Anemia In Premature Infants Research Articles

Severe anemia in preterm infants associated with increased bacterial virulence potential and metabolic disequilibrium.

Anemia in preterm infants is associated with gut dysbiosis and necrotizing enterocolitis. Our study aimed to identify the bacterial functions and metabolites that can explain the underlying mechanisms of anemia associated disease conditions. We conducted a case control study in preterm infants with cases having a hematocrit 25%. The control infants were matched by birth gestational age and weight. Fecal samples were collected before, at the onset, and after the onset of anemia in cases and with matched postnatal age in controls for metagenomics and metabolomics analyzes. 18 anemic and 20 control infants with fecal samples collected at 17 days, 5 weeks, and 7 weeks postnatal age were included. Virulence factor potential, decrease in beta diversity evolution, and larger changes in metabolome were associated with severe anemia. Metabolite abundances of N-acetylneuraminate and butyrobetaine were associated with virulence factor potential. Anemic group had decreased prostaglandin and lactic acid levels. Fecal omics data showed that severe anemia is associated with a pro-inflammatory gut microbiota with more virulent and less commensal anaerobic bacterial activities. Future studies can examine the link between anemia-associated dysbiosis and clinical outcomes and predict an infant-specific hematocrit threshold that negatively affects clinical outcomes. Severe anemia in preterm infants contributes to a pro-inflammatory gut with greater bacterial virulence and less commensal bacterial activities. The multiomics approach using non-invasive fecal biospecimens identified functional and metabolic changes in the gut microbiota and these mechanistic changes are plausible explanations for anemia-associated disease conditions in preterm infants. Our findings identified biological changes of the gut environment in severely anemic preterm infants that can offer guidance for clinical management.

Noninvasive pressure-strain loop quantitative assessment of left ventricular function in anemic preterm infants with different modes of respiratory support

To investigate noninvasive pressure-strain loop (PSL) combined with two-dimensional speck tracking imaging and left ventricular pressure measurement in the evaluation of cardiac function changes in anemia of prematurity (AOP) with different modes of respiratory support, and to explore its value in detecting subclinical myocardial injury in preterm infants. This retrospective study included 79 preterm infants with anemia, according to different modes of respiratory support, who were divided into invasive respiratory support group (39 cases) and noninvasive respiratory support group (40 cases). A control group of 40 nonanemic preterm infants with matched age, sex, and gestational age were also included. Complete echocardiography was performed for each included infant. There are PSL parameters that used to evaluate cardiac function, including global longitudinal strain (GLS), global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) among the three groups were compared. Compared with the control group, the value of GWI, GCW, and GWE were significantly lower and GWW was higher in the AOP groups (P < 0.05), and GWI, GCW and GWE were much significantly lower in the invasive respiratory support group than in the noninvasive respiratory support group (P < 0.05). There was no significant difference in GLS among the three groups (P > 0.05). Noninvasive PSL analysis can quantitatively assess myocardial work in AOP with different respiratory support, which is more sensitive than other conventional echocardiographic indices. This technique may provide a new method for monitoring subclinical myocardial injury with AOP.

Comparison of restrictive and liberal red blood cell suspension transfusion and analysis of influencing factors on prognosis of premature infants.

To investigate the influence of restrictive and liberal red blood cell suspension (RBCs) transfusions on the prognosis of premature infants and to analyze the influencing factors to provide a reference for the transfusion strategy of preterm infants. Retrospective analysis was conducted on 85 cases of anemic premature infants treated in our center, including 63 cases in the restrictive transfusion group and 22 in the liberal transfusion group. RBCs transfusions were effective in both groups, and there were no statistically significant differences in post-transfusion hemoglobin and hematocrit between the two groups (P>0.05). The outcome events: the duration of ventilatory support was statistically prolonger in the restrictive group compared with the liberal group (P<0.001); however, the differences in mortality, the increased weight before discharge, and length of stay in the hospital within the two groups were not statistically significant (P=0.237, 0.36 and 0.771, respectively). Univariate survival analysis showed that age, birth weight, Apgar 1 min and Apgar 10 min scores were the influencing factors for death, with P values of 0.035, 0.004, <0.001, and 0.013, respectively; COX regression analysis showed that Apgar 1 min score was an independent factor of the survival time of preterm infants (P=0.002). Compared with the restrictive transfusion group, liberal transfusion patients presented a shorter duration of ventilatory support, which is more beneficial to the prognosis of premature infants.

