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PubMed1981

Rh isoimmunization: a 24 year experience at Duke University Medical Center.

A retrospective analysis was made of Rh-sensitized patients delivered of their babies at Duke University Medical Center during a 24 year period. Records of 202 obstetric patients representing 280 sensitized pregnancies from a pool of 39,910 deliveries were analyzed for past obstetric history, blood group information, antibody determinations, amniocentesis data, and details of the pregnancy and delivery. The medical records of the corresponding infants were analyzed for their neonatal course. A severity index (SI) was devised to classify the degree of severity of the erythroblastosis fetalis. A significant correlation between SI and the delta OD450 of amniotic fluid, umbilical cord hematocrit, and bilirubin was noted. The evaluation of amniotic fluid delta OD450 is considered to be the cornerstone of clinical management. Twenty-nine patients had initial Liley zone 1 determinations which decreased to delta OD450 = 0.000; however, only 10 of 29 (34.5%) of the infants were unaffected, and 13 of 29 (44.8%) had mild sensitization, four of 29 (13.8%) had moderate sensitization, and two of 29 (6.9%) had severe sensitization. The previously held concept of "critical titer" as a guide for initiating amniocentesis is challenged, and the recommendation is made that amniocentesis for amniotic fluid determination should be undertaken in any patient with a positive indirect Coombs titer.

Adolescent↗
PubMed1983

Oral desensitization in Rh disease.

Four pregnancies managed with erythrocyte membrane oral therapy because of severe Rh disease are presented. Reduction in anti-(D) production was the goal of the study. A patient was classified as having severe Rh immunization if there was a history of fetal loss due to erythroblastosis fetalis prior to 26 weeks.

Administration, Oral↗
PubMed1988

The effect of replacing fetal hemoglobin with adult hemoglobin on blood gas and acid-base parameters in human fetuses.

In order to determine whether the differences between fetal and adult hemoglobins are important to fetal oxygenation, pH, PO2, PCO2, bicarbonate, and base excess were measured in umbilical venous and arterial blood samples obtained from fetuses with erythroblastosis fetalis. The values from fetuses that had previously been transfused and had predominantly adult hemoglobins were compared with those that had not been transfused and had predominantly fetal hemoglobin. Umbilical arterial blood was more acidotic and had a greater base deficit, while the umbilical venous PO2 was 4.8 mm Hg higher in the samples with adult hemoglobins than in those with fetal hemoglobin. The results suggest that oxygenation of fetal tissue is better with fetal hemoglobin but that adult hemoglobin can be compensated by an increase in oxygen transfer.

Acid-Base Equilibrium↗
PubMed1989

Acid-base status in fetal heart blood in erythroblastotic fetuses: a study with special reference to the effect of transfusions with adult blood.

Blood gas levels, pH, and lactate concentration were studied in fetal heart blood on 70 occasions in 26 fetuses with erythroblastosis. A decreasing hemoglobin concentration correlated to a fall in pH (p = 0.006) and bicarbonate (p = 0.015) and to a rise in base deficit (p = 0.002) and lactate concentration (p = 0.05). Twenty of the fetuses underwent 63 intracardiac transfusions. A multivariance analysis for hemoglobin concentration, percentage of fetal to adult blood, and different acid-base parameters revealed a significant correlation between the presence of adult blood and a rise in PO2 (p = 0.047), but failed to demonstrate any correlation to the other studied acid-base variables. Thus the present study suggests that the fetus can compensate for the physiologic properties of adult hemoglobin that are disadvantageous to itself by increasing PO2 and thereby maintaining oxygen supply. The physiologic background and the clinical implication are discussed.

Acid-Base Equilibrium↗
PubMed1994

Erythropoietic suppression in fetal anemia because of Kell alloimmunization.

