Search

Importance: Neonatal anemia has a long-term effect on children's growth and development. Anemia during pregnancy is also the most widespread nutritional deficiency among pregnant women in the world; If it leads to anemia in newborns, it will affect a wide range of people and be a public health problem worthy of attention., Objective: To study the relationship between maternal anemia during pregnancy and neonatal hemoglobin levels., Data Sources: PubMed, Web of science, Scopus, MEDLINE, Embase, ProQuest, Dissertations & Theses Global, The Cochrane Library, China Biology Medicine Database, Chinese CNKI Database, and Chinese Wanfang Database were systematically searched from inception to August 31, 2022., Study Selection: The meta-analysis included all original studies which pertain to   cohort studies, case-control studies or cross-sectional studies that investigated the relationship between maternal anemia during pregnancy and neonatal hemoglobin levels., Data Extraction and Synthesis: Hemoglobin level of both anemic and non-anemic  pregnant mothers and their paired newborns were pooled from the selected studies. The random-effects model was used to assess the risk of getting a lower neonatal hemoglobin level between mothers with and without pregnant anemia. Data analyses were performed from September 5, 2022, to March 10, 2023., Main Outcomes and Measures: Maternal anemia during pregnancy is a risk factor of lower neonatal hemoglobin levels., Results: The initial search yielded 4267 records of which 116 articles underwent full-text evaluation, which identified 18 articles and a total of 1873 patients that were included. The findings of the meta-analysis showed a significant difference between the two groups(MD=-1.38; 95%CI:[-1.96,-0.80]. p<0.01), while the co-effect showed that the neonatal hemoglobin value of anemic mothers was 1.38g/dL lower than that of non-anemic mothers(-1.96,-0.80), suggesting a correlation between maternal anemia lower neonatal hemoglobin levels., Conclusions and Relevance: This systematic review and meta-analysis demonstrated that maternal anemia during pregnancy were associated with a lower level of newborn hemoglobin levels. This may enable a better understanding of neonatal anemia and provide guidance towards future development of nutritional supplementation during pregnancy and the prediction of postpartum outcomes., Trial Registration: PROSPERO Identifier: CRD42022352759., (© 2024. The Author(s).)

Infantile pyknocytosis (IP) is a rare, probably misestimated, cause of non-immune neonatal hemolytic anemia evolving in two phases: an initial phase with severe jaundice, followed by a second phase with hemolytic anemia, which may require neonatal intensive care. The diagnosis of IP is based on the transient presence on blood smear of hyperdense, contracted, and/or spiculated red blood cells (pyknocytes), associated with the spontaneous resolution of clinico-biological features and the exclusion of other causes. If the etiology remains undetermined, some contributing factors, such as oxidative stress, have been proposed. We report the description of 16 patients with IP aiming at clarifying the circumstances associated with the development of this acquired disorder. In the acute phase, the mean hemoglobin nadir and pyknocyte count were 7.8 g/dL and 11%, respectively, and strikingly, Heinz bodies were evident in 50% of the newborns, but in 100% after prolonged incubation (4 hours). A high proportion of Mediterranean or African ancestry was noted in newborns, as well as a significant number of peripartum events, such as respiratory distress. If the etiology of IP is certainly multifactorial, our series reinforces the role of oxidative stress, which may, at least in part, find origin in desaturation episodes in newborns., (© 2024 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Importance: Red blood cell (RBC) transfusion is a common medical intervention to treat anemia in very preterm neonates; however, best transfusion practices, such as thresholds, remain uncertain., Objective: To develop recommendations for clinicians on the use of RBC transfusions in very preterm neonates., Evidence Review: An international steering committee reviewed evidence from a systematic review of 6 randomized clinical trials (RCTs) that compared high vs low hemoglobin-based or hematocrit-based transfusion thresholds. The steering committee reached consensus on certainty-of-evidence ratings and worked with a panel from stakeholder organizations on reviewing the evidence. With input from parent representatives and the stakeholder panel, the steering committee used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to develop recommendations., Findings: A systematic review of 6 RCTs encompassing 3483 participants (1759 females [51.3%]; mean [SD] age range, 25.9-29.8 [1.5-3.0] weeks) was used as the basis of the recommendations. The ranges for higher hemoglobin concentration (liberal) vs lower hemoglobin concentration (restrictive) threshold study arms were similar across the trials. However, specific thresholds differed based on the severity of illness, which was defined using variable criteria in the trials. There was moderate certainty of evidence that low transfusion thresholds likely had little to no difference in important short-term and long-term outcomes. The recommended hemoglobin thresholds varied on the basis of postnatal week and respiratory support needs. At postnatal weeks 1, 2, and 3 or more, for neonates on respiratory support, the recommended thresholds were 11, 10, and 9 g/dL, respectively; for neonates on no or minimal respiratory support, the recommended thresholds were 10, 8.5, and 7 g/dL, respectively (to convert hemoglobin to grams per liter, multiply by 10.0)., Conclusions and Relevance: This consensus statement recommends a restrictive RBC transfusion strategy, with moderate certainty of evidence, for preterm neonates with less than 30 weeks' gestation.

Background and Objectives: Diagnostic blood loss is a significant factor in the development of anaemia in neonates with very low birth weight. This study aimed to assess the clinical efficacy of intervention approaches involving varying diagnostic blood loss and red blood cell transfusion volumes in neonates with very low birth weights experiencing anaemia during hospitalization., Materials and Methods: A total of 785 newborns with anaemia weighing less than 1500 g were enrolled from 32 hospitals in China. The study involved monitoring diagnostic blood loss and red blood cell transfusion and evaluating relevant interventions such as red blood cell transfusion and clinical outcomes. Three intervention approaches were established based on the difference between blood loss and transfusion (Intervention Approaches 0, 1 and 2). The primary outcomes measured were unsatisfactory weight gain during hospitalization and neonatal mortality. The secondary outcomes included related complications., Results: In the non-hospital-acquired anaemia group, Intervention Approach 2 had the highest incidence of below-normal weight gain (odds ratio [OR]: 3.019, 95% confidence interval [CI]: 1.081-8.431, p = 0.035). Multivariate analysis revealed that Intervention Approach 1 had a protective effect on weight gain. In the hospital-acquired anaemia group, Intervention Approach 2 had the highest incidence of below-normal weight gain (OR: 3.335, 95% CI: 1.785-6.234, p = 0.000) and mortality (OR: 5.341, 95% CI: 2.449-11.645, p = 0.000), while Intervention Approach 1 had the lowest incidence of intraventricular haemorrhage. Intervention Approach 1 demonstrated favourable outcomes in both anaemia groups., Conclusion: Intervention Approach 1 improved weight gain and reduced mortality and complications in both the non-hospital-acquired and hospital-acquired anaemia groups., (© 2024 The Authors. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.)

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)., (© 2020 British Society for Haematology and John Wiley & Sons Ltd.)

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., Competing Interests: Declaration of Competing Interest The authors declared that there is no conflict of interest., (Copyright © 2019 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.)

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.

