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Keywords = hemolytic disease of the fetus and newborn (HDFN)

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15 pages, 218 KiB  
Article
Patient-Reported Disease Presentation, Interventions, and Outcomes in United States Pregnancies Affected by Alloimmunization at Risk of Hemolytic Disease of the Fetus and Newborn
by Molly R. Sherwood, Bethany M. Weathersby, Marion E. Granger Howard and Kara B. Markham
Children 2025, 12(7), 822; https://doi.org/10.3390/children12070822 - 22 Jun 2025
Viewed by 473
Abstract
Background/Objectives: Pregnancies complicated by red cell alloimmunization can progress to hemolytic disease of the fetus and newborn (HDFN), requiring close monitoring and timely intervention to prevent fetal/neonatal morbidity and mortality. This study investigated disease presentation, interventions, and outcomes in respondents with a history [...] Read more.
Background/Objectives: Pregnancies complicated by red cell alloimmunization can progress to hemolytic disease of the fetus and newborn (HDFN), requiring close monitoring and timely intervention to prevent fetal/neonatal morbidity and mortality. This study investigated disease presentation, interventions, and outcomes in respondents with a history of alloimmunized pregnancy. Methods: This was a retrospective cross-sectional survey study administered online to alloimmunized patients between November 2022–February 2023. A total of 127 participants reported on 200 alloimmunized pregnancies. Distribution of pregnancy characteristics, antibodies and titers, monitoring, treatments and fetal outcomes were described and stratified where appropriate by fetal antigen status and disease severity. Outcomes and management practices in subsequent pregnancies following fetal loss to HDFN are reported. Results: Multiple antibodies were present in 42% of pregnancies with known antibody type (80/192). Titers reached critical levels (any titer for Anti-K; ≥16 for all other antibodies) in 71% (125/176) of pregnancies where titer was reported. Among fetal antigen positive pregnancies with critical titers, intrauterine transfusions were conducted in 40% (42/106), intravenous immunoglobulin was administered in 14% (15/106), plasmapheresis in 7% (7/106), and phenobarbital in 9% (9/106). Complications from transfusion were reported in 38% of pregnancies receiving intrauterine transfusion (17/45). Fetal death due to HDFN or complications from intrauterine transfusion was reported in 9% of antigen positive pregnancies with critical titers (10/106) and 16% of pregnancies receiving intrauterine transfusion (7/45). Conclusions: Disease presentation and severity complements previous research in this disease population, however, monitoring practices were diverse. Fetal death and intrauterine complication rates were higher than those previously reported in large international referral centers. Development of best practices and centralized referral centers may improve disease outcomes. Full article
(This article belongs to the Special Issue Genetics and Precision Medicine with Hematologic Diseases in Children)
11 pages, 224 KiB  
Article
Management and Treatment Outcomes of Hemolytic Disease of the Fetus and Newborn (HDFN)—A Retrospective Cohort Study
by Agnieszka Drozdowska-Szymczak, Sabina Łukawska, Natalia Mazanowska, Artur Ludwin and Paweł Krajewski
J. Clin. Med. 2024, 13(16), 4785; https://doi.org/10.3390/jcm13164785 - 14 Aug 2024
Cited by 2 | Viewed by 2866
Abstract
Background: Hemolytic disease of the fetus and newborn (HDFN) is caused by maternal antibodies attacking fetal blood cell antigens. Despite routine antenatal anti-D prophylaxis, intrauterine transfusions (IUTs) are still needed in some HDFN cases. Methods: We conducted a retrospective cohort study on newborns [...] Read more.
