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    The effect of different blood components on exchange transfusion outcomes. Ghaemi Sedigheh,Saneian Hosein,Mo'ayedi Behjatosadat,Pourazar Abbasali JPMA. The Journal of the Pakistan Medical Association BACKGROUND:Exchange transfusion (ET) has been known as an effective treatment in sever neonatal jaundice. Prescribing appropriate blood group makes an important role in patient's outcome and no single component is unequivocally the best. The purpose of this study was to evaluate the effect of ABO compatible packed cell, dried O, and routine O groups on exchange transfusion outcomes. METHODS:This multicenter clinical trial study is the combination of two studies which were conducted at three university hospitals (Isfahan University of Medical Sciences, Isfahan, Iran). A hundred full term infants with more than 2.5 kg body weight, serum bilirubin > or = 20 mg/dl and confirmed ABO-Hemolytic Disease of the Newborn (HDN) were participated in first study. Among 40 infants, 20 underwent the exchange transfusion with O packed cell (group 1) and other 20 were transfused with O dried packed cell (Hematocrit = 90%) (group 2). In the second study with the same eligibility criteria with first study, among the 60 infants, 30 had exchange transfusion with O packed cell (group 3) and the rest were transfused with infant isogroup (group 4). Serum bilirubin and hemoglobin (Hb) were evaluated before and 6, 12, 24 and 48 hours after the exchange transfusion. RESULTS:The means of Hb after the exchange transfusion were 14.3 mg/dl in group 1, 15.62 mg/dl in group 2, 14.98 mg/dl in group 3 and 14.30 mg/dl in group 4 with significantly higher in group 2 compared with others (p = 0.02). The mean of the bilirubin after the exchange transfusion had no statistical significant difference between the four groups (p > 0.05). The mean of Hb and bilirubin before exchange transfusion had no statistically difference between all groups (p > 0.05). The mean of bilirubin before the exchange transfusion in infants who had two transfusion was significantly higher than the mean of the bilirubin before the exchange transfusion in infants with one time transfusion (p = 0.05). There was no significant difference between four groups in exchange transfusion frequency (p > 0.05). DISCUSSION:This study indicated that the level of bilirubin before exchange transfusion is the only important factor which sometimes causes the necessity of second or third exchange.
    Severe ABO Hemolytic Disease of the Newborn Requiring Exchange Transfusion. Metcalf Ryan A,Khan Jenna,Andrews Jennifer,Mayock Dennis,Billimoria Zeenia,Pagano Monica B Journal of pediatric hematology/oncology ABO incompatibility (ABOi), the most common cause of hemolytic disease of the newborn (HDN), is nearly always mild and treatable with phototherapy. Reports of ABOi HDN requiring neonatal exchange transfusion are extremely rare since the inception of modern guidelines. Here, a case of ABOi HDN clearly met criteria for exchange transfusion. An O-positive African American mother delivered a B-positive neonate that quickly developed hyperbilirubinemia. The neonatal DAT was positive from anti-B and anti-A,B, and maternal IgG titer was 1024. Double volume exchange transfusion resulted in a favorable outcome. Given early discharge of newborns, further understanding of factors predicting severe disease is needed. 10.1097/MPH.0000000000001248
    Ernst A,Schlattmann P,Waldfahrer F,Westhofen M Laryngo- rhino- otologie The BEMED study (BMJ 2016; 352: DOI 10.1136) was designed as multi-centric, double-blind, plaebo-controlled study in patients with Menière's disease. It should compare a low-level (2 × 24 mg/d) vs. high-level (3 × 48 mg/d) betahstine intake vs. placebo. The primary endpoint was the "number of vertigo attacks lasting longer than 20 min as documented in a patient's diary". The main finding of the study was that betahistine did not significantly better reduced the number of vertigo attacks than placebo. Therefore, the BEMED study should be critically discussed in the present paper. 10.1055/s-0043-113690
    Indirect neonatal hyperbilirubinemia in hospitalized neonates on the Thai-Myanmar border: a review of neonatal medical records from 2009 to 2014. Thielemans L,Trip-Hoving M,Landier J,Turner C,Prins T J,Wouda E M N,Hanboonkunupakarn B,Po C,Beau C,Mu M,Hannay T,Nosten F,Van Overmeire B,McGready R,Carrara V I BMC pediatrics BACKGROUND:Indirect neonatal hyperbilirubinemia (INH) is a common neonatal disorder worldwide which can remain benign if prompt management is available. However there is a higher morbidity and mortality risk in settings with limited access to diagnosis and care. The manuscript describes the characteristics of neonates with INH, the burden of severe INH and identifies factors associated with severity in a resource-constrained setting. METHODS:We conducted a retrospective evaluation of anonymized records of neonates hospitalized on the Thai-Myanmar border. INH was defined according to the National Institute for Health and Care Excellence guidelines as 'moderate' if at least one serum bilirubin (SBR) value exceeded the phototherapy threshold and as 'severe' if above the exchange transfusion threshold. RESULTS:Out of 2980 records reviewed, 1580 (53%) had INH within the first 14 days of life. INH was moderate in 87% (1368/1580) and severe in 13% (212/1580). From 