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The influence of the blood group on the occurrence and severity of diseases has aroused the curiosity of scientists for many years. The AB0 group system is the best known and described blood group system. It is also the only system whose antibodies are constantly present in the blood serum. The most common blood type in Poland, according to data provided by Honorary blood donation and blood therapy, is group A Rh + (plus), while the least common is group AB Rh – (minus). In studies of pregnant women scientists discovered the influence of blood type in the development of preeclampsia, gestational diabetes, the risk of preterm labor, and even COVID-19 infection. The impact of the mothers’ blood group also affects the birth weight of newborns, as well as the development of hemolytic disease of the newborn due to the heterospecificity of AB0. The influence of the blood group on the increased risk of developing certain diseases and complications of the neonatal period has also been proven. Therefore, it seems important to study blood groups of pregnant women and newborns of different nationalities, correlate the results with available reports and use this knowledge in everyday clinical practice. This will help to increase the speed of detection of diseases in pregnancy and neonatal period. It will also facilitate the management of the patient depending on their blood group.

Akshay Kiran Myle,1,2 Ghanim Hamid Al-Khattabi2 1Department of Clinical Research, General Medicine, Pharmacology, Integrative Medicine, Clinical Researcher. National Institute of Medicine Sciences, Poduru Mandalam City, Andhra Pradesh State, India; 2Preventive Medicine and Public Health, Ministry of Health, Makkah City, Kingdom of Saudi-ArabiaCorrespondence: Akshay Kiran Myle Email myleakshaykiran@gmail.comAbstract: Hemolytic disease of the newborn (HDN), also known as Erythroblastosis fetalis, is a hemolytic condition that predominantly affects rhesus-positive fetuses and infants born to rhesus-negative mothers. The pathophysiology of HDN begins with maternal antibodies attacking fetal red blood cells following alloimmunization due to rhesus or ABO incompatibility between the maternal and fetal blood. Previously, HDN was known to cause fetal death in 1% of all pregnancies, but with the advent of immunoprophylactic therapies, the condition can be currently fairly well managed with fewer complications if diagnosed early. Diagnosis calls for extensive history taking, physical examination, serological studies, and imaging modalities such as pelvic ultrasound scans. To prevent the disease, earlier intravenous immunoglobulin (IVIG) should be given to pregnant Rh- women who have not been sensitized. It is also vital to understand prospective complications such as severe hyperbilirubinemia and develop appropriate remedies. Because of its great incidence and nature, HDN has been thoroughly explored, and more studies are being conducted each year, revealing new insights about the condition. This review covers the disorder’s etiology, diagnosis, and management, including the most current findings as of 2021, as well as trends and prospects, to help in future research and evidence-based medical practice.Keywords: alloimmunization, fetomaternal hemorrhage, hemolysis, immunoprophylaxis

An early-term, 2,860-g female infant is delivered via caesarean section by a 28-year-old gravida 3, para 1-1-1 woman. Her second pregnancy had terminated in an abortion 4 years ago with the cause unknown. Results of serologic studies at the time of her previous pregnancies are not available, but the antibody screen (3-cell panel, Immucor Inc, Peachtree Corners, GA) during the present pregnancy is positive. The mother’s red blood cells (RBCs) are typed as B Rh (D) positive. The sample reacts with all cells in the 16-cell panel (Capture-R Ready-ID, Immucor Inc) and 11 cell panels (ID DiaPanel, Biorad Labs, Hercules, CA). The auto control and direct antiglobulin test results are negative. The reaction pattern seen on screening and identification panels indicates the presence of an RBC alloantibody to a high-frequency antigen. Crossmatch with multiple B-positive and O-positive RBC units are incompatible on Coombs testing. Extended phenotyping of the mother for minor blood group antigens of high frequency reveals her minor blood group phenotype to be K−, k+, Kp (a−b+), Js (a+b−), Lu(a–b+) and In(a–b+). Allogeneic adsorption studies done using 0.01%-ficin treated RBCs of known phenotype to deliberately adsorb the anti-Jsb from the mother’s serum confirms the absence of other common alloantibodies. The antibody is confirmed to be anti-Jsb alloantibody. The anti-Jsb titer using the antiglobulin technique Jsb(+) red cells is 128. …

Suzan A AlKhater,1,2 Rana A Albalwi,2 Sara A Alomar,1 Anfal A Alsultan,1 Halah R Almuhaidib,1 Rahaf A Almousa,1 Sarah M Alanezi,1 Raghad K Alghamdi,1 Hwazen A Shash1,2 1College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 2Department of Pediatrics, King Fahad Hospital of the University, Al-Khobar, Saudi ArabiaCorrespondence: Hwazen A ShashDepartment of Pediatrics, King Fahd Hospital of the University, Al Khobar 31952, Saudi ArabiaTel +966540353333Email hashash@iau.edu.saPurpose: Guidelines for managing neonatal hemolytic disease of the newborn (HDN) recommend a selective approach in the use of direct antiglobulin test (DAT). In Saudi Arabia, many hospitals still perform routine DAT for all newborns. This study assessed the need for phototherapy in relation to DAT results in full-term healthy newborns.Patients and Methods: A retrospective analysis of all healthy newborns admitted during 2018 was performed. The primary outcome was the association of positive DAT results with phototherapy.Results: There were 1463 newborns born during the study period. The DAT was positive at 4.4%. The 24-hour bilirubin levels were higher in DAT-positive cases (P=0.06); however, peak bilirubin levels were not correlated with the DAT results (P=0.717). Thirty-six neonates (2.46%) required phototherapy, and the need was similar among DAT-positive and DAT-negative cases (P=0.271). The most common indication for phototherapy was clinical jaundice in 22 neonates (61.1%), followed by DAT positivity in 12 (33.3%) and hospital protocol in 2 patients (5.6%) (P < 0.01 by chi-square overall comparison).Conclusion: Our results indicate that factors other than DAT positivity are important in assessing the need for phototherapy in newborns. Clinical signs of jaundice were indicators of high serum bilirubin levels and subsequent phototherapy, further indicating that the DAT test was overused in predicting the need for phototherapy.Keywords: hemolytic disease of the newborn, neonatal jaundice, neonatology, screening

of the study is to research the epidemiological aspects of maternal alloimmunization against erythrocyte antigens of fetuses (AB0, Rhesus, Lewis, Kell, Duffy and others) and to identify the most common types of hemolytic disease of the newborn (HDN) in the West Herzegovina region.The 20-year retrospective epidemiological study includes all pregnant women who had been immunologically tested and newborn treated for HDN.The indirect antiglobulin (IAT) detected antibodies against antigens in 545 (1.8%) pregnant women of the 29 663 who were tested at the Department of Transfusion Medicine. During the 20-year-long study 310 (1.0%) newborn with HDN were treated. Our results indicate that 42% (230/545) of the pregnant women had AB0 immunization. The most common form of HDN is AB0 HDN 64% (199/310), whereas RhD HDN was treated in 19% (59/310) of the newborn infants. ETR was performed on 29 (19%) infants, 21 (72.4%) with AB0 HDN, and 7 (26%) with RhD HDN.This 20-year-long study concludes that, even though there has been significant progress in the prevention of immunization and proactive treatment of HDN, precautionary measures are still required as is the need for gynecologists and obstetricians to be active. The reasons for this are the non-existence of preventive measures for non-RhD immunization, the irregular immunological screening of RhD positive women in pregnancy in the region encompassed by the study in the past few years. The above raises new questions and recommends further research and monitoring of immunization and HDN treatment worldwide.ZIEL DIESER STUDIE: war die Untersuchung von epidemiologischen Aspekten mütterlicher Immunisierung gegen fetale Erythrozytenantigene(AB0, Rhesus, Lewis, Kell, Duffy und andere) und die Feststellung von häufigsten Ursachen der hämolytischen Erkrankung des Neugeborenen (MHN) in der Region der West-Herzegowina.20-jährige retrospektive epidemiologische Studie umfasste alle Schwangeren, die immunologische getestet sowie Neugeborene, die wegen MHN behandelt wurden.Durch den indirekten antiglobulin Test (IAT) wurden bei 545 (1,8%) Schwangeren Antikörper gegen Antigene nachgewiesen, von 29 663 Probanden, die an der Transfusionsanstalt UHC Mostar getestet wurden. Während der zwanzigjährigen Studie hatten 310 (1,0%) Neugeborene MHN. Unsere Ergebnisse zeigten, dass 42% (230/545) der Schwangeren die AB0-Immunisierung hatten. Die häufigste MHN bei dieser Forschung war die AB0 MHN 64% (199/310), während RhD MHN bei 19% (59/310) der Neugeborenen behandelt wurde.Die Blutaustauschtransfusion (ETR) erfolgte bei 29 (19%) Neugeborenen, 21 (72,4%) bei Neugeborenen mit AB0 MHNund 7 (26%) mit Rh D MHN.Obwohl es zu während dieser 20-jährigen Studie zu einem bedeutenden Fortschritt bei der Vorbeugung der Immunisierung und der proaktiven MHN-Behandlung kam, erfordert es weiterhin Vorsichtsmaßnahmen und die Aktivitäten der Gynäkologen und Neonatologen. Grund dafür ist das Nichtbestehen von Vorbeugungsmaßnahmen zur nicht-RhD Immunisierung (67% der Schwangeren hatten Nicht-RhD Antikörper), unregelmäßiges immunologisches Testen von RhD-positiven Schwangeren in den letzten Jahren im Untersuchungsgebiet. All dies eröffnet neue Fragen und Empfehlungen zur Erforschung und Beobachtung der Immunisierung sowie MHN-Behandlung auf der globalen immunologischen Szene.