Background: Hemolytic disease of the fetus and newborn (HDFN) is caused by maternal antibodies attacking fetal blood cell antigens. Despite routine antenatal anti-D prophylaxis, intrauterine transfusions (IUTs) are still needed in some HDFN cases. Methods: We conducted a retrospective cohort study on newborns with HDFN born in the 1st Department of Obstetrics and Gynecology of the Medical University of Warsaw. We analyzed 274 neonates with HDFN, identifying 46 who required IUT due to fetal anemia and 228 who did not. The laboratory results, management, and outcomes were compared between these groups. Results: Comparative analysis showed that newborns treated with IUT were more likely to have significant anemia, hyperbilirubinemia, and iron overload, indicated by a high ferritin concentration. These neonates more often required top-up transfusions, phototherapy, intravenous immunoglobulin infusions, and exchange transfusions. The length of stay was longer for newborns who received IUT. Conclusions: HDFN requiring IUT is associated with a greater number of complications in the neonatal period and more often requires additional treatment compared to HDFN not requiring IUT. Full article
(This article belongs to the Special Issue Clinical Outcomes in Maternal–Fetal Medicine)
10 pages, 221 KiB  
Article
Incidence and Risk Factors of Cholestasis in Newborns with Hemolytic Disease—A Case-Control Study
by Agnieszka Drozdowska-Szymczak, Natalia Mazanowska, Tomasz Pomianek, Artur Ludwin and Paweł Krajewski
J. Clin. Med. 2024, 13(11), 3190; https://doi.org/10.3390/jcm13113190 - 29 May 2024
Cited by 4 | Viewed by 1952
Abstract
Background/Objectives: One of the rare causes of cholestasis may be hemolytic disease of the fetus and newborn (HDFN). Methods: We retrospectively analyzed 88 medical records of HDFN newborns with cholestasis and 186 records of children with HDFN without cholestasis and conducted [...] Read more.
Background/Objectives: One of the rare causes of cholestasis may be hemolytic disease of the fetus and newborn (HDFN). Methods: We retrospectively analyzed 88 medical records of HDFN newborns with cholestasis and 186 records of children with HDFN without cholestasis and conducted an observational, case-control, retrospective study. Results: Factors influencing the risk of cholestasis were lower gestational age at birth (36.83 ± 1.9 vs. 37.57 ± 1.8, p = 0.002), Rh or Kidd HDFN (80.7% vs. 53.2%), and the need for intrauterine transfusion (27.3 vs. 11.8%). The subjects had lower hemoglobin concentrations at birth (14.01 ± 3.8 vs. 16.39 ± 2.8 g/dL) and during whole hospital stay, higher cord blood total bilirubin concentration (4.26 ± 1.8 vs. 2.39 ± 1.4 mg/dL), higher maximum bilirubin concentration (15.27 ± 5.8 vs. 10.24 ± 3.4 mg/dL), and more frequent liver ultrasound abnormalities (19.9 vs. 6.3%). They also required more extended hospitalization due to higher rates of postnatal blood transfusion (33 vs. 3.8%), more frequent need for exchange transfusion (8.8% vs. 2.2%), more extended time and higher risk of phototherapy (94.3 vs. 59.1%), and higher usage of immunoglobulins (55.7 vs. 8.1%), parenteral nutrition (45.5 vs. 12.9%), and antibiotics (14.8 vs. 4.8%). Conclusions: The risk factors for cholestasis in children with HDFN are lower gestational age at delivery, Rh and Kidd serological type of HDFN, and the need for intrauterine transfusions. Full article
(This article belongs to the Special Issue Clinical Outcomes in Maternal–Fetal Medicine)
8 pages, 470 KiB  
Case Report
Severe Cholestasis in Neonates with Hemolytic Disease of the Fetus and Newborn—A Case Report
by Agnieszka Drozdowska-Szymczak, Julia Proczka, Natalia Mazanowska, Artur Ludwin and Paweł Krajewski
J. Clin. Med. 2024, 13(5), 1272; https://doi.org/10.3390/jcm13051272 - 23 Feb 2024
Cited by 4 | Viewed by 2269
Abstract
Hemolytic disease of the fetus and newborn (HDFN) may cause severe cholestasis with direct bilirubin concentrations reaching up to 50 times the upper limit of normal. This case report describes twins whose highest direct bilirubin concentrations were 32.2 mg/dL and 50.2 mg/dL, with [...] Read more.
