Erythroblastosis Research Articles

A Description of IVIG Use in Term Neonates with ABO Incompatibility.

This study aimed to determine if treatment with IVIG of neonates with ABO incompatibility (without Rh incompatibility) results in decreased number of packed red blood cell (pRBC) transfusions and phototherapy use. An Institutional Review Board (IRB)-approved, single-institution retrospective study was conducted. Neonates ≥38 weeks' gestational age born between January 1, 2007, and December 31, 2016, with ABO incompatibility were included. The comparison among groups was performed using chi-square and Fisher's exact tests for categorical variables; continuous variables were assessed by Kruskal-Wallis test. Six hundred and sixty-eight neonates with ABO incompatibility met inclusion criteria, 579 were included in the analyses. From these, 431 (74%) neonates had positive Direct Antiglobulin Test (DAT); 98 (17%) received IVIG and 352 (61%) received phototherapy. Thirty-six (6%) neonates received pRBC and 6 (1%) required exchange transfusions. Only 3 (0.5%) infants received pRBC transfusions postdischarge, by 3 months of age. Neonates requiring IVIG had lower initial hemoglobin (13.6 vs. 16.0 g/dL, p ≤ 0.0001) and higher bilirubin at start of phototherapy (9.1 vs. 8.1 mg/dL, p = 0.0064). From the 42 (7%) neonates who received simple and exchange transfusions, IVIG use was not associated with decreased use or number of transfusions (p = 0.5148 and 0.3333, respectively). Newborns with A+ and B+ blood types had comparable initial hemoglobin, DAT positivity, APGAR, and bilirubin. However, infants with B+ blood group were more likely (than A + ) to require phototherapy (p < 0.001), receive IVIG (p = 0.003), and need phototherapy for a longer duration (p = 0.001). The results of this large retrospective study reveal that giving IVIG to neonates with ABO incompatibility was associated with increased simple or exchange transfusions. Newborns with B+ blood type required more phototherapy and IVIG. Further studies are needed to better stratify neonates who would benefit from IVIG use in order to optimize treatment strategies and avoid unnecessary risks and adverse events. · IVIG use not associated with decreased use of pRBC or exchanges.. · Phototherapy duration associated with increased IVIG and pRBC use.. · Newborns with B+ blood type had worse hemolytic anemia..

Maternal and child life years gained by transfusing low titer group O whole blood in trauma: A computer simulation.

Using low titer group O whole blood (LTOWB) is increasingly popular for resuscitating trauma patients. LTOWB is often RhD-positive, which might cause D-alloimmunization and hemolytic disease of the fetus and newborn (HDFN) if transfused to RhD-negative females of childbearing potential (FCP). This simulation determined the number of life years gained by the FCP and her future children if she was resuscitated with LTOWB compared with conventional component therapy (CCT). The model simulated 500,000 injured FCPs of each age between 0 and 49 years with LTOWB mortality relative reductions (MRRs) compared with components between 0.1% and 25%. For each surviving FCP, number of life years gained was calculated using her age at injury and average life expectancy for American women. The number of expected future pregnancies for FCPs that did not survive was also based on her age at injury; each future child was assigned the maximum lifespan unless they suffered perinatal mortality or serious neurological events from HDFN. The LTOWB group with an MRR 25% compared with CCT had the largest total life years gained. The point of equivalence for RhD-positive LTOWB compared to CCT, where life years lost due to severe HDFN was equivalent to life years gained due to FCP survival/future childbearing, occurred at an MRR of approximately 0.1%. In this model, RhD-positive LTOWB resulted in substantial gains in maternal and child life years compared with CCT. A >0.1% relative mortality reduction from LTOWB offset the life years lost to HDFN mortality and severe neurological events.