OBJECTIVE: Our purpose was to test the hypothesis that maternal anti-Kell alloimmunization produces fetal anemia by erythroid suppression. STUDY DESIGN: Erythropoiesis in 11 anemic fetuses from maternal anti-Kell alloimmunization was compared with that in 11 fetuses where the mother was alloimmunized to RhD; each was matched for hematocrit, gestational age, hydrops, and perinatal outcome. Comparisons of the difference were performed by either paired t or Wilcoxon tests. RESULTS: The anti-Kell group had reduced reticulocytosis (p = 0.007) and erythroblastosis (p = 0.045) and lower amniotic fluid bilirubin concentrations (p = 0.02) in comparison with the anti-D group. No correlation was found between hematocrit and reticulocytosis in the anti-Kell group, whereas the anti-D group had a significant linear relationship (r = 0.63, p < 0.05), indicating a progressive reticulocytosis in response to the degree of anemia. CONCLUSION: These findings suggest that erythroid suppression, rather than hemolysis, is the predominant mechanism in producing fetal anemia related to maternal Kell alloimmunization. Fetal blood sampling is the investigation of choice in the evaluation of anemia related to maternal Kell alloimmunization, because reduced hemolysis means amniotic fluid bilirubin concentrations correlate poorly with anemia.

Erythroblastosis, Fetal↗
PubMed1996

Haemolytic disease of the newborn due to anti-K antibodies.

We describe a case of intrauterine foetal death at 32 weeks gestation with signs of hydrops foetalis without erythroblastosis. The hydrops foetalis appeared to be caused by blood group incompatibility. Irregular antibodies of anti-K specificity were found in the serum of the mother, while the father was positive for the K-antigen. The antibody dependent cell-mediated cytotoxicity (ADCC) test with serum of the mother was positive. This case shows the characteristics of haemolytic disease of the newborn by anti-K. Moreover, it underlines the necessity of both adequate follow-up of individual cases, and screening for irregular antibodies in all pregnancies as well as central registration of screening results.

Adult↗
PubMed1988

Reassessment of the utility of fetal umbilical vein diameter in the management of isoimmunization.

High-resolution ultrasound has been recently introduced in the management of many conditions in which the fetus is at risk. In the detection of severe erythroblastosis fetalis, sonographic evaluation of fetal anatomic changes is being used in association with amniotic fluid spectral analysis to assess the degree of the hemolytic process. In 1981 it was reported that sonographically detected umbilical vein dilatation, resulting from hepatic congestion, could be used as a sign of impending fetal compromise. We analyzed data obtained from 47 patients in a total of 76 examinations, including sonographic measurement of umbilical vein diameter, associated ultrasound findings, results of amniotic fluid spectral analyses, and neonatal outcome. The collected data, divided in two groups according to the results of amniotic fluid spectral analyses (less than high zone II and greater than or equal to high zone II), showed that the sonographic measurement of umbilical vein diameter does not differ significantly between the two groups (p greater than 0.05). Therefore, the present and relatively large series demonstrates that dimensions of the umbilical vein cannot be used as a reliable predictor of worsening fetal disease.

Erythroblastosis, Fetal↗
PubMed1976

Possible effect of maternal promethazine therapy on neonatal immunologic functions.

The effect of the administration of promethazine in the treatment of erythroblastosis fetalis was studied in four maternal-fetal pairs. The three infants exposed for a prolonged period of time had decreased neonatal number and function of T cells, and abnormal specific humoral immune responses. The possible role of promethazine in the induction of fetal immunoincompetence is discussed.

Antibodies↗
PubMed1994

Cerebral blood volume changes during exchange transfusions in infants born at or near term.

We investigated the effects on cerebral hemodynamics of blood pressure changes during exchange transfusions in infants born at or near term, using near infrared spectroscopy in eight stable infants (mean gestational age, 36.2 +/- 1.3 weeks) who underwent a total of 21 exchange transfusions for erythroblastosis fetalis (rhesus hemolytic disease). Changes in mean arterial blood pressure derived from an indwelling umbilical arterial catheter, transcutaneous arterial oxygen and carbon dioxide tension, as well as changes in cerebral oxygenated hemoglobin (HbO2), deoxygenated hemoglobin (HbR), and total hemoglobin (Hbtot = HbO2 + HbR), were recorded continuously from 15 minutes before until the completion of the exchange transfusion. Relative change(s) in cerebral blood volume (dCBV) were calculated as follows: dCBV = change in Hbtot x 0.89/Venous hemoglobin. Changes in mean arterial blood pressure and dCBV were observed during all exchange transfusions; a decrease was found during the withdrawal period and an increase during the infusion period. The mean response of dCBV to a change in mean arterial blood pressure was 0.011 ml.100 gm-1.mm Hg. Multivariate analysis showed that dCBV were primarily associated with changes in mean arterial blood pressure, followed by changes in arterial oxygen tension and in exchange cycle duration. We conclude that in stable term and near-term infants, hemorrhagically induced blood pressure changes provoke dCBV.