Effect of autologous umbilical cord blood transfusion in the development of retinopathy of prematurity: randomized clinical trial - study protocol.

Currently, the treatment of anemia in preterm infants is based on packed red blood cell (RBC) transfusions from adult donors. Oxygen (O2) is mainly transported to the tissues bound to hemoglobin (Hb). In extremely low gestational age neonates (ELGANs), fetal hemoglobin (HbF), which has a higher affinity for O2, represents up to 95% of circulating hemoglobin. During the first month of life, the majority of ELGANs will require an adult-donor RBC transfusion causing HbF levels to rapidly drop. HbA releases 50% more oxygen in peripheral tissues than HbF. Increased release of O2 in the retina is one of the main factors related to the development of retinopathy of prematurity (ROP). Collecting umbilical cord blood and using autologous umbilical cord whole blood (UCB) transfusions would contribute to maintaining physiological HbF concentrations in newborns and avoid oxygen-in-excess derived damage. This is a randomized, double-blinded, multicenter clinical trial. ELGANs ≤28 weeks of gestational age will be randomized 1:1 to receive an autologous umbilical cord blood transfusion (intervention arm) or standard transfusion of packed RBC from an adult donor (control arm) to assess ROP development. Assuming a 50% reduction in ROP incidence, 134 patients (67 per group) will be recruited. When blood transfusion is indicated, the Blook Bank will supply UCB or RCB according to the patient's group. The primary endpoint is the incidence of any ROP. Secondary endpoints are assessessment of treatment safety, results of biomarkers related to ROP and its chronology, and urine oxidative stress markers. In addition, the cellular composition of umbilical cord blood and its relationship with prematurity-related pathologies will be analyzed. All patients will be followed-up to 24 months of corrected age to evaluate their neurodevelopment. ROP is a major cause of irreversible blindness in preterm newborns. Transfusions with adult donor blood can lead to complications, including ROP. UCB transfusions offer advantages by maintaining physiological HbF levels and potentially optimizing postnatal development. Moreover, autologous UCB transfusion could reduce risks associated with heterologous blood products, although volume collection remains challenging. UCB contains growth factors and progenitor cells that may impact ROP.

Comparative efficacy and safety of restrictive versus liberal transfusion thresholds in anemic preterm infants: a meta-analysis of 12 randomized controlled trials

The comparative efficacy and safety of restrictive with liberal transfusion thresholds remain controversial in anemic preterm infants. This meta-analysis aimed to compare the efficacy and safety of these two transfusion thresholds for anemic preterm infants. We searched PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI) for relevant randomized controlled trials (RCTs) comparing restrictive with liberal transfusion thresholds in anemic preterm infants through April 30, 2022. Two independent investigators screened literature, extracted data, and appraised the methodological quality of eligible studies. Meta-analysis was conducted using RevMan version 5.3.5. Twelve RCTs with 4380 preterm infants were included. Liberal transfusion threshold significantly increased the level of hemoglobin after transfusion (mean difference (MD): −10.03; 95% confidence interval (CI): −15.98 to −4.08; p=0.001; I2=94%) and hematocrit (MD: −3.62; 95%CI: −6.78 to −0.46; p=0.02; I2=80%) compared with restrictive transfusion. Infants’ age at first transfusion in restrictive transfusion group was higher than that of infants in liberal transfusion group (MD: 5.08; 95%CI: 2.27 to7.89; p=0.004; I2=54%); however, restrictive transfusion was associated with more time on supplemental oxygen (MD: 3.56; 95%CI: 1.93 to 5.18; p<0.001; I2=62%) and ventilator or CPAP (MD: 3.31; 95%CI: 1.42 to 5.20; p=0.006; I2=75%). For the remaining outcomes, two transfusion strategies were comparable. Furthermore, a series of sensitivity analyses confirmed the robustness of the level of hemoglobin after transfusion, age at first transfusion, time on ventilator or CPAP, and safety outcomes. Evidence with substantial heterogeneity indicates that liberal and restrictive transfusion thresholds are effective and safe blood cell transfusion strategies in anemic preterm infants, but the liberal strategy may be more effective in shortening the length of necessary respiratory support.