A rare presentation of severe alloimmune hemolytic disease of newborn pertaining to minor blood group ‘c’ incompatibility: a case report and review of literature

Hyperbilirubinemia is one of the most widely seen causes of neonatal morbidity. Haemolytic disease of fetus and newborn is caused by maternal alloantibodies to the fetal RBCs. It is responsible for incompatibility between maternal and fetal blood groups, which results in destruction of fetal red blood cells causing hyperbilirubinemia. ABO and Rh incompatibility are the most common causes of severe indirect hyperbilirubinemia. Besides ABO and Rh isoimmunization, minor blood group incompatibilities such as anti-Kell, anti-C, anti-c, anti-E, anti MNS, Duffy, KIDD, P, Lutheran and Lewis have also been identified as causes of severe neonatal jaundice with an incidence of 385/1,00,000 live births in South-East Asia. We, hereby report a rare case of a full term 2.2 kg newborn presented with severe anemia with reticulocytosis and neonatal hyperbilirubinemia at second hour of life. In view of strongly positive DCT and no Rh negative or ABO setting, minor blood group incompatibility screening test was performed in the mother which revealed presence of multiple alloantibodies; however, the red cell phenotyping confirmed the presence of anti-c antibodies in maternal sera responsible for neonatal alloimmune haemolytic anemia. The baby was offered intensive phototherapy with intravenous immunoglobulin.

Characterization of Novel RHD Allele Variants and Their Implications for Routine Blood Group Diagnostics.

The Rh system, including the highly immunogenic D antigen, is one of the clinically most important blood group systems in transfusion medicine. Numerous alleles of the RHD gene are associated with variant RhD phenotypes. In case of Rh incompatibility, some of them can induce hemolytic transfusion reactions and hemolytic disease of the fetus and newborn. Thus, accurate blood group diagnostics are critical for safe transfusion therapy. We characterized phenotypes of four individuals revealing weakened D expression during routine pre-transfusion testing. Standard gel card matrix techniques with monoclonal and polyclonal anti-D antibodies were used for serological typing, complemented using D epitope and antigen density analysis. Genotyping employing PCR with sequence-specific primers, genomic and allele-specific Sanger sequencing and in silico protein analysis were performed. Four novel RHD alleles associated with weak D or partial D phenotypes were identified. One of the mutations is predicted to disrupt the terminal stop codon and result in an elongated translation of the mutant D protein that phenotypically exhibits a loss of D epitopes. Furthermore, a hybrid gene formed with the homologue RHCE gene is described. The presented data enhances the understanding of the Rh system and may contribute to continued advances in blood group diagnostics.

Phenotyping of Rh and Kell blood group antigen in thalassemia and its impact on alloimmunization in a tertiary care hospital

Objectives: Alloimmunization to red cell antigens is a dreaded complication in multitransfused patients, leading to difficulty in obtaining compatible red blood cell units and development of delayed hemolytic transfusion reactions. The objective of this study was to assess the impact of partial matched phenotype blood (for RhD, C, c, E, e, and Kell antigens) on alloimmunization in thalassemics versus non-phenotype matched blood (ABO &amp; RhD). Materials and Methods: This cross-sectional study was conducted over a period of two years where 250 patients with thalassemias were enrolled. They were divided into two groups, patients in Group I (n = 180) who received partial matched phenotype blood since initiation of transfusion therapy and those in Group II (n = 70) subjects who received usual matched blood. Statistical analysis: All statistical calculations were done using statistical package for the social sciences (SPSS) 21 version. Data were described in terms of range, median (interquartile range [IQR]), frequencies, etc. Results: The median (IQR) age of the study population was 12 (7–18) years (range 6 months–36 years). The most common Rh antibodies were anti-D (2.85%), anti-E (2.85%), anti-C (1.42%), and anti-c (1.42%), and Kell antibodies were (7.1%). It was seen that chances of developing autoantibodies (37% vs. 5%), alloantibodies 11 (15.7% vs. 0%), and transfusion reactions 25 (35.7% vs. 3.3%) were more in Group II subjects as compared to Group I. A significant difference was seen with febrile non-hemolytic transfusion reactions in between two groups 0.001 (95% confidence interval 2.98–65.73). Conclusions: Patients with thalassemia should be typed for RhD (C, c, E, and e) and Kell antigen before initiation of transfusion, which will help in reducing the rate of alloimmunization, autoimmunization, and frequency of transfusion and will improve the overall survival rate in thalassemia.

Hemolytic Disease in Newborn Due to Jka Antibody: A Unique Clinical Presentation

Hemolytic disease in newborn results from alloimmune-mediated destruction of fetal or neonatal red blood cells caused by maternal alloantibodies. While ABO and Rh (D) incompatibilities are common causes, other minor antigenic mismatches such as Kidd are relatively infrequent. Here, we report a case of a female infant displaying conjugated hyperbilirubinemia and hepato-splenomegaly. Lab tests revealed both mother’s and baby’s blood groups as A positive, along with elevated reticulocyte count and a positive direct antiglobulin test. An abdominal ultrasound unveiled inspissated bile syndrome, likely due to calcium bilirubin sludge, leading to the conjugated hyperbilirubinemia. Further assessment revealed the infant and the father had a JKa-positive RBC phenotype, while the mother had a JKa-negative phenotype. This case highlights the significance of blood group antigen beyond the Rh system as a potential cause of hemolytic disease in newborn.