Since its discovery in 1953, the presence of the antigen Diego (Di) has been related to the Mongoloid populations and American natives. Given its immunogenic potential, the presence of the mentioned antigen is related to the development of hemolytic disease of the newborn (HDN). We present the case of a puerperal patient with no known history who was detected the presence of antibodies to Di b during study of a mild HDN presented by her daughter. When studying the patient's family, the presence of Dib antigen was reported in a brother as well as in both parents. We consider that being a rare event, this type of case should be reported promptly to promote the exchange of knowledge with other health professionals and the community.

Background. This study is devoted to a rare variation of the -D- phenotype . The -D- phenotype was first discovered by R. Race, R. Sanger and J.G. Selwyn in 1951. In Russia, the phenotype -D- was first discovered by V. Morokov in 1985. Typically, the -D- phenotype is detected when physicians examine post-transfusion complications or hemolytic disease of the newborn, since such patients demonstrate high antibody titres to absent antigens. In the present study, the -D- phenotype was detected in a primary blood donor at the clinical laboratory of the Ulyanovsk Regional Blood Transfusion Station (Ulyanovsk, Russia). Aim. To study specific features of immunohematological and hematological blood parameters in a donor with a rare variation of the -D- phenotype.Materials and methods. The detection of the -D- phenotype by immunohematological methods was carried out using automatic analysers. Molecular DNA typing was used to confirm the -D- phenotype. The shape of erythrocytes of the donor with the -D- phenotype was evaluated using an atomic force microscope. The characteristics of the erythroid lineage were studied using an automatic hematological analyser.Results. The -D- phenotype was detected in a primary blood donor. Due to the extreme rarity of the -D- phenotype and the lack of programmed algorithms, the validation of the results by automatic analysers was incorrect. Of critical importance was the visual assessment of gel ID cards by the medical staff. Genotyping confirmed the lack of C, c, E, e, Cw specificities in the RHCE gene. The hematological parameters of the donor were within the age norm. An assessment of the image of a cytological blood preparation did not reveal changes in the shape of erythrocytes and their size.Conclusions. The primary determination of the -D- phenotype using automatic immunohematological analysers can be complicated by the impossibility of validating the results, the incorrect operation of the installed software and the need for expert evaluation of blood samples by the staff. The presented case of the -D- phenotype was not associated with changes in the shape of erythrocytes and blood hematological parameters.

Background The clinical and laboratory features of hemolytic disease of the newborn can be challenging to diagnose during pregnancy in the apparent absence of a blood group antibody. Low-frequency antibodies go undetected due to the lack of appropriate antigen-positive reagent red blood cells (RBCs). Case report A pregnant woman of Southeast Asian descent was referred to a maternal-fetal medicine outpatient clinic due to a complicated obstetric history and a negative antibody screen. This initial visit at 29 weeks and 0 days' gestational age (GA) was unremarkable. A hydropic infant, born at 29 weeks and 5 days' GA, succumbed on the seventh day of life. Comprehensive laboratory testing was performed after birth. The hospital blood bank performed a maternal antibody identification. Direct antiglobulin test was performed on the cord blood. A reference laboratory confirmed an anti-Mia , performed paternal Mia phenotyping, and identified a hybrid glycophorin B-A-B GP*Mur allele. Discussion Maternal alloimmunization to low-frequency antigens remains a challenge. Southeast Asians make up a significant percentage in some US locations. Worldwide reports on the frequency of maternal alloimmunization of the MNS system can be used to guide the use of specific reagent RBCs for testing. Such strategies rely on the identification of blood donor units for reagent manufacture and use in perinatal antibody screens. Conclusion The incidence of Mia and related antibodies is significant among Southeast Asians. In North America, prenatal antibody screening cells are not routinely chosen to match this population. The clinical and societal implications are discussed.

Background Anti-D antibody is not the common cause of Rh-isoimmunization in Chinese neonatal jaundice. Recent change in national population policy has followed by an increase in Rh-isoimmunization related hemolytic disease of the newborn (HDN). Unfortunately, regional status of Rh-HDN is unavailable. We hypothesize that Rh-HDN in our region is most commonly due to anti-E antibody. Aim To investigate the prevalence of hemolytic disease of the newborn due to Rh-isoimmunization in Hefei City. Methods Retrospective review of data obtained from Children's Hospital of Anhui and Hefei Blood Center between January 2017 and June 2019. Status of minor blood group antibody was studied in the corresponding mothers. Results Totally 4138 newborns with HDN admitted during the study period and 116 (2.8%) received blood exchange transfusion (BET). Eighteen newborns (0.43%) with proven Rh-incompatible HDN were identified. All were not the first-born baby. Thirteen mothers were RhD (+) (72%) and five were RhD (-). The distribution of Rh-related antibodies in mothers was ten anti-E (55%), five anti-D (27%), and for one anti-C, anti-c, and anti-E/c (6%) each. Thirteen (72.2%) were qualified for BET, relative risk for BET was 28.9 as compared to other types of HDN, but only 10 received due to parenteral refusal. All (100%) RhD related HDN received BET which is not significantly different from RhE related HDN (81.8%). Conclusion As expected, all Rh-incompatible HDN newborns were not the first-born. Contrary to the Caucasian population, anti-D induced HDN is not the most common etiology. In our region, anti-E (11/18, 61%) is the most common cause of Rh-HDN.

We report on a term infant with clinically significant hemolysis and hyperbilirubinemia. Testing revealed ABO incompatibility between maternal type A and infant type AB. The maternal alloantibody screen was negative. The infant’s direct antiglobulin test was positive, and anti-B IgG was eluted off the infant’s red blood cells (RBCs). Testing of the mother’s plasma revealed a high anti-B titer. The infant was successfully treated with phototherapy and intravenous immunoglobulin. The bilirubin and hematocrit stabilized, and the infant was discharged home. This case was unusual because of its severity and unusual ABO constellation. Furthermore, this report is an exemplary educational case study on how effective collaboration between the clinical team and the blood bank laboratory is critical in reaching the correct diagnosis. In summary, the differential diagnosis of more unusual and atypical ABO-incompatible constellations must be considered when an infant presents with unexplained hemolysis.

Background and objective The exact burden of hemolytic disease of the newborn (HDN) attributed to neonatal unconjugated hyperbilirubinemia (NUH) in developing nations is still unclear. Still, anti-D is reported to be the most common cause of HDN in India. ABO incompatibility has emerged as a leading cause of exchange transfusion (ET) in many countries. But many centers in our country rely on direct antiglobulin test (DAT) as a screening tool to evaluate immunological causes, whereas advanced immunohematological workup like antibody screening, identification, and elution tests are also required. Early identification of implicated antibodies resulting in HDN can aid in the proper selection of blood units when ET is indicated, and hence also in managing the subsequent pregnancy. This study focused on determining the causes of neonatal hyperbilirubinemia (NH), especially with respect to immunohematological evaluation. This cross-sectional study was conducted on 240 neonates requiring neonatal intensive care unit (NICU) support for NUH at a tertiary care hospital. Materials and methods Demographic data, along with detailed history pertaining to the cause of hyperbilirubinemia, was collected. Clinical and laboratory evaluation and complete immunohematological work including DAT, heat elution, antibody screening, antibody identification, and Rh Kell phenotyping were performed from neonate blood samples. Data were analyzed using SPSS Statistics version 19 (IBM Corp., Armonk, NY). Results Pathological jaundice was more common (62.1%) than physiological jaundice (37.9%). The various pathological causes identified were HDN (42.6%), sepsis (12%), cephalohematoma (5.4%), and idiopathic (1.7%). Among HDN cases, ABO incompatibility (39.2%) was the most prevalent cause, followed by Rh HDN and G6PD deficiency (1.7% each). DAT was positive in only 14 cases out of 94 ABO-incompatible cases. Elution revealed antibodies in four DAT-negative neonates with ABO incompatibility and more specificity to the OA setting. DAT was positive with 100% sensitivity in Rh HDN cases (n=4). Elution demonstrated the presence of anti-D (n=2), anti-D + anti-C (n=1) and anti-E (n=1), confirming Rh HDN. DAT strength was found to be significantly associated with hemoglobin (Hb) level (p=0.048). The majority of cases were treated with phototherapy only (94.1%), and 10 cases received both ET and phototherapy. Four neonates' condition improved without any intervention. Conclusion This study highlighted the shift in the trend from Rh HDN to ABO incompatibility as the cause of hemolytic jaundice in NICU neonates. Elution tests can aid in the diagnosis of DAT-negative ABO-incompatible hemolytic anemia. Early diagnosis, along with timely intervention and appropriate measures, can prevent neonatal morbidity and mortality. Negative DAT does not rule out HDN. Sensitive techniques like elution must be used in the presence of clinical suspicion.