Hemolytic disease of the fetus and newborn (HDFN) may cause severe cholestasis with direct bilirubin concentrations reaching up to 50 times the upper limit of normal. This case report describes twins whose highest direct bilirubin concentrations were 32.2 mg/dL and 50.2 mg/dL, with no significant signs of hepatic impairment. The index pregnancy was complicated by Rhesus factor immunization with anti-D antibodies present in maternal serum, which caused fetal anemia requiring intrauterine blood transfusions. Complementary tests demonstrated Rhesus D alloimmunization as the sole cause of cholestasis. To the best of our knowledge, this is the first study to describe such elevated direct bilirubin concentrations caused by HDFN. Full article
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8 pages, 747 KiB  
Case Report
Liver Dysfunction with Severe Cholestasis and Coagulation Disorders in the Course of Hemolytic Disease of the Newborn Requiring Chelation Therapy—A Case Report and Review of the Literature
by Agnieszka Drozdowska-Szymczak, Julia Proczka, Danuta Chrzanowska-Liszewska, Krzysztof Truszkowski, Natalia Mazanowska and Paweł Krajewski
J. Clin. Med. 2023, 12(24), 7645; https://doi.org/10.3390/jcm12247645 - 13 Dec 2023
Cited by 5 | Viewed by 2132
Abstract
Severe hemolytic disease of the fetus and newborn (HDFN) requiring intrauterine transfusions (IUTs) may cause iron accumulation, resulting in liver damage, which may lead to cholestasis and coagulation disorders. In this article, we reported a case of a female neonate who underwent chelation [...] Read more.
Severe hemolytic disease of the fetus and newborn (HDFN) requiring intrauterine transfusions (IUTs) may cause iron accumulation, resulting in liver damage, which may lead to cholestasis and coagulation disorders. In this article, we reported a case of a female neonate who underwent chelation therapy with a positive outcome, and we reviewed the English and Polish literature on chelation therapy in HDFN available in PubMed. The patient with maximum ferritin concentration above 33,511.2 ng/mL developed liver dysfunction with coagulation disorders requiring multiple transfusions of fresh frozen plasma (FFP), Octaplex® and cryoprecipitate, and hypoalbuminemia treated with numerous albumin infusions. Furthermore, severe cholestasis was observed with direct bilirubin levels up to 33.14 mg/dL. Additionally, the child developed transient myelosuppression with neutropenia, thrombocytopenia, and low reticulocyte count due to several blood transfusions. The differential diagnosis tests were conducted to rule out any causes of hepatic failure other than hemolytic disease of the newborn. This case proves that adequate treatment of severe HDFN with anemia requiring IUT and hepatic failure can lead to positive outcomes with no long-term consequences. Full article
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10 pages, 578 KiB  
Article
Fetal RHD Screening in RH1 Negative Pregnant Women: Experience in Switzerland
by Bernd Schimanski, Rahel Kräuchi, Jolanda Stettler, Sofia Lejon Crottet, Christoph Niederhauser, Frederik Banch Clausen, Stefano Fontana, Markus Hodel, Sofia Amylidi-Mohr, Luigi Raio, Claire Abbal and Christine Henny
Biomedicines 2023, 11(10), 2646; https://doi.org/10.3390/biomedicines11102646 - 27 Sep 2023
Cited by 4 | Viewed by 2191
Abstract
RH1 incompatibility between mother and fetus can cause hemolytic disease of the fetus and newborn. In Switzerland, fetal RHD genotyping from maternal blood has been recommended from gestational age 18 onwards since the year 2020. This facilitates tailored administration of RH immunoglobulin (RHIG) [...] Read more.
