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.

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.

UNASSIGNED: Plasmapheresis and IVIG use in cases of alloimmunization during pregnancy are effective strategies when severe early fetal anemia is anticipated. Despite no change in antibody titer levels before and after plasmapheresis, clinical response was observed in both fetuses, and both had an excellent obstetrical outcome.
UNASSIGNED: Hemolytic disease of the fetus and newborn is a potentially lethal complication of alloimmunization, and intrauterine fetal blood transfusion (IUBT) is the standard treatment and care plan for severe fetal anemia. However, IUBT is technically unattainable before 20 weeks of gestation. Plasmapheresis and intravenous immunoglobulin (IVIG) are the two treatment modalities described in the literature that postpone the need for transfusion until after 20 weeks. Here, we present two cases of alloimmunization (one with anti-Kell and the other with anti-D). Both had poor outcomes in previous pregnancies because of the early development of severe fetal anemia and hydrops before 24 weeks of gestation. Both patients underwent three sessions of plasmapheresis before 18 weeks, followed by weekly IVIG infusion, which continued until 23-27 weeks of pregnancy. Antibody titers were measured before and after plasmapheresis. In addition, weekly MCA Doppler was performed to monitor the development of severe fetal anemia requiring blood transfusion, which was diagnosed when the peak systolic velocity (PSV) was 1.5 multiples of the median or more. The first patient underwent IUBT at 24 weeks and the second at 28 weeks, as indicated by the MCA Doppler. Both patients were delivered by cesarean section, the first at 34 weeks and the second at 36 weeks, for different obstetrical indications. Both pregnancies resulted in a live birth. We conclude that the use of plasmapheresis and IVIG in alloimmunization during pregnancy is an effective treatment strategy when severe early fetal anemia is anticipated before 20 weeks of gestation. Despite no change in antibody titer levels before and after plasmapheresis, a clinical response was observed in both fetuses, and both had excellent obstetrical outcomes.

K-associated anemic disease of the fetus and newborn (K-ADFN) is a rare but life-threatening disease in which maternal alloantibodies cross the placenta and can mediate an immune attack on fetal red blood cells expressing the K antigen. A considerably more common disease, D-associated hemolytic disease of the fetus and newborn (D-HDFN), can be prophylactically treated using polyclonal α-D antibody preparations. Currently, no such prophylactic treatment exists for K-associated fetal anemia, and disease is usually treated with intrauterine blood transfusions. Here we review current understanding of the biology of K-associated fetal anemia, how the maternal immune system is sensitized to fetal red blood cells, and what is understood about potential mechanisms of prophylactic HDFN interventions. Given the apparent challenges associated with preventing alloimmunization, we highlight novel strategies for treating sensitized mothers to prevent fetal anemia that may hold promise not only for K-mediated disease, but also for other pathogenic alloantibody responses.

In the setting of maternal alloimmunization to antigen(s) on fetal red blood cells, significant fetal anemia may develop, and an intrauterine transfusion may be required. When selecting a blood product for intrauterine transfusion, the priority should be crossmatch compatibility with the mother. Preventing fetal alloimmunization is not practical or necessary. Universal use of O- red blood cells is not appropriate for pregnant women who are alloimmunized to c or e antigens and require an intrauterine transfusion. Essentially, 100% of people who are D- are homozygous for both c and e antigens. Thus, it is logistically impossible to find red blood cells that is D-c- or D-e-, and O+ red blood cells is necessary in the context of maternal alloimmunization to c or e antigens.

UNASSIGNED: Hemolytic disease of the fetus and newborn (HDFN) due to red cell alloimmunization, is an important cause of fetal and neonatal morbidity and mortality. However, fetal and neonatal outcome of HDFN managed with intrauterine transfusion (IUT) in China are unknown. In addition, fetal and neonatal outcomes according to the type of maternal red cell alloantibodies involved and outcomes of hydrops fetalis are also unclear.
UNASSIGNED: The objective of this study was to evaluate fetal and neonatal outcomes of severe red-cell alloimmunization treated by IUT, to compare the outcomes according to the type of antibody, and to investigate the perinatal and postnatal outcomes of hydrops fetalis due to red cell alloimmunization.
UNASSIGNED: A retrospective study of pregnancies affected by HDFN and managed with IUT at a tertiary care university hospital in China between January 2001 and December 2018 was performed. Fetal and neonatal outcomes were investigated, and comparison of outcomes depending on the type of antibody and comparison of outcome between hydrops fetalis and fetuses without hydrops were also conducted.
UNASSIGNED: 244 IUTs were performed in 81 fetuses from 80 pregnancies. Anti-RhD was the major etiology of HDFN requiring IUT (71.6%). The fetal survival rate was 90.1%. The survival rate of the hydropic fetuses was significantly lower than those of the non hydropic fetuses (61.2% vs. 95.6%) (P = 0.002**). Compared with non hydropic fetuses, hydropic fetuses had significantly lower gestational age and lower hemoglobin level at first IUT. The neonatal survival rate was 98.6%. Exchange transfusions were required in 26% of the neonates. 30.1% of neonates had late anemia and required top-up transfusions, and hydropic fetuses required more late top-up transfusions than fetuses without hydrops. No significant difference in fetal and neonatal outcomes was found among the four subgroups stratified by the antibody involved.
UNASSIGNED: Our study demonstrates that IUT is an effective and safe therapy for severe HDFN at our institution. Early detection and treatment of hydrops is critical for perinatal outcomes. Particular attention should be paid to late postnatal anemia in affected neonates and top-up transfusion is still commonly needed.