Background Transplacental or fetomaternal hemorrhage (FMH) may occur during pregnancy or at delivery and lead to immunization to the D antigen if the mother is Rh-negative and the baby is Rh-positive. This can result in hemolytic disease of the fetus and newborn (HDFN) in subsequent D-positive pregnancies. Therefore, the aim of this systematic review and meta-analysis was to estimate distribution of ABO and Rh (D) blood groups among pregnant women in Ethiopia. Method We searched PubMed, Google Scholar, EMBASE, Cochrane Library, HINARI, AFRO Library Databases, and African Online Journal databases for all available studies using the following keywords: “High rhesus (Rh(D)) negative frequency”, “ABO blood group distribution”, “haemolytic disease of the newborn (HDN)”, “rh isoimmunization”, “anti-RhD immunoglobulin”, “D-negative pregnancies”, “Frequency”, “ABO and Rh blood group distribution”, “feto-maternal hemorrhage”, “rhesus D negative pregnant mothers”, “kleihauer-betke test (KBT)”, “Neonatal Hyperbilirubinemia”, “non-sensitized RhD-negative pregnant women”, “antenatal anti-D immunoglobulin prophylaxis”, “Hemolytic disease of the newborn (alloimmunization), Ethiopia. The search string was developed using “AND” and “OR” Boolean operators. All published and unpublished observational studies reporting the distribution of ABO and Rh (D) blood groups among pregnant women in Ethiopia were included. The study participants were all pregnant women in Ethiopia, and the main outcome measure of this systematic review and meta-analysis was Rhesus D-negative blood type and ABO blood group distribution among pregnant women in Ethiopia. The data was extracted by the author (AAA) by using a standardized JBI data extraction format. Microsoft Excel (2016), and Stata version 11.0 (Stata Corporation, College Station, Texas, USA) software were used for data entry and analysis, respectively. The random effect model was used for estimating the pooled effects, and the publication bias was assessed by visual inspection of the funnel plots and objectively by using the Egger’s test (i.e. p Results One hundred thirty-two articles were identified through electronic database searching. Of which, 34 were excluded due to duplication, 65 through review of titles and abstracts, and 22 full-text articles were excluded for not reporting the outcome variable and other reasons. Finally, 7 were included to estimate the distribution of ABO and Rh (D) blood groups among pregnant women in Ethiopia. The pooled distribution of Rh-negative blood group among pregnant women in Ethiopia was 10.8% (95%CI: 7.53–14.07, I2 = 85%, p –42.38), followed by A (30.59% (26.00–35.18)), B (23.04% (20.03–26.05)), and AB the least (4.82%(3.17–6.47)), in the pattern O > A > B > AB. Conclusion The pooled distribution of Rh-negative blood group among pregnant women in Ethiopia was high. Rh alloimmunization remains a major factor responsible for perinatal morbidity in Ethiopia and may result in the compromise of the woman’s obstetric care due to the unaffordability of anti-D immunoglobulin. There is the urgent need for the implementation of universal access to anti-D immunoglobulin for the Rh-negative pregnant population in Ethiopia.

Anti-D is the most common cause of hemolytic disease of the newborn (HDN) in the developing countries even after the introduction of anti-D immunoprophylaxis. Still, ABO incompatibility and other alloantibodies against minor blood group antigens have emerged as significant causes of HDN. Moreover, ABO incompatibility acts as a protective barrier to the expression of Rh isoimmunization. Here we are presenting a case of HDN where both Rh and ABO incompatibility co-existed with their manifestations in a B positive neonate born to an O positive mother. Use of appropriate elution technique can aid in the diagnosis of such cases. Hence, antenatal screening of all mothers irrespective of their Rh D status can help in early diagnosis and proper management that can decrease the neonatal morbidity and mortality.

The Rh blood group system is a complex blood group which includes different antigen specificities such as c antigen. Anti-c antibody is associated with both acute and delayed hemolytic transfusion reactions as well as hemolytic disease of the newborn (HDN). Rh mediated hemolytic transfusion reactions (HTR) are mostly immunoglobulin G (IgG) mediated and results in extravascular hemolysis and delayed HTR (DHTR). However, we are presenting a case of acute intravascular hemolytic transfusion reaction due to anti-c in a patient with acute subdural hematoma. A 77-year-old woman was referred to our hospital with a loss of conscious and left-sided hemiparesis. After an emergency MRI, she was diagnosed with Acute Subdural hematoma, and an emergency craniotomy was performed. Since Acute Subdural hematoma is a neurosurgery emergency, laboratory technician performed an Immediate-spincrossmatchedd for blood bag to preserve time. During the transfusion of the first packed cell, the patient developed severe hypotension and tachycardia. Thus, the transfusion was stopped. Laboratory results raised the suspicion of an Acute Intravascular Hemolysis. Antibody identification revealed that the patient had an irregular blood phenotype (C2+/c-/E-/e3+/K-), and the presence of alloantigen-c Rh antibody confirmed the suspicion of HTR. In patients with multi transfusion history and pregnant women, pre-transfusion screening of irregular antibodies must be performed. The immediate spincrossmatchh must be prevented in patients with a history of multi transfusions, even in emergency situations.

Background RhD typing has remained of primary importance, as being the leading cause of hemolytic disease of the newborn. Among Rh system’s 55 blood group antigens, RhD is the most immunogenic. We aimed with this study to determine weak D/partial D variant frequency in blood donors who were admitted to our blood center and have serologically designated blood group weak D. Materials and methods We screened blood donors who admitted between 2011 and 2017 to our blood center. Sixty-seven serologically weak D phenotyped donors have participated in the study. These donors' samples were studied further by Polymerase Chain Reaction Sequence- Specific Primers (PCR-SSP) for determining D variants. Results Weak D phenotype was detected in 228(0.12 %) out of 177,554 donors. Sixty-seven of them agreed to take part in the study. The frequency of weak D and partial D was 68.7 % (n = 46), and 22.4 % (n = 15), in order. The most encountered weak D and partial D variant was type 15 and DFR type, respectively. Conclusions The prevalence of serologically weak D phenotypes varies by race and ethnicity. Turkey is a country covering a mixture of European and Asian DNA with different ethnic groups. Thus, our research as giving the overall distribution of RHD variants from the largest city of Turkey, which may reflect the general ethnic background of the country, would help to the establishment of a databank for blood banking. This paper is the first molecular study on RHD variants in Turkey. New molecular research would be more reliable and precise.

