Extension with cE-matching of the transfusion policy for women under 45 years to prevent alloimmunization and hemolytic disease of the foetus and newborn (HDFN) was evaluated. After implementation of cEK-matching, anti-c occurrence decreased from 46.8 to 30.4 per 100 000 pregnancies (RR 0.65, 95% CI 0.54-0.79), while anti-E occurrence decreased from 122.1 to 89.9 per 100 000 pregnancies (RR 0.74, 95% CI 0.66-0.84). The c-negative women showed a higher anti-E occurrence before cEK-matching and a more pronounced decline with the new policy. This indicates that cEK-matched transfusion effectively reduces alloimmunization, and that a cK-matched approach could prevent most transfusion-related alloimmunization and HDFN.

BACKGROUND: Hemolytic disease of the fetus and newborn is a public health problem caused by maternal-fetal incompatibility; no prophylaxis is available for most alloantibodies that induce this disease. This study reviews the literature regarding which antibodies are the most common in maternal plasma and which were involved in hemolytic disease of the fetus and newborn.
METHODS: Seventy-five studies were included in this review using a systematic search. Two independent authors identified studies of interest from the PubMed and SciELO databases.
RESULTS: Forty-four case reports were identified, of which 11 babies evolved to death. From 17 prevalence studies, the alloimmunization rate was 0.17 % with 161 babies receiving intrauterine transfusions and 23 receiving transfusions after birth. From 28 studies with alloimmunized pregnant women (7616 women), 455 babies received intrauterine transfusions and 21 received transfusions after birth.
CONCLUSIONS: Rh, Kell, and MNS were the commonest blood systems involved. The geographical distribution of studies shows that as these figures vary between continents, more studies should be performed in different countries. Investing in early diagnosis is important to manage the risks and complications of hemolytic disease of the fetus and newborn.

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.

OBJECTIVE: To perform cost analyses of foregoing RhD blood type testing and administration of Rh immunoglobulin (RhIg) for bleeding in pregnancy at <12 weeks gestation in the United States.
METHODS: We created a decision-analytic model comparing the current standard treatment pathway for patients who have threatened, spontaneous, or induced abortion in the United States, with a new pathway foregoing RhD testing and administration of RhIg for those who are RhD-negative at <12 weeks gestation, assuming that the risk of sensitization is 0%. We derived population and cost estimates from the current literature and calculated the number needed to treat (NNT) and number needed to screen to avoid one case of fatal hemolytic disease of the fetus and newborn. We performed sensitivity analyses assuming Rh-sensitization risks of 1.5% and 3% and varying the subsequent pregnancy rates from 44% to 100%.
RESULTS: The annual savings to health care payers in the United States of foregoing RhD testing and RhIg administration with bleeding events at <12 weeks are $5.5 million/100,000 total pregnancies, assuming the sensitization risk is 0%. In sensitivity analyses with a sensitization risk of 1.5% and subsequent pregnancy rate of 84.3% foregoing Rh testing and RhIg administration would save $2.8 million/100,000 pregnancies, with a NNT of 7322 and a number needed to screen of 48,816. At a 3% sensitization rate, the current standard treatment pathway is most economical.
CONCLUSIONS: There is an opportunity to save as much as $5.5 million/100,000 pregnancies by withholding RhIg in specific situations and conserving it for use later in pregnancy.
CONCLUSIONS: Cost analyses support foregoing RhD blood type screening and RhIg administration at <12 weeks gestation if the sensitization rate is <3%. By deimplementing this low-value care, payers in the United States can save as much as $5.5 million/100,000 pregnancies and conserve RhIg for use later in pregnancy.

OBJECTIVE: To evaluate the knowledge of pregnant women and the clinical management of hemolytic disease of the fetus and newborn, as well as to describe the gestational profile, risk factors and socio-epidemiological profile of pregnant women treated at two municipal health units in Belém (Pará, Brazil).
METHODS: This was a cross-sectional analytical study, which consisted in the application of questionnaires to pregnant women who underwent prenatal care at the municipal health units.
RESULTS: A total of 104 pregnant women were evaluated; most were aged between 24 and 29 years old, had high school degrees (38 %), family incomes between 1 and 2 minimum wages (45 %) and blood type O+ (43 %). Regarding the gestational profile, the participants were predominantly in the third trimester of pregnancy (49 %), started prenatal care in the first gestational trimester (81 %) and were primiparous (61 %). Failures in the management of prenatal care were observed, especially with regard to access to information about the disease, since most pregnant women did not receive information about blood incompatibility during prenatal care. This led to limited knowledge about the pathology of the disease evidenced by the fact that most of the correct answers were between Questions 0-4, which were significantly associated with the women\'s education and income.
CONCLUSIONS: Although hemolytic disease of the fetus and newborn is serious, the pregnant women in this study demonstrated little knowledge about the disease and had inadequate care by health professionals, reinforcing the importance of improving care for women\'s health and prenatal care.