Background: Preterm infants have low plasma levels of erythropoietin (EPO), providing a rationale for the use of erythropoiesis-stimulating agents (ESAs) to prevent or treat anaemia and to provide neuro protection and protection against necrotising enterocolitis (NEC). Darbepoetin (Darbe) and EPO are currently available ESAs., Objectives: To assess the effectiveness and safety of ESAs (erythropoietin (EPO) and/or Darbe) initiated early (before eight days after birth) compared with placebo or no intervention in reducing red blood cell (RBC) transfusions, adverse neurological outcomes, and feeding intolerance including necrotising enterocolitis (NEC) in preterm and/or low birth weight infants. Primary objective for studies that primarily investigate the effectiveness and safety of ESAs administered early in reducing red blood cell transfusions: To assess the effectiveness and safety of ESAs initiated early in reducing red blood cell transfusions in preterm infants. Secondary objectives: Review authors performed subgroup analyses of low (≤ 500 IU/kg/week) and high (> 500 IU/kg/week) doses of EPO and the amount of iron supplementation provided: none, low (≤ 5 mg/kg/d), and high (> 5 mg/kg/d). Primary objective for studies that primarily investigate the neuro protective effectiveness of ESAs: To assess the effectiveness and safety of ESAs initiated early in reducing adverse neurological outcomes in preterm infants. Primary objective for studies that primarily investigate the effectiveness of EPO or Darbe administered early in reducing feeding intolerance: To assess the effectiveness and safety of ESAs administered early in reducing feeding intolerance (and NEC) in preterm infants. Other secondary objectives: To compare the effectiveness of ESAs in reducing the incidence of adverse events and improving long-term neurodevelopmental outcomes., Search Methods: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 2), MEDLINE via PubMed (1966 to 10 March 2017), Embase (1980 to 10 March 2017), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 10 March 2017). We searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomised and quasi-randomised controlled trials., Selection Criteria: Randomised and quasi-randomised controlled trials of early initiation of EAS treatment versus placebo or no intervention in preterm or low birth weight infants., Data Collection and Analysis: We used the methods described in the Cochrane Handbook for Systematic Reviews of Interventions and the GRADE approach to assess the quality of evidence., Main Results: This updated review includes 34 studies enrolling 3643 infants. All analyses compared ESAs versus a control consisting of placebo or no treatment. Early ESAs reduced the risk of 'use of one or more [red blood cell] RBC transfusions' (typical risk ratio (RR) 0.79, 95% confidence interval (CI) 0.74 to 0.85; typical risk difference (RD) -0.14, 95% CI -0.18 to -0.10; I 2 = 69% for RR and 62% for RD (moderate heterogeneity); number needed to treat for an additional beneficial outcome (NNTB) 7, 95% CI 6 to 10; 19 studies, 1750 infants). The quality of the evidence was low. Necrotising enterocolitis was significantly reduced in the ESA group compared with the placebo group (typical RR 0.69, 95% CI 0.52 to 0.91; typical RD -0.03, 95% CI -0.05 to -0.01; I 2 = 0% for RR and 22% for RD (low heterogeneity); NNTB 33, 95% CI 20 to 100; 15 studies, 2639 infants). The quality of the evidence was moderate. Data show a reduction in 'Any neurodevelopmental impairment at 18 to 22 months' corrected age in the ESA group (typical RR 0.62, 95% CI 0.48 to 0.80; typical RD -0.08, 95% CI -0.12 to -0.04; NNTB 13, 95% CI 8 to 25. I 2 = 76% for RR (high heterogeneity) and 66% for RD (moderate); 4 studies, 1130 infants). The quality of the evidence was low. Results reveal increased scores on the Bayley-II Mental Development Index (MDI) at 18 to 24 months in the ESA group (weighted mean difference (WMD) 8.22, 95% CI 6.52 to 9.92; I 2 = 97% (high heterogeneity); 3 studies, 981 children). The quality of the evidence was low. The total volume of RBCs transfused per infant was reduced by 7 mL/kg. The number of RBC transfusions per infant was minimally reduced, but the number of donors to whom infants who were transfused were exposed was not significantly reduced. Data show no significant difference in risk of stage ≥ 3 retinopathy of prematurity (ROP) with early EPO (typical RR 1.24, 95% CI 0.81 to 1.90; typical RD 0.01, 95% CI -0.02 to 0.04; I 2 = 0% (no heterogeneity) for RR; I 2 = 34% (low heterogeneity) for RD; 8 studies, 1283 infants). Mortality was not affected, but results show significant reductions in the incidence of intraventricular haemorrhage (IVH) and periventricular leukomalacia (PVL)., Authors' Conclusions: Early administration of ESAs reduces the use of red blood cell (RBC) transfusions, the volume of RBCs transfused, and donor exposure after study entry. Small reductions are likely to be of limited clinical importance. Donor exposure probably is not avoided, given that all but one study included infants who had received RBC transfusions before trial entry. This update found no significant difference in the rate of ROP (stage ≥ 3) for studies that initiated EPO treatment at less than eight days of age, which has been a topic of concern in earlier versions of this review. Early EPO treatment significantly decreased rates of IVH, PVL, and NEC. Neurodevelopmental outcomes at 18 to 22 months and later varied in published studies. Ongoing research should evaluate current clinical practices that will limit donor exposure. Promising but conflicting results related to the neuro protective effect of early EPO require further study. Very different results from the two largest published trials and high heterogeneity in the analyses indicate that we should wait for the results of two ongoing large trials before drawing firm conclusions. Administration of EPO is not currently recommended because limited benefits have been identified to date. Use of darbepoetin requires further study., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Low plasma levels of erythropoietin (EPO) in preterm infants provide a rationale for the use of EPO to prevent or treat anaemia., Objectives: To assess the effectiveness and safety of early versus late initiation of EPO in reducing red blood cell (RBC) transfusions in preterm and/or low birth weight (LBW) infants., Search Methods: The standard search of the Cochrane Neonatal Review Group (CNRG) was performed in 2006 and updated in 2009. Updated search in September 2009 as follows: The Cochrane Library, MEDLINE (search via PubMed), CINAHL and EMBASE were searched from 2005 to September 2009. The searches were repeated in March 2012. The Pediatric Academic Societies' Annual meetings were searched electronically from 2000 to 2012 at Abstracts2View TM as were clinical trials registries (clinicaltrials.gov; controlled-trials.com; and who.int/ictrp)., Selection Criteria: Randomised or quasi-randomised controlled trials enrolling preterm or LBW infants less than eight days of age., Intervention: Early initiation of EPO (initiated at less than eight days of age) versus late initiation of EPO (initiated at eight to 28 days of age)., Data Collection and Analysis: The standard methods of the CNRG were followed. Weighted treatment effects included typical risk ratio (RR), typical risk difference (RD), number needed to treat to benefit (NNTB), number needed to treat to harm (NNTH) and mean difference (MD), all with 95% confidence intervals (CI). A fixed-effect model was used for meta-analyses and heterogeneity was evaluated using the I-squared (I 2 ) test., Main Results: No new trials were identified in March of 2012. Two high quality randomised double-blind controlled studies enrolling 262 infants were identified. A non-significant reduction in the 'Use of one or more RBC transfusions' [two studies 262 infants; typical RR 0.91 (95% CI 0.78 to 1.06); typical RD -0.07 (95% CI -0.18 to 0.04; I 2 = 0% for both RR and RD] favouring early EPO was noted. Early EPO administration resulted in a non-significant reduction in the "number of transfusions per infant" compared with late EPO [typical MD - 0.32 (95% CI -0.92 to 0.29)]. There was no significant reduction in total volume of blood transfused per infant or in the number of donors to whom the infant was exposed. Early EPO led to a significant increase in the risk of retinopathy of prematurity (ROP) (all stages) [two studies, 191 infants; typical RR 1.40 (95% CI 1.05 to 1.86); typical RD 0.16 (95% CI 0.03 to 0.29); NNTH 6 (95% CI 3 to 33)]. There was high heterogeneity for this outcome (I 2 = 86% for RR and 81% for RD). Both studies (191 infants) reported on ROP stage > 3. No statistically significant increase in risk was noted [typical RR 1.56 (95% CI 0.71 to 3.41); typical RD 0.05 (-0.04 to 0.14)] There was no heterogeneity for this outcome (0% for both RR and RD). No other important favourable or adverse neonatal outcomes or side effects were reported., Authors' Conclusions: The use of early EPO did not significantly reduce the 'Use of one or more RBC transfusions' or the 'Number of transfusions per infant" compared with late EPO administration. The finding of a statistically significant increased risk of ROP (any grade) and a similar trend for ROP stage > 3 with early EPO treatment is of great concern., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Preterm infants have low plasma levels of erythropoietin (EPO), providing a rationale for the use of erythropoiesis-stimulating agents (ESAs) to prevent or treat anaemia. Darbepoetin (Darbe) and EPO are currently available ESAs., Objectives: To assess the effectiveness and safety of late initiation of ESAs, between eight and 28 days after birth, in reducing the use of red blood cell (RBC) transfusions in preterm or low birth weight infants., Search Methods: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 5), MEDLINE via PubMed (1966 to 5 June 2018), Embase (1980 to 5 June 2018), and CINAHL (1982 to 5 June 2018). We searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials., Selection Criteria: Randomised or quasi-randomised controlled trials of late initiation of EPO treatment (started at ≥ eight days of age) versus placebo or no intervention in preterm (< 37 weeks) or low birth weight (< 2500 grams) neonates., Data Collection and Analysis: We performed data collection and analyses in accordance with the methods of the Cochrane Neonatal Review Group. We used the GRADE approach to assess the quality of the evidence., Main Results: We include 31 studies (32 comparisons) randomising 1651 preterm infants. Literature searches in 2018 identified one new study for inclusion. No new on-going trials were identified and no studies used darbepoetin. Most included trials were of small sample size. The meta-analysis showed a significant effect on the use of one or more RBC transfusions (21 studies (n = 1202); typical risk ratio (RR) 0.72, 95% confidence interval (CI) 0.65 to 0.79; typical risk difference (RD) -0.17, 95% CI -0.22 to -0.12; typical number needed to treat for an additional beneficial outcome (NNTB) 6, 95% CI 5 to 8). There was moderate heterogeneity for this outcome (RR I² = 66%; RD I² = 58%). The quality of the evidence was very low. We obtained similar results in secondary analyses based on different combinations of high/low doses of EPO and iron supplementation. There was no significant reduction in the total volume (mL/kg) of blood transfused per infant (typical mean difference (MD) -1.6 mL/kg, 95% CI -5.8 to 2.6); 5 studies, 197 infants). There was high heterogeneity for this outcome (I² = 92%). There was a significant reduction in the number of transfusions per infant (11 studies enrolling 817 infants; typical MD -0.22, 95% CI -0.38 to -0.06). There was high heterogeneity for this outcome (I² = 94%). Three studies including 404 infants reported on retinopathy of prematurity (ROP) (all stages or stage not reported), with a typical RR 1.27 (95% CI 0.99 to 1.64) and a typical RD of 0.09 (95% CI -0.00 to 0.18). There was high heterogeneity for this outcome for both RR (I² = 83%) and RD (I² = 82%). The quality of the evidence was very low.Three trials enrolling 442 infants reported on ROP (stage ≥ 3). The typical RR was 1.73 (95% CI 0.92 to 3.24) and the typical RD was 0.05 (95% CI -0.01 to 0.10). There was no heterogeneity for this outcome for RR (I² = 18%) but high heterogeneity for RD (I² = 79%). The quality of the evidence was very low.There were no significant differences in other clinical outcomes including mortality and necrotising enterocolitis. For the outcomes of mortality and necrotising enterocolitis, the quality of the evidence was moderate. Long-term neurodevelopmental outcomes were not reported., Authors' Conclusions: Late administration of EPO reduces the use of one or more RBC transfusions, the number of RBC transfusions per infant (< 1 transfusion per infant) but not the total volume (mL/kg) of RBCs transfused per infant. Any donor exposure is likely not avoided as most studies included infants who had received RBC transfusions prior to trial entry. Late EPO does not significantly reduce or increase any clinically important adverse outcomes except for a trend in increased risk for ROP. Further research of the use of late EPO treatment, to prevent donor exposure, is not indicated. Research efforts should focus on limiting donor exposure during the first few days of life in sick neonates, when RBC requirements are most likely to be required and cannot be prevented by late EPO treatment. The use of satellite packs (dividing one unit of donor blood into many smaller aliquots) may reduce donor exposure., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Currently the question of whether to maintain a higher hemoglobin level by transfusing more liberally, as opposed to a more restrictive strategy with lower hemoglobin maintenance levels, has not been answered. We review summarized conclusions of a Cochrane systematic review and meta-analysis of 614 infants in 4 randomized controlled trials (RCT) pooling data. This suggests potential benefits of higher hemoglobin levels, i.e., a possible improved cognition of infants at 18-21 months' corrected age and a reduction of apnea. However, the data on cognition is hypothesis generating as it derives from a post hoc analysis from a single trial in 451 infants. Moreover, the data on apnea need confirmation in larger trials. The effect of adding data of cognitive 2-year outcomes of 1,744 infants from 2 RCT, which will be reported soon, should expand our understanding. This new data will need to be integrated with the older generation of RCTs but also with emerging suggestions from observational data on potential risks of blood transfusions. We discuss some of these warnings from observational studies. Finally, we ask whether we are ready to individualize blood transfusion to physiological measures made in individual infants, and we point to some current difficulties hindering this step., (© 2019 S. Karger AG, Basel.)