Background: Isoimmune hemolytic disease is a major cause of neonatal severe indirect hyperbilirubinemia that requires phototherapy or exchange transfusion which is an invasive procedure to avoid brain injury. Administration of intravenous immunoglobulin (IVIG) is used as an adjunct treatment to phototherapy in order to decrease the rate of exchange transfusion. Methods: This retrospective case-control study aimed to describe the safety and efficacy of IVIG therapy in newborns with isoimmune hemolytic disease and to compare their clinical outcomes to those of a control group who were treated only with phototherapy. Criteria for IVIG treatment were variable; when phototherapy threshold was reached or when exchange transfusion level was approached, using either indication is based on the attending discretion. Results: Ninety-four infants were included in the IVIG group, compared to 108 infants in the control group. Most of the included infants were term infants and most common cause was ABO incompatibility. There were no side effects documented in all the included infants. The IVIG group had more severe hemolysis with average highest bilirubin of 14.6 ± 3.7 mg/dL in the IVIG group versus 12.6 ± 3 in the control group (P = 0.0001). Complication of hemolysis was seen more in the IVIG group with higher rate of rebound hyperbilirubinemia, blood transfusion and exchange transfusion. Conclusions: IVIG use as an adjunct treatment to phototherapy in isoimmune hemolytic disease of the newborns is safe. The favorable results of the phototherapy only group were supportive of using selective criteria for administration of IVIG in neonates with isoimmune hemolytic disease. J Clin Med Res. 2019;11(11):760-763 doi: https://doi.org/10.14740/jocmr4003

Background: hemolytic disease of the newborn is an autoimmune haemolytic disease and caused by antibodies produced due to Rh and ABO incompatibilities. Neonatal jaundice is a common clinical problem encountered during the neonatal period. To avoid the associated neurological complications; exchange transfusion and phototherapy have been traditionally used. Aim of the work: was to assess the efficacy of intravenous immunoglobulins in neonates with Rh and/or ABO incompatibility in reducing the duration of phototherapy and the need for exchange transfusion and hospital stay. Subjects and Methods: in this clinical intervention study 40 patients diagnosed with hemolytic disease of newborn were grouped into group A and B. All neonates were treated with standard protocol for phototherapy and exchange transfusion. Group A patients received only phototherapy. Group B patients received intravenous immunoglobulins in a dose of 0.5 gm/kg of body weight single dose and phototherapy. Exchange transfusion was given to the patients of both groups if the bilirubin rose by 0.5 mg/dl per hour. Results: there was a significant decrease of bilirubin level in group B [that received phototherapy plus Intravenous Immunoglobulin (IVIG)] than group A [that received phototherapy only]. Hospital stay and duration of phototherapy decreased in group B than group A. Number of cases exchanged blood in group A was higher than cases of group B. Conclusion: addition of intravenous immunoglobulins for treatment of hemolytic disease of newborn significantly reduces bilirubin levels, duration of phototherapy, need for exchange transfusion and hospital stay.

Pemahaman penyakit hemolitik pada bayi baru lahir telah berubah selama beberapa dekade terakhir. Penyakit hemolitik akibat inkompatibilitas ABO dan aloantibodi lainnya kini muncul sebagai penyebab utama. Banyak negara telah mengidentifikasi aloantibodi selain anti D sebagai penyebab penyakit hemolitik dengan gejala klinis sedang sampai dengan berat. Prevalensi dan frekuensi populasi antibodi anti-A dan anti B dari golongan darah ABO berguna dalam memprediksi perkiraan anak yang lahir oleh wanita golongan darah O yang menikahi suami golongan darah bukan O yang berisiko menjadi ABO HDN. Kelainan ABO HDN disebabkan oleh antibodi IgG pada ibu disebabkan kemampuan IgG untuk melewati sawar darah plasenta. Eritrosit yang peka oleh antibodi dihancurkan oleh makrofag pada limpa janin dengan gejala klinis hiperbilirubinemia. Kelainan ABO HDN memberikan gambaran klinis yang lebih ringan pada populasi, dan ditandai dengan derajat hemolisis yang ringan. Diagnosis biasanya dilakukan dengan pemeriksaan bayi baru lahir yang telah mengalami ikterus pada hari pertama kehidupan. Keywords: Penyakit hemolitik bayi baru lahir, aloantibodi golongan darah, ikterus Abstract. The spectrum of hemolytic disease of the newborn has changed over the last decades. Hemolytic disease due to ABO incompatibility and other alloantibodies has now emerged as major causes. Many countries have identified alloantibodies other than anti D as a cause of moderate-severe hemolytic disease. The prevalence of immune anti A and anti B antibodies and the population and gene frequencies of the various ABO blood groups are useful in predicting an estimate of children born by blood group O women married to non-group O husband who are at risk of developing ABO HDN. ABO HDN is caused by IgG maternal antibodies which have the ability to cross the placental barrier. The red cells which are sensitized by the antibodies are destroyed by macrophages in fetal spleen with consequent hyperbilirubinemai. ABO HDN is described as a condition having a very low incidence in the population and characterized by a a mild degree of hemolysis. Diagnosis is usually made by investigation of a newborn baby who has developed jaundice during the first day of life. Keywords: Hemolytic disease of the newborn, blood groups alloantibodies, joundice

Hemolytic disease of newborn (HDN) is a condition that develops in a fetus, when the IgG molecules produced by the mother pass through the placenta and attack the fetal red blood cells. HDN can occur due to Rh and ABO incompatibilities between the mother and the fetus as well as due to other allo-immune antibodies belonging to Kell (K and k), Duffy (Fya), Kidd (Jka and Jkb), and MNS (M, N, S, and s) systems. Role of intravenous immunoglobulin in management of HDN is not clear.SARA red blood cell antigen, first discovered in 1990 is a low frequency antigen. We report, a multiparous female whose pregnancy was complicated by HDN due to anti-SARA antibodies requiring both exchange transfusion and intravenous immunoglobulin. The response was sustained after intravenous immunoglobulin (IVIG) rather than after exchange transfusion.

BACKGROUND In low-resource countries, screening for D antibodies to detect pregnancies at risk for hemolytic disease of the newborn is not routine practice. Retrospective data showed that 5.5% of Surinamese newborns of D-negative women had a positive direct antiglobulin test (DAT), indicating the presence of maternal antibodies against fetal antigens. Here, the frequency and clinical relevance of DAT positivity is evaluated. STUDY DESIGN AND METHODS Between April 2015 and June 2016, an observational, multicenter cohort study was undertaken among Surinamese newborns born to D-negative women. In newborns, the DAT was performed, and clinical outcomes between DAT-negative and DAT-positive newborns were compared. RESULTS Of the 232 evaluable newborns, 19 (8.2%) had a positive DAT, of which 11 of 15 antibody-tested newborns had D antibodies. DAT-positive newborns had lower hemoglobin levels (p = 0.02) and a trend toward higher bilirubin concentrations (p = 0.09) in the first days of life compared with DAT-negative newborns. DAT-positive newborns were admitted more frequently (p = 0.02), needed phototherapy treatment almost four times as often as DAT-negative newborns (26% vs. 7%; p = 0.008), and therapy took 2 days longer (p = 0.01). Exchange transfusions were performed in two newborns with D antibodies, both complicated with sepsis. The hospital stay was 2.5 days longer for DAT-positive newborns (p = 0.007). Overall, the prevalence of hemolytic disease of the newborn requiring treatment was 2.2% among the whole cohort of newborns. CONCLUSION We found a high prevalence of DAT positivity with substantial need for hyperbilirubinemia treatment in newborns in Suriname. These results stress the necessity for better management procedures in D-negative women.

Hemolytic disease of the newborn (HDN) occurs due to maternal IgG antibodies crossing the placenta, thereby producing hemolysis mainly due to Rh incompatibility and to a lesser extent by ABO and Kell groups. Clinical presentation of HDN depends upon the severity of red cell lysis. It may develop mild jaundice and anemia to hydrops fetalis. In the most severe cases of HDN, the fetus may die in utero or be born with severe anemia that requires replacement of red cells by exchange transfusion. In order to diagnose hemolytic disease of the newborn, it is necessary to determine ABO/Rh blood group and to perform direct and indirect antiglobulin test in newborns. HDN can be effectively prevented by administering Rho(D) immunoglobulin (human) for intramuscular injection. Rho(D) immunoglobulin should be given to the mother with Rh-positive baby postpartum to prevent subsequent sensitization.

Recommendations for the screening of hemolytic disease of the newborn (HDN) advise taking a selective approach in using the direct antiglobulin test (DAT) for mothers with blood group O or RhD-negative. This study assessed the relation of DAT results to maternal and neonatal blood groups and evaluated the risk of HDN. A retrospective analysis of all healthy newborns admitted during 2018 was performed. Of 1463 newborns, 4.4% had a positive DAT. There were 541 (37%) maternal–neonatal pairs with ABO incompatibility, most commonly born to mothers with blood group O. The cohort of neonates born to mothers with blood group O was divided into three groups: the O-A and O-B groups and the O-O group as a control. The DAT was positive in 59 (8.3%) neonates, most were in the O-B group (49.2%), whereas 13.6% were in the control group (p &lt, 0.01). While the neonates in the O-B group were more likely to require phototherapy (p = 0.03), this finding was not related to DAT results. We found that selective testing of mothers with blood group O, mothers with blood group O or RhD-negative, neonates with blood group B, and neonates with blood group B born to mothers with blood group O or RhD-negative was ineffective in detecting phototherapy requirements. Our results indicate no difference regarding the need for phototherapy in neonates born to mothers with different blood types regardless of the DAT results.