Blood Pressure↗
PubMed2001

Fetal splenic rupture following transfusion.

BACKGROUND: Splenic rupture in the newborn is a rare complication in erythroblastosis fetalis. There are no reports of splenic rupture in the fetus affected by hemolytic disease of the newborn. CASE: A 41-year-old gravida 3, para 2-0-0-2 with severe rhesus alloimmunization was managed with serial intrauterine transfusions resulting in fetal death after the fourth procedure. Autopsy findings revealed intra-abdominal clotted blood and splenic capsular defects consistent with splenic rupture. CONCLUSION: Fetal splenic rupture might occur in hemolytic disease of the newborn associated with splenomegaly. Acute hemodynamic changes with increased intra-abdominal pressure from intrauterine transfusion might precipitate splenic rupture. (Obstet Gynecol 2001;97:824-5.

Adult↗
PubMed1978

Formation of 15alpha-hydroxyestriol and 15alpha-hydroxyestradiol from C19 15alpha-hydroxylated precursors in human pregnancy.

A mixture of 3H-15alpha-hydroxyandrostenedione and 14C-15alpha-hydroxydehydroisoandrosterone was injected intravenously into two subjects in the third trimester of pregnancy and, in a second study, directly into two fetuses in utero during transfusion for erythroblastosis fetalis. The urine was collected for 4-5 days and steroid conjugates in the urine were hydrolyzed into sulfate and glucosiduronate fractions. From the glucosiduronate fraction 15alpha-hydroxyestriol, 15alpha-hydroxyestradiol, 15alpha-hydroxyandrostenedione and 15alpha-hydroxydehydroisoandrosterone were isolated. No metabolites were identified in the sulfate fraction of the urine. A marked difference was observed in the metabolism of 15alpha-hydroxyandrostenedione and 15alpha-hydroxydehydroisoandrosterone which is dependent on the route of administration of the substrates. Both substrates were converted to 15alpha-hydroxyestriol and 15alpha-hydroxyestradiol, and the 3H/14C ratios and percentage conversions suggest that 15alpha-hydroxyandrostenedione seems to be a better precursor of the urinary 15alpha-hydroxylated estrogens than 15alpha-hydroxydehydroisoandrosterone. The 3H/14C ratios also suggest that 15alpha-hydroxydehydroisoandrosterone was converted to 15alpha-hydroxyestriol via 15alpha-hydroxyandrostenedione, and that the formation of 15alpha-hydroxyestradiol from 15alpha-hydroxydehydroisoandrosterone via 15alpha-hydroxyandrostenedione is a pathway of minor importance. Finally, 15alpha-hydroxydehydroisoandrosterone was recovered from the urine only when the precursors were injected into the maternal circulation. Also, an unknown metabolite containing only 14C was detected in the glucosiduronate fraction of the urine of each subject.

Androstenedione↗
PubMed1988

2,3-Diphosphoglycerate in normal, anaemic and transfused human fetuses.

1. The effect of anaemia and transfusion with adult blood on fetal 2,3-diphosphoglycerate levels was investigated by studying fetal blood from 45 normal pregnancies at 17-42 weeks of gestation and in 34 pregnancies complicated by erythroblastosis fetalis. 2. In normal fetuses, 2,3-diphosphoglycerate concentration was higher than in adults and did not change significantly with gestational age. 3. In erythroblastotic fetuses, there was a significant negative correlation between 2,3-diphosphoglycerate concentration and haemoglobin concentration. 4. When adult blood was transfused into the fetal circulation, 2,3-diphosphoglycerate concentration reached similar levels to that found in untransfused fetuses after allowing for the severity of anaemia.

2,3-Diphosphoglycerate↗
PubMed1997

A severe transfusion-dependent congenital dyserythropoietic anaemia presenting as hydrops fetalis.

We describe a case of congenital dyserythropoietic anaemia (CDA) presenting at week 20 of pregnancy with hydrops fetalis and very severe anaemia. Fetal blood examination showed marked erythroblastosis with morphologic alterations while the basic haematological and biochemical tests were in the normal range. The fetus received intravascular red blood cells transfusion at 20 and 25 weeks of gestation. After a caesarean section at week 33 the child became transfusion dependent. Haematological investigations demonstrated that the child is affected by a CDA-like picture which, although morphologically similar to CDA II, is Ham test negative and does not show the typical membrane proteins alterations.