Regional tissue oxygenation and conventional indicators of red blood cell transfusion in anaemic preterm infants

SummaryBackgroundIt is unresolved whether low haemoglobin (Hb) and symptoms of anaemia reflect oxygen delivery-consumption imbalances (fractional tissue oxygen extraction [FTOE]). Here, we test whether pre-transfusion Hb and symptoms of anaemia correlate with pre-transfusion cerebral and splanchnic FTOE.MethodsThis prospective cohort study was carried out between Sept 1, 2014 and Nov 30, 2016 at Nepean Hospital, Sydney, Australia. The study enroled haemodynamically stable preterm infants: gestation <32 weeks; birth weight <1500 gs; postmenstrual age <37weeks, who received 15 mL/kg packed red blood cell transfusion (PRBCT) based on low Hb and symptoms of anaemia. FTOE was determined using simultaneous monitoring of near-infrared spectroscopy and pulse oximetry for 4 h before PRBCT.FindingsThe study enroled 29 infants born with a median gestation of 26.4 weeks (IQR 25.4–28.1), birth weight 922 g (655–1064), at postmenstrual age 33.6 weeks (31.7–34.9), and weight 1487 g (1110–1785). There was no significant correlation between Hb (median 97 g/L, IQR 87–100) and cerebral FTOE (r=–0.12, 95% CI –0.47 to 0.27; p = 0.54, n = 29) as well as splanchnic FTOE (r=–0.09, 95% CI –0.45 to 0.29; p = 0.64, n = 29). Median cerebral FTOE (p = 0.67) and splanchnic FTOE (p = 0.53) did not differ between symptomatic and asymptomatic groups.InterpretationOur preliminary findings suggest that pre-transfusion Hb and symptoms of anaemia might not accurately reflect oxygen delivery-consumption imbalances in both the brain and the gut. A lack of correlation with cerebral FTOE might be presumed to be due to the brain-sparing effect. However, the lack of correlation with splanchnic FTOE is more concerning. Hence, these results warrant larger studies incorporating FTOE along with the conventional criteria in the transfusion algorithm.FundingThe study was funded (for the purchase of NIRS sensors) by the Australian Women and Children's Research Foundation.

Hematological changes in neonatal mice with phlebotomy-induced anemia.

Anemia is a nearly universal diagnosis in preterm infants, caused by phlebotomy, and exacerbated by the underlying erythropoietic immaturity. Newborn infants are exposed to the unique stressor of fetal-to-neonatal transition, which requires significant adaptation ex utero. Accordingly, the preterm infant's response to anemia may alter the ability to confront underlying illness. This study utilized our preclinical mouse model of phlebotomy-induced anemia (PIA) to comprehensively investigate associated hematological changes. C57BL/6 mice were subjected to timed phlebotomy between postnatal days 2--10 to induce severe anemia. Complete blood counts were determined by the Sysmex XT-2000iV analyzer. Anemic pups showed a gradual reduction of RBC and hemoglobin (Hb) and increased reticulocyte (RET) counts and red cell distribution width (RDW), however, with reduced RET-Hb from postnatal day (P) of 4 onwards. Elevated levels of high fluorescent RET and immature reticulocyte fraction (IRF) were noted in anemic mouse pups, but low and medium fluorescent RET were reduced. Also, the reduction of mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) were noted in anemic pups. No changes were seen in lymphocytes, but monocytes and neutrophils were significantly elevated from P4-P6. PIA in mouse pups is associated with hematological changes that may be exacerbating factors in neonatal diseases. Anemia is common and often severe in premature infants. Investigation of hematological parameters in settings of preclinical anemia may be an index of therapeutic strategies. Preclinical model evaluating the effects of neonatal anemia on the remainder of complete blood count. Detailed time kinetic phlebotomy-induced anemic mice enable us to study the impact on developmental delays in erythropoiesis and possible strategic intervention. Hematological effects of severe anemia in mice might provide insight on how best to investigate anemia in preterm infants.