Purpose: Ischemia-modified albumin (IMA) is used to determine tissue hypoxia. We aimed to evaluate the serum IMA levels in preterm infants requiring transfusion due to anemia of prematurity, a clinical condition to cause tissue hypoxia., Materials and Methods: This prospective study was performed in Etlik Zubeyde Hanim Hospital, Turkey. Preterm infants with birth weight less than 1500 g and born between 25 and 32 weeks were included during assessment for anemia of prematurity. The transfused infants with anemia of prematurity formed the "transfusion group", the control group consisted of gender, gestational and postnatal age-matched infants without transfusion requirement. Serum samples of control group and pre-transfusion and post-transfusion samples of transfusion group were analyzed for IMA (ABS unit). Serum IMA levels were compared between control group and pre-transfusion samples of transfusion group and were also evaluated for the significance of change after transfusion., Results: Sixty-two infants were included (transfusion group: 31, control group: 31). The pretransfusion serum IMA levels were higher than that of infants in the control group [ABS unit; transfusion group; pre-transfusion: 1.00 (0.76-1.09) and control group: 0.81 (0.52?1.04); p = .03]. Serum IMA levels decreased significantly to 0.79 (0.59-0.95) after transfusion; p = .007. Infants with hematocrit higher than 30% had lower IMA levels [0.69 (0.54-0.96)] than infants with lower hematocrit [0.96 (0.75-1.05)]; p = .002., Conclusions: Clinicians may bear in mind that serum IMA levels could be utilized as a marker in deciding on erythrocyte transfusion in premature anemia.

PurposeTo identify if there is an association between foetal haemoglobin (HbF) concentration and retinopathy of prematurity (ROP) in very preterm infants.Patients and methodsProspective cohort study. Infants born <32 weeks' gestational age or <1501 g in two tertiary neonatal units between January 2012 and May 2013 (n=42) were enrolled. HbF and adult haemoglobin (HbA) concentrations were measured using high-pressure liquid chromatography from blood samples sent as part of routine neonatal care once routinely requested laboratory tests had been performed. Clinical data were obtained from case notes. We calculated odds ratios (ORs) (95% confidence intervals (CIs)) to quantify the relationship between initial and mean %HbF with ROP severity (none, stages 1-3).ResultsA total of 42 infants were recruited: mean gestation 28.0 weeks (SD 1.91); mean birth weight 1042 g (SD 264). Six infants died before ROP screening; 14/36 developed ROP (39%); and 22/36 (61%) did not. Infants who developed ROP had similar initial %HbF (83.3 vs 92.3%, P=0.06), but significantly lower mean %HbF (61.75 vs 91.9%, P=0.0001) during their inpatient stay than those who did not develop ROP. In ordinal logistic regression models adjusted for birth weight, gestation and transfusion volume, mean post-natal %HbF was negatively associated with ROP severity: adjusted OR 0.94 (0.90-0.99), while initial %HbF at birth was not: adjusted OR 1.05 (0.97-1.16).ConclusionReplacing HbF by HbA during transfusion may promote ROP development by rapidly increasing oxygen availability to the retina. Conversely, maintaining a higher %HbF may be a protective factor against ROP.