Rare combination of alloantibodies causing hemolytic disease of the newborn – Challenge for identification

Abstract Hemolytic disease of the newborn (HDN) refers to the destruction of the fetal and newborn red cells by maternal red cell antibodies specific for paternally inherited antigens on fetal red cells or erythroid precursors.[1] ABO-incompatibility is the most common cause of HDN. Rh-negative mothers can be alloimmunized with Rh-positive fetus. Prophylactic Rh immunoglobulin use has greatly reduced the HDN due to Rh incompatibility. Alloimmunization can also occur due to other clinically significant minor blood group antigens such as E, c, C, k, KP(a), Js(a), Js(b), Jk(a), Jk(b), Fy(a), Fy(b), S, s, and U. Multiple alloantibodies in mothers’ blood can pose a difficult challenge for identification and finding compatible blood for exchange transfusion. We report a case of HDN due to multiple antibodies and a rare combination of anti-c and anti-Jkb, challenges associated with the identification, confirmation, and finding of compatible blood units.

Magnitude and its associated factors of neonatal jaundice among neonates admitted to the neonatal intensive care unit of Dessie Town public hospitals, Amhara region, Ethiopia, 2020: a multicenter cross-sectional study.

Neonatal jaundice is a prevalent illness affecting approximately 60%-80% of newborns. In severe cases, it can result in severe neurological distress. Approximately 1.1 million neonates are affected annually on a global scale, with the vast majority living in sub-Saharan Africa and southern Asia. It is common in newborns in the first week of life. This study aims to assess the magnitude and determinants of jaundice in newborns admitted to the neonatal intensive care unit (NICU) of public hospitals in the city of Dessie in northern Ethiopia. An institutional cross-sectional study was conducted at the NICU at Dessie town public hospitals from 30 March to 30 April 2020. A systematic random sampling procedure was used to select the study participants. Data were collected through face-to-face interviews with mothers using a structured questionnaire and by reviewing neonatal medical records using a checklist. Binary logistic regression analysis was used to identify the determinants of neonatal jaundice. A significance level of less than 0.05 was used to declare the statistical significance in the final model. A total of 218 neonates with their mothers were included in the study. The prevalence rate of neonatal jaundice was found to be 28.4%. The major associated factors for neonatal jaundice were sepsis [adjusted odds ratio (AOR): 10.13, 95% confidence interval (CI) = 2.36, 43.56], preterm < 37 weeks (AOR: 6.03, 95% CI = 1.41, 25.79) low APGAR score < 7 (AOR: 7.34, 95% CI = 1.34, 39.65), ABO incompatibility (AOR: 24.55 95% CI = 1.58, 68.83), prolonged labor (AOR 9.03, 95% CI = 1.67, 48.33), and Rh incompatibility (AOR = 30.40, 95% CI = 2.01, 66.20). The magnitude of neonatal jaundice among neonates was determined to be high. Therefore, both maternal and neonatal factors contributed significantly to the management of neonatal jaundice and also influenced the use of phototherapy treatment. Proper consideration of these factors is crucial for the prevention and treatment of neonatal jaundice.

Low titer group O whole blood and risk of RhD alloimmunization: Rationale for use in Finland.

Prehospital low-titer group O whole blood (LTOWB) used for patients with life-threatening hemorrhage is often RhD positive. The most important complication following RhD alloimmunization is hemolytic disease of the fetus and newborn (HDFN). Preceding clinical use of RhD positive LTOWB, we estimated the risk of HDFN due to LTOWB prehospital transfusion in the Finnish population. We collected data on prehospital transfusions in Tampere and Helsinki University Hospital areas. Using the mean of reported alloimmunization rates in trauma studies (24%) and a higher reported rate representing trauma patients of 13-50 years old (42.7%), we estimated the risk of HDFN and extrapolated it to the whole of Finland. We estimated that in Finland, with the current prehospital transfusion rate we would see 1-3 cases of severe HDFN due to prehospital LTOWB transfusions every 10 years, and fetal death due to HDFN caused by LTOWB transfusion less than once in 100 years. The estimated risk of serious HDFN due to prehospital LTOWB transfusion in the Finnish population is similar to previous estimates. As Finland routinely screens expectant mothers for red blood cell antibodies and as the contemporary treatment of HDFN is very effective, we support the prehospital use of RhD positive LTOWB in all patient groups.