Predicting early anemia of premature infants with body weight less than 1500 g

Early anemia of premature children is a characteristic disease of preterm infants, especially those with extremely low and very low body weight at birth. The study of new formation mechanisms will help to carry out preventive measures in a timely manner and prevent this pathology in the neonatal period.Objective. To study insulin-like growth factor-1 and protein-3, which binds insulin-like growth factor, to predict early anemia and its severe variant in premature infants.Characteristics of the children and research methods. The authors carried out the clinical and laboratory examination of 65 newborns of gestational age up to 32 weeks with a birth weight of less than 1500 g. The authors determined the content of insulin-like growth factor-1 and protein-3, which binds insulin-like growth factor in venous blood on the 3-5th day of life.Results. The authors revealed new predictors of early anemia of premature children: the content of protein-3, which binds insulin-like growth factor, on the 3-5th day of life of 0.766 μg/ml or less, and the content of insulin-like growth factor of 25.9 ng/ml or less predict the formation of early anemia in premature and very preterm patients. The authors established the predictors of the severe variant of early anemia of premature children, requiring blood transfusion, namely: the content of protein-3, which binds insulin-like growth factor, taking into account the anthropometric parameters of the child at birth. They developed and implemented the methods for predicting early anemia and its severe variant in premature patients.Conclusion. The results make it possible to timely carry out preventive measures in order to prevent the disease and improve the indicators of health and life quality in very premature patients.

Regional Oxygenation and Perfusion Monitoring to Optimize Neonatal Packed Red Blood Cell Transfusion Practices: A Systematic Review.

Contemporary packed red blood cell transfusion practices in anaemic preterm infants are primarily based on measurement of hemoglobin or haematocrit. In neonatal intensive care units, most preterm infants receive at least 1 packed red cell transfusion as standard treatment for anaemia of prematurity. Clinicians are faced with a common question "at what threshold should anaemic preterm infants receive packed red blood cell transfusion?". While evidence from interventional trials offers a range of haemoglobin levels to clinicians on thresholds to initiate red cell transfusion, it does not offer identification of exact haemoglobin level at which regional oxygenation and perfusion gets compromised. Assessment of regional oxygenation using near infrared spectroscopy and perfusion using ultrasound could offer a personalized transfusion medicine approach to optimize transfusion practices. We conducted a systematic review of the literature to identify the role of both regional oxygenation and/or ultrasound-based perfusion monitoring as a potential trigger to initiate packed red blood cell transfusion in anaemic preterm infants. MEDLINE, Embase, Maternity and Infant Care database were searched up to March 2021. Publications identified were screened and relevant data was extracted. Changes to regional oxygenation and/or perfusion monitoring before and after packed red blood cell transfusion were the primary outcomes. 44 out of 755 studies met the inclusion criteria and were included in the final analysis. Most were prospective, observational studies in stable preterm infants. Overall, studies reported an improvement in regional oxygenation and/or ultrasound-based perfusion after packed red blood cell transfusion. These changes were more consistently observed when hemoglobin <9.6g/dL or hematocrit was <0.30. Significant variation was found for patient characteristics, postnatal age at the time of monitoring, criteria for diagnosis of anaemia, and period of monitoring as well as regional oxygenation monitoring methodology. Regional oxygenation and/or perfusion monitoring can identify at-risk anaemic preterm infants and are promising tools to individualize packed red blood cell transfusion practices. However, there is lack of evidence for incorporating this monitoring, in their present form, into standard clinical practice. Additionally, consistency in reporting of study methodology should be improved.