RH1 incompatibility between mother and fetus can cause hemolytic disease of the fetus and newborn. In Switzerland, fetal RHD genotyping from maternal blood has been recommended from gestational age 18 onwards since the year 2020. This facilitates tailored administration of RH immunoglobulin (RHIG) only to RH1 negative women carrying a RH1 positive fetus. Data from 30 months of noninvasive fetal RHD screening is presented. Cell-free DNA was extracted from 7192 plasma samples using a commercial kit, followed by an in-house qPCR to detect RHD exons 5 and 7, in addition to an amplification control. Valid results were obtained from 7072 samples, with 4515 (64%) fetuses typed RHD positive and 2556 (36%) fetuses being RHD negative. A total of 120 samples led to inconclusive results due to the presence of maternal or fetal RHD variants (46%), followed by women being serologically RH1 positive (37%), and technical issues (17%). One sample was typed false positive, possibly due to contamination. No false negative results were observed. We show that unnecessary administration of RHIG can be avoided for more than one third of RH1 negative pregnant women in Switzerland. This reduces the risks of exposure to a blood-derived product and conserves this limited resource to women in actual need. Full article
(This article belongs to the Special Issue Advances in Molecular Diagnostics of Transfusion Medicine)
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11 pages, 1711 KiB  
Article
Development of Mia Phenotyping Using Paper-Based Device
by Sirinart Chomean, Jirapat Attapong, Sumittra Jitsuvantaya, Komin Poomsaard, Chadchadaporn Dongwilai, Pished Bunnun and Chollanot Kaset
Diagnostics 2022, 12(12), 3104; https://doi.org/10.3390/diagnostics12123104 - 9 Dec 2022
Cited by 1 | Viewed by 2257
Abstract
The MNS7 (Mia) blood group antigen is found at a different prevalence among different ethnic groups. Anti-Mia can cause hemolytic disease of the fetus and newborn (HDFN) and both acute- and delayed-type hemolytic transfusion reactions (HTR). Mia typing should [...] Read more.
The MNS7 (Mia) blood group antigen is found at a different prevalence among different ethnic groups. Anti-Mia can cause hemolytic disease of the fetus and newborn (HDFN) and both acute- and delayed-type hemolytic transfusion reactions (HTR). Mia typing should be performed in donors to prevent life-threatening hemolytic transfusion reactions. The gel card and standard tube methods still need specialized equipment, centrifugation, and expertise for result interpretation. We used a novel paper-based analytical device (PAD) pre-coated with monoclonal IgM anti-Mia for Mia phenotyping. We measured grey pixel intensity in blood typing results for interpretation processing using OpenCV at the sample (SP) and elution parts (EP); furthermore, we used the SP: EP ratio and F-score as analysis criteria. We typed 214 blood EDTA samples with PAD–Mia and then compared with gel card results for setting an analysis criterion. We observed 100% sensitivity, specificity, and accuracy when we applied the SP: EP ratio and F-score with the optimal criterion (1.07 and 0.17 for SP: EP ratio and F-score, respectively). The validation of PAD–Mia typing for blood donor samples (n = 150) via F-score gave 100% sensitivity and specificity when compared with the gel card method; therefore, we argue that PAD–Mia typing can be used for Mia phenotyping without sero-centrifugation. Moreover, to study the correlation between genotype and phenotype, PCR-SSP was performed to identify GYP(B-A-B) hybrids. The results revealed that all Mia+ blood samples gave a positive with GP. Hut, GP. HF, GP. Mur, GP. Hop, and GP. Bun. Results of the gel card method and PCR-SSP were concordant. Hence, using PAD–Mia typing in blood donors would be helpful for creating a phenotype database of blood donors for reducing alloimmunization risks. Full article
(This article belongs to the Section Point-of-Care Diagnostics and Devices)
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12 pages, 264 KiB  
Review
Noninvasive Prenatal Testing in Immunohematology—Clinical, Technical and Ethical Considerations
by Jens Kjeldsen-Kragh and Åsa Hellberg
J. Clin. Med. 2022, 11(10), 2877; https://doi.org/10.3390/jcm11102877 - 19 May 2022
Cited by 5 | Viewed by 3221
Abstract
Hemolytic disease of the fetus and newborn (HDFN), as well as fetal and neonatal alloimmune thrombocytopenia (FNAIT), represent two important disease entities that are caused by maternal IgG antibodies directed against nonmaternally inherited antigens on the fetal blood cells. These antibodies are most [...] Read more.