Erythrokinetic mechanism(s) causing the "late anemia" of hemolytic disease of the fetus and newborn.

A transfusion-requiring "late anemia" can complicate the management of neonates convalescing from hemolytic disease of the fetus and newborn (HDFN). This anemia can occur in any neonate after HDFN but is particularly prominent in those who received intrauterine transfusions and/or double-volume exchange transfusions. Various reports describe this condition as occurring based on ongoing hemolysis, either due to passive transfer of alloantibody through breast milk or persistence of antibody not removed by exchange transfusion. However, other reports describe this condition as the result of inadequate erythrocyte production. Both hypotheses might have merit, because perhaps; (1) some cases are primarily due to continued hemolysis, (2) others are primarily hypoproductive, and (3) yet others result from a mixture of these two mechanisms. We propose prospective collaborative studies that will resolve this issue by serially quantifying end-tidal carbon monoxide. Doing this will better inform the assessment and treatment of neonates recovering from HDFN.

Maternal IVIG Administration in Rhesus Alloimmunized Pregnancies: A Systematic Review

Background: Rhesus (Rh) alloimmunization occurs when an Rh negative mother is exposed to red blood cells (RBC) from an Rh positive fetus. The mother develops antibodies in the current pregnancy that attack Rh positive fetus in subsequent pregnancy, causing hemolytic disease of the fetus and newborn (HDFN). RhD is the most common antigen to result in fetal anemia requiring intrauterine transfusions (IUT). Although the traditional method of management and highly effective, IUTs carry significant risk particularly when performed early in gestation, potentially resulting in procedure-related fetal deaths. Intravenous immunoglobulin (IVIG) therapy may postpone or even replace invasive intrauterine treatment in fetuses of mothers with severe alloimmunization in previous pregnancies.&#x0D; Objective: To evaluate whether maternal administration of IVIG in high-risk Rhesus alloimmunized pregnancies is effective in delaying the need for IUTs as well as delaying the onset of severe fetal anemia and thus in diminishing its clinical consequences.&#x0D; Study design: A systematic literature search was conducted for maternal intravenous immunoglobulin administration in pregnancies with Rh isoimmunization in the following databases: Medline, Embase and Cochrane Library from 1946 to 2 February 2023. Inclusion criteria was studies done during pregnancy in which IVIG was administered to the mother in Rh alloimmunized pregnancies/fetal anemia. All non-english papers, animal papers, systematic reviews, editorials and studies in which IVIG was administered to non-pregnant patients were excluded. Data was extracted from these full texts and analyzed for inclusion based on the quantity of usable data and patient information. Extracted data included maternal antibody type and titer, number of maternal IVIG administrations, number of IUTs, and fetal Hb levels prior to first IUT and at delivery. Time interval (weeks) between IVIG and first IUT was also included in the extracted data along with gestational age at delivery. Individual patient data extraction was done for studies that provided data.&#x0D; Results: 16 studies were included in data analysis. Analysis of extracted data is ongoing.

Successful management of severe Kell alloimmunization in pregnancy with intravenous immune globulin

Hemolytic Disease of the Fetus and Newborn (HDFN) is a condition that affects 1 to 2 out of 1000 patients during pregnancy (1). When an alloantibody is present, it is essential to identify its nature in order to organize appropriate follow-up. Kell-mediated HDFN is rare; it occurs in about 5% of Kell alloimmunized pregnant women. It is important to note that in case of anti-Kell immunization, the severity of HDFN is not correlated with maternal antibody titers, and anemia tends to occur earlier and more severely. Therefore, early diagnosing and management of this condition is crucial. In the management of severe fetal anemia due to Kell immunization, available treatments include in utero transfusion (IUT), immunoglobulin therapy. Other alternative treatments exist, such as plasmapheresis. Intravenous immunoglobulin (IVIG), a noninvasive therapeutic approach, acts through multiple mechanisms. IVIG has been evaluated in cases of RhD immunization with high maternal antibody titers and a history of pregnancies involving early hydrops or intrauterine death. Regarding the potential benefits of intravenous IgG therapy, it may delay the need for early IUT, reduce the overall reliance on IUT, and have a positive impact on obstetric outcomes. This case of IV IgG therapy of anti-Kell immunization offers a thought-provoking avenue for future exploration.