Efficacy and safety of parenteral nutrition with iron sucrose for anemia prevention in preterm infants: A randomized, double-blind controlled study.

Our objective is to study the efficacy and safety of parenteral nutrition (PN) with iron sucrose to prevent anemia in preterm infants. We performed a randomized, double-blind controlled trial in which preterm infants were divided into five groups randomly: a control group (PN without iron sucrose, namely group Iron-0), and intervention groups (PN with iron sucrose 100 μg/kg/d, 200 μg/kg/d, 300 μg/kg/d and 400 μg/kg/d, namely group Iron-1, 2, 3, and 4, respectively). The indicators were red blood cell (RBC) parameters, iron storage and oxidant stress. One hundred infants completed this study. Excepting the RBC count in Iron-2, the value of erythrocyte parameters in intervention groups decreased less than that in the control group. And the decrease of RBC count in Iron-1 (-0.6×1012/L vs -0.9×1012/L, p=0.033), hemoglobin in Iron-4 (-26.0 g/L vs -41.0 g/L, p=0.03) and hematocrit in Iron-1(-9.5% vs -14.0%, p=0.014) was significantly less than in the control group. The change of ferritin in Iron-4 was significantly higher than in the control group (280 ng/ml vs 118 ng/ml, p=0.04). There was no difference in serum iron in intervention groups when compared to the control group (p>0.05). Except for the change of malondialdehyde (MDA) in Iron-1, the increase in other intervention groups was higher than in the control group (p>0.05). PN with iron sucrose for prevention of anemia in preterm infants is safe and efficacious to some extent.

Neonatal anemia relates to intestinal injury in preterm infants.

BackgroundAnemia 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.MethodsA 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 (rsSO2) and rsSO2 variability.ResultsThirty-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). RsSO2 and rsSO2 variability were lower in cases than controls shortly before transfusion. Hemoglobin levels correlated negatively with rsSO2 and rsSO2 variability in cases, and negatively with I-FABP in cases and controls together.ConclusionsUrinary 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.

Determinants of anemia in premature newborns and the immediate outcome at the Mother and Child Center of the Chantal BIYA Foundation, Cameroon

Background: Anemia is a common and serious health problem, especially in premature infants. The objective of this study was to identify the determinants of anemia in premature infants and the factors influencing their hospital outcome. Methods: This was a retrospective study in the neonatal unit of the Mother Child Center of the Chantal Biya Foundation. Were included, all premature babies admitted between January 1, 2013 and December 31, 2017, who at least had a full blood count done. Data collected from medical records focused on maternal and neonatal characteristics, clinical and laboratory features, treatment received and hospital outcome. Results: Among the 425 premature babies included, 140 (32.9%) had anemia and 14 (10%) died. The risk factors for anemia in the premature infants were age at admission over 24 hours (p = 0.002) and gestational age less than 32 weeks (p &lt;0.001). The factors associated with mortality were female sex (p = 0.030), birth weight &lt;1500g (p = 0.029), gestational age &lt;32 weeks (p = 0.024). The presence of respiratory distress (p = 0.009), thrombocytopenia (p = 0.011), the need for oxygen (p &lt;0.001) and the need for blood transfusion (p = 0.004) were risk factors for death. However only bradycardia was an independent clinical feature associated with death (p = 0.037). Conclusion: Anemia is very common in premature babies, and remains a high risk factor for death. The clinical and laboratory monitoring of anemic premature babies must be rigorous especially in babies born very preterm and with very low birth weight.