Hemolytic disease of the fetus and newborn (HDFN) is an immune-mediated condition caused by the production of maternal antibodies to fetal red blood cells. This condition most commonly arises due to Rh factor incompatibility. The case presented here displays an example of HDFN in which the mother and fetus\'s blood type was O+. Upon further investigation, it was determined that the mother is a producer of anti-Gonzales antibodies (anti-Go(a)). With no cases published in the 21st century, this antibody is a rare cause of HDFN. Anti-Go(a) is produced against the Go antigen, a low-frequency Rh antigen found predominantly in African and Puerto Rican populations. Bringing awareness to this rare cause of HDFN may accelerate diagnosis when the physician is faced with non-ABO and non-Rh isoimmunization in these ethnic groups.

UNASSIGNED: Maternal red cell alloimmunization to Rh antigen in pregnant women occurs when the immune system is sensitized by foreign red blood cell surface antigens, in this case fetal red blood cells, inducing an immune response. Various antigens of blood group systems may cause alloimmunization, especially the Rh, Kel, Fy, JK, and MNS systems. This study aimed to determine alloimmunization to the different frequencies of Rh antigen among pregnant women in South Western Uganda.
UNASSIGNED: A total of 1369 pregnant women consented and were recruited into a cross-sectional study during their regular antenatal visits during the period August 2020 to July 2021. Samples (4 mL) of anticoagulated and coagulated blood were obtained, and Rh blood grouping including Rh antigen and the indirect antiglobulin test (IAT) was carried out using the agglutination technology of the LISS ID-Card technique in the Ortho Biovue ID-Micro Typing System.
UNASSIGNED: Out of 1369 participants recruited to the study, 78 (5.7%) were D-, 1291 were D+, and 134 (9.8%) had alloantibodies. Among those with alloantibodies, 115 (85.8%) were D+ and 19 (14.2%) D-. The percentage alloimmunization according to the Rh antigens was highest in e (9.72%), c (2.48%), C (2.34%) and E (0.94%) antigens. With the ABO system, alloimmunization was highest in blood group B (10.7%), followed by A (10.6%), O (9.2%) and then AB (7.1%). Alloimmunization was more prevalent in D- (24%) than in D+ participants (8.9%). Rhesus antigen e was the most prevalent antigen (99.8%), followed by c. The alloimmunization rate of 9.8% among these participants is high, and appears in both D+ and D- women. The other Rhesus antigens are seen to cause alloimmunization, with antigen e causing the highest prevalence. In conclusion, there is a need to identify antibodies and study the outcome for clinical significance, especially in D+ women, to facilitate proper pregnancy management.

The widespread use of anti-D immunoglobulin has resulted in a relative increase in the importance of non-D alloimmunization as a cause of hemolytic disease of the fetus and newborn (HDFN). Non-D alloantibodies that are capable of causing severe HDFN include anti-K, anti-E, and anti-c. Anti-c is clinically the most important Rh system antibody after anti-D. Here, we report three cases of neonates presenting with anemia and hyperbilirubinemia with strongly positive direct antiglobulin test who required phototherapy and neonatal exchange transfusion due to non-D antibody in RhD positive antenatal women. Anti-c was common in all the three cases while two cases have one additional non-D antibody. Due to faulty practices, antenatal antibody screening was not done for any case considering the mother\'s RhD positive status. Hence, antenatal antibody screening should be performed routinely, in all RhD positive pregnant women to reduce the delay in diagnosis and the management of HDFN occurring due to non-D antibodies.

UNASSIGNED: In the Kell blood group system, the K and k antigens are the clinically most important ones. Maternal anti-K IgG antibodies can lead to the demise of a K-positive fetus in early pregnancy. Intervention can save the fetus. Prenatal K status prediction of the fetus in early pregnancy is desirable and gives a good basis for pregnancy risk management. We present the results from 7 years of clinical experience in predicting fetal K status as well as some theoretical considerations relevant for design of the assay and evaluation of results.
UNASSIGNED: Blood was collected from 43 women, all immunized against K, at a mean gestational age of 18 weeks (range 10-38). A total of 56 consecutive samples were tested. The KEL *01.01 /KEL *02 single nucleotide variant that determines K status was amplified from maternal plasma DNA by PCR without allele specificity. The PCR product was sequenced by NGS technology, and the number of sequenced KEL *01.01 and KEL *02 reads were counted. Prediction of the fetal K status was based on this count and was compared with the serologically determined K status of the newborns.
UNASSIGNED: All fetal K predictions were in accordance with postnatal serology where available (n = 34), using our current data analysis.
UNASSIGNED: We have developed an NGS-based method for the non-invasive prediction of fetal K status. This approach requires special considerations in terms of primer design, stringent preanalytical sample handling, and careful analytical procedures. We analyzed samples starting at GA 10 weeks and demonstrated the correct prediction of fetal K status. This assay enables timely clinical intervention in pregnancies at risk of hemolytic disease of the fetus and newborn caused by maternal anti-K IgG antibodies.