2009 to 2011, the proportion of severe INH decreased from 37 to 15% and the mortality dropped from 10% (8/82) to 2% (7/449) coinciding with the implementation of standardized guidelines and light-emitting diode (LED) phototherapy. Severe INH was associated with: prematurity (< 32 weeks, Adjusted Odds Ratio (AOR) 3.3; 95% CI 1.6-6.6 and 32 to 37 weeks, AOR 2.2; 95% CI 1.6-3.1), Glucose-6-phosphate dehydrogenase deficiency (G6PD) (AOR 2.3; 95% CI 1.6-3.3), potential ABO incompatibility (AOR 1.5; 95% CI 1.0-2.2) and late presentation (AOR 1.8; 95% CI 1.3-2.6). The risk of developing severe INH and INH-related mortality significantly increased with each additional risk factor. CONCLUSION:INH is an important cause of neonatal hospitalization on the Thai-Myanmar border. Risk factors for severity were similar to previous reports from Asia. Implementing standardized guidelines and appropriate treatment was successful in reducing mortality and severity. Accessing to basic neonatal care including SBR testing, LED phototherapy and G6PD screening can contribute to improve neonatal outcomes. 10.1186/s12887-018-1165-0
    Neonatal hyperbilirubinemia and Rhesus disease of the newborn: incidence and impairment estimates for 2010 at regional and global levels. Bhutani Vinod K,Zipursky Alvin,Blencowe Hannah,Khanna Rajesh,Sgro Michael,Ebbesen Finn,Bell Jennifer,Mori Rintaro,Slusher Tina M,Fahmy Nahed,Paul Vinod K,Du Lizhong,Okolo Angela A,de Almeida Maria-Fernanda,Olusanya Bolajoko O,Kumar Praveen,Cousens Simon,Lawn Joy E Pediatric research BACKGROUND:Rhesus (Rh) disease and extreme hyperbilirubinemia (EHB) result in neonatal mortality and long-term neurodevelopmental impairment, yet there are no estimates of their burden. METHODS:Systematic reviews and meta-analyses were undertaken of national prevalence, mortality, and kernicterus due to Rh disease and EHB. We applied a compartmental model to estimate neonatal survivors and impairment cases for 2010. RESULTS:Twenty-four million (18% of 134 million live births ≥ 32 wk gestational age from 184 countries; uncertainty range: 23-26 million) were at risk for neonatal hyperbilirubinemia-related adverse outcomes. Of these, 480,700 (0.36%) had either Rh disease (373,300; uncertainty range: 271,800-477,500) or developed EHB from other causes (107,400; uncertainty range: 57,000-131,000), with a 24% risk for death (114,100; uncertainty range: 59,700-172,000), 13% for kernicterus (75,400), and 11% for stillbirths. Three-quarters of mortality occurred in sub-Saharan Africa and South Asia. Kernicterus with Rh disease ranged from 38, 28, 28, and 25/100,000 live births for Eastern Europe/Central Asian, sub-Saharan African, South Asian, and Latin American regions, respectively. More than 83% of survivors with kernicterus had one or more impairments. CONCLUSION:Failure to prevent Rh sensitization and manage neonatal hyperbilirubinemia results in 114,100 avoidable neonatal deaths and many children grow up with disabilities. Proven solutions remain underused, especially in low-income countries. 10.1038/pr.2013.208
    Recommendations for the prevention and treatment of haemolytic disease of the foetus and newborn. Bennardello Francesco,Coluzzi Serelina,Curciarello Giuseppe,Todros Tullia,Villa Stefania, Blood transfusion = Trasfusione del sangue 10.2450/2014.0119-14
    Risk factors for severe neonatal hyperbilirubinemia in low and middle-income countries: a systematic review and meta-analysis. Olusanya Bolajoko O,Osibanjo Folasade B,Slusher Tina M PloS one BACKGROUND:Available evidence suggests that low- and middle-income countries (LMICs) bear the greatest burden of severe neonatal hyperbilirubinemia characterized by disproportionately high rates of morbidity, mortality and neurodevelopmental disorders compared to high-income countries. We set out to identify the risk factors that contribute to the burden of severe hyperbilirubinemia in the most developmentally disadvantaged LMICs to highlight areas for action and further research. METHODS:We systematically searched PubMed, Scopus, Ovid EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), WHO Library Database (WHOLIS), African Index Medicus (AIM), African Journals Online (AJOL), LILACS, and IndMed for reports published between January 1990 and June 2014. We included only studies that controlled for the effects of confounding variables in determining maternal and infant risk factors for severe hyperbilirubinemia. We conducted meta-analysis of the eligible studies and computed the summary risk estimates with random effects models. RESULTS:A total of 13 studies with 1,951 subjects and 32,208 controls from India, Nigeria, Pakistan, Nepal and Egypt were identified and analyzed. The pooled data showed that primiparity (OR, 1.59; 95% CI:1.26-2.00), delivery outside public hospitals (OR, 6.42; 95% CI:1.76-23.36), ABO incompatibility (OR, 4.01; 95% CI:2.44-6.61), Rhesus hemolytic disease (OR, 20.63; 95% CI:3.95-107.65), G6PD deficiency (OR, 8.01; 95% CI:2.09-30.69), UGT1A1 polymorphisms (OR, 4.92; 95% CI:1.30-18.62), low gestational age (OR, 1.71; 95% CI:1.40-2.11), underweight/weight loss (OR, 6.26; 95% CI:1.23-31.86), sepsis (OR, 9.15; 95% CI:2.78-30.10) and high transcutaneous/total serum bilirubin levels (OR, 1.46; 95% CI:1.10-1.92) placed infants at increased risk of severe hyperbilirubinemia or bilirubin induced neurologic dysfunctions. Low social class was not associated with an increased risk of severe hyperbilirubinemia. CONCLUSIONS:Infants at risk of severe hyperbilirubinemia in LMICs are associated with maternal and neonatal factors that can be effectively addressed by available interventions to curtail the disease burden prevailing in the affected countries. 10.1371/journal.pone.0117229