Prevalence and Clinical Significance of Immunoglobulin G1 and Immunoglobulin G3 Subclasses of Anti-D Antibody in Rh D Alloimmunized Antenatal Women

ABSTRACT Background and Objectives: Hemolytic disease of the fetus and newborn (HDFN) occurs as a result of maternal sensitization to paternal antigens. Studies have shown that the immunoglobulin G (IgG) subclass in maternal serum – particularly the presence of IgG1 and IgG3 either singly or in combination, has an impact on the presence and severity of HDFN. The column agglutination technology is used for the identification of IgG1 and IgG3 subclasses. Therefore, the prevalence of IgG1 and IgG3 subclasses in a cohort of alloimmunized Rh (D) antenatal women at our center was studied and was correlated with severity of HDFN. The aims of this study were as follows: (1) to find out the prevalence of IgG1 and IgG3 subclasses among Rh (D) alloimmunized women and (2) to assess the clinical outcome of newborns born to mothers with respect to IgG subclass. Methodology: This was a descriptive study done on 75 antenatal Rh (D) alloimmunized women who fulfilled the inclusion criteria. Blood samples from study participants were subjected to IgG subtyping using the “DAT IgG1/IgG3 ID card” (Bio-Rad, Switzerland), and the outcome of pregnancy was assessed by categorizing the newborns into mild, moderate, and severe HDFN. The data obtained were analyzed using SPSS version 16. Prevalence was calculated and severity of HDFN was correlated with subclass. Results: Among the study population, 23% of mothers had IgG1 alone. Majority (72%) had both IgG1 + IgG3 subclasses and a few (5%) had IgG2 + IgG4. When the mother had both IgG1 + IgG3 subclasses in their body most newborns had only mild HDFN. Few cases of moderate-to-severe cases of HDFN were seen. Most newborns had only mild HDFN even though there were few moderate-to-severe cases of HDFN. No significant association could be demonstrated between severity of HDFN and type of IgG subclasses. Conclusion: Majority of maternal IgG found in HDFN was a combination of IgG1+IgG3.Such cases exhibited stronger grades of reaction in Indirect Coombs Test. A significant association could not be demonstrated between severity of HDFN and type of IgG subclasses.

Haemolytic Disease of Newborn in a baby Delivered by Mother with Complete Anti-D Prophylaxis: An Unusual Case Report

Haemolytic Disease of the Newborn (HDN), also known as erythroblastosis foetalis, is an immune-mediated disorder among neonates with a wide range of clinical presentations. The occurrence of HDN due to ABO-Rh incompatibility between the mother and baby is becoming rare due to increased knowledge of the disease and adherence to Good Clinical Practices (GCP) during pregnancy. This case report highlights a rare case of HDN in which, despite following GCP, standard care, an uneventful antenatal period, and timely administration of Anti-D immunoprophylaxis, the mother delivered a baby with HDN. The baby was successfully managed by a group of skilled and caring clinicians. Therefore, it is crucial to screen all at-risk mothers for HDN to identify it earlier and treat it successfully. This case report is rare in terms of the baby’s survival with HDN born to a mother who had already received timely Anti-D immunoprophylaxis. Additionally, there is a need to emphasise on recent advances in diagnosis, such as foetal Doppler studies, and treatment options.

