Conservative Management of Hyperferritinemia in Hemolytic Disease of the Fetus and Newborn: A Case Report and Review of the Literature.

We report a newborn with hemolytic disease of the fetus and newborn (HDFN) with rapid resolution of extreme hyperferritinemia without chelation. An infant born at 35+3 weeks with HDFN and a history of 3 intrauterine transfusions developed severe hyperferritinemia (maximum, 8258 mcg/L) without evidence of toxic iron deposition on liver biopsy. Her hyperferritinemia was managed with observation alone, and ferritin levels normalized rapidly. This case supports observation as being the preferred alternative to chelation therapy for significant hyperferritinemia in newborns with HDFN in the absence of demonstrated toxic end-organ iron deposition. We also include a review of the related available literature.

Changes in middle cerebral artery velocimetry of fetuses diagnosed postnatally with mild or moderate hemolytic disease.

OBJECTIVES: To determine the longitudinal trends of middle cerebral artery peak systolic velocity (MCA PSV) in fetuses with mild or moderate hemolytic disease according to the need for postnatal therapy. DESIGN: Prospective cohort study. SETTING: University referral center. SAMPLE: Twenty-three fetuses from singleton alloimmunized pregnancies. METHODS: Serial measurements of MCA PSV were performed. After delivery, newborns were grouped by the need for postnatal management into mild hemolytic disease, which required no or only phototherapy (n = 14, group 1), and moderate hemolytic disease, where postnatal top-up or exchange transfusions were required (n = 9, group 2). MAIN OUTCOME MEASURES: Serial Doppler MCA PSV data transformed to multiples of the median, analyzed with linear regression and exponential models. RESULTS: We performed 83 measurements in group 1: 3-8 per fetus; mean GA at inclusion, 23 weeks and 65 measurements in group 2: 4-15 per fetus; mean GA at inclusion, 22 weeks. The estimated mean slopes of the MCA PSVs increased with the degree of postnatal therapy required (group 1: MCA PSV = 0.003 GA + 1.298; group 2: MCA PSV = 0.035 GA + 0.436). The relative average increments (RAI) were 4.7% and 7.1%, respectively. The two groups exhibited significant differences in mean slope and RAI (p<0.05). CONCLUSIONS: Fetuses that required postnatal transfusions due to hemolytic disease showed an enhanced progressive increase in MCA PSVs compared to those without transfusion requirement. This information might enable their identification during pregnancy.

Unbound bilirubin predicts abnormal automated auditory brainstem response in a diverse newborn population.

OBJECTIVE: The objective of this study was to determine if plasma unbound or 'free' bilirubin concentration (B(f)) measured during the first 30 days of life is associated with subsequent abnormal hearing screening testing by automated auditory brainstem response (AABR) in a diverse population of newborns. STUDY DESIGN: An observational study of newborns receiving AABR, plasma total bilirubin concentration (TBC) and B(f) measurements and without underlying conditions known to affect hearing was conducted. Logistic regression was used to determine associations between abnormal AABR and B(f) or TBC. The impacts of a variety of clinical factors on the regression model were also assessed. RESULT: A total of 191 patients with birth weights and gestations ranging from 406 to 4727 g and 24 to 42 weeks, respectively, were studied. Among them, 175 (92%) had normal (bilateral PASS) AABR and 16 had abnormal AABR (6 had unilateral REFER AABR, and 10 had bilateral REFER AABR). Mean TBC was not significantly different in babies with normal or abnormal AABR, but mean B(f) was greater in the latter group (1.76 versus 0.93 microg per 100 ml, respectively, P=0.012). B(f), but not TBC, was associated with an abnormal AABR (B(f) adjusted odds ratio 3.3, 95% CI 1.8 to 6.1). Comparing receiver-operating characteristics curves, the B(f)/TBC ratio was a better predictor of an abnormal AABR than B(f) alone. Intraventricular hemorrhage was the only confounding clinical variable. CONCLUSION: An abnormal AABR is associated with an elevated B(f) or B(f)/TBC ratio, but not the TBC alone. The prevalence of bilirubin neurotoxicity as a cause of audiological dysfunction may be underestimated if the TBC alone is used to assess the severity of newborn jaundice.

Lutheran.

The Lutheran blood group system consists of 19 antigens: four pairs of antithetical antigens--Lu(a)/Lu(b), Lu6/Lu9, Lu8/Lu14, and Au(a)/Au(b)--and 11 antigens of very high frequency. These antigens are located on four of the five immunoglobulin-like domains of both isoforms of the Lutheran glycoprotein. The LU gene is on chromosome 19 and comprises 15 exons. The two glycoprotein isoforms differ in the length of their cytoplasmic tails as a result of alternative splicing of intron 13. Lu(null) phenotype arises from homozygosity for inactivating mutations in the LU gene.The dominantly inherited Lu(mod) phenotype, In(Lu), results from heterozygosity for inactivating mutations in KLF1, the gene for the erythroid transcription binding factor EKLF. Clinically, antibodies of the Lutheran system are relatively benign. When hemolytic, they generally cause only mild, delayed hemolytic transfusion reactions or hemolytic disease of the fetus and newborn that can be treated by phototherapy. The Lutheran glycoproteins, which are members of the immunoglobulin superfamily of adhesion molecules and receptors, bind isoforms of laminin with alpha5 chains,components of the extracellular matrix abundant in vascular endothelia. The primary function of the Lutheran glycoproteins on RBCs could involve the transfer of maturing RBCs from the bone marrow to the peripheral circulation. They could also be involved in vascular occlusion and thrombotic events as complications of sickle cell disease and polycythemia vera, respectively.

Severe hemolytic disease of the newborn from anti-e.

