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.

UNASSIGNED: Hemolytic disease of the newborn (HDN) is a common condition that can have a severe impact on the health of newborns due to the hemolytic reactions it triggers. Although numerous studies have focused on understanding the pathogenesis of HDN, there are still many unanswered questions.
UNASSIGNED: In this retrospective study, serum samples were collected from 15 healthy newborns and 8 infants diagnosed with hemolytic disease. The relationship between different metabolites and various IgG subtypes in Healthy, HDN and BLI groups was studied by biochemical technique and enzyme-linked immunosorbent assay (ELISA). Metabolomics analysis was conducted to identify the differential metabolites associated with HDN. Subsequently, Pearson\'s correlation analysis was used to determine the relation of these differential metabolites with IgG isoforms. The relationship between the metabolites and IgG subtypes was observed after treatment.
UNASSIGNED: The study results revealed that infants with hemolytic disease exhibited abnormal elevations in TBA, IgG1, IgG2a, IgG2b, IgG3, and IgG4 levels when compared to healthy newborns. Additionally, differences in metabolite contents were also observed. N, N-DIMETHYLARGININE showed negative correlations with TBA, IgG1, IgG2a, IgG2b, IgG3, and IgG4, while 2-HYDROXYBUTYRATE, AMINOISOBUTANOATE, Inosine, and ALLYL ISOTHIOCYANATE exhibited positive correlations with TBA, IgG1, IgG2a, IgG2b, IgG3, and IgG4. Through metabolomics-based research, we have discovered associations between differential metabolites and different IgG isoforms during the onset of HDN.
UNASSIGNED: These findings suggest that changes in metabolite and IgG isoform levels are linked to HDN. Understanding the involvement of IgG isoforms and metabolites can provide valuable guidance for the diagnosis and treatment of HDN.

Augustine is a newly identified blood group system comprising four antigens, one of which is the high-frequency antigen Ata in the original \"series\". Four antigens are located on a multipass membrane glycoprotein equilibrative nucleoside transporter 1 (ENT1), and equilibrative nucleoside transporter is encoded by SLC29A1. In 2016, the International Society of Blood Transfusion (ISBT) recognised Augustine as a blood group system and numbered it as 036. The glycoprotein ENT1 transports nucleotides into cells to participate in the synthesis of DNA and RNA, and this is an important link for chemotherapeutic glycosides to enter tumour cells. Augustine antibodies are clinically relevant in blood transfusion and pregnancy.

Deoxynivalenol (DON) is by far the most common mycotoxin contaminating cereal foods and feeds. Furthermore, cleaning up DON from contaminated cereal items is challenging. Low-dose DON consumption poses a danger to humans and agricultural animals. The benefits of hesperidin (HDN) include liver protection, anti-oxidative stress, nontoxicity, and a broad range of sources. The study used immunoblotting, immunofluorescence, and transmission electron microscopy to identify factors associated with mitophagy in vitro and in vivo. We demonstrated that low-dose DON exposure inhibited mitophagy in the liver tissue of mice. SIRT1 was a crucial regulator of mitophagy. Moreover, DON stimulated the dephosphorylation of SIRT1 and the acetylation-regulated FOXO3 protein, which resulted in the transcriptional inhibition of FOXO3-driven BNIP3 and compromised the stability of the PINK1 protein mediated by BNIP3. Moreover, HDN\'s effect was comparable to that of a SIRT1 agonist, which led to a significant decrease in the level of mitophagy inhibition caused by low-dose DON exposure. When combined, these findings suggested that HDN might be a useful treatment approach for liver damage brought on by low-dose DON exposure. Above all, this research will offer fresh perspectives on a viable approach that will encourage further research into risk reduction initiatives for low-dose DON exposure.

Hemolytic disease of the newborn (HDN) occurs in approximately 1 out of 3000 live births. Severe presentations are atypical but must be recognized and treated rapidly to avoid life-threatening organ dysfunction.
Here we report an unusual case of neonatal ABO HDN that illustrates the enormous inflammatory potential of maternal-fetal blood group mismatch. Following an uneventful delivery notable only for HDN caused by maternal anti-B IgG, our patient developed shock, DIC, and renal failure. Despite numerous interventions, she experienced a rapid clinical decline and died 10 days after birth. Treatment with whole blood exchange and a monoclonal antibody directed at complement component 5 (eculizumab) were attempted late in the disease course but were unsuccessful. Importantly, this patient had several known risk factors for severe ABO HDN, including the pentad of a group O mother with a group B neonate, high newborn red blood cell B antigen expression, presence maternal anti-B isohemagglutinin in high titer, presence of a maternal IgG anti-B isohemagglutinin, and African ancestry.
Clinicians should be aware of the potential for severe ABO HDN and consider earlier diagnostic workup and more aggressive therapy in patients with high-risk features.