The aim of this study was to investigate the relationships between oxidative stress, haematology and iron profile in neonatal dairy calves. Serum and haemolysate malondialdehyde (MDA), serum total antioxidant capacity, thiol groups, iron, total iron binding capacity, transferrin saturation and red blood cell (RBC) parameters were assessed in two groups: anaemic calves (n=14) and non-anaemic calves (n=16). Blood samples were collected from all of the calves within 24-48 hours after birth and at 7, 14, 21 and 28 days of age. A significant decrease in serum iron amount and transferrin saturation value (P<0.05) and a significant increase in haemolysate MDA concentration (P<0.05) in the anaemic calves were observed, when compared with non-anaemic calves. Total antioxidant capacity and thiol groups showed a significant positive correlation with iron profile and RBC parameters (haematocrit and haemoglobin) in the anaemic calves at day 21 (P<0.05). On the other hand, the concentration of haemolysate MDA was inversely correlated with the value of serum total antioxidant capacity (P<0.05). The results of the present study revealed that anaemic calves showed more severe oxidative stress than non-anaemic calves. In addition, iron insufficiency may be linked to the impairment of antioxidant defence system and oxidative damage of erythrocytes in the neonatal calves., Competing Interests: Competing interests: None declared., (© British Veterinary Association (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Measuring thyrotropin (TSH) eluted from a dried blood spot (DBS) is used to screen an estimated 30 million newborns annually for congenital hypothyroidism (CH). Newborn thyroid screening has eliminated cretinism from the industrialized world and decreased the adverse effects of unrecognized CH on neurocognitive development. Hematocrit, a pre-analytic variable that affects the measurement of TSH from a DBS, contributes to the imprecision of DBS TSH measurement and could account for false-negative and false-positive DBS newborn screening test results. To assess whether variations in hematocrit found in newborns have a clinical effect in DBS-based newborn thyroid screening, the effects of hematocrit variability on the measurement of DBS TSH were studied., Methods: U.S. Centers for Disease Control and Prevention procedures for manufacturing DBS performance testing standards were used to generate DBSs from blood samples, with hematocrits of 35%, 40%, 45%, 50%, 55%, 60%, and 65% and serum TSH concentrations of 6.3 ± 0.4 and 26.6 ± 8.0 mIU/L. TSH was measured in the eluates of four replicate DBS 3 mm punches at each hematocrit using the Thailand Ministry of Public Health Newborn Screening Operation Center enzyme-linked immunosorbent assay. Data were analyzed using a linear mixed-effects model., Results: Based on the mixed-effects model, hematocrit significantly affected DBS TSH measurement (p < 0.001). A 1% increase in hematocrit resulted in a 0.06 mIU/L decrease in eluate TSH when TSH was 6.3 + 0.4 mIU/L, and a 0.21 mIU/L decrease in eluate TSH when TSH was 26.6 + 8.0 mIU/L., Conclusions: DBS TSH is significantly affected by the blood sample hematocrit. The pre-analytic variability due to hematocrit is independent of TSH assay sensitivity, specificity, precision, repeatability, and reference intervals. The effect of hematocrit on DBS TSH measurement is clinically relevant, could account for geographic and ethnic variation in the incidence of CH, and may result in both false-positive and false-negative CH screening results. Individual newborn and population-specific hematocrit correction factors may improve the precision of DBS TSH measurement.

Background and Objectives: 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., Materials and Methods: 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., Results: 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)., Conclusion: 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., (© 2017 International Society of Blood Transfusion.)

Transcription factor control of cell-specific downstream targets can be significantly altered when the controlling factor is mutated. We show that the semi-dominant neonatal anemia (Nan) mutation in the EKLF/KLF1 transcription factor leads to ectopic expression of proteins that are not normally expressed in the red blood cell, leading to systemic effects that exacerbate the intrinsic anemia in the adult and alter correct development in the early embryo. Even when expressed as a heterozygote, the Nan-EKLF protein accomplishes this by direct binding and aberrant activation of genes encoding secreted factors that exert a negative effect on erythropoiesis and iron use. Our data form the basis for a novel mechanism of physiological deficiency that is relevant to human dyserythropoietic anemia and likely other disease states., (© 2017. Published by The Company of Biologists Ltd.)

Introduction: Anemia in preterm infants is the pathophysiological process with greater and more rapid decline in hemoglobin compared to the physiological anemia in infants. There is a need for transfusions and administration of human recombinant erythropoietin., Aim: To determine the frequency of anemia in premature infants at the Pediatric Clinic, University Clinical Center Sarajevo, as well as parameter values in the blood count of premature infants and to explore a relationship between blood transfusions with the advent of intraventricular hemorrhage (determine treatment outcome in preterm infants)., Patients and Methods: Research is retrospective study and it included the period of six months in year 2014. Research included 100 patients, gestational age < 37 weeks (premature infants). Data were collected by examining the medical records of patients at the Pediatric Clinic, UCCS., Results: The first group of patients were premature infants of gestational age ≤ 32 weeks (62/100) and the second group were premature infants of gestational age 33-37 weeks (38/100). Among the patients, 5% were boys and 46% girls. There was significant difference in birth weight and APGAR score among the groups. In the first group, there were 27.42% of deaths, while in the second group, there were only 10.53% of deaths. There was a significant difference in the length of treatment. There was a statistically significant difference in the need for transfusion among the groups. 18 patients in the first group required a transfusion, while in the second group only 3 patients., Conclusions: Preterm infants of gestational age ≤ 32 weeks are likely candidates for blood transfusion during treatment. Preterm infants of gestational age ≤ 32 weeks have the risk of intracranial bleeding associated with the application of blood transfusion in the first week of life., Competing Interests: • Conflict of interest: none declared.

Introduction: Fetomaternal hemorrhage (FMH) is a transfu-sion of fetal blood into the maternal circulation. A volume of transfused fetal blood required to cause severe, life-threatening fetal anemia, is not clearly defined. Some authors suggest vol-umes of 80 mL and 150 mL as a threshold which defines mas-sive FMH. Therefore, a rate of massive FMH is 1 : 1,000 and 1 : 5,000 births, respectively. Fetal and neonatal anemia is one of the most serious complications of the FMH. Clinical manifesta-tions of FMH are nonspecific, and mostly it presented as re-duced fetal movements and changes in cardiotocography (CTG). The standard for diagnosing FMH is Kleihaurer-Betke test., Case Report: A 34-year-old gravida (G) 1, para (P) 1 was hospitalized due to uterine contractions at 39 weeks of gesta-tion. CTG monitoring revealed sinusoidal fetal heart rate and clinical examination showed complete cervical dilatation. Im-mediately after admission, the women delivered vaginally. Ap-gar scores were 1 and 2 at the first and fifth minute, respec-tively. Immediately baby was intubated and mechanical ventila-tion started. Initial analysis revealed pronounced acidosis and severe anemia. The patient received intravenous fluid therapy with sodium-bicarbonate as well as red cell transfusion. With all measures, the condition of the baby improved with normaliza-tion of hemoglobin level and blood pH. Kleihaurer-Betke test revealed the presence of fetal red cells in maternal circulation, equivalent to 531 mL blood loss. The level of maternal fetal hemoglobin (HbF) and elevated alpha fetoprotein also con-firmed the diagnosis of massive FMH., Conclusion: For the successful diagnosis and management of FMH direct commu-nication between the obstetrician and the pediatrician is neces-sary as presented in this report.

Aim: To evaluate the short-term effects of blood transfusion on iron status [hemoglobin, ferritin, soluble transferrin receptor (sTfR), and reticulocyte count], hepcidin, and erythropoietin in stable preterm infants., Method: Sixty-three preterm infants treated with red blood cell transfusions (RBCTs) were included. Venous blood samples were collected before and within 24 h after each transfusion., Results: Hemoglobin concentration increased after RBCT (7.2±1.2 g/dL vs. 13.7±2.3 g/dL, P=0.02), as well as ferritin [131 (63-110.4) ng/mL vs. 211 (125.7-299.2) ng/mL, P=0.05); reticulocyte count decreased. sTfR did not change. Hepcidin serum levels increased from 37.5 (21.3-84.7) ng/mL to 72.6 (31.3-126.2) ng/mL, (P=0.04) and erythropoietin decreased (48±19 pg/mL vs. 29±17 pg/mL, P=0.06) after RBCT. A positive linear correlation was found (R2=0.76, P=0.0001) between hepcidin and ferritin levels of post-minus-pre RBCT. Hepcidin levels increased significantly in preterm infants who received RBCT after 1 month of age compared to those who received RBCT at <1 month (P=0.03). No correlation was found between gestational age, weight appropriate for age, or length of blood storage and hepcidin levels., Conclusion: Preterm infants can control iron levels by regulating hepcidin and decreasing erythropoietin. This ability varies with postnatal age.