    Considerations of red blood cell molecular testing in transfusion medicine. Svensson Annika M,Delaney Meghan Expert review of molecular diagnostics The field of transfusion medicine is on the threshold of a paradigm shift, as the technology for genotyping of red blood cell antigens, including US FDA-approved arrays, is now moving into standard practice. Access to cost-efficient, high-resolution genotyping has the potential to increase the quality of care by decreasing the risk for alloimmunization and incompatible transfusions in individuals on long-term blood transfusion protocols, including patient groups with hemoglobinopathies and other chronic diseases. Current and future applications of molecular methods in transfusion medicine and blood banking are discussed, with emphasis on indications for genotyping in various clinical scenarios. Furthermore, limitations of the current gold standard methodology and serology, as well as of contemporary molecular methodology, are examined. 10.1586/14737159.2015.1086646
    [Management of feto-maternal red cell allo-immunizations]. Bricca P,Guinchard E,Guitton Bliem C Transfusion clinique et biologique : journal de la Societe francaise de transfusion sanguine Feto-maternal red cell alloimmunization is defined by the presence in a pregnant woman of alloantibodies directed against blood group antigens present on the red blood cells of the fetus and inherited from the father. It arises from the immune response to a first contact to these same antigens during a prior transfusion, transplant or pregnancy. The placental transfer and the fixation of the antibodies on the fetal red cells antigenic targets lead to a haemolysis in the fetus and the newborn. The resulting haemolytic disease can show different clinical forms, from a mild anaemia with neonatal hyperbilirubinemia to a major fetal damage with stillbirth caused by hydrops fetalis. The objective of management strategies of feto-maternal alloimmunization is to detect and monitor maternal alloimmunization and to appreciate the effects on the fetus or the newborn. Since a few years, some new non-invasive techniques of surveillance are used, for instance fetal RHD genotyping on maternal plasma and evaluation of fetal anaemia through velocimetry measurement of the blood flow in the middle cerebral artery. The need for a careful postnatal surveillance has to be emphasized due to the neonatal anaemia, which can be prolonged, and to the resurgence of cases of severe neonatal icteruses recently reported by the Académie de Médecine. The policy of prevention of anti-RH1 alloimmunization should also benefit from the evolution of biological techniques by allowing an improved targeting of concerned women. 10.1016/j.tracli.2011.01.005
    Hematological morbidity and management in neonates with hemolytic disease due to red cell alloimmunization. Rath Mirjam E A,Smits-Wintjens Vivianne E H J,Walther Frans J,Lopriore Enrico Early human development Treatment of severe anemia with intrauterine red cell transfusions in fetuses with red cell alloimmunization has led to a dramatic increase in perinatal survival. Due to this increased survival focus is nowadays shifting towards improving postnatal treatment options. Phototherapy, exchange transfusions and intravenous immunoglobulin are used to treat hyperbilirubinemia and prevent kernicterus. Postnatal treatment of anemia consists of top-up transfusions, supplements to support erythropoiesis such as folic acid and iron, and occasionally erythropoietin treatment. In addition to anemia, other hematological complications such as thrombocytopenia, coagulation disturbances, leucopenia and iron overload have been reported. This review focuses on the hematological morbidity in neonates with red cell alloimmunization and summarizes the current evidence on management options. 10.1016/j.earlhumdev.2011.07.010
    Should intravenous immunoglobulin be used in infants with isoimmune haemolytic disease due to ABO incompatibility? Keir Amy K,Dunn Michael,Callum Jeannie Journal of paediatrics and child health The use of intravenous immunoglobulin in isoimmune haemolytic disease due to ABO incompatibility is recommended by the American Academy of Pediatrics and the National Blood Authority, Australia. However, the evidence these recommendations are based on appears limited and, in some instances, outdated. In our article, we review the current available literature to help answer the question, 'In infants with isoimmune haemolytic disease due to ABO incompatibility [P], does use of intravenous immunoglobulin and intensive phototherapy [I] compared with intensive phototherapy alone [C] provide any clinically important benefits [O]?' 10.1111/jpc.12440