BACKGROUND Minor red blood cell antibodies are becoming a more common cause of hemolytic disease of the newborn. Anti-U are a rare alloantibody found almost exclusively in people of black descent. There is limited experience to guide the management of pregnancies complicated by anti-U. Furthermore, there is often no suitable cross-matched blood available for transfusion of a patient with anti-U. CASE REPORT A 21-year-old P0G1 presented at 25 weeks' gestation with D– disease in pregnancy. She had a significant indirect antiglobulin test titer of 512. Anti-U were identified and no suitable cross-matched blood was available. Maternal blood was prepared for autologous intrauterine fetal transfusion. Two such transfusions were performed. RESULTS A healthy fetus delivered at 32 weeks that did not require phototherapy or an exchange transfusion. CONCLUSION Autologous transfusion of prepared maternal blood provides a safe option for intrauterine fetal therapy in pregnancies complicated by rare alloantibodies.

The article presents the opportunity to identify the phenomenon of microchimerism in the genes of HLA loci A, B, C, DRB1, DQB1 by PCR-SSP. The sample group consists of the mothers and newborns with intrauterine growth retardation (IUGR) (20 pairs), hemolytic disease of the newborn (HDN) (21 pairs), after external rotation of the fetus (11 pairs), from women with malignancy (1 pair), autoimmune thrombocytopenia (1 pair), tuberous sclerosis (1 pair), bradyarrhythmias (1 pair). The control group consists of 13 pairs. Of the 138 studied blood samples microchimerism was detected in 33.9 % of patients and in 19.2 % of control group. Maternal microchimerism was found only in patients with perinatal pathology and was not met in the control group. Fetal microchimerism was distributed in all studied groups, but among patients with perinatal pathology, it was met three times more frequent than in the control group (23.9 % and 7.7 %, respectively). Significantly more frequent microchimerism was found in the group of patients with HDN than in the control (p = 0.04). In the other groups the occurrence of the chimeric gene from the control group was not statistically significant

BACKGROUND Intravenous immunoglobulin (IVIG) is used to treat a variety of diseases in the neonatal intensive care unit (NICU). Although audits have reported on the spectrum of IVIG use in adults, the indications and utilization in neonates has not been investigated. The objectives of this study were to describe the usage pattern of and indications for IVIG in a tertiary care NICU. STUDY DESIGN AND METHODS A retrospective chart review was performed of all neonates who received IVIG in the NICU from January 2003 to December 2013. Data collected included patient demographic features, antenatal maternal details, neonatal laboratory results, treatment details, adverse events, and patient outcome. RESULTS Thirty-seven neonates received IVIG over the 11-year period. Twenty-three (67%) were treated for hemolytic disease of the newborn (HDN); 13 treatments were ABO related, six were anti-D related, and four were for clinically significant antibodies. Fourteen (33%) were treated for non-HDN causes, including eight for septic neonates, two for neonates with necrotizing enterocolitis, two for neonates with a clinically significant antibody but without evidence of hemolysis, and two for neonates with glucose 6-phosphate dehydrogenase deficiency. A complete hemolytic workup was not performed consistently before the receipt of IVIG. CONCLUSIONS This novel assessment of IVIG use in the NICU revealed the spectrum of disease for which IVIG is ordered. This study also found that key diagnostic tests needed to confirm an immune etiology for idiopathic jaundice are not performed routinely before IVIG receipt. Neonatal transfusion-related databases are needed to carry out pragmatic clinical trials to establish better evidence-based guidelines for IVIG therapy in the NICU.

Background The distribution of the Mur blood group antigen is 5–7% in the south of China, and a much higher prevalence is observed in some areas of the region. Anti-Mur can cause hemolytic disease of the newborn and severe transfusion reactions. Objectives Genetic testing is more ideal than conventional serological tests because antibodies for detection are usually not available. Methods In this study, a novel loop-mediated isothermal amplification (LAMP) assay for the detection of Mur blood group antigen was established. Results Fifteen of 275 (5·5%) samples were confirmed by LAMP as Mur antigen positive. All the Mur antigen-positive samples were GP.Mur subtype which was confirmed with sequencing. Conclusion The LAMP method has identical results with conventional serology method but more suitable for large-scale screening.

Exchange transfusion (ET) is an established, efficacious, and reliable practice for severe neonatal hyperbilirubinemia, hemolytic disease of the newborn, and neonatal sepsis. This study assessed the indications and clinical outcomes of ET performed in a tertiary hospital in Korea.We studied 64 ET sessions performed on 23 neonates between March 1999 and March 2018. ET was performed based on estimated double volume exchange transfusion using fresh red blood cells and fresh frozen plasma. Patients' clinical information, including demographic data and ET indication, and laboratory data were collected pre- and post-ET.The most common ET indication was hyperbilirubinemia with hemolytic anemia due to non-ABO maternal blood group discrepancies. In three preterm babies, ETs were performed for severe anemia, leukocytosis, and hyperkalemia cases. Before ET, the patients showed slightly high WBC counts, low hemoglobin levels, and low platelet counts. After ET, blood examination revealed normal WBC counts, increased hemoglobin levels, and decreased platelet counts (all P0.001). Bilirubin levels decreased immediately after ET (P0.001). Electrolyte and C-reactive protein levels showed no significant changes after ETs. Adverse events occurred in 11 (47.8 %) patients; the most common were hypoxemia and hypotension. One infant experienced cardiorespiratory arrest due to hypercalcemia and was successfully resuscitated. No one died within 24 h of ET. However, five infants showed hyperbilirubinemia aggravation.ET is an effective treatment modality for leukocytosis and hyperbilirubinemia with low mortality but involves common adverse events post-ET. This report provides an overview of current ET practices in Korea.

Background: Exchange transfusion and phototherapy have traditionally been used to treat jaundice and avoid the associated neurological complications. Because of the risks and burdens of exchange transfusion, intravenous immunoglobulin (IVIg) has been suggested as an alternative therapy for alloimmune hemolytic disease of the newborn (HDN) to reduce the need for exchange transfusion. Objectives: To assess the effect and complications of IVIg in newborn infants with alloimmune HDN on the need for and number of exchange transfusions. Search methods: We performed electronic searches of CENTRAL, PubMed, Embase (Ovid), Web of Science, CINAHL (EBSCOhost), Academic Search Premier, and the trial registers ClinicalTrials.gov and controlled-trials.com in May 2017. We also searched reference lists of included and excluded trials and relevant reviews for further relevant studies. Selection criteria: We considered all randomized and quasi-randomized controlled trials of IVIg in the treatment of alloimmune HDN. Trials must have used predefined criteria for the use of IVIg and exchange transfusion therapy to be included. Data collection and analysis: We used the standard methods of Cochrane and its Neonatal Review Group. We assessed studies for inclusion and two review authors independently assessed quality and extracted data. We discussed any differences of opinion to reach consensus. We contacted investigators for additional or missing information. We calculated risk ratio (RR), risk difference (RD) and number needed to treat for an additional beneficial outcome (NNTB) for categorical outcomes. We calculated mean difference (MD) for continuous variables. We used GRADE criteria to assess the risk of bias for major outcomes and to summarize the level of evidence. Main results: Nine studies with 658 infants fulfilled the inclusion criteria. Term and preterm infants with Rh or ABO (or both) incompatibility were included. The use of exchange transfusion decreased significantly in the immunoglobulin treated group (typical RR 0.35, 95% CI 0.25 to 0.49; typical RD -0.22, 95% CI -0.27 to -0.16; NNTB 5). The mean number of exchange transfusions per infant was also significantly lower in the immunoglobulin treated group (MD -0.34, 95% CI -0.50 to -0.17). However, sensitivity analysis by risk of bias showed that in the only two studies in which the treatment was masked by use of a placebo and outcome assessment was blinded, the results differed; there was no difference in the need for exchange transfusions (RR 0.98, 95% CI 0.48 to 1.98) or number of exchange transfusions (MD -0.04, 95% CI -0.18 to 0.10). Two studies assessed long-term outcomes and found no cases of kernicterus, deafness or cerebral palsy. Authors' conclusions: Although overall results show a significant reduction in the need for exchange transfusion in infants treated with IVIg, the applicability of the results is limited because of low to very low quality of evidence. Furthermore, the two studies at lowest risk of bias show no benefit of IVIg in reducing the need for and number of exchange transfusions. Based on these results, we have insufficient confidence in the effect estimate for benefit of IVIg to make even a weak recommendation for the use of IVIg for the treatment of alloimmune HDN. Further studies are needed before the use of IVIg for the treatment of alloimmune HDN can be recommended, and should include blinding of the intervention by use of a placebo as well as sufficient sample size to assess the potential for serious adverse effects.