Background and Objective: Several studies have shown the benefits of delayed cord clamping (DCC) in preterm and in healthy newborns at short and long term. Our objective was to evaluate the potentials benefits and risks of DCC in red cell alloimmunization., Methods: This was a comparative before/after study of all living born neonates followed after fetal anemia requiring in utero transfusion. DCC was defined as cord clamping 30 seconds after birth., Results: We included a continuous series of 72 neonates: 36 without DDC (group 1) and 36 with DDC (group 2). Hemoglobin at birth was lower in group 1 (10.2 vs 13.4 g/dL, P = .0003); 7 (25%) neonates in group 1 vs 24 (70.6%) in group 2 had no anemia at birth (P = .004). The rate of transfusion was similar between the 2 groups. Postnatal exchange transfusions were more likely performed in the group without DCC than in the group with DCC (47.2% vs 19.4%, P = .0124). Delay between birth and first transfusion was higher in group 2 (0 [0-13] vs 1 [0-21], P = .0274). The maximum level of bilirubin, the rate of intensive phototherapy, and the total duration of phototherapy were similar in the 2 groups., Conclusions: This study highlights a significant benefit of DCC in anemia secondary to red blood cell alloimmunization with a resulting decreased postnatal exchange transfusion needs, an improvement in the hemoglobin level at birth and longer delay between birth and first transfusion with no severe hyperbilirubinemia., (Copyright © 2016 by the American Academy of Pediatrics.)

Aim: The purpose of this study was to prospectively estimate the incidence of spontaneous twin anemia-polycythemia sequence (TAPS) in monochorionic-diamniotic twin pregnancies., Methods: We prospectively examined umbilical cord hemoglobin (Hb) and reticulocyte count of consecutive monochorionic-diamniotic twin pregnancies delivered at Seirei Hamamatsu General Hospital from December 2006 to September 2013. We excluded cases of twin-twin transfusion syndrome, intrauterine fetal demise, and missing data (Hb and reticulocyte count missing from the medical record). TAPS was diagnosed using the postnatal criteria of intertwin Hb difference >8.0 g/dL and reticulocyte count ratio >1.7. Acute feto-fetal hemorrhage was defined as Hb difference >7 g/dL and reticulocyte count ratio <1.7., Results: A total of 185 monochorionic-diamniotic twin pregnancies were included in this study. Three fulfilled the diagnostic criteria for postnatal TAPS, and one fulfilled the diagnostic criteria for acute feto-fetal hemorrhage., Conclusion: The incidence of spontaneous TAPS in monochorionic-diamniotic twin pregnancies was 1.6% (3/185) at Seirei Hamamatsu General Hospital., (© 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.)

We describe a case of severe neonatal anemia with kernicterus caused by compound heterozygosity for null mutations in KLF1, each inherited from asymptomatic parents. One of the mutations is novel. This is the first described case of a KLF1-null human. The phenotype of severe nonspherocytic hemolytic anemia, jaundice, hepatosplenomegaly, and marked erythroblastosis is more severe than that present in congenital dyserythropoietic anemia type IV as a result of dominant mutations in the second zinc-finger of KLF1. There was a very high level of HbF expression into childhood (>70%), consistent with a key role for KLF1 in human hemoglobin switching. We performed RNA-seq on circulating erythroblasts and found that human KLF1 acts like mouse Klf1 to coordinate expression of many genes required to build a red cell including those encoding globins, cytoskeletal components, AHSP, heme synthesis enzymes, cell-cycle regulators, and blood group antigens. We identify novel KLF1 target genes including KIF23 and KIF11 which are required for proper cytokinesis. We also identify new roles for KLF1 in autophagy, global transcriptional control, and RNA splicing. We suggest loss of KLF1 should be considered in otherwise unexplained cases of severe neonatal NSHA or hydrops fetalis., (© 2015 by The American Society of Hematology.)

Unlabelled: A newborn boy was referred to our hospital because of hemolytic anemia and severe hyperbilirubinemia. Extensive investigations aimed at determining the cause of hemolysis was initiated at the time of admission and 3 months after blood transfusion. Notably, no intrinsic erythrocyte abnormalities could be detected. The only possible cause explaining the progressive anemia and unconjugated hyperbilirubinemia was the finding of pyknocytes, severely distorted erythrocytes, on the blood film at hospital admission. We propose a role for an increased free fraction of plasma unconjugated bilirubin in the formation of pyknocytes through bilirubin membrane toxicity with subsequent anemia and progressive hyperbilirubinemia., Conclusion: Pyknocytosis is a transitory erythrocyte-related condition which can result in severe anemia and hyperbilirubinemia. Recognition of pyknocytes by microscopic analysis of a blood film is essential for a correct diagnosis. Treatment consists of correction of the anemia by top-up blood transfusion and light therapy to prevent toxic bilirubin buildup. High levels of free unconjugated bilirubin could be the underlying cause for the formation of pyknocytes.

Objective: The aim of this study was to evaluate the effects of umbilical cord milking (UCM) on the need for packed red blood cell (PRBC) transfusion and hematologic and hemodynamic parameters in very-low-birth-weight infants., Methods: The infants were randomized into 2 groups: group 1 (UCM) and group 2 (control). The primary outcome was the number of PRBC transfusions during the first 35 days of life. The secondary outcome measures were the hemodynamic variables during the first 24 hours of life., Results: A total of 44 infants were included with 22 infants in each group. Two of 21 infants in group 1 and 4 of 21 infants in group 2 received transfusion in the first 3 days of life (P=0.384). The number and volume of PRBC transfusions were similar in both groups. However, the levels of hemoglobin (Hb) at the first and 24th hour of life were significantly higher in group 1. Phlebotomy volume was found as a statistically significant risk factor for the need for PRBC transfusion (P=0.005)., Conclusions: UCM in delivery room results in a higher Hb level in the first day of life. In these groups of infants, phlebotomy losses may impact the transfusion need.

Purpose: To evaluate the clinical efficacy of cord blood erythrocytes autotransfiusion for the correction of anemia in the intra-and postoperative periods in infants requiring early surgical correction of congenital malformations., Methods: Washed autoemythrocytes from placental umbilical blood were transfused for correction of intra and post-operative anemias. Umbilical blood assembly was carried out after extraction of the child and navel intersection by the occluded mean by a vein puncture distal (placental) end of a navel by the drainage needle which is a part of special transfiusion system. Further blood in the marked containers was pitched in branch of gravitational surgery of blood where its centrifiugal separation on erythrocyte mass and plasma was made. Then concentrated red cells it was put on storage for 21 day in a cooler at temperature 40 °C. Directly ahead of autotransfusion concentrated red cells was exposed to washing out in sterile physiological solution and a filtration through the micromodular filter. Then the marked package with the washed erythrocytes was pitched in branch of surgery of newborns for the purpose offurther anttqtransfusion under indications. The transfusion autoerythrocytes was made according to reacting at the moment of carrying out of work to orders of Ministry of Health of the Russian Federation: to the Order of Ministry of Health of the Russian Federation from November, 25th, 2002 No 363 "About the statement of the Instruction on application of components of blood" and to the Order of Ministry of Health of the Russian Federation from April, 2nd, 2013 N 183n "About the statement of rules of clinical use of donor blood and (or) its components"., Results: Total 122 newborns received an autotransfiusion of washed erythrocytes of placental/umbilical cord blood for the correction of anemia in the department of neonatal surgery in the period from 2005 to 2013. 66 children who are in the first two weeks of life were performed surgical intervention for malformation of the gastrointestinal tract (gastorshizis (22), omphalocele (2). itestinal atresia (10), esophageal atresia or doubling (4)), congenital diaphragmatic hernia (15), space-occupying lesions (teratoma (6) and lymphangioma (3)) and other pathologies (adenomatous lung (1), the sequestration of the lung (2). ovarian cyst (1)). Control group consisted of39 infants operated on for similar malformations , which in the absence of prior communication harvested autologous red blood cells in the first three weeks of life sparkled donor erythrocytes. Inmost cases (57 newborns - 86.4%) of the amount harvested and transfused blood autokonmpo tov was sufficient for the relief ofanemia, despite the fact that the volume of transfused autoeritrotsitnoy mass per kilogram of body weight was almost two times lower than the amount of donor erythrocyte mass used in the comparison group. Additional donor transfusion of red blood cells in the group of children who had autotransfusion, it took nine newborns (13.6%). The main indications for repeated transfusions were clinical and laboratory signs of anemia, persisting after autotransfusion or resulting from repeated operations. After transfusion of washed autoerythrocytes value of clinical and biochemical. blood tests, urinalysis were within the age norm. Post-transfusion reactions in children who have received a transfusion autoerythrocytes not mentioned, Conclusion: The use of placental/umbilical cord blood autoe,ythrocyvtes in children requiring early surgical correction of congenital malformations can significantly reduce the need for donor red blood cells. Autologous red blood cells use is a safe and effective alternative to transfusion of donor red blood cells.