The effectiveness of umbilical cord milking/ delayed cord clamping and recombinant human erythropoietin in reducing red blood cell transfusions in extremely and very low birth weight infants

Anemia of prematurity is one of the most common and serious problems of neonatology. The main focus is to prevent of anemia in preterm infants. The aim of the study was to assess effectiveness of umbilical cord milking/delayed cord clamping and erythropoietin therapy in reducing red blood cell transfusions in extremely and very low birth weight infants. This clinical study was approved by the Commission on ethics of biomedical research (Protocol No. 12 November 17, 2016) and approved by the Scientific Council of National Medical Research Center for obstetrics, gynecology and perinatology named academician V.I. Kulakov of the ministry of Healthcare of the Russian Federation (Protocol No. 19 of November 29, 2016). Analysis of 482 extremely and very low birth weight infants was conducted (from 2008 to 2018). Umbilical cord milking or delayed umbilical cord clamping, both, and in combination with recombinant human erythropoietin therapy, decreasing the phlebotomy losses significantly reduces the need for transfusions of red blood cells in extremely and very low birth weight infants. The effectiveness of erythropoietin therapy, time of its start and various treatment schemes remain controversial, therefore further researches are necessary.

Cardiorespiratory monitoring of red blood cell transfusions in preterm infants

Clinical improvement after red blood cell (RBC) transfusions in preterm infants remains debated. This study aims to investigate the effect of RBC transfusion on the occurrence of desaturations and hypoxia, and other cardiorespiratory outcomes in preterm infants. In this longitudinal observational study, prospectively stored cardiorespiratory parameters of preterm infants who received at least one RBC transfusion between July 2016 and June 2017 were retrospectively analyzed. Sixty infants with 112 RBC transfusions, median GA of 26.7 weeks, were included. The number of desaturations and area < 80% SpO2 limit, as a measure of the hypoxic burden, were calculated in 24 h before and after RBC transfusion. A mixed effects model was used to account for repeated measurements. Overall, the mean (SE) number of desaturations per hour decreased from 3.28 (0.55) to 2.25 (0.38; p < 0.001), and area < 80% SpO2 limit decreased from 0.14 (0.04) to 0.08 (0.02) %/s (p = 0.02). These outcomes were stratified for the number of desaturations in 24 h prior to RBC transfusion. The largest effect was observed in the group with the highest mean number of desaturations (≥ 6) prior to RBC transfusion, with a decrease from 7.50 (0.66) to 4.26 (0.38) (p < 0.001) in the number of desaturations and 0.46 (0.13) to 0.20 (0.06) in the area < 80% SpO2. Perfusion index increased significantly after RBC transfusion (p < 0.001). No other significant effects of RBC transfusion on cardiorespiratory data were observed.Conclusions: RBC transfusions in preterm newborns could help decrease the incidence of desaturations and the area < 80% SpO2 as a measure of the hypoxic burden. The higher the number of desaturations prior to the RBC transfusion, the larger the effect observed.What is Known:•Red blood cell transfusions potentially prevent hypoxia in anemic preterm infants by increasing the circulatory hemoglobin concentration and improving tissue oxygenation.•There is not a predefined hemoglobin concentration cut-off for the occurrence of symptomatic anemia in preterm infants.What is New:•Oxygen desaturations and hypoxia in anemic preterm infants can be improved by RBC transfusions, especially if more desaturations have occurred before transfusion.•Cardiorespiratory monitor data may help identify infants who will benefit most from red blood cell transfusions.