Hemolytic disease of the fetus and newborn (HDFN), as well as fetal and neonatal alloimmune thrombocytopenia (FNAIT), represent two important disease entities that are caused by maternal IgG antibodies directed against nonmaternally inherited antigens on the fetal blood cells. These antibodies are most frequently directed against the RhD antigen on red blood cells (RBCs) or the human platelet antigen 1a (HPA-1a) on platelets. For optimal management of pregnancies where HDFN or FNAIT is suspected, it is essential to determine the RhD or the HPA-1a type of the fetus. Noninvasive fetal RhD typing is also relevant for identifying which RhD-negative pregnant women should receive antenatal RhD prophylaxis. In this review, we will give an overview of the clinical indications and technical challenges related to the noninvasive analysis of fetal RBCs or platelet types. In addition, we will discuss the ethical implications associated with the routine administration of antenatal RhD to all pregnant RhD-negative women and likewise the ethical challenges related to making clinical decisions concerning the mother that have been based on samples collected from the (presumptive) father, which is a common practice when determining the risk of FNAIT. Full article
(This article belongs to the Special Issue Update on Prenatal Diagnosis and Maternal Fetal Medicine)
10 pages, 638 KiB  
Article
Risk Minimization of Hemolytic Disease of the Fetus and Newborn Using Droplet Digital PCR Method for Accurate Fetal Genotype Assessment of RHD, KEL, and RHCE from Cell-Free Fetal DNA of Maternal Plasma
by Radek Vodicka, Jana Bohmova, Iva Holuskova, Eva Krejcirikova, Martin Prochazka and Radek Vrtel
Diagnostics 2021, 11(5), 803; https://doi.org/10.3390/diagnostics11050803 - 28 Apr 2021
Cited by 2 | Viewed by 3104
Abstract
The molecular pathology of hemolytic disease of the fetus and newborn (HDFN) is determined by different RHD, RHCE, and KEL genotypes and by blood group incompatibility between the mother and fetus that is caused by erythrocyte antigen presence/absence on the cell [...] Read more.
The molecular pathology of hemolytic disease of the fetus and newborn (HDFN) is determined by different RHD, RHCE, and KEL genotypes and by blood group incompatibility between the mother and fetus that is caused by erythrocyte antigen presence/absence on the cell surface. In the Czech Republic, clinically significant antierythrocyte alloantibodies include anti-D, anti-K, anti C/c, and anti-E. Deletion of the RHD gene and then three single nucleotide polymorphisms in the RHCE and KEL genes (rs676785, rs609320, and rs8176058) are the most common. The aim of this study is to develop effective and precise monitoring of fetal genotypes from maternal plasma of these polymorphisms using droplet digital (dd)PCR. Fifty-three plasma DNA samples (from 10 to 18 weeks of gestation) were analyzed (10 RHD, 33 RHCE, and 10 KEL). The ddPCR methodology was validated on the basis of the already elaborated and established method of minisequencing and real-time PCR and with newborn phenotype confirmation. The results of ddPCR were in 100% agreement with minisequencing and real-time PCR and also with newborn phenotype. ddPCR can fully replace the reliable but more time-consuming method of minisequencing and real-time PCR RHD examination. Accurate and rapid noninvasive fetal genotyping minimizes the possibility of HDFN developing. Full article
(This article belongs to the Special Issue Maternal-Fetal Medicine)
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