PICU) have anemia, and approximately 15% receive packed red blood cell (pRBC) transfusions. Current literature supports a pRBC transfusion threshold of hemoglobin less than or equal to seven for most PICU patients. Our objective was to determine pRBC transfusion rates, assess compliance with transfusion guidelines, understand patient-level variables that affect transfusion practices, and use cross-industry innovation to implement a practice strategy. This was a pre-post study of pediatric patients admitted to our PICU. We collected baseline data on pRBC transfusion practices. Next, we organized an innovation platform, which generated multi-industry ideas and produced an awareness campaign to effect pRBC ordering behavior. Innovative educational interventions were implemented, and postintervention transfusion practices were monitored. Statistical analysis was performed using linear mixed models. A p value < .05 was considered statistically significant. At baseline, 41% of pRBC transfusions met restrictive transfusion guidelines with a pretransfusion hemoglobin less than or equal to 7 g/dl. In the postintervention period, 53% of transfusions met restrictive transfusion guidelines (odds ratio 1.66, 95% confidence interval 1.21-2.28). Implementation of a behavioral campaign using multi-industry innovation led to improved adherence to pRBC transfusion guidelines in a tertiary care PICU.