Changes in urinary kidney injury molecule-1 levels after blood transfusions in preterm infants

Literature supports an association between transfusions and gut injury in preterm infants. We hypothesized that packed red blood (PRBC) transfusions are associated with kidney inflammation marked by a rise in urinary levels of Kidney Injury Molecule 1 (KIM-1). Prospectively, KIM-1 levels were measured before and then at 6, 12 and 24 h after a PRBC transfusion. Results are presented as mean (± SD) and median (IQR). Thirty-four infants, birth weight 865 (± 375) g, had higher pretransfusion KIM-1 levels of 2270 (830, 3250) pg/mg than what is normal for age. These were not associated with hematocrit levels. KIM-1 levels peaked between 6 and 12 h after the transfusion. Levels peaked to 3300 (1990, 6830) pg/mg; levels returned to pretransfusion levels of 2240 (1240, 3870) pg/mg by 24 h, p < 0.01. The 24-h post-transfusion KIM-1 levels were similar to pretransfusion levels, p = 0.63. PRBC transfusions in preterm infants are associated with an elevation in urinary KIM-1 levels. The mechanism of this association may be important in studying transfusion associated organ injury. KIM-1, as an inflammatory marker, may be helpful in assessing the effect of different transfusion volumes or in evaluating operational thresholds of anemia in premature infants.

Anemia, Hepcidin, and Vitamin D in Healthy Preterm Infants: A Pilot Study.

The etiology of anemia in premature neonates is multifactorial and may involve anemia of inflammation mediated by hepcidin. Hepcidin expression is suppressed by vitamin D. We aimed to investigate the interrelationship between hepcidin, anemia, and vitamin D status in preterm infants. Preterm infants aged 1 to 5 weeks were prospectively recruited at the neonatal intensive care unit of the Dana Dwek Children Hospital. Blood counts and serum levels of hepcidin, ferritin, iron, 25-hydroxyvitamin D [25(OH)D] and C-reactive protein (CRP) were measured and compared between anemic and nonanemic preterm infants. Forty-seven preterm infants (mean ± standard deviation gestational age at birth 32.8 ± 1.1 weeks, 66% males) were recruited. In total, 36% of the preterm infants were vitamin D deficient [25(OH)D < 20 ng/mL] and 15% were anemic. Hepcidin levels were significantly higher in anemic premature infants than in the nonanemic group (55.3 ± 23.9 ng/mL vs. 30.1 ± 16.3 ng/mL, respectively, p < 0.05). No differences were found in iron, ferritin, 25(OH)D, and CRP levels between anemic and nonanemic premature newborn infants. A positive correlation was found between hepcidin and ferritin (R 2 = 0.247, p = 0.02) and a negative correlation was found between 25(OH)D and CRP (R 2 = 0.1, p = 0.04). No significant correlations were found between 25(OH)D and hepcidin, iron, ferritin, or CRP. Anemia of prematurity was associated with high hepcidin serum levels. The exact mechanisms leading to anemia and the role of vitamin D warrant further investigation. · Hepcidin levels were significantly higher in anemic premature infants.. · A positive correlation was found between hepcidin and ferritin.. · Negative correlation was found between 25(OH)D and CRP..

Anemia of prematurity: how low is too low?

Anemia of prematurity (AOP) is a common condition with a well-described chronology, nadir hemoglobin levels, and timeline of recovery. However, the underlying pathophysiology and impact of prolonged exposure of the developing infant to low levels of hemoglobin remains unclear. Phlebotomy losses exacerbate the gradual decline of hemoglobin levels which is insidious in presentation, often without any clinical signs. Progressive anemia in preterm infants is associated with poor weight gain, inability to take oral feeds, tachycardia and exacerbation of apneic, and bradycardic events. There remains a lack of consensus on treatment thresholds for RBC transfusion which vary considerably. This review elaborates on the current state of the problem, its implication for the premature infant including association with subphysiologic cerebral tissue oxygenation, necrotizing enterocolitis, and retinopathy of prematurity. It outlines the impact of prophylaxis and treatment of anemia of prematurity and offers suggestions on improving monitoring and management of the condition.