    Red blood cell alloimmunization mitigation strategies. Hendrickson Jeanne E,Tormey Christopher A,Shaz Beth H Transfusion medicine reviews Hemolytic transfusion reactions due to red blood cell (RBC) alloantibodies are a leading cause of transfusion-associated death. In addition to reported deaths, RBC alloantibodies also cause significant morbidity in the form of delayed hemolytic transfusion reactions. These alloantibodies may also cause morbidity in the form of anemia, with compatible RBC units at times being unable to be located for highly alloimmunized patients, or in the form of hemolytic disease of the newborn. Thus, preventing RBC alloantibodies from developing in the first place, or mitigating the dangers of existing RBC alloantibodies, would decrease transfusion-associated morbidity and mortality. A number of human studies have evaluated the impact on RBC alloimmunization rates of providing partially phenotypically or genotypically matched RBCs for transfusion, and a number of animal studies have evaluated the impact of single variables on RBC alloimmunization. The goal of this review is to take a comprehensive look at existing human and animal data on RBC alloimmunization, focusing on strategies that may mitigate this serious hazard of transfusion. Potential factors that impact initial RBC alloimmunization, on both the donor and recipient sides, will be discussed. These factors include, but are not limited to, exposure to the antigen and an ability of the recipient's immune system to present that antigen. Beyond these basic factors, coexisting "danger signals," which may come from the donor unit itself or which may be present in the recipient, also likely play a role in determining which transfusion recipients may become alloimmunized after RBC antigen exposure. In addition, to better understanding factors that influence the development of RBC alloantibodies, this review will also briefly discuss strategies to decrease the dangers of existing RBC alloantibodies. 10.1016/j.tmrv.2014.04.008
    Bilirubin-albumin binding, bilirubin/albumin ratios, and free bilirubin levels: where do we stand? Hulzebos Christian V,Dijk Peter H Seminars in perinatology Treatment for unconjugated hyperbilirubinemia is predominantly based on one parameter, i.e., total serum bilirubin (TSB) levels. Yet, overt kernicterus has been reported in preterm infants at relatively low TSB levels, and it has been repeatedly shown that free unconjugated bilirubin (freeUCB) levels, or bilirubin/albumin (B/A) ratios for that matter, are more closely associated with bilirubin neurotoxicity. In this article, we review bilirubin-albumin binding, UCBfree levels, and B/A ratios in addition to TSB levels to individualize and optimize treatment especially in preterm infants. Methods to measure bilirubin-albumin binding or UCBfree are neither routinely performed in Western clinical laboratories nor incorporated in current management guidelines on unconjugated hyperbilirubinemia. For bilirubin-albumin binding, this seems justified because several of these methods have been challenged, and sufficiently powered prospective trials on the clinical benefits are lacking. Technological advances in the measurement of UCBfree may provide a convenient means for integrating UCBfree measurements into routine clinical management of jaundiced infants. A point-of-care method, as well as determination of UCBfree levels in various newborn populations, is desirable to learn more about variations in time and how various clinical pathophysiological conditions affect UCBfree levels. This will improve the estimation of approximate UCBfree levels associated with neurotoxicity. To delineate the role of UCBfree in the management of jaundiced (preterm) infants, trials are needed using UCBfree as treatment parameter. The additional use of the B/A ratio in jaundiced preterms has been evaluated in the Bilirubin Albumin Ratio Trial (BARTrial; Clinical Trials: ISRCTN74465643) but failed to demonstrate better neurodevelopmental outcome in preterm infants <32 weeks assigned to the study group. Awaiting a study in which infants are assigned to be managed solely on the basis of their B/A ratio (with TSB excluded ) versus TSB levels alone-and determining which group does better-the additional use of the B/A ratio in the management of hyperbilirubinemia in preterms is not advised. In conjunction with TSB levels, other parameters possibly allow for more accurate prediction of bilirubin toxicity. Yet, different methodologies for estimating these parameters exist, and sufficiently powered, prospective clinical trials supporting their clinical benefit, i.e., reduced bilirubin neurotoxicity when using these parameters, are lacking. Their use in addition to TSB needs to be prospectively evaluated, especially in preterm neonates, and preferentially in randomized clinical trials, which include specific risk factors and assessment of clinical relevant outcome measures for detecting those infants at risk of bilirubin toxicity. 10.1053/j.semperi.2014.08.004