Normal hemoglobin is made of a tetramer of 2 α-globin and 2 β-globin polypeptide chains. Deletions in the β-globin gene cluster can range from a few hundred base pairs to loss of the entire cluster resulting in rare, but clinically significant, thalassemias. One such entity is εGγAγδβ0-thalassemia, a condition that presents within the first few weeks of life as a Coombs-negative hemolytic anemia and is not identified on routine newborn screening or hemoglobin electrophoresis.

Objective: To evaluate the efficacy and safety of iron protein succinylate (IPS) oral solution in preventing and treating anemia of prematurity (AOP)., Methods: Sixty premature infants less than 35 weeks of gestation were randomly divided into IPS (n=30) and polysaccharide iron complex (PIC) groups(n=30). Treatment began at two weeks after birth. The infants received IPS or PIC in addition to recombinant human erythropoietin. On days 14, 28, 42, and 60 after treatment, hemoglobin (Hb), red blood cell count(RBC), hematocrit (HCT), percentage of reticulocytes, serum iron, and serum ferritin were determined. Liver and renal functions were evaluated before and after treatment., Results: There were significant differences in the changing trends of RBC and HCT between the two groups (P<0.05). In the IPS group, RBC and HCT gradually decreased after birth, but began to rise gradually on days 28 and 42 of treatment; in the PIC group, RBC and HCT kept decreasing from birth to day 60 of treatment. On day 60 of treatment, the IPS group had significantly higher levels of Hb, RBC, HCT, serum iron, and serum ferritin than the PIC group (P<0.05). No notable adverse events occurred in either group., Conclusions: IPS oral solution has good efficacy and tolerability in preventing and treating AOP.

Background: A novel erythropoiesis stimulating agent (ESA), darbepoetin alfa (Darbe), increases hematocrit in anemic adults when administered every 1 to 3 weeks. Weekly Darbe dosing has not been evaluated in preterm infants. We hypothesized that infants would respond to Darbe by decreasing transfusion needs compared with placebo, with less-frequent dosing than erythropoietin (Epo)., Methods: Preterm infants 500 to 1250 g birth weight and ≤48 hours of age were randomized to Darbe (10 μg/kg, 1 time per week subcutaneously), Epo (400 U/kg, 3 times per week subcutaneously) or placebo (sham dosing) through 35 weeks' gestation. All received supplemental iron, folate, and vitamin E, and were transfused according to protocol. Transfusions (primary outcome), complete blood counts, absolute reticulocyte counts (ARCs), phlebotomy losses, and adverse events were recorded., Results: A total of 102 infants (946 ± 196 g, 27.7 ± 1.8 weeks' gestation, 51 ± 25 hours of age at first dose) were enrolled. Infants in the Darbe and Epo groups received significantly fewer transfusions (P = .015) and were exposed to fewer donors (P = .044) than the placebo group (Darbe: 1.2 ± 2.4 transfusions and 0.7 ± 1.2 donors per infant; Epo: 1.2 ± 1.6 transfusions and 0.8 ± 1.0 donors per infant; placebo: 2.4 ± 2.9 transfusions and 1.2 ± 1.3 donors per infant). Hematocrit and ARC were higher in the Darbe and Epo groups compared with placebo (P = .001, Darbe and Epo versus placebo for both hematocrit and ARCs). Morbidities were similar among groups, including the incidence of retinopathy of prematurity., Conclusions: Infants receiving Darbe or Epo received fewer transfusions and fewer donor exposures, and fewer injections were given to Darbe recipients. Darbepoetin and Epo successfully serve as adjuncts to transfusions in maintaining red cell mass in preterm infants.

Objective: The incidence of fetomaternal hemorrhage that is severe enough to cause neonatal anemia is not known. Owing to its relative rarity, much of the literature describing this condition is in the form of case reports and small case series. We performed a large, muiticentered, sequential, case series to determine the incidence, antecedents and outcomes., Study Design: From the multicentered databases of Intermountain Healthcare, we obtained records of all neonates with hematocrit (Hct) <30% or hemoglobin (Hgb) <10 g dl(-1) on the day of birth, who had Kleihauer-Betke staining or flow cytometric evidence of fetomaternal hemorrhage., Result: Among 219,853 live births, 24 had anemia with evidence of fetomaternal hemorrhage (incidence estimate, 1 per 9160 live births). The initial Hgb ranged from 1.4 to 10.2 g dl(-1) (Hct 29.8%). The initial Hgb was <7 g dl(-1) in 18 (67%), <5 g dl(-1) in 12 (50%) and was <3 g dl(-1) in 7 (29%). All 7 mothers in whom neonatal Hgb was <3 g dl(-1) had reported absent fetal movement, as did 13 of 18 mothers when the initial Hgb was <7 g dl(-1). Outcomes were poorer in those with the lowest initial Hgb; in the two lowest, one died on day 1, and the other developed a grade 4 intraventricular hemorrhage (IVH). The adverse outcomes of death, IVH, periventricular leukomalacia, bronchopulmonary dysplasia or hypoxic-ischemic encephalopathy were common; occurring in 71% (17 of the 24), including all with an initial Hgb <5 g dl(-1) and all born at ≤35 weeks of gestation., Conclusion: Fetomaternal hemorrhage is a rare but sometimes devastating condition. Those with fetomaternal hemorrhage and an initial Hgb of <5 g dl(-1) are expected to need resuscitation at birth, to receive emergent transfusion support and to be at risk for death and major morbidities. Antenatal suspicion of this diagnosis should occur when absent fetal movement is reported. Improvements in rapid diagnosis are needed to prepare first responders and transfusion services.

Background: The criteria for erythrocyte transfusion in stable premature infants are currently controversial. Haemodynamic measurements are not common in transfusion practice. The purpose of this study was to determine whether haemodynamic measurements could be helpful as objective criterion for transfusion decisions. We, therefore, evaluated clinical and haemodynamic changes in stable, anaemic, premature infants before and after transfusion using our current blood transfusion protocol based on a haematocrit threshold (<24%) and the neonatologist's discretion., Material and Methods: Stable premature infants with a haematocrit level ≤30% were prospectively enrolled into the study. Cerebral, intestinal and renal blood flow velocities, cardiac function parameters and vital signs were measured up to three times following every routine haematocrit analysis. Moreover, transfused infants were evaluated three more times: directly before transfusion, and 24 hours and 72 hours after transfusion., Results: Thirty-six infants were enrolled and 23 of them were transfused. Subgroup analysis of transfused infants showed a significant decrease in cerebral blood flow velocities, cardiac output and heart rate. These changes persisted after transfusion. In the entire cohort, the degree of anaemia correlated with the increase of cerebral blood flow velocities, heart rate and cardiac output., Discussion: Cerebral blood velocities in the anterior cerebral artery might represent an objective Doppler sonographic criterion indicating the need for transfusion. The measurement of these velocities is non-invasive and quick and easy to perform. However, a randomised, controlled trial is necessary before a formal recommendation can be made.

Background: Alloanti-Kp(b) is a rare, clinically significant antibody against high frequency red cell antigen Kp(b) of Kell blood group system. We report here a case of Haemolytic disease of newborn (HDN) due to anti-Kp(b), which manifested as severe anaemia at the age of 1 month., Aim: To diagnose and successfully manage anti-Kp(b) induced HDN., Methodology: Direct antiglobulin test (DAT), antigen typing, irregular antibody screening and identification were done by polyspecific LISS Coombs Gel card and standard methods., Results: At presentation the neonate had severe anemia with reticulocytopenia. Blood group was B, Rh D positive and DAT was 2+. Anti-Kp(b) was detected in mother's serum. Due to unavailability of Kp(b) negative red cells and incompatible blood group of mother (A(1)B Rh D positive) infant was transfused group B Rh D, Kp(b) positive PRBCs under steroid cover. He was symptom free at 4 months of age and DAT became negative at 6 months., Conclusion: Anti-Kp(b) is capable of causing severe late HDN. Infants born to irregular antibody positive mothers should be investigated and closely monitored for several weeks after birth for immune HDN even if asymptomatic at birth., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Infantile pyknocytosis (IP) is an under-recognized hematological entity of newborns that can cause a severe neonatal hemolytic anemia. A careful, prompt, and accurate peripheral blood smear examination is essential to establish the diagnosis. Here we describe the clinical features and histological parameters of 1 case of IP. Spontaneous resolution usually occurs by 4 to 6 months, but red blood cell transfusion may be needed if the anemia is severe.