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.

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.

To determine the predictive ability of cord blood bilirubin (CBB) for hyperbilirubinemia in a population at risk for maternal-fetal blood group incompatibility and hemolytic disease of the newborn.This is a single center retrospective case-control study. Cases received phototherapy; controls did not. Cases were matched 1:3 to controls by gender and treating physician. Inclusion criteria included: ≥35 weeks gestation, CBB, and one or more total serum bilirubin (TSB) concentrations. The primary outcome was CBB. Secondary outcomes were a TSB75th percentile, length of stay, and neonatal intensive care unit admission. The prognostic ability of CBB for phototherapy and TSB75th percentile was assessed using area under the receiver operating characteristic (ROC) curve. Logistic regression analyses were performed to determine predictors for phototherapy and TSB75th percentile.When compared to controls (n = 142), cases (n = 54) were more likely to have a positive Coombs' test (82% vs. 41% , p 0.001) and TSB75th percentile (85% vs. 21% , p 0.001). When compared to controls, cases had a higher mean (±SD) CBB (2.5 ± 0.5 vs. 1.8 ± 0.4 mg/dL, p 0.001). The area under the ROC curve (±SEM) for CBB for phototherapy and TSB75th percentile was 0.87 ± 0.03 (p 0.001, 95% CI 0.82, 0.93) and 0.87 ± 0.03 (p 0.001, 95% CI 0.82, 0.92), respectively.In this study, the mean CBB concentration was higher in neonates who received phototherapy compared to those who did not. CBB concentrations may help predict severe hyperbilirubinemia and phototherapy in a population at risk for hemolytic disease of the newborn.

Background The direct antiglobulin test (DAT) is the cornerstone of the diagnosis of hemolytic disease of the newborn (HDN). The aim of this study was to review the incidence and causes of positive DAT in cord blood in relation to development of HDN. Methods We retrospectively reviewed all results of DAT, which is routinely performed in cord blood samples, along with the laboratory and infants' medical records. Results DAT was positive in 70/2695 (2.59%) cases. In 64/70 (91.43%) cases, DAT positivity was attributed to ABO incompatibility. There were 50/218 (22.93%) DAT (+) cases in the A/O group and 13/97 (13.40%) cases in the B/O group ( p = 0.0664). Two DAT (+) cases were attributed to maternal alloimmunization (anti-Fya and anti-JKb, respectively), and one to maternal IgG autoantibodies that developed after methyldopa treatment. Among the 70 DAT (+) cases, 30 (42.86%) cases required phototherapy with no difference between the A/O and B/O groups. The duration of phototherapy in the B/O group was significantly longer than in the A/O group ( p = 0.024). There was a trend of correlation of increasing strength of DAT positivity with phototherapy need. No false positive DAT case was detected. Conclusions Although ABO incompatibility remains the main reason of DAT (+), other causes (e.g., alloimmunization, drugs) should also be explored. The relevant impact of DAT (+) on HDN development should be considered.

ABO incompatibility of red blood cells leads to brisk complement-mediated lysis, particularly in the setting of red cell transfusion. The ABO blood group is the most clinically significant blood group because of preformed immunoglobulin M (IgM) and IgG antibodies to ABO blood group antigens (isohemagglutinins) in everyone except group AB individuals. In addition to transfusion, ABO incompatibility can cause hemolysis in hematopoietic and solid organ transplantation, hemolytic disease of the newborn, and intravenous immunoglobulin infusion. It is important to prevent ABO incompatibility when possible and to anticipate complications when ABO incompatibility is unavoidable.

Introduction: Since anti-D immunoprophylaxis given to D-negative pregnant women is a blood product, blood donations have an impact on the availability of prophylactic doses. The Pan American Health Organization reported, in June 2017, that less than half of blood donors are volunteers in Latin America and the Caribbean. In these countries, guidelines for use of anti-D prophylaxis are still controversial. The aim of this study was to demonstrate the convenience of a simple and cost-effectivene non-invasive prenatal diagnostic assay for anti-D prophylaxis optimization in multiethnic populations. Methods: Cell-free fetal DNA from plasma samples of D-negative pregnant women were analyzed by real-time PCR for simultaneous amplification of sequences of exons 5 and 10 of the RHD gene. Fetal RHD genotype was determined in 111 pregnant women. Neonates' phenotype was determined 72 h after birth. Results: Genotyping predicted fetal phenotype with 100% accuracy. Prenatal diagnosis showed 78% RHD-positive and 22% RHD-negative neonates. Conclusion: We demonstrated that, beyond the large genetic variation of the Rh system and the numerous D variants present in multiethnic groups, non-invasive fetal RHD genotyping using two sequences of the gene can be enough for clinical application in an admixed population. This robust technique of simple implementation allows to determine fetal RHD in maternal blood with high sensitivity, specificity, and accuracy. The introduction of fetal RhD genotyping as part of an antenatal screening program constitutes a reliable manner to optimize anti-D prophylaxis; however, it has not been implemented so far in most American countries.

In Palestine, antibody screening is done antenatally only for pregnant women who are Rh-D negative. However, we report the first hemolytic disease of the newborn (HDN) due to anti-e in Palestine, illustrating the importance of alloantibodies other than anti-D as a cause of HDN. A pregnant woman had e-antigen negative and her blood group was B positive developed alloantibody against her infant erythrocyte e-antigen that lead to severe jaundice due to fetal erythrocyte destruction by this maternal alloantibody. Postnatal workup for the severe hyperbilirubinemia indicated that the newborn' erythrocytes were sensitized by the maternal anti-e alloantibody. Furthermore, the positive direct Coombs test was reported. This case highlights the importance of antibody screening for all pregnant women irrespective of the D antigen status to detect and manage erythrocyte alloimmunization to any other clinically significant blood group antigens.

Background and objectives To determine the effects of intravenous immunoglobulin (IVIg) on the course of late hyporegenerative anemia and the requirement for exchange transfusions, phototherapy and top-up red blood cell transfusions due to rhesus hemolytic disease of the newborn (Rh-HDN). Patients and methods This is retrospective cohort study of newborns with Rh-HDN who were treated with or without IVIg. Relevant maternal and neonatal data were obtained and analyzed. All infants were followed up as outpatients for a period of 2–3 months, and during the follow ups, complete blood counts (RBCs) were performed every two weeks to diagnose late hyporegenerative anemia. Results Sixty-six infants with Rh-HDN were enrolled in this study (42 in the IVIg group and 24 in the no-IVIg group). We observed no significant differences between the two groups in terms of maternal age, number of previous children affected with Rh-HDN, intrauterine transfusions, gestational age (GA), birth weight (BW), Apgar scores at the 1st or 5th minutes, exchange transfusions, or days on phototherapy. The serum bilirubin immediately after birth and the maximum serum bilirubin during the hospital course were significantly higher in the IVIG group (P = 0.0035 and P = 0.0225, respectively). Although there were no statistically significant differences, there was a trend toward the late anemia in the IVIg group being diagnosed and resolved earlier than in the no-IVIg group. Additionally, a greater proportion of the IVIg group required three or more top-up transfusions compared to the no-IVIg group, but this difference was not statistically significant. Conclusion IVIg might have had an effect on the early development of late anemia and might have shortened the duration of late anemia relative to the infants who did not receive IVIg. The exchange transfusions and the days on phototherapy were not affected by IVIg.

BACKGROUND: RhIG is used worldwide to reduce the incidence of alloimmunization to D during pregnancy. We report a case of clinically significant neonatal hemolysis mediated by maternally administered RhIG. CASE REPORT: A 25-year-old, O‐, primigravid mother with a negative antenatal antibody screen delivered a 6-lb 4-oz, blood group A, D+ baby girl at 36.5 weeks’ gestation. Prenatal care included a dose of intramuscular RhIG at 28 weeks’ gestation. At delivery, the newborn was markedly jaundiced with a total bilirubin of 6.3 mg/dL, which reached more than 20 mg/dL after 6 days. The newborn’s lactate dehydrogenase (LDH) was 485 U/L (normal

Background The RhD antigen is very immunogenic and is a significant cause of hemolytic disease of the newborn (HDN). The RHD-CE(8-9)-D hybrid allele is commonly associated with a D– phenotype. Here, we report a case of high-titer maternal anti-D and late onset of HDN in a newborn carrying a RHD-CE(9)-D variant supposedly encoding the same partial D antigen as the RHD-CE(8-9)-D allele, but with significant expression of D antigen. Study Design and Methods To elucidate the blood group antigen background of the case, we carried out serologic, flow cytometric, and genetics studies of the newborn and his father. Conclusion Individuals carrying the RHD-CE(9)-D allele do express D antigen, but do so at significantly lower levels than those carrying the more common D+ phenotypes (e.g., DCe/dce). It may mitigate and delay otherwise severe HDN in pregnancies complicated by high-titer anti-D.