    Revisiting the Criteria for Exchange Transfusion for Severe Neonatal Hyperbilirubinemia in Resource-Limited Settings. Olusanya Bolajoko O,Imam Zainab O,Emokpae Abieyuwa A,Iskander Iman F Neonatology BACKGROUND:Exchange transfusion (ET) for severe neonatal hyperbilirubinemia (SNH) is frequently undertaken in low- and middle-income countries (LMIC), in sharp contrast to the prevailing practice in high-income countries. However, the criteria for initiating this procedure in settings with limited resources for treating infants with SNH have not been systematically explored. OBJECTIVE:To identify key considerations for initiating ET in resource-poor countries to curtail its unnecessary use for the prevention of kernicterus. METHODS:A review of the existing guidelines and literature on the management of neonatal hyperbilirubinemia worldwide was conducted to identify criteria and underlying factors for initiating ET. RESULTS:There is a dearth of evidence from randomized clinical trials to support clear criteria for indicated ET worldwide. Because risk assessment for kernicterus based solely on the levels of total serum bilirubin (TSB) has often proved inadequate, a combination of plasma/serum bilirubin estimation and clinical evaluation for acute bilirubin encephalopathy (ABE) has been recommended for predicting the risk of kernicterus. However, there is a lack of consistency regarding the TSB levels for which ET should be initiated in relation to the clinical signs/symptoms of ABE and hemolytic disorders. CONCLUSIONS:A decision-making framework that combines TSB thresholds and evidence of neurotoxicity is needed for evaluating the risk of kernicterus and prioritising infants for ET in LMICs to curtail unnecessary interventions. 10.1159/000441324
    Hyperbilirubinemia in Preterm Neonates. Bhutani Vinod K,Wong Ronald J,Stevenson David K Clinics in perinatology Preterm neonates with increased bilirubin production loads are more likely to sustain adverse outcomes due to either neurotoxicity or overtreatment with phototherapy and/or exchange transfusion. Clinicians should rely on expert consensus opinions to guide timely and effective interventions until there is better evidence to refine bilirubin-induced neurologic dysfunction or benefits of bilirubin. In this article, we review the evolving evidence for bilirubin-induced brain injury in preterm infants and highlight the clinical approaches that minimize the risk of bilirubin neurotoxicity. 10.1016/j.clp.2016.01.001
    Intravenous immunoglobulin in isoimmune haemolytic disease of newborn: an updated systematic review and meta-analysis. Louis Deepak,More Kiran,Oberoi Sapna,Shah Prakesh S Archives of disease in childhood. Fetal and neonatal edition BACKGROUND:Intravenous immunoglobulin (IVIg) is used in neonates with isoimmune haemolytic disease to prevent exchange transfusion (ET). However, studies supporting IVIg had methodological issues. OBJECTIVE:To update the systematic review of efficacy and safety of IVIg in neonates with isoimmune haemolytic disease. METHODS:MEDLINE, Embase databases and Cochrane Central Register of Controlled Trials (Cochrane Library) were searched (from inception to May 2013) for randomised or quasi-randomised controlled trials comparing IVIg with placebo/controls in neonates with isoimmune haemolytic disease without any language restriction. Three investigators assessed methodological quality of included trials. Meta-analyses were performed using random effect model and risk ratio (RR)/risk difference (RD) and mean difference with 95% CI calculated. MAIN RESULTS:Twelve studies were included, ten trials (n=463) of Rh isoimmunisation and five trials (n=350) of ABO isoimmunisation (three studies had both population). Significant variations in risk of bias precluded an overall meta-analysis of Rh isoimmunisation. Studies with high risk of bias showed that IVIg reduced the rate of ET in Rh isoimmunisation (RR 0.23, 95% CI 0.13 to 0.40), whereas studies with low risk of bias that also used prophylactic phototherapy did not show statistically significant difference (RR 0.82, 95% CI 0.53 to 1.26). For ABO isoimmunisation, only studies with high risk of bias were available and meta-analysis revealed efficacy of IVIg in reducing ET (RR 0.31, 95% CI 0.18 to 0.55). CONCLUSIONS:Efficacy of IVIg is not conclusive in Rh haemolytic disease of newborn with studies with low risk of bias indicating no benefit and studies with high risk of bias suggesting benefit. Role of IVIg in ABO disease is not clear as studies that showed a benefit had high risk of bias. 10.1136/archdischild-2013-304878
    Serum bilirubin and bilirubin/albumin ratio as predictors of bilirubin encephalopathy. Iskander Iman,Gamaleldin Rasha,El Houchi Salma,El Shenawy Amira,Seoud Iman,El Gharbawi Nesrin,Abou-Youssef Hazem,Aravkin Aleksandr,Wennberg Richard P Pediatrics BACKGROUND AND OBJECTIVE:Bilirubin/albumin ratio (B/A) may provide a better estimate of free bilirubin than total serum bilirubin (TSB), thus improving identification of newborns at risk for bilirubin encephalopathy. The objective of the study was to identify thresholds and compare specificities of TSB and B/A in detecting patients with acute and posttreatment auditory and neurologic impairment. METHODS:A total of 193 term/near-term infants, admitted for severe jaundice to Cairo University Children's Hospital, were evaluated for neurologic status and auditory impairment (automated auditory brainstem response), both at admission and posttreatment by investigators blinded to laboratory results. The relationships of TSB and B/A to advancing stages of neurotoxicity were compared by using receiver operating characteristic curves. RESULTS:TSB and B/A ranged from 17 to 61 mg/dL and 5.4 to 21.0 mg/g, respectively; 58 (30%) of 193 subjects developed acute bilirubin encephalopathy, leading to kernicterus in 35 infants (13 lethal). Auditory impairment was identified in 86 (49%) of 173 infants at admission and in 22 of 128 at follow-up. In the absence of clinical risk factors, no residual neurologic or hearing impairment occurred unless TSB exceeded 31 mg/dl. However, transient auditory impairment occurred at lower TSB and B/A (22.9 mg/dL and 5.7 mg/g, respectively). Intervention values of TSB and B/A set at high sensitivity to detect different stages of neurotoxicity had nearly the same specificity. CONCLUSIONS:Both TSB and B/A are strong predictors of neurotoxicity, but B/A does not improve prediction over TSB alone. Threshold values detecting all affected patients (100% sensitivity) increase with advancing severity of neurotoxicity. 10.1542/peds.2013-1764