Objective: To assess the effectiveness of a hospital policy change toward delayed cord clamping on infant hemoglobin (Hb) levels and anemia status at 4 and 8 months of age., Methods: A cohort of Peruvian mothers and infants, originating from a pre/post study investigating a change in hospital policy from early to delayed cord clamping, was followed until 8 months postpartum. Infant hemoglobin levels and anemia status were measured at 4 and 8 months postpartum., Results: Following the hospital policy change, adjusted mean infant Hb levels improved by 0.89 gdl(-1) [95% confidence interval (95% CI) 0.57-1.22] and anemia was significantly reduced (aOR = 0.38; 95% CI 0.19-0.78) at 8 months postpartum., Conclusions: A hospital policy change toward delayed cord clamping is effective in improving Hb levels and the anemia status of 8-month-old infants. Prior to scaling-up this intervention, issues related to training, monitoring, safety, additional long-term benefits and specific local conditions should be investigated.

Background: Fetal anemia is common in malarious areas and is a risk factor for infant morbidity and mortality. Malaria during pregnancy may cause decreased cord hemoglobin (Hb) and fetal anemia among newborns. Intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is protective against malaria but may also affect hematopoiesis and contribute to fetal anemia., Methods: Peripheral, placental, and cord blood were examined for malaria parasitemia and Hb concentration in a cross-section of 3848 mothers and infants delivered at Queen Elizabeth Central Hospital in Blantyre, Malawi between 1997 and 2006. Unconditional linear and logistic regressions were performed with multiple imputation for missing covariates to assess the associations between malaria, IPTp with SP, and fetal anemia., Results: The overall prevalence of fetal anemia was 7.9% (n = 304). Malaria parasitemia at delivery was associated with an adjusted decrease in cord Hb of -0.24 g/dL (95% confidence interval [CI], -.42 to -.05). The adjusted prevalence odds ratio for the effect of malaria on fetal anemia was 1.41 (95% CI, 1.05-1.90). Primigravidae who did not take IPTp had infants at highest risk for fetal anemia, and density of parasitemia was correlated with the decrease in cord Hb. There was no significant association between SP use and cord Hb or fetal anemia., Conclusions: Malaria during pregnancy, but not IPTp, decreases cord Hb and is a risk factor for fetal anemia in Malawi. Intermittent preventive treatment during pregnancy with SP may continue to be safe and effective in preventing malaria during pregnancy and fetal anemia despite development of SP resistance.

Background: Low plasma levels of erythropoietin (EPO) in preterm infants provide a rationale for the use of EPO to prevent or treat anaemia., Objectives: To assess the effectiveness and safety of early initiation of EPO in reducing red blood cell (RBC) transfusions in preterm and/or low birth weight infants., Search Methods: The Cochrane Central Register of Controlled Trials (The Cochrane Library), MEDLINE, EMBASE, CINAHL, abstracts from scientific meetings published in Pediatric Research and reference lists of identified trials and reviews were searched through July 2009. Searches were repeated in March 2012 including searches of Pediatric Academic Societies Annual meetings 2000 to 2012 (Abstracts2View(TM)) and clinical trials registries (clinicaltrials.gov; controlled-trials.com; and who.int/ictrp)., Selection Criteria: Randomised or quasi-randomised controlled trials of early (< eight days of age) initiation of EPO treatment versus placebo or no intervention in preterm and/or low birth weight neonates., Data Collection and Analysis: Data collection and analysis were accomplished using the methods of the Neonatal Cochrane Review Group., Main Results: The May 2012 update did not identify any new studies for inclusion. A number of randomised controlled trials were excluded as they compared one EPO dosing regimen with another, did not provide the numbers of infants randomised to the EPO and the placebo group, or the dose of EPO was not stated. The update includes 27 studies that enrolled 2293 preterm infants. Early EPO reduced the risk of the "use of one or more RBC transfusions" [typical risk ratio (RR); 0.80 (95% confidence interval (CI) 0.75 to 0.86); typical risk difference (RD) -0.13, (95% CI -0.17 to -0.09); number needed to benefit (NNTB) = eight, (95% CI 6 to 11); 16 studies, 1,825 infants].There was moderate heterogeneity for this outcome [RR (P = 0.004; I(2) = 56.7%); RD (P = 0.003; I(2) = 56.0%)].A total of six studies enrolling 515 infants reported on the total volume of red blood cells transfused per infant. The significant typical mean difference (MD) was a reduction of 6 mL/kg of blood transfused (mL/kg) per infant (95% CI -11 to - 1). There was moderate heterogeneity for this outcome (P = 0.02; I(2) = 63.0%). The results from 14 studies enrolling 1131 infants reported on the number of red blood cell transfusions per infant. The significant typical MD for number of red blood cell transfusions per infant was -0.33, (95% CI -0.48 to -0.18). There was high heterogeneity for this outcome (P = 0.00001, I(2) = 78%). Two studies enrolling 188 infants reported on the number of donors to whom the infant was exposed; the MD was significantly reduced -0.63, (-1.07 to -0.19). There was no heterogeneity for this outcome (P = 0.59; I(2) = 0%).There was a significant increase in the risk of stage ≥ 3 retinopathy of prematurity (ROP) in the early EPO group [typical RR; 1.65, (95% CI 1.12 to 2.43); typical RD; 0.05 (95% CI 0.01 to 0.08); number needed to harm (NNTH); 20, (95% CI 13 to 100); eight studies, 984 infants]. There was no heterogeneity for this outcome for RR (P = 0.87; I(2) = 0%), but there was moderate heterogeneity for RD (P = 0.006; I(2) = 65%). The rates for mortality and other neonatal morbidities were not significantly changed by early EPO treatment nor were neurodevelopmental outcomes at 18 to 22 months in the small number of infants tested to-date., Authors' Conclusions: Early administration of EPO reduces the use of RBC transfusions and the volume of RBCs transfused. These small reductions are of limited clinical importance. Donor exposure is probably not avoided since most studies included infants who had received RBC transfusions prior to trial entry. There was a significant increase in the rate of ROP (stage ≥ 3). Early EPO does not significantly decrease or increase any of the other important adverse outcomes. Ongoing research should deal with the issue of ROP and evaluate the current clinical practice that will limit donor exposure. Due to the limited benefits and the increased risk of ROP, early administration of EPO is not recommended. Evidence is lacking for the possible neuro protective role of EPO in preterm infants. This topic will be reviewed in separate Cochrane reviews for preterm and term and late preterm infants.

Background: The Premature Infants in Need of Transfusion (PINT) Outcome Study showed no significant difference in the primary outcome of death or neurodevelopmental impairment (NDI) in extremely low birthweight (ELBW) infants. However, a post-hoc analysis expanding the definition of NDI to include borderline intellectual functioning (Mental Development Index (MDI) <85) found an improvement in outcomes in the group maintained at higher haemoglobin levels., Objective: To determine the cost effectiveness of more frequent red blood cell transfusions (high-Hb threshold) compared with less frequent transfusions (low-Hb threshold) in ELBW infants., Design/methods: The authors performed an economic evaluation using patient-level data collected during the PINT randomised trial. The authors measured comprehensive costs from a third-party payer's perspective over a time horizon from birth through 18-21 months corrected age., Results: The average total cost in the high-Hb threshold group was CAN$149 767 compared with CAN$150 227 in the low-Hb threshold group (difference of CAN$460, p=0.96). Cost-effectiveness analysis estimated savings of CAN$6879 for every additional infant surviving without severe NDI. There was a 48% chance that the high-Hb threshold reduced costs while improving outcome and a 90% chance that it would be cost effective at a willingness-to-pay threshold of CAN$250 000 per additional survivor without severe NDI. Post-hoc analysis defining cognitive delay as MDI score <85, instead of <70, revealed savings in the high-Hb threshold group of CAN$4457 per additional survivor without NDI. Results were robust to deterministic sensitivity analyses., Conclusion: A high-Hb threshold for transfusion, as measured in ELBW PINT study infants through 18 months corrected gestational age, may be an economically appealing intervention. The estimates were associated with moderate statistical uncertainty that should be targeted in larger, future studies.