Hemolytic disease of the newborn (HDN) arising from MNSs incompatibility is rare, with few reports of prolonged anemia and reticulocytopenia following HDN. We report the younger of 2 male siblings, both of whom had anti-M-induced HDN and anemia persisting for over a month. Peripheral reticulocytes remained inappropriately low for the degree of anemia, and they needed multiple red cell transfusions. Viral infections were ruled out. Corticosteroids were given for suspected pure red cell aplasia. Anemia and reticulocytopenia subsequently improved. Colony-forming unit erythroid assay revealed erythropoietic suppression of M antigen-positive erythroid precursor cells cultured with maternal or infant sera containing anti-M. In conclusion, maternal anti-M caused HDN and prolonged anemia by erythropoietic suppression in 2 siblings.

OBJECTIVE: To investigate the effects of blood transfusion and number of pregnancies on ABO antibody titers and irregular antibodies in pregnant women with type O blood. MATERIALS AND METHODS: The study included 4,200 pregnant women with type O blood (their husbands were with non-O type blood) that were divided into transfusion group and non-transfusion group, according to whether they had a history of blood transfusion. The both groups were respectively divided into three subgroups (the number of pregnancies was one, two, and > or = three). The ABO antibody titers and irregular antibodies were detected at the same time. The effects ofABO antibody titers and irregular antibodies on hemolytic disease of the newborn (HDN) were discussed. RESULTS: There was no consistency of ABO antibody titers and existence of irregular antibody. The positive rates of irregular antibody of transfusion group and of the subgroup (number of pregnancies > or = three) were far higher than that of non-transfusion group and of the subgroups (number of pregnancies or = three or with history of blood transfusion, the prenatal joint detection of ABO antibody titers and irregular antibodies is helpful for accurately reflecting the in vivo antibody type and level.

Background Quantitation of fetomaternal hemorrhage (FMH) is performed to determine the dose of prophylactic anti-D (RhIG) required to prevent D immunization of D– women. Flow cytometry (FC) is the most accurate method. However, maternal white blood cells (WBCs) can give high background by binding anti-D nonspecifically, compromising accuracy. Study Design and Methods Maternal blood samples (69) were sent for FC quantitation of FMH after positive Kleihauer-Betke test (KBT) analysis and RhIG administration. Reagents used were BRAD-3–fluorescein isothiocyanate (FITC; anti-D), AEVZ5.3-FITC (anti–varicella zoster [anti-VZ], negative control), anti-fetal hemoglobin (HbF)-FITC, blended two-color reagents, BRAD-3-FITC/anti-CD45-phycoerythrin (PE; anti-D/L), and BRAD-3-FITC/anti-CD66b-PE (anti-D/G). PE-positive WBCs were eliminated from analysis by gating. Full blood counts were performed on maternal samples and female donors. Results Elevated numbers of neutrophils were present in 80% of patients. Red blood cell (RBC) indices varied widely in maternal blood. D+ FMH values obtained with anti-D/L, anti-D/G, and anti-HbF-FITC were very similar (r = 0.99, p

Introduction. In order to diagnose hemolytic disease of the newborn it is necessary to determine ABO/Rh blood group, direct antiglobulin test and indirect antiglobulin test in newborns as well as ABO/Rh and indirect antiglobulin test in their mothers due to a possible incompatibility between the blood types of the mother and her baby. The study was aimed at reviewing and analyzing the results of screening of the newborns and pregnant women on the territory of South Backa District during 2011, as well as at estimating the necessity to give blood transfusion to the newborns in the same period. Material and Methods. Data obtained from the information system and protocol of the Institute for Blood Transfusion of Vojvodina were used in a retrospective analysis of screening of newborns and pregnant women. Results. Blood samples taken from 3313 newborns were tested and the following distribution of the ABO blood types was recorded: O in 45.6%, A in 35%, B in 15.9%, in 3.5%; 78.9%, newborns were found to be D-positive, 21.1% were D-negative. The direct antiglobulin test was positive in 165 (4.9%) cases, it was weakly positive +/- in 85 (51.5%) , positive 1+ in 45 (27.3%), positive 2+ in 17 (10.3%), positive 3+ in 12 (7.3%), positive 4+ in 6 (3.6%). In all cases, the monospecific direct antiglobulin test was positive with IgG antibodies. Of four newborns with positive direct antiglobulin test who required exchange blood transfusion, two had RhD incompatibility and two had ABO incompatibility. Blood samples of 3429 (100%) women were tested and 36 (1.05%) were actively immunized: 23 (0.67%) to RhD antigen, 8 (0.23%) to blood group antigens other than ABH and Rh, specificity could not be determined in 5 (0.15%). Anti-D antibodies were found in 19 (0.55%) pregnant women, in two (0.06%) cases newborns required exchange blood transfusion. Conclusion. Testing neonates and pregnant women contributes to the detection of blood type incompatibility between the mother and her child; it provides an opportunity for clinicians to implement the adequate prevention of RhD alloimmunization as well as to make timely diagnosis and to introduce treatment of hemolytic disease in newborns.

Aim: This study was aimed to review and establish the practice of exchange transfusion (ET) with whole blood reconstituted (WBR) in hemolytic disease of newborn (HDN). Objectives: To observe fall in indirect serum bilirubin, correction of anemia and comparison with related studies. Background: Hemolytic disease of the Newborn is characterized by presence of IgG antibodies in maternal circulation, which causes hemolysis in the fetus by crossing the placenta and sensitizing red cells for destruction by macrophages in the fetal spleen with consequent hyperbilirubinemia. Exchange transfusion with or without phototherapy is the method of choice for treating the newborn with on going hemolysis Methods/Materials: Sample size consisted of 110 neonates in whom 119 exchange transfusions were carried out with WBR. WBR was prepared by suspending O Rhesus-D (RhD) positive/negative cells (compatible with neonate’s/ mother’s serum) in AB plasma. Double volume exchange transfusion(s) were carried out through umbilical vein by push-pull technique. Results: Out of 110 cases, 61 (55.5%) were of RhD HDN whereas ABO and other group HDN cases were 30 (27.3%) and 19 (17.3%) respectively. An average post-ET fall in indirect serum bilirubin by 54.6% and correction of anemia by3.7 gm/dl were reported in the study. Conclusion: An average post-ET fall in indirect serum bilirubin and correction of anemia was found to be more significant when compared to other studies. Hence we recommend exchange transfusion in HDN with WBR to obtain reasonable fall in indirect serum bilirubin and high average rate of correction of anemia.

Hemolytic disease of the newborn (HDN), an alloimmune disorder due to maternal and fetal blood type incompatibility, is associated with fetal and neonatal complications related to red blood cell (RBC) hemolysis. After delivery, without placental clearance, neonatal hyperbilirubinemia may develop from ongoing maternal antibody-mediated RBC hemolysis. In cases refractory to intensive phototherapy treatment, exchange transfusions (ET) may be performed to prevent central nervous system damage by reducing circulating bilirubin levels and to replace antibody-coated red blood cells with antigen-negative RBCs. The risks and costs of treating HDN are significant, but appear to be decreased by delayed umbilical cord clamping at birth, a strategy that promotes placental transfusion to the newborn. Compared to immediate cord clamping (ICC), safe and beneficial short-term outcomes have been demonstrated in preterm and term neonates receiving delayed cord clamping (DCC), a practice that may potentially be effective in cases RBC alloimmunization.