    Changes in transfusion practice over time in the PICU. Dallman Michael D,Liu Xinggang,Harris Anthony D,Hess John R,Edelman Bennett B,Murphy David J,Netzer Giora Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies OBJECTIVES:Recent randomized clinical trials have shown the efficacy of a restrictive transfusion strategy in critically ill children. The impact of these trials on pediatric transfusion practice is unknown. Additionally, long-term trends in pediatric transfusion practice in the ICU have not been described. We assessed transfusion practice over time, including the effect of clinical trial publication. DESIGN:Single-center, retrospective observational study. SETTING:A 10-bed PICU in an urban academic medical center. PATIENTS:Critically ill, nonbleeding children between the ages of 3 days and 14 years old, admitted to the University of Maryland Medical Center PICU between January 1, 1998, and December 31, 2009, excluding those with congenital heart disease, hemolytic anemia, and hemoglobinopathies. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:During the time period studied, 5,327 patients met inclusion criteria. Of these, 335 received at least one RBC transfusion while in the PICU. The overall proportion transfused declined from 10.5% in 1998 to 6.8% in 2009 (p = 0.007). Adjusted for acuity, the likelihood of transfusion decreased by calendar year of admission. In transfused patients, the pretransfusion hemoglobin level declined, from 10.5 g/dL to 9.3 g/dL, though these changes failed to meet statistical significance (p = 0.09). Neonatal age, respiratory failure, shock, multiple organ dysfunction syndrome, and acidosis were associated with an increased likelihood of transfusion in both univariate and multivariable models. CONCLUSIONS:The overall proportion of patients transfused between 1998 and 2009 decreased significantly. The magnitude of the decrease varied over time, and no additional change in transfusion practice occurred after the publication of a major pediatric clinical trial in 2007. Greater illness acuity and younger patient age were associated with an increased likelihood of transfusion. 10.1097/PCC.0b013e31829b1bce
    Management and outcome of pregnancies in women with red cell isoimmunization: a 15-year observational study from a tertiary care university hospital. Sánchez-Durán María Ángeles,Higueras María Teresa,Halajdian-Madrid Cecilia,Avilés García Mayte,Bernabeu-García Andrea,Maiz Nerea,Nogués Nuria,Carreras Elena BMC pregnancy and childbirth BACKGROUND:The aims of this study were to determine the prevalence of the different anti-erythrocytic alloantibodies, to describe pregnancy outcomes according to a low-risk and high-risk classification for fetal anemia and to determine the factors that influence adverse perinatal outcomes. METHODS:This retrospective observational study included women referred to our center following the identification of maternal anti-erythrocytic alloantibodies between 2002 and 2017. Pregnancies were classified as high risk for fetal anemia in cases with clinically significant antibodies, no fetal-maternal compatibility and titers ≥1:16 or any titration in cases of Kell system incompatibility. In high-risk pregnancies, maternal antibody titration and the fetal middle cerebral artery peak systolic velocity (MCA-PSV) were monitored. Low-risk pregnancies underwent routine pregnancy follow-up. RESULTS:Maternal antibodies were found in 337 pregnancies, and 259 (76.9%) of these antibodies were clinically significant. The most frequent antibodies were anti-D (53%) and anti-K (19%). One hundred forty-three pregnancies were classified as low risk for fetal anemia, 65 (25%) cases were classified as no fetal-maternal incompatibility, 78 had clinically nonsignificant antibodies, 4 (2.8%) resulted in first-trimester pregnancy loss, and 139 (97.2%) resulted in livebirths. Of the 194 high-risk pregnancies, 38 had titers < 1:16 (resulting in 38 livebirths), and 156 had titers ≥1:16 or anti-K antibodies. In the last group, 6 cases miscarried before 18 weeks, 93 had a MCA-PSV < 1.5 multiples of the median (MoM), resulting in 3 perinatal deaths that were unrelated to fetal anemia, one termination and 89 livebirths; and 57 had a MCA-PSV > 1.5 MoM, resulting in 3 intrauterine deaths, 6 terminations and 48 livebirths. Ninety-two intrauterine transfusions were performed in 45 fetuses (87% anti-D). Adverse outcomes were related to a MCA-PSV > 1.5 MoM (p < 0.001), hydrops (p < 0.001) and early gestational age at first transfusion (p = 0.029) CONCLUSION: Anti-D remains the most common antibody in fetuses requiring intrauterine transfusion. A low or high-risk classification for fetal anemia based on the type of antibody, paternal phenotype and fetal antigen allows follow-up of the pregnancy accordingly, with good perinatal outcomes in the low-risk group. In the high-risk group, adverse perinatal outcomes are related to high MCA-PSV, hydrops and early gestational age at first transfusion. 10.1186/s12884-019-2525-y