Hydrodenitrogenation (HDN) experiments and density functional theory (DFT) calculations were combined herein to study the substituent effects of the nitrogen heterocycle on the HDN behaviors of indole and quinoline. Indole (IND), 2-methyl-indole (2-M-IND), 3-methyl-indole (3-M-IND), quinoline (QL), 2-methyl-quinoline (2-M-QL) and 3-methyl-quinoline (3-M-QL) were used as the HDN reactant on the NiMo/γ-Al2O3 catalyst. Some key elementary reactions in the HDN process of these nitrogen compounds on the Ni-Mo-S active nanocluster were calculated. The notable difference between IND and QL in the HDN is that dihydro-indole (DHI) can directly convert to O-ethyl aniline via the C-N bond cleavage, whereas tetrahydro-quinoline (THQ) can only break the C-N single bond via the full hydrogenation saturation of the aromatic ring. The reason for this is that the -NH and C=C groups of DHI can be coplanar and well adsorbed on the Ni-Mo-edge simultaneously during the C-N bond cleavage. In comparison, those of THQ cannot stably simultaneously adsorb on the Ni-Mo-edge because of the non-coplanarity. Whenever the methyl group locates on the α-C or the β-C atom of indole, the hydrogenation ability of the nitrogen heterocycle will be evidently weakened because the methyl group increases the space requirement of the sp3 carbon, and the impaction of the C=C groups on the Ni-S-edge cannot provide enough space. When the methyl groups are located on the α-C of quinoline, the self-HDN behavior of 2-M-QL is similar to quinoline, whereas the competitive HDN ability of 2-M-QL in the homologs is evidently weakened because the methyl group on the α-C hinders the contact between the N atom of 2-M-QL and the exposed metal atom of the coordinatively unsaturated active sites (CUS). When the methyl group locates on the β-C of quinoline, the C-N bond cleavage of 3-methyl-quinoline becomes more difficult because the methyl group on the β-C increases the steric hindrance of the C=C group. However, the competitive HDN ability of 3-M-QL is not evidently influenced because the methyl group on the β-C does not evidently hinder the adsorption of 3-M-QL on the active sites.

The Jr blood group system includes a single, high-prevalence antigen, Jra , encoded by the ABCG2 gene. The impact of anti-Jra in pregnancy is variable, ranging from no clinical effect to severe anemia including some fetal deaths. Case reports have postulated that anti-Jra mediated fetal anemia is poorly hemolytic, suggesting other mechanisms of anemia may be involved.
We describe the case of severe anti-Jra mediated fetal anemia. At Canadian Blood Services laboratories, maternal anti-Jra was tested for phagocytic activity via a monocyte monolayer assay (MMA) and erythroid suppression via inhibition of burst forming unit-erythroid (BFU-E) colony formation assays. The New York Blood Center sequenced exons 4 and 7 of the ABCG2 gene.
Sequencing of exons 4 and 7 of the ABCG2 gene revealed maternal compound heterozygosity for two nonsense mutations at exon 7 (c.706 C > T and c.784G > T). Fetal sequencing revealed the c.706C > T polymorphism. The MMA showed a borderline phagocytic index (around the cutoff of five for both donor segments tested [5 ± 1 and 7 ± 3]). The BFU-E colony formation inhibition assay suggested a dose-dependent inhibition of BFU-E colony formation with inhibition percentages of 4%, 11%, and 43% at maternal serum concentrations of 2%, 5%, and 10%, respectively. Our findings support the hypothesis that anti-Jra may impair erythropoiesis leading to clinically significant fetal/neonatal anemia. A referral to maternal fetal medicine is recommended if anti-Jra is detected in pregnancy, regardless of the titer.