In Anaemic Preterm Infants, Regional Tissue Oxygenation Poorly Correlates With Conventional Indicators of Red Blood Cell Transfusion

In Anaemic Preterm Infants, Regional Tissue Oxygenation Poorly Correlates With Conventional Indicators of Red Blood Cell Transfusion

Effect of early prophylactic low-dose recombinant human erythropoietin on retinopathy of prematurity in very preterm infants

BackgroundVery preterm infants are at risk of developing retinopathy of prematurity (ROP). Recombinant human erythropoietin (rhEPO) is routinely used to prevent anemia in preterm infants; however, the effect of rhEPO on ROP development is still controversial. The purpose of this study was to evaluate the effect of early prophylactic low-dose rhEPO administration on ROP development in very preterm infants.MethodsA total of 1898 preterm infants born before 32 weeks of gestation were included. Preterm infants received rhEPO (n = 950; 500 U/kg, rhEPO group) or saline (n = 948, control group) intravenously within 72 h of birth and then once every other day for 2 weeks.ResultsThe total incidence of ROP was not significantly different between the two groups (10.2% vs. 13.2%, p = 0.055). Further analysis showed that rhEPO group had lower rates of type 2 ROP than the control group (2.2% vs. 4.1%, RR 0.98; 95% CI 0.96–1.00; p = 0.021). Subgroup analysis found that rhEPO treatment significantly decreased the incidence of type 2 ROP in infant boys (1.8% vs. 4.3%, p = 0.021) and in those with a gestational age of 28–296/7 weeks (1.1% vs. 4.9%, p = 0.002) and birth weight of 1000–1499 g (1.2% vs. 4.2%, p = 0.002). There was a small increasing tendency for the incidence of ROP in infants with a gestational age of < 28 weeks after rhEPO treatment.ConclusionsRepeated low-dose rhEPO administration has no significant influence on the development of ROP; however, it may be effective for type 2 ROP in infant boys or in infants with gestational age > 28 weeks and birth weight > 1500 g.Trial registration The data of this study were retrieved from two clinical studies registered ClinicalTrials.gov (NCT 02036073) on January 14, 2014, https://clinicaltrials.gov/ct2/show/NCT02036073; and (NCT03919500) on April 18, 2019. https://clinicaltrials.gov/ct2/show/NCT03919500.

Effect of delayed cord clamping on stem cell transfusion and hematological parameters in preterm infants with placental insufficiency: a pilot randomized trial.

The feasibility of delayed cord clamping (DCC) in preterm infants with placental insufficiency (PI) is questionable. We aimed to study the effect of DCC on stem cell transfusion, hematological parameters, and clinical outcomes in preterm infants born to mothers with PI. Preterm infants, < 34weeks' gestation, born to mothers with PI were randomized based on the timing of umbilical cord clamping into delayed clamping for 60s (DCC group) or immediate cord clamping (ICC group) groups at time of birth. CD34 percentage as a marker of stem cell transfusion, early and late-onset anemia, hypothermia, hypotension, polycythemia, hyperbilirubinemia, duration of oxygen therapy, bronchopulmonary dysplasia, intra-ventricular hemorrhage, necrotizing enterocolitis, sepsis, mortality, and length of hospital stay were compared between studied groups. We found that peripheral blood CD34 percentage was significantly higher in DCC compared with that in the ICC group (median (IQR) of 0.5 (0.40-0.7) versus 0.35 (0.20-0.5), p = 0.004). Infants in the DCC group had significantly lower episodes of anemia of prematurity at 2months, red blood cell transfusion, and shorter duration of oxygen therapy compared with those in the ICC group.Conclusion: In conclusion, DCC compared with ICC increased stem cell transfusion and decreased early- and late-onset anemia in preterm infants with placental insufficiency.Trial registration: NCT03731546 www.clinicaltrials.gov What is Known: • Delayed cord clamping has been recommended by the American Academy of Pediatrics as a standard of care practice during delivery of preterm infants. • The feasibility of DCC in preterm infants with placental insufficiency (PI) is uncertain. What is New: • This randomized controlled trial demonstrated that DCC in the delivery room care of preterm infants born to mothers with placental insufficiency increased stem cell transfusion and decreased early- and late-onset anemia.