    Prevalence, specificity and risk of red blood cell alloantibodies among hospitalised Hubei Han Chinese patients. Xu Pu,Li Yan,Yu Hua Blood transfusion = Trasfusione del sangue BACKGROUND:The prevalence, specificity and risk of red blood cell alloantibodies vary widely among different geographic areas, races, and diseases and according to different methods of study, but no data are available on the Chinese Han population, who were investigated in the present study. MATERIALS AND METHODS:Antibody screening was conducted among 42,517 hospitalised Hubei Han Chinese individuals using column agglutination technology. Samples that were positive in antibody screening were subjected to antibody identification by the tube test. Clinical data, including gender, age, race, transfusion history and records of alloantibody detection, transfusion reactions or haemolytic disease of the newborn, were collected to analyse the prevalence and specificity of alloantibodies and complications associated with them. RESULTS:A total of 212 patients with alloantibodies were identified among 42,517 patients, yielding a prevalence of 0.50% in this study. Significantly different prevalence rates were observed according to age and sex. The most frequently identified alloantibodies were anti-E (87/212, 41.0%), anti-D (45/212, 21.2%), anti-M (41/212, 19.3%) and a combination of anti-E and anti-c (13/212, 6.1%). Haemolytic disease was observed in 13 infants with anti-D, three infants with anti-E and one infant with anti-Fy(a) alloantibodies. Delayed haemolytic transfusion reactions occurred in four patients with alloantibodies. DISCUSSION:In hospitalised Hubei Han Chinese individuals, the overall prevalence of alloantibodies was 0.50%, with anti-E, anti-D and anti-M being the most frequently identified alloantibodies. These results indicate that anti-D and anti-E alloantibodies were major risk factors for haemolytic disease of the newborn or delayed haemolytic transfusion reactions in this study population. 10.2450/2013.0013-13
    A correlation between severe haemolytic disease of the fetus and newborn and maternal ABO blood group. Doyle B,Quigley J,Lambert M,Crumlish J,Walsh C,McParland P,Culliton M,Murphy K,Fitzgerald J Transfusion medicine (Oxford, England) OBJECTIVE:To analyse anti-D quantification levels and frequency of intrauterine transfusion (IUT), per maternal ABO blood group. BACKGROUND:Maternally derived red cell allo-antibodies can target fetal red cell antigens in utero leading to haemolytic disease and fetal anaemia. When a clinically significant allo-antibody is formed the priority is ascertaining the risk to the fetus and maternal ABO blood groups are not considered relevant. MATERIALS AND METHODS:This was a 10-year retrospective, observational study carried out on women referred for anti-D quantification (n = 1106), and women whose fetuses required an IUT to treat fetal anaemia (n = 62) due to anti-D, in the Republic of Ireland. RESULTS:Relative to the overall incidence of RhD allo-immunisation by blood group, women of blood group A were more likely to require IUT compared with those who were blood group O (P = 0.002). CONCLUSION:It is known that ABO feto-maternal compatibility can influence the incidence and level of red cell allo-antibodies in pregnancy; however, it does not account for the significantly high rate of severe haemolytic disease requiring IUT seen in blood group A women. 10.1111/tme.12132
    Intravenous immunoglobulin in neonates with rhesus hemolytic disease: a randomized controlled trial. Smits-Wintjens Vivianne E H J,Walther Frans J,Rath Mirjam E A,Lindenburg Irene T M,te Pas Arjan B,Kramer Christine M,Oepkes Dick,Brand Anneke,Lopriore Enrico Pediatrics BACKGROUND:Despite limited data, international guidelines recommend the use of intravenous immunoglobulin (IVIg) in neonates with rhesus hemolytic disease. OBJECTIVE:We tested whether prophylactic use of IVIg reduces the need for exchange transfusions in neonates with rhesus hemolytic disease. DESIGN AND SETTING:We performed a randomized, double-blind, placebo-controlled trial in neonates with rhesus hemolytic disease. After stratification for treatment with intrauterine transfusion, neonates were randomly assigned for IVIg (0.75 g/kg) or placebo (5% glucose). The primary outcome was the rate of exchange transfusions. Secondary outcomes were duration of phototherapy, maximum bilirubin levels, and the need of top-up red-cell transfusions. RESULTS:Eighty infants were included in the study, 53 of whom (66%) were treated with intrauterine transfusion(s). There was no difference in the rate of exchange transfusions between the IVIg and placebo groups (7 of 41 [17%] vs 6 of 39 [15%]; P = .99) and in the number of exchange transfusions per patient (median [range]: 0 [0-2] vs 0 [0-2]; P = .90) or in duration of phototherapy (4.7 [1.8] vs 5.1 [2.1] days; P = .34), maximum bilirubin levels (14.8 [4.7] vs 14.1 [4.9] mg/dL; P = .52), and proportion of neonates who required top-up red-cell transfusions (34 of 41 [83%] vs 34 of 39 [87%]; P = .76). CONCLUSIONS:Prophylactic IVIg does not reduce the need for exchange transfusion or the rates of other adverse neonatal outcomes. Our findings do not support the use of IVIg in neonates with rhesus hemolytic disease. 10.1542/peds.2010-3242