Adult↗
PubMedDate not supplied

Fatal hemolytic disease of a newborn due to anti-D in an Rh-positive Du variant mother.

This report presents an account of fatal hemolytic disease of the newborn (HDN) due to anti-D in a mother whose red cells showed the phenotypic characteristics of Rh positive Du variant. The proposita's third pregnancy was uneventful until the eighth month, when she presented with an unusually large abdomen. A sonogram showed fetal hydrops, and amniocentesis yielded a delta OD450 reading in Zone 3. Anti-D with a titer of 4096 was identified in the mother's serum. Following delivery by cesarean section, the premature infant did not respond to resuscitation. The autopsy findings were consistent with Rh erythroblastosis fetalis. The proposita has been classified as a Category VI Du variant with anti-D in her serum.

Adult↗
PubMed1989

Preparation of packed red cells suitable for intravascular transfusion in utero.

Intra-cardiac transfusion in utero is a recent development in the treatment of erythroblastosis foetalis. As with intra-umbilical cord transfusion, the procedure has been described as having a high risk of complication characterized by bradycardia and cardiac-arrest. Intra-coronary hyperkalemia was suspected as being a major contributing factor towards the complications experienced, particularly by the intra-cardiac delivery. The procedure is warranted, however, in cases where intra-umbilical cord transfusion is not possible. Therefore, studies comparing various methods of preparing packed cells for intravascular transfusion were initiated. The plasma potassium levels of gravity sedimented packed cells and saline washed red cells resuspended in either Ringer's lactate, pooled donor plasma or saline were measured. Products of saline washed/resuspended packed red cells transfused within 2 hours of preparation were found to have low potassium levels while exposing the fetus to minimal risk of transfusion transmitted infection and were therefore selected to be the most suitable product. Using this product, a significant decrease in the incidence of severe bradycardia resulting in cardiac-arrest, following intravascular transfusion (32 procedures) was observed.

Blood Transfusion, Intrauterine↗
PubMed1996

[Functional evaluation of erythrocytic antibodies by photometric detection of erythrophagocytosis in the monocyte monolayer assay].

In haemolytic disease of newborn (erythroblastosis fetalis) the in vivo behaviour of erythrocytic IgG antibodies is of particular significance. The monocyte monolayer assay (MMA), which determines by microscopy the number of erythrocytes phagocytosed by monocytes, is an important functional test for the qualitative assessment of erythrocytic IgG antibodies. We set up a photometric MMA and compared it with the microscopic MMA. In both tests we employed commercially available rhesus antibody sera and examined 8 sera of pregnant women with mild and severe courses of haemolytic disease of newborn by the photometric MMA. Good agreement was found between the microscopic and photometric MMA (r = 0.93). Over and above this the photometric MMA correlated with the course of haemolytic disease of newborn in 7 out of 8 cases (with one false-positive finding). The photometric technique permits rapid, sensitive and reproducible determination of erythrophagocytosis in microtitre plates. This method is based on the photometric detection of haemoglobin of phagocytosed erythrocytes via a peroxidase reaction. Standardised photometric MMA could in future be more widely applied especially in haemolytic disease of newborn for the functional characterisation of erythrocytic antibodies, the incidence of intra-assay and inter-assay errors being low.

Coombs Test↗
PubMed1993

Monocyte monolayer assay as a predictor of severity of hemolytic disease of the fetus and newborn.

The monocyte monolayer assay (MMA), an in vitro model of in vivo antibody-mediated red blood cell destruction, was previously reported to predict the severity of hemolytic disease of the fetus and newborn accurately when only Rh antibodies and antigen-positive babies were studied. We studied 33 women whose serum contained antibodies with the potential to cause erythroblastosis fetalis; 7 of the 33 women had antibodies other than Rh. None of the babies of the ten women who had consistently negative test results required intrauterine or neonatal transfusions. False-positive MMA results were sometimes found when the fetus was antigen negative. Although the predictive value of a negative MMA was 100%, the efficiency of the MMA was no better than that of the antibody titer. Because of the lack of advantage of the MMA as well as the time and expense it requires, we cannot recommend the general clinical application of this test at this time.

Antibodies↗