Maternal antibody-mediated fetal red blood cell destruction secondary to non-D Rhesus (Rh) antibodies is a significant cause of hemolytic disease of the newborn (HDN). Here, we report a rare case of severe HDN associated with maternal antibody to Rh e. In addition to severe anemia, the infant developed thrombocytopenia, conjugated hyperbilirubinemia and cholelithiasis. Resolution of the infant's cholelithiasis occurred following treatment with ursodeoxycholic acid.

Serial blood donations for intrauterine transfusions of severe hemolytic disease of the newborn with the use of recombinant erythropoietin in a pregnant woman alloimmunized with anti-Ku.

BACKGROUND: The management of a pregnant woman with the rare Ko phenotype and anti-Ku is a special challenge, because matched blood is extremely rare and the possibility of severe hemolytic disease of the newborn is high. CASE REPORT: A 30-year-old woman with rare Ko (Knull) phenotype presented at 18 weeks of gestation with positive indirect agglutination test results. She had anti-Ku due to previous blood transfusion, one pregnancy, and two abortions. STUDY DESIGN AND METHODS: During this pregnancy, anti-Ku titers ranged from 1024 to 4096. At the 26th week of gestation ultrasound showed a hydropic fetus and urgent intrauterine exchange transfusion was performed with the maternal red blood cells (RBCs). Recombinant human erythropoietin (rHu-EPO) and intravenous (IV) iron were administered to the mother to ensure an adequate supply of matched RBCs for intrauterine transfusions and possible perinatal hemorrhage. RESULTS: Intrauterine transfusions were repeated every 1 to 3 weeks. By 35 weeks 2 days of gestation, the mother had donated 4 units of blood, and four intrauterine transfusions had been performed. Cesarean section was then decided and a healthy male newborn was born. He was treated with phototherapy but without exchange transfusions. By the 15th day of life rHu-EPO was administrated to the newborn because of anemia. The maternal RBCs completely disappeared from the child's blood by Day 100. CONCLUSIONS: As shown in this case, treatment with rHu-EPO and IV Fe has effectively increased the mother's capacity to donate RBCs for autologous use and intrauterine transfusions, with no adverse effects to the mother or the child.

Donación autóloga en una gestante con anticuerpos antieritrocitarios anti-U y anti-He (Henshaw) / Autologous tranfussion in a pregnant with anti-U and anti-He (Henshaw)

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Neurodesarrollo al año de vida en infantes con antecedentes de enfermedad hemolítica por factor Rh / Neurodevelopment at one year of age in infants of Rhesus hemolytic disease

Introducción. Los reportes de seguimiento en infantes con antecedente de enfermedad hemolítica del recién nacido (EHRN) por factor Rh informan coeficientes intelectuales menores en estos pacientes. El objetivo del presente estudio fue analizar el estado neurológico al año de vida de infantes con EHRN y su relación con algunas variables neonatales.Material y métodos. Los pacientes se analizaron en función de las tres zonas de Liley-Sentíes, de la presencia de anemia (hematócrito menor de 40 por ciento), número de transfusiones intrauterinas, calificación de Apgar, edad gestacional, peso, bilirrubinas, número de exanguinotransfusiones, días de fototerapia, hospitalización y del resultado de la valoración neurológica y audiológica al año de vida.Resultados. Se estudiaron 56 pacientes; solamente el peso y la edad gestacional fueron significativamente menores para los de la zona III de la clasificación de Liley-Sentíes. No se encontraron diferencias neurológicas entre los pacientes de las 3 zonas. El grupo de infantes anémicos tuvo un número significativamente mayor de alteraciones neurológicas severas, así como menor edad gestacional y mayor número de días en fototerapia. La transfusión intrauterina no tuvo relación con la anemia ni sobre el estado neurológico al año de vida. El porcentaje de infantes con alteración neurológica fue de 30 por ciento, de los cuales 76 por ciento estuvieron asociados a anemia. Conclusión. Los resultados están de acuerdo a lo reportado en la literatura, donde se describe una relación significativa entre anormalidad neurológica y menor nivel de hemoglobina. Se observó que la gravedad de la hemólisis por factor Rh evaluada por el esquema de Liley-Sentíes no se relaciona con el estado neurológico al año de vida.

ABO hemolytic disease of the newborn: a unique constellation of findings in siblings and review of protective mechanisms in the fetal-maternal system.

Two siblings born 6 years apart presented with similar findings of hepatosplenomegaly, dermal hematopoiesis, hemoglobinuria, and increased platelet consumption, but only moderate anemia and normal serum bilirubin. ABO incompatibility was identified, and other causes were excluded. A review of the current understanding of mechanisms that promote and prevent antibody-mediated hemolysis in the fetus is reviewed. Due to the low ratio of observed to expected significant clinical events among ABO incompatible mother-infant pairs, and the multiplicity of mechanisms that diminish hemolysis, we speculate that severe ABO hemolytic disease of the newborn occurs when there is a specific failure in one of these preventive mechanisms.

The bronze baby syndrome: evidence of increased tissue concentration of copper porphyrins.

A case regarding a newborn infant with severe Rh haemolytic disease, who presented with the bronze baby syndrome and eventually died, is reported. The postmortem examination showed marked extramedullary haematopoiesis in the liver and spleen, heavy hepatic haemosiderosis and mild intralobular cholestasis. The porphyrin content, which was assayed in different tissues, was very high in the liver, suggesting that the increased erythropoiesis seen in Rh haemolytic disease leads to an increased synthesis of porphyrins as by-products of haem synthesis. Phototherapy causes photodestruction, sensitized by bilirubin, of porphyrins (mainly copper porphyrins), yielding brown photoproducts.