    Immunoglobulins in Neonates with Rhesus Hemolytic Disease of the Fetus and Newborn: Long-Term Outcome in a Randomized Trial. van Klink Jeanine M M,van Veen Suzanne J,Smits-Wintjens Vivianne E H J,Lindenburg Irene T M,Rijken Monique,Oepkes Dick,Lopriore Enrico Fetal diagnosis and therapy OBJECTIVE:Prophylactic intravenous immunoglobulin (IVIg) does neither reduce the need for exchange transfusion nor the rates of other adverse neonatal outcomes in neonates with rhesus hemolytic disease of the fetus and newborn (rhesus HDFN) according to our randomized controlled trial analysis. Our objective was to assess the long-term neurodevelopmental outcome in the children included in the trial and treated with either IVIg or placebo. METHODS:All families of the children included in the trial were asked to participate in this follow-up study. The long-term neurodevelopmental outcome in children at least 2 years of age was assessed using standardized tests. The primary outcome was the incidence of neurodevelopmental impairment defined as at least one of the following: cerebral palsy, severe cognitive and/or motor developmental delay (with a test score of less than -2 SD), bilateral deafness or blindness. RESULTS:Sixty-six of the 80 children (82.5%) who had been recruited to the initial randomized controlled trial participated in the follow-up study. The children were assessed at a median age of 4 years (range 2-7). The median cognitive score was 96 (range 68-118) in the IVIg group and 97 (range 66-118) in the placebo group (p = 0.79). There was no difference in the rate of neurodevelopmental impairment between the IVIg and the placebo group [3% (1/34) vs. 3% (1/32); p = 1.00]. CONCLUSIONS:The long-term neurodevelopmental outcome in children treated with IVIg was not different from that in children treated with placebo. Standardized long-term follow-up studies with large enough case series and sufficient power are needed to replicate these findings. 10.1159/000434718
    Characteristics of Bilirubin According to the Results of the Direct Antiglobulin Test and Its Impact in Hemolytic Disease of the Newborn. Shin Kyung-Hwa,Lee Hyun-Ji,Song Duyeal,Lee Sun-Min,Kim In Suk,Kim Hyunghoi,Yang Eu Jeen,Park Kyung-Hee Laboratory medicine BACKGROUND:Hyperbilirubinemia, which is a sign of hemolytic disease of the newborn (HDN), can irreversibly damage the central nervous system. OBJECTIVES:To determine the etiology of HDN in affected patients and characterize the changing pattern of bilirubin using direct antiglobulin testing (DAT). METHODS:We collected clinical data from newborns who underwent perinatal DAT and from their mothers, between August 2008 and July 2017. RESULTS:Among 303 neonates, 37 (12.2%) showed positive DAT results. The positive predictive values (PPVs) and negative predictive values (NPVs) based on DAT results were 75.7% and 28.9%, respectively, for starting phototherapy. Bilirubin levels increased more rapidly in the DAT-positive group, compared with the DAT-negative group. The initial bilirubin level differed significantly according to the etiology of hyperbilirubinemia. Further, neonates with anti-D showed higher delta bilirubin per day than neonates with other antibodies. CONCLUSION:Our results may help to determine the measurement period for bilirubin according to DAT results and etiology. 10.1093/labmed/lmy050
    Severe ABO Hemolytic Disease of Newborn with High Maternal Antibody Titres in a Direct Antiglobulin Test Negative Neonate. Kumar Rakesh,Saini Nishant,Kaur Paramjit,Sood Tanvi,Kaur Gagandeep,Bedi Ravneet K,Mittal Kshitija Indian journal of pediatrics 10.1007/s12098-015-1926-9
    Early intravenous immunoglobin (two-dose regimen) in the management of severe Rh hemolytic disease of newborn--a prospective randomized controlled trial. Elalfy Mohsen Saleh,Elbarbary Nancy Samir,Abaza Heba Wegdan European journal of pediatrics Phototherapy is the standard treatment in moderately severe hemolytic disease of newborn (HDN), whereas exchange transfusion (ET) is the second line in progressive cases. Intravenous immunoglobin (IVIG) has been suggested to decrease the need for ET. We aimed at assessing the efficacy of early two-dose regimens of IVIG to avoid unnecessary ET in severe Rh HDN. The study included 90 full-term neonates with Rh incompatibility unmodified by antenatal treatment and not eligible for early ET and which were randomly assigned into one of three groups: group (I), treated by conventional method; groups IIa and IIb received IVIG once at 12 h postnatal age if PT was indicated, in a dose of 0.5 and 1 g/kg, respectively. Analysis revealed 11 neonates (22%) in the conventional group and 2 (5%) in the intervention group who administered low-dose IVIG at 12 h, while none in group IIb required exchange transfusion (p = 0.03). Mean bilirubin levels were significantly lower during the first 96 h in the intervention group compared to the conventional group (p < 0.0001). Shorter duration of phototherapy (52.8 ± 12.39 h) and hospital stay (3.25 ± 0.71 days) in the IVIG group compared to conventional group (84 ± 12.12 h and 4.72 ± 0.78 days, p < 0.0001, respectively) were observed. We conclude that IVIG administration at 12 h was effective in the treatment of severe Rh HDN; the low-dose IVIG (0.5 g/kg) was as effective as high dose (1 g/kg) in reducing the duration of phototherapy and hospital stay, but less effective in avoiding exchange transfusion. 10.1007/s00431-010-1310-8