Anti-PP1PK alloimmunization is rare given ubiquitous P1PK expression. Prevention of recurrent miscarriages and hemolytic disease of the fetus and newborn (HDFN) in pregnant individuals with anti-PP1PK antibodies has relied upon individual reports. Here, we demonstrate the successful management of maternal anti-PP1PK alloimmunization in a 23-year-old, G2P0010, with therapeutic plasma exchange (TPE), intravenous immunoglobulin (IVIG), and monitoring of anti-PP1Pk titers. Twice-weekly TPE (1.5 plasma volume [PV], 5% albumin replacement) with weekly titers and IVIG (1 g/kg) was initiated at 9 weeks of gestation (WG). The threshold titer was ≥16. Weekly middle cerebral artery-peak systolic velocities (MCA-PSV) for fetal anemia monitoring was initiated at 16 WG. PVs were adjusted throughout pregnancy based on treatment schedule, titers, and available albumin. Antigen-negative, ABO-compatible RBCs were obtained through the rare donor program and directed donation. An autologous blood autotransfusion system was reserved for delivery. Titers decreased from 128 to 8 by 10 WG. MCA-PSV remained stable. At 24 WG, TPE decreased to once weekly. After titers increased to 32, twice-weekly TPE resumed at 27 WG. Induction of labor was scheduled at 38 WG. Vaginal delivery of a 2950 g neonate (APGAR score: 9, 9) occurred without complication (Cord blood: 1+ IgG DAT; Anti-PP1Pk eluted). Newborn hemoglobin and bilirubin were unremarkable. Discharge occurred postpartum day 2. Anti-PP1Pk alloimmunization is rare but associated with recurrent miscarriages and HDFN. With multidisciplinary care, a successful pregnancy is possible with IVIG and TPE adjusted to PV and titers. We also propose a patient registry and comprehensive management plan.

BACKGROUND: We report an obstetric case involving an RhD-positive woman who had developed a red blood cell (RBC) antibody that was not detected until after delivery of a newborn, who presented with a positive direct antiglobulin test result. Immunohematology studies suggested that the maternal antibody was directed against a low-prevalence antigen on the paternal and newborn RBCs.
RESULTS: Comprehensive blood group profiling by targeted exome sequencing revealed a novel nonsynonymous single nucleotide variant (SNV) RHCE c.486C>G (GenBank MZ326705) on the RHCE*Ce allele, for both the father and newborn. A subsequent genomic-based study to profile blood groups in an Indigenous Australian population revealed the same SNV in 2 of 247 individuals. Serology testing showed that the maternal antibody reacted specifically with RBCs from these two individuals.
CONCLUSIONS: The maternal antibody was directed against a novel antigen in the Rh blood group system arising from an RHCE c.486C>G variant on the RHCE*Ce allele linked to RHD*01. The variant predicts a p.Asn162Lys change on the RhCE protein and has been registered as the 56th antigen in the Rh system, ISBT RH 004063.
CONCLUSIONS: This antibody was of clinical significance, resulting in a mild to moderate hemolytic disease of the fetus and newborn (HDFN). In the past, the cause of such HDFN cases may have remained unresolved. Genomic sequencing combined with population studies now assists in resolving such cases. Further population studies have potential to inform the need to design population-specific red cell antibody typing panels for antibody screening in the Australian population.

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.

BACKGROUND: Low-titer group O whole blood (LTOWB) for treatment of hemorrhagic shock sometimes necessitates transfusion of RhD-positive units due to short supply of RhD-negative LTOWB. Practitioners must choose between using RhD-positive LTOWB when RhD-negative is unavailable against the risk to a female of childbearing potential of becoming RhD-alloimmunized, risking hemolytic disease of the fetus and newborn (HDFN) in future children, or using component therapy with RhD-negative red cells. This survey asked females with a history of red blood cell (RBC) alloimmunization about their risk tolerance of RhD alloimmunization compared to the potential for improved survival following transfusion of RhD-positive blood for an injured RhD negative female child.
METHODS: A survey was administered to RBC alloimmunized mothers. Respondents were eligible if they were living in the United States with at least one red cell antibody known to cause HDFN and if they had at least one RBC alloimmunized pregnancy.
RESULTS: Responses from 107 RBC alloimmmunized females were analyzed. There were 32/107 (30%) with a history of severe HDFN; 12/107 (11%) had a history of fetal or neonatal loss due to HDFN. The median (interquartile range) absolute improvement in survival at which the respondents would accept RhD-positive transfusions for a female child was 4% (1%-14%). This was not different between females with and without a history of severe or fatal HDFN (p = .08 and 0.38, respectively).
CONCLUSIONS: Alloimmunized mothers would accept the risk of D-alloimmunization in a RhD-negative female child for improved survival in cases of life-threatening bleeding.

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.