The large majority (> 90%) of very premature infants and newborn infants with haemolysis receive one or more red blood cell (RBC) transfusions. Up to 35% of newborn infants have thrombocytopenia (platelet count < 150 x 109/l). Following an unambiguous blood transfusion guideline leads to decrease in the number of transfusions given. The necessity for RBC transfusions can be diminished by use of diagnostic tests, micro-analysis techniques and delay of umbilical cord clamping (waiting for 30 seconds to 3 minutes after birth). Newborn infants with a gestational age < 32 weeks or birth weight < 1500 g must receive irradiated and Parvovirus-B19 safe blood products until 6 months post-term. It is still unclear whether lower Hb values and thrombocyte counts can be accepted as a transfusion limit without negative effect on the (neurological) long term outcomes and without increase in risk of intraventricular bleeding.

Objective: To investigate the effects of delayed umbilical cord clamping, compared with early clamping, on infant iron status at 4 months of age in a European setting., Design: Randomised controlled trial., Setting: Swedish county hospital., Participants: 400 full term infants born after a low risk pregnancy., Intervention: Infants were randomised to delayed umbilical cord clamping (≥ 180 seconds after delivery) or early clamping (≤ 10 seconds after delivery)., Main Outcome Measures: Haemoglobin and iron status at 4 months of age with the power estimate based on serum ferritin levels. Secondary outcomes included neonatal anaemia, early respiratory symptoms, polycythaemia, and need for phototherapy., Results: At 4 months of age, infants showed no significant differences in haemoglobin concentration between the groups, but infants subjected to delayed cord clamping had 45% (95% confidence interval 23% to 71%) higher mean ferritin concentration (117 μg/L v 81 μg/L, P < 0.001) and a lower prevalence of iron deficiency (1 (0.6%) v 10 (5.7%), P = 0.01, relative risk reduction 0.90; number needed to treat = 20 (17 to 67)). As for secondary outcomes, the delayed cord clamping group had lower prevalence of neonatal anaemia at 2 days of age (2 (1.2%) v 10 (6.3%), P = 0.02, relative risk reduction 0.80, number needed to treat 20 (15 to 111)). There were no significant differences between groups in postnatal respiratory symptoms, polycythaemia, or hyperbilirubinaemia requiring phototherapy., Conclusions: Delayed cord clamping, compared with early clamping, resulted in improved iron status and reduced prevalence of iron deficiency at 4 months of age, and reduced prevalence of neonatal anaemia, without demonstrable adverse effects. As iron deficiency in infants even without anaemia has been associated with impaired development, delayed cord clamping seems to benefit full term infants even in regions with a relatively low prevalence of iron deficiency anaemia. Trial registration Clinical Trials NCT01245296.

Background: Infants of very low birth weight often receive multiple transfusions of red blood cells, usually in response to predetermined haemoglobin or haematocrit thresholds. In the absence of better indices, haemoglobin levels are imperfect but necessary guides to the need for transfusion. Chronic anaemia in premature infants may, if severe, cause apnoea, poor neurodevelopmental outcomes or poor weight gain.On the other hand, red blood cell transfusion may result in transmission of infections, circulatory or iron overload, or dysfunctional oxygen carriage and delivery., Objectives: To determine if erythrocyte transfusion administered to maintain low as compared to high haemoglobin thresholds reduces mortality or morbidity in very low birth weight infants enrolled within three days of birth., Search Methods: Two review authors independently searched the Cochrane Central Register of Controlled Trials (The Cochrane Library) , MEDLINE,EMBASE, and conference proceedings through June 2010., Selection Criteria: We selected randomised controlled trials (RCTs) comparing the effects of early versus late, or restrictive versus liberal erythrocyte transfusion regimes in low birth weight infants applied within three days of birth, with mortality or major morbidity as outcomes.

Preterm neonates represent a category of patients with high transfusion needs. Ideally, red blood cells (RBC) transfusion should be tailored to the individual requirements of the single infant. However, despite the progress in neonatal transfusion medicine, many controversies still remain, and the decision on whether to transfuse or not is often made on empirical basis, with large variation in transfusion practices among neonatologists. Recently, a few clinical trials have been performed with the aim to compare the risk/benefit ratio of restrictive versus liberal transfusion criteria. Most of the studies failed to demonstrate significant differences in short-term outcomes, suggesting that the restrictive criteria may reduce the need for transfusion and the related side effects. Neurodevelopmental long-term outcome seemed more favorable in the liberal group at a first evaluation, especially for boys, and significantly better in the restrictive group at a later clinical investigation. Magnetic resonance imaging scans, performed at an average age of 12 years, showed that intracranial volume was substantially smaller in the liberal group compared with controls. When sex effects were evaluated, the girls in the liberal group had the most significant abnormalities. In conclusion, when preventive measures, as favoring cord clamping delay or cord milking, ensuring optimal nutrition, and minimizing phlebotomy losses, fail to avoid the need for transfusion, it is preferable to adopt restrictive criteria.

Objectives: To assess whether blood transfusions for infants with birth weights of 1000 g or less are a source of mercury and whether any mercury delivered through the transfusion is above the currently set oral reference dose., Patients and Methods: We studied an observational cohort. Inclusion criteria included birth weight 1000 g or less and receipt of 1 or more packed red blood cell transfusions. Packed red blood cell units were tested prospectively for mercury levels. The quantity of transfused mercury was calculated on the basis of transfused volume and packed red blood cell mercury level. The resulting mercury level was compared with the reference dose as set by the Agency for Toxic Substances and Disease Registry, the World Health Organization, and the US Environmental Protection Agency., Results: Thirty-seven infants (birth weight: 736 ± 157 g; gestational age: 25.5 ± 1.5 weeks) met the inclusion criteria. A total of 325 transfusions from 49 packed red blood cell units were administered. Mercury was detected in 40 units. The average mercury level in a packed red blood cell unit was 1.9 ± 2.6 μg/L (median: 0.9 μg/L [interquartile range: 0.3-2.5]). None of the infants received any mercury above the reference dose set by the Agency for Toxic Substances and Disease Registry and the World Health Organization. Twelve infants received 1 transfusion, and 5 infants received 2 transfusions above the Environmental Protection Agency reference dose during their entire hospitalization., Conclusions: Packed red blood cells are a source of mercury for infants. However, the amount delivered is low compared with currently set safety levels. The episodes in which mercury intake exceeded the reference dose were rare. However, without long-term follow-up, no conclusions can be made about the cognitive implications of these episodes.

Objective: The safe lower limit of haematocrit or haemoglobin that should trigger a red blood cell (RBC) transfusion has not been defined. The objective of this study was to examine the physiological effects of anaemia and compare the acute responses to transfusion in preterm infants who were transfused at higher or lower haematocrit thresholds., Methods: The authors studied 41 preterm infants with birth weights 500-1300 g, who were enrolled in a clinical trial comparing high ('liberal') and low ('restrictive') haematocrit thresholds for transfusion. Measurements were performed before and after a packed RBC transfusion of 15 ml/kg, which was administered because the infant's haematocrit had fallen below the threshold defined by study protocol. Haemoglobin, haematocrit, RBC count, reticulocyte count, lactic acid and erythropoietin were measured before and after transfusion using standard methods. Cardiac output was measured by echocardiography. Oxygen consumption was determined using indirect calorimetry. Systemic oxygen transport and fractional oxygen extraction were calculated., Results: Systemic oxygen transport rose in both groups following transfusion. Lactic acid was lower after transfusion in both groups. Oxygen consumption did not change significantly in either group. Cardiac output and fractional oxygen extraction fell after transfusion in the low haematocrit group only., Conclusions: These study's results demonstrate no acute physiological benefit of transfusion in the high haematocrit group. The fall in cardiac output with transfusion in the low haematocrit group shows that these infants had increased their cardiac output to maintain adequate tissue oxygen delivery in response to anaemia and, therefore, may have benefitted from transfusion.