The prevention of Rhesus D alloimmunization through Rh immune globulin (RhIg) administration is the major indication for the accurate detection and quantification of fetomaternal hemorrhage (FMH). In the setting of D incompatibility, D-positive fetal cells can sensitize the D-negative mother, resulting in maternal anti-D alloantibody production. These anti-D alloantibodies may lead to undesirable sequelae such as hemolytic disease of the newborn (HDN). Since the widespread adoption of FMH screening and RhIg immunoprophylaxis, the overall risk of Rh alloimmunization and infant mortality from HDN has substantially decreased. The rosette screen, the initial test of choice, is highly sensitive in qualitatively detecting 10 mL of fetal whole blood in the maternal circulation. As the screen is reliant on the presence of the D antigen to distinguish fetal from maternal cells, it cannot be used to detect FMH in D-positive mothers or in D-negative mothers carrying a D-negative fetus. The Kleihauer-Betke acid-elution test, the most widely used confirmatory test for quantifying FMH, relies on the principle that fetal RBCs contain mostly fetal hemoglobin (HbF), which is resistant to acid-elution whereas adult hemoglobin is acid-sensitive. Although the Kleihauer-Betke test is inexpensive and requires no special equipment, it lacks standardization and precision, and may not be accurate in conditions with elevated F-cells. Anti-HbF flow cytometry is a promising alternative, although its use is limited by equipment and staffing costs. Hematology analyzers with flow cytometry capabilities may be adapted for fetal cell detection, thus giving clinical laboratories a potentially attractive automated alternative for quantifying FMH.

Hemolytic disease of the newborn is a clinical condition in which maternal and paternal Rh blood group antigens are incompatible and the mother is negative for the antigen whereas the father is positive. Analysis of fetal cells recovered from maternal plasma can provide a highly sensitive prenatal diagnosis. The fetal RHD gene in plasma DNA is detected by real-time PCR amplification of two different segments of the RHD gene (exons 7 and 10). Each amplicon is revealed with specific probes. We examined 40 female blood samples to verify the specificity of RHD exons (7 and 10) amplified by real-time PCR. Thirty fetuses were predicted to be RHD-positive based on analysis of plasma DNA. Seven fetuses were predicted to be RHD-negative. One fetus was negative for RHD on exon 10, and positive for RHD on exon 7 (early gestation age); two fetuses were RHD-negative on exon 7, and RHD-positive on exon 10 (RHD-CE-D(s) or RHDΨ), indicative of a maternal RHD allele. We conclude that it is necessary to analyze at least two exon regions in the RHD gene.

The prevalence of D alloimmunization occurs between 0.15% and 0.4%. The anti-D can cross the placenta and cause hemolysis and fetal anemia. At present, a Doppler study of the middle cerebral artery allows the monitoring of the degree of fetal anemia. The treatment in cases of moderate to severe anemia in fetuses of less than 34–35 weeks of gestation is intrauterine transfusion via cordocentesis. However, with high titers of anti-D, in the absence of fetal anemia it is possible to modulate the maternal immune response by plasmapheresis and intravenous immunoglobulin administration. We present a case report of an Rh(D) alloimmunized pregnancy treated with plasmapheresis followed by intravenous immunoglobulin administration. We performed a caesarean section at 31 weeks, 5 days of gestation. The hemoglobin at birth was 13.8 g/dl and hematocrit 40.8%. Intrauterine transfusion was not necessary.

Hemolytic disease of the newborn (HDN) is a clinic phenomenon which occurs during pregnancy due to the Rhesus (Rh) D alloimmunization between a Rh (-) pregnant woman, who has become sensitive to RhD antigens, and her Rh (+) fetus. As a result of the attack of maternal RhD antibodies on fetal RhD antigens, fetal anemia, HDN and fetal death may occur. % 40 of Rh (-) pregnant women carry Rh (-) fetus. However, all Rh (-) pregnant women are offered anti-D Immunoglobulin (Anti-D Ig) at 28 weeks' gestation in case of fetomaternal haemorrhage, so the pregnant women carrying Rh (-) fetus are exposed to blood products unnecessarily. Although the RhD of fetus can be detected, methods used for prenatal diagnosis recently are invasive tests and they can result in abortion in a certain percentage. The discovery of circulating cell-free fetal nucleic acids in maternal plasma has opened up new possibilities for non invasive prenatal diagnosis. The aim of this study was to detect prenatal RhD by analysing the presence of the RhD gene of fetal DNA in maternal blood.Total free DNA was isolated from the blood of 19 Rh (-) pregnant women, who had RhD alloimmunization with their husbands, in the 11-14 th week of their pregnancy. The existence of a gene in isolated DNA was investigated with TaqMan prob and "Real-time PCR" method by using primers belonging to exon 7 of RhD gene.Using a quantitative real-time PCR assay, the presence of RhD gene sequences was evaluated in the serum of patients at the onset of pregnancy. We have analyzed 19 Rh (-) pregnant women. Twelve of them were Rh (-) and the rest of them were 7 Rh (+). After birth the baby's blood groups were concordant with our results.The results obtained by RhD primer were analysed. The possibility of detection of fetal RhD gene in maternal blood contributed to noninvasive prenatal diagnosis.Yeni doğanın hemolitik hastalığı, daha önce “Rhesus” (Rh) D antijenleri ile duyarlı hale gelmiş Rh (−) anne ile Rh (+) çocuğu arasındaki RhD uyumsuzluğuna bağlı olarak hamilelik sürecinde ortaya çıkan klinik bir tablodur. Maternal RhD antikorlarının fetal RhD antijenlerini yok etmesiyle, fetusta kansızlık, yenidoğanda sarılık veya fetal ölüm gerçekleşebilir. Rh (−) gebelerin yaklaşık % 40′ı Rh (−) fetus taşımaktadır. Buna rağmen tüm gebelere olası bir fetal kanama riskine karşı hamileliklerinin 28. haftasında anti D immünglobulin (Anti-D Ig) uygulanmakta ve Rh (−) fetus taşıyan gebeler gereksiz aşı ürününe maruz kalmaktadır. Doğum öncesi tanı ile fetusun RhD tayini yapılabilse de, günümüzde kullanılan doğum öncesi tanı metodları girişimsel tetkikler olup belli oranlarda gebelik kayıplarına neden olabilmektedir. Anne kanında fetusa ait nükleik asitlerin hücre dışında serbest dolaşabileceklerinin keşfi noninvazif prenatal tanı için yeni olanaklar açmıştır. Bu çalışmada da maternal kandan fetal DNA’da RhD geninin varlığına bakılarak doğum öncesi RhD tayini yapılabilmesi amaçlanmıştır.11–14. gebelik haftalarında bulunan ve eşleriyle aralarında RhD uyumsuzluğu olan 19 Rh (−) gebeden kan alınarak total serbest DNA izolasyonu yapılmıştır. İzole edilen DNA’larda RhD geninin ekson 7 bölgesine ait primerler kullanılarak, TaqMan prob yöntemi ile ve “Real-time PCR” aracılığıyla genin varlığı araştırılmıştır.“Real-time PCR” kullanılarak gebeliklerinin başında olan hastaların serumlarında RhD gen dizilerinin varlığı değerlendirildi. Analiz edilen 19 Rh (−) gebenin 12′sinin (Rh−), 7′sinin Rh (+) olduğu belirlendi. Doğum sonrasında bebeklerin kan grupları ile bizim sonuçlarımız birebir uyumlu çıkmıştır.RhD primeri ile alınan sonuçlar analiz edilmiştir. Fetüse ait RhD geninin maternal kanda belirlenebilmesi girişimsel olmayan doğum öncesi tanı için önemli bir katkı sağlamıştır.

Background Hemolytic disease of the newborn (HDN) due to ABO blood type incompatibility is one of the most common cause of neonatal hyperbilirubunemia that potentially leads to bilirubin encephalopathy. Data on ABO-hemolytic disease of the newborn (ABO-HDN), especially regarding umbilical cord blood serological profile, are limited. Objective To identify the serological profile and hemolytic disease in term neonates with ABO incompatibility. Methods This was a cross-sectional descriptive study, conducted at RSIA Budi Kemuliaan Jakarta. Results We found 68 healthy term neonates with ABO incompatibility, nine of them had positive direct antiglobulin test (OAT) result, and 38 subjects had a positive result on OAT with elution method. The highest titer of IgG was 1:8. Hyperbilirubinemia was found in 30 ( 44%) subjects, and ABO-HDN was diagnosed in 28 (41 %) subjects. Within the positive OAT group, eight out of nine subjects had suffered from hyperbilirubinemia and ABO-HDN. Meanwhile, within the positive OAT with elution method group; 24 subjects had suffered from hyperbilirubinemia with 23 of them having ABOHDN. Based on the chi-square analysis; those with positive OAT with elution method had 3.2 times higher risk of suffering from ABO-HDN. Furthermore, there was a 3.6 times higher risk of sufferring from hyperbilirubinemia. Conclusion In healthy term neonates with ABO incompatibility, the incidence of ABO-HDN is 41%. OAT serological examination with elution method is better than OAT in assessing risk for hyperbilirubinemia and ABO-HDN.