OBJECTIVE: Haemolytic disease of the newborn (HDN) is an immune haemolytic anaemia from maternal alloantibodies. Rh immunoglobulin (RhIg) prophylaxis can prevent alloimmunization to the D antigen. However, RhIg is not universally available in Uganda. ABO incompatibility also causes HDN. We determined the prevalence of HDN among newborn infants with jaundice in Uganda.
METHODS: We conducted a prospective cross-sectional study at Kawempe National Referral Hospital, Kampala, Uganda. Infants aged 0-14 days with neonatal jaundice (or total bilirubin >50 μmol/L) were enrolled. Clinical evaluation and laboratory testing, including ABO, RhD typing and maternal antibody screen, were performed.
RESULTS: A total of 466 babies were enrolled. The mean (SD) age was 3.4 (1.5) days. Of newborn babies with jaundice, 17.2% (80/466) had HDN. Babies with HDN had lower haemoglobin (SD); 15.7 (2.7) compared with those without HDN; 16.4 (2.4) g/dL, p = 0.016; and a higher bilirubin (interquartile range); 241 (200-318) compared with those without HDN; 219 (191-263) μmol/L, p < 0.001. One baby had anti-D HDN, while 46/466 had HDN from an ABO incompatibility (anti-A 43.5% and anti-B 56.5%); 82% of babies with HDN also had suspected neonatal sepsis or birth asphyxia. About 79.2% (57/72) of mothers did not have ABO/Rh blood group performed antenatally. All infants with HDN survived except one.
CONCLUSIONS: Among newborn infants with jaundice, HDN is not rare. The majority is due to ABO HDN affecting group A and group B babies equally. Ensuring routine ABO/Rh grouping for all pregnant women is an area for improvement.

Hemolytic disease of the fetus and newborn (HDFN) due to rhesus D (RhD) immunization is a potentially life-threatening situation for which use of Rh Immunoglobulin (RhIg) has decreased risk drastically. Determination of fetal RHD on maternal plasma can be used to restrict prenatal RhIg administration to women carrying an RhD-positive child, avoiding unnecessary administration of blood-derived products.
The aim of this study is to determine the performance of fetal RHD typing in our center. We prospectively collected 205 fetal RHD and 127 serological cord blood RhD data from RhD-negative women starting at 11 weeks of pregnancy (from October 2019 to October 2021). Real-time polymerase chain reaction targeting RHD exon 5 and 7 was used, similar to the screening program in The Netherlands, supplemented with an amplification control (beta-actin; ACTB) and a sex determination marker located on the Y-chromosome (SRY gene).
Fetal RHD testing reached a sensitivity and specificity of 100%. No false-negative nor false-positive results were reported. Inconclusive results (6%, 13/205) were due to weak amplification in 10 cases, a maternal RHD variant in 2 cases (RHD*01N.71 and partial DVI), and a fetal RHD variant (partial DVI) in 1 case. Unnecessary administration of RhIg prophylaxis was avoided in 33% of cases and on the other hand was administered in one case (fetal partial DVI) which would have been missed with cord blood serology.
This study demonstrates the high accuracy of routine prenatal fetal RHD gene screening after 11 weeks of pregnancy, encouraging routine clinical practice.

BACKGROUND: Hemolytic disease of the fetus and newborn (HDFN) is a clinically significant problem that may potentially affect any pregnancy. Direct antiglobulin test (DAT) is considered to be an important test in identifying newborns who are suspected to have HDN. This study aims in reviewing data regarding a positive DAT result concerning etiology and the development of HDN over a period of 10 years.
METHODS: A retrospective study of all neonates with a positive DAT result between January 2011 and December 2020 was performed. Data were obtained from patients\' electronic hospital files, transfusion medicine databases, and medical birth records. Laboratory parameters along with clinical interventions in neonates with a DAT-positive result and a comparison group of DAT-negative neonates were performed.
RESULTS: 36,000 deliveries were registered in this period. 176 (2.65 %) neonates had a positive DAT result. ABO-incompatibility was the most common cause with 59.1 %; Rh incompatibility 13.8 %, minor blood group incompatibility, and other RBC-related antibodies 10.1 %, and unspecified etiology in 17 % of cases. Among DAT-positive cases, 32.7 % of neonates were diagnosed with HDN. ABO-incompatibility was the major reason as well. Initial mean total bilirubin levels were higher in the DAT-positive group than the control group (p < 0.001), and these neonates also had a lower initial hemoglobin level (p < 0.001). The need for therapeutic interventions was significantly higher in DAT-positive neonates (p < 0.001) as 86.8 % underwent phototherapy, with 32.7 %, and 17.6 % receiving exchange transfusion (ET) and intravenous immunoglobulin (IVIG), respectively.
CONCLUSIONS: In conclusion, ABO incompatibility was the most common cause for neonatal DAT positivity. Besides the common causes of DAT positivity, there would be rare but important conditions that may lead to a positive result, such as antibodies passively acquired from mothers in the context of alloimmunizations or using drugs. In addition, as a high rate of therapeutic intervention was identified among neonates with a DAT-positive result, there is a crucial need for increasing awareness regarding early diagnosis of the condition, careful monitoring, and the employment of prenatal alloimmunization screening tests.