A RETROSPECTIVE STUDY OF JAUNDICE IN INFANTS IN KYIV FROM 2017 TO 2021

Study objectives. The aim of the study was to evaluate the effectiveness of inpatient medical care in Kyiv (diagnostic capabilities and prescription of phototherapy) for newborns with various clinical forms of jaundice during 2017–2021. Methods. We performed a retrospective analysis of 616 infant jaundice cases of various clinical forms at the Department of Neonatal Pathology at Children's Clinical Hospital No. 6 in Kyiv (2017–2021), diagnosed as ICD P59 neonatal jaundice (NJ) and prolonged jaundice (PJN) and P55 hemolytic disease of the newborn (HDN) based on the relevant criteria. For statistical analysis, MedStat (v2.6.2) and EZR (v1.61) were used. The analysis showed that hospitalization with various forms of jaundice decreased in 2021 by about 2.1 times vs. 2018 and by 1.5 times vs. 2017 (p &lt; 0.001). PJN was more common (55.0%) than NJ (39.8%) and HDN (5.2%), p &lt; 0.001. A logistic regression model (AUC = 0.785) showed that the manifestation of PJN might be influenced by a history of cesarean section. At the time of hospitalization, there was no significant difference between the bilirubin levels measured by two methods: total serum bilirubin (TSBa) and transcutaneous bilirubin (TcBa), p = 0.380. Children with HDN (84.4%) were more likely to require phototherapy for more than 5 days than children with NJ (63.7%) and PJN (62.2%), p &lt; 0.05. Conclusion. The study showed a decrease in the number of hospitalizations for jaundice in infants from 2017 to 2021. The prevalence of PJN was higher than NJ. A history of cesarean section was associated with PJN. Median bilirubin levels showed no significant difference between the two methods. Children with HDN more often required prolonged phototherapy, which was probably due to a less effective daily decline in bilirubin levels.

Prevalence and Characterisation of Irregular RBC Antibodies in Antenatal Females from a Tertiary Care Center in Northern India: A Cross-sectional Study

Introduction: Haemolytic Disease of the Foetus and Newborn (HDFN) is widely known to be caused by the presence of irregular Red Blood Cell (RBC) antibodies in pregnant females. To prevent HDFN, it is crucial to identify these antibodies in pregnant women. Aim: To evaluate the prevalence of irregular red cell antibodies in pregnant women in a tertiary care hospital. Materials and Methods: A cross-sectional retrospective study was conducted in the Department of Transfusion Medicine at Indraprastha Apollo New Delhi, from November 2009 to December 2017. A total of 8,217 prenatal females were examined for irregular red cell antibodies. Antibody screening and blood grouping were performed. The Capture-R ready screen was used to confirm screen-positive tests. Adsorption, elution, and other advanced techniques were utilised as needed. Data was collected from patient records and entered into a Microsoft excel spreadsheet. The statistical analysis was conducted using Statistical Package for Social Sciences (SPSS) software version 14.0 (USA). Statistical tests, including the Chi-squared and Fisher’s exact test, were performed, with a p-value less than 0.05 considered statistically significant. Results: Out of the 8,217 prenatal females examined, 105 (1.27%) had positive screening results with the four cell panel. Red cell alloimmunisation was observed in groups that were RhD negative (n=93/105; 88.57%) and positive (n=12/105; 11.42%). The most prevalent alloantibody among RhD negative individuals was alloantibody anti-D (n= 83/93; 89.24%), followed by alloantibody anti C+ anti D (n=13/93; 13.97%). Anti-D was the most prevalent alloantibody overall (n=83/105; 79.04%). Conclusion: Alloimmunisation rates were notably high among women lacking the Rh D antigen. Individuals with a history of adverse obstetric outcomes showed a statistically significant association with alloimmunisation. Therefore, it is recommended to screen such individuals for alloantibodies to enable early detection and improve the management of HDFN.

Prevalence of unexpected red blood cell antibodies in pregnant women and follow-up of pregnancy outcome in pregnant women treated with intra-uterine transfusion.

For the management of hemolytic disease of the fetus and newborn (HDFN), it is important to detect unexpected red cell antibody in pregnant women. We assessed the prevalence of unexpected red cell antibodies in consecutive pregnant women attending antenatal clinic (ANC). More importantly, cases with unexpected antibody causing severe anemia were followed-up for intervention (Intra-uterine transfusion {IUT}) and outcome of pregnancy (still-birth/live-healthy). The study was conducted with an objective to find the prevalence of unexpected RBC antibodies in pregnant women, their specificity and to do the follow-up for IUT and outcome of pregnancy (still-birth, live-birth) in antibody positive women. This was a prospective study from January 2021 to May 2022 at two tertiary care centres. All antenatal samples received by the laboratory were screened for unexpected red cell antibody. Whenever antibody screen was positive, antibody identification was performed. Patients, positive for unexpected antibody and anemia were followed up for any transfusion-based intervention and outcome of pregnancy. A total of 539 consecutive samples were worked up and among these, 10 samples (1.85%) were found to be antibody positive. The antibodies identified were Anti-D (n=6), anti-Leb (n=1), anti-M (n=1), anti-C (n=1) and anti-E (n=1).The prevalence of unexpected antibodies in Rh positive and Rh negative pregnant women was 0.83% and 10.9% respectively. Follow-up was done for all 10 cases with unexpected antibody and anemia was monitored by MCA PSV (middle cerebral artery peak systolic velocity).Two women developed severe anemia thus requiring single intrauterine transfusion (at 26 weeks and 28 weeks respectively) each, for correction of anemia. In both these cases, healthy male child was delivered. At 3-month follow-up both children were alive and healthy. The study found prevalence of unexpected RBC antibodies in pregnant women as 1.85%. The study also underlined importance of transfusion-based interventions contributing to successful outcome in couple of cases with severe anemia.

Cell-Free DNA and Next-Generation Sequencing for Prenatal Diagnosis.

Deep sequencing by NGS of targeted amplicons can identify rare genetic variants in a pool of DNA where the vast majority of genomic DNA does not contain the variant. This approach can be used to detect a previously described paternally inherited, fetal variant in cell-free DNA (cfDNA) in maternal plasma. This is useful in cases where risk for the fetus is contingent upon inheritance of a paternal variant that the woman does not have. Both pathogenic and non-pathogenic variants that the woman does not have can be detected. In cases of compound heterozygosity, presence of the paternal pathogenic variant also requires detection of the maternal variant for risk assessment, which requires a chorion villus biopsy.We have used this approach to focus on detection of fetal blood groups in cases of presence of maternal alloantibodies against blood group antigens in pregnancy, to predict whether the fetus has inherited a blood group antigen that is targeted by the alloantibodies. In cases of maternal alloantibodies against blood group antigens, the fetus is at risk of hemolytic disease of the fetus and newborn (HDFN). With a known specificity of the maternal antibodies and if the fetal blood group can be determined in the pregnancy, then it can be ascertained if the fetus is at risk of HDFN and rational pregnancy care can be instituted. A noninvasive procedure avoids risks for the fetus. We have reported a procedure based on NGS analysis of PCR amplified cfDNA from maternal plasma. Some fetuses may die as early as week 18. We use this approach to predict fetal K, k, RhC, Rhc, RhE, and ABO blood groups in cases with a risk of HDFN due to the corresponding maternally produced antibodies.The NGS-based analysis can predict the presence or absence of incompatible antigens on the fetal RBCs.In this chapter, a noninvasive method for predicting some fetal blood groups early in pregnancy is described. There is a clinical need for such assays, and they may be a useful tool for management of pregnancies complicated by these alloantibodies within the field of precision medicine.

362 Identifying hemolytic disease of the fetus and newborn (HDFN) in a large integrated healthcare system

362 Identifying hemolytic disease of the fetus and newborn (HDFN) in a large integrated healthcare system

Como a hiperbilirrubinemia deve ser considerada na definição do protocolo da triagem auditiva para neonatos de risco?

ABSTRACT Purpose To analyze hyperbilirubinemia as an indicator for the definition of risk protocol in newborn hearing screening (NHS) and in auditory monitoring in full-term and preterm neonates. Methods This is an observational, cross-sectional and retrospective study. A total of 554 children born in a public maternity hospital were included and divided into two groups: (G1) with 373 full-terms neonates; (G2) with 181 preterm neonates. Data were collected from the participant’s medical records to obtain information regarding the result of the NHS, performed by recording the automated auditory brainstem response (AABR), birth conditions, clinical characteristics, interventions performed, and results of the first test of total bilirubin (TB) and indirect bilirubin (IB) as well as the peak of TB and IB. A descriptive statistical analysis of the results was performed, and the level of significance adopted was 5%. Results On the NHS test, quotes of retest referral rates were smaller in G1 when compared to G2. There was no significant difference between the groups regarding type of delivery, gender, presence of Rh and ABO incompatibility, G6PD enzyme deficiency, and performance of phototherapy. TB and IB levels at the first exam and at peak time did not differ between neonates with “pass” and “fail” results on the NHS test in both groups. Conclusion Bilirubin levels in the neonatal period below the recommended values for indication of exchange transfusion are not directly related to the “fail” result on the NHS tests in term and preterm neonates.