Rhesus Haemolytic Disease Research Articles

High dose intravenous immunoglobulin therapy in the treatment of rhesus hemolytic disease.

High dose intravenous immunoglobulin therapy in the treatment of rhesus hemolytic disease.

Sir Cyril Astley Clarke, C.B.E. 22 August 1907 – 21 November 2000

Cyril Clarke was an outstanding physician, medical scientist and lepidopterist. His career was unusual in that he developed a serious interest in medical research only after many years in clinical practice, a change of direction from the life of a busy consultant physician that was undoubtedly stimulated by his lifelong interest in butterflies. This remarkable transition was to result in his leading the team in Liverpool that developed a method for preventing rhesus haemolytic disease of the newborn, one of the major advances in preventative medicine of the second half of the twentieth century.

Cholesterol dynamics in the foetal and neonatal brain as reflected by circulatory levels of 24S‐hydroxycholesterol

Oxysterols, particularly those hydroxylated in the steroid side‐chain, are formed from cholesterol by specific cytochrome P450 enzymes and may facilitate elimination of cholesterol from extrahepatic sources. In humans, the greatest portion of circulating 24S‐hydroxycholesterol (24S‐OH‐Chol) is derived from the brain and the absolute concentration depends on age. In the present study, concentrations of 24S‐OH‐Chol and for comparison 27‐OH‐Chol were determined by a highly sensitive isotope dilution method using gas chromatography‐mass spectrometry in serum samples from normal preterm and term neonates and those with Rhesus haemolytic disease, taken serially for diagnostic purposes. Serum concentrations of cholesterol, 24S‐OH‐Chol and 27‐OH‐Chol were similar in venous versus arterial cord blood of 6 term neonates. Serum concentrations of 24S‐OH‐Chol and 27‐OH‐Chol in 12 small for gestational age (SGA) preterm neonates were significantly lower than those in 12 appropriate for gestational age (AGA) preterm neonates (p < 0.001), and also lower than those in 12 SGA (p < 0.001) and 12 AGA term neonates (p < 0.05). Serum cholesterol was significantly higher in preterm than in term neonates (p < 0.001). 24S‐OH‐Chol serially determined in 8 infants with Rhesus haemolytic disease increased 5‐6‐fold during the first 3 mo after birth (from 42 ± 20 ng ml−1 to 227 ± 71 ng ml−1). 27‐OH‐Chol increased simultaneously from 30 ± 14 ng m ml−1 to 100 ± 39 ng m ml−1. Conclusion: Serum concentrations of 24S‐OH‐Chol increased 5‐6‐fold after birth. This could be an indication of normal cholesterol metabolism in the developing neonatal brain.

Cyril Astley Clarke

The passing of Cyril Clarke marks the end of the era of great medical all rounders. His career as a clinician ranged through life insurance practice, medical specialist in the...

The role of immunoglobulins in neonatal Rhesus haemolytic disease.

Rhesus (Rh) isoimmunisation is the most common form of severe haemolytic disease of the newborn (HDN). The introduction of prophylaxis with anti-D Rh0 immunoglobulin (anti-D) has resulted in a marked reduction in the sensitisation of Rh-negative women and deaths attributable to Rh HDN. The sensitisation rate could be further decreased if there was strict adherence to the guidelines for administration of anti-D prophylaxis. Whether additional prophylaxis at 28 and 34 weeks of gestation would be cost effective is controversial. Intrauterine transfusions to treat fetal anaemia, postnatal exchange transfusions and phototherapy are all part of the standard management of affected individuals. Intravenous immunoglobulin given to pregnant women can reduce fetal haemolysis, and when administered to neonates with Rh isoimmunisation has been associated with a reduction in the requirement for exchange transfusion. There are, however, potential risks of immunoglobulin administration, including haemolysis due to the presence of anti-A or anti-B antibodies, allergy and the transmission of disease.

Successful chelation therapy in a case of neonatal iron overload following intravascular intrauterine transfusion.

We report a newborn infant who was successfully treated with chelation therapy having developed severe liver disease secondary to iron overload following multiple intrauterine, intravascular transfusions (IVTs). Case report with review of the literature. An infant was born at 33 weeks' gestation having received multiple IVTs for severe rhesus hemolytic disease. At birth there was severe anemia with hydrops and ascites. Severe liver disease was present with portal hypertension, coagulopathy and abnormal liver enzymes. A liver biopsy showed histologic features consistent with iron overload. The serum ferritin was in excess of 4000 micrograms/l. A 7-week course of deferoxamine resulted in a marked reduction in ferritin levels and significant improvement in liver function. The possibility of neonatal iron overload following multiple IVTs should be borne in mind. Successful chelation therapy is possible in such cases.

Rhesus disease: postnatal management and outcome.

The incidence of rhesus haemolytic disease has been markedly reduced. Affected infants who have had intrauterine transfusions suffer a late hyporegenerative anaemia. Postnatal haemolysis and hence treatment for hyperbilirubinaemia is less commonly needed. Optimal phototherapy reduces the need for postnatal exchange transfusions, but data on the efficacy of inhibitors of bilirubin production such as haem oxygenase inhibitors or immunoglobulin are less secure. Even hydropic infants have less than 20% mortality and bilirubin encephalopathy is uncommon. There is, however, very limited information on the long-term outcome of infants with rhesus haemolytic disease. Multicentre collaboration is required to test strategies to improve the management of affected individuals further and to provide meaningful data on their prognosis.

Non-Protein-Bound Iron and Free Radical Damage in Fetuses with Rhesus Hemolytic Disease; Influence of Intra-Uterine Transfusions

Non-Protein-Bound Iron and Free Radical Damage in Fetuses with Rhesus Hemolytic Disease; Influence of Intra-Uterine Transfusions

Severe late anemia of hemolytic disease of the newborn

Late anemia is a well-recognized complication of Rhesus hemolytic disease of the newborn (HDN). The incidence of Rhesus HDN is declining, with a tendency for more severely affected pregnancies to be managed in specialist centres. Consequently, many paediatric departments may see relatively few affected infants with comparatively mild disease, and the risk of late anemia in such cases may not always be appreciated. Two cases of infants born with evidence of Rhesus isoimmunization noted at birth and encountering no immediate problems other than mild hyperbilirubinemia are described. After an uneventful early neonatal course, both infants were discharged without follow-up and presented in the second to third weeks of life with severe, life-threatening anemia, leading to neurological sequelae in one case. The importance of close surveillance, including hemoglobin measurements, in all infants with Rhesus hemolytic disease, irrespective of initial severity, is reiterated.

Late hyporegenerative anemia in neonates with rhesus hemolytic disease.

This study was conducted to determine the risk factors of the late hyporegenerative anemia in Rh-isoimmunized infants. Data on 36 infants with rhesus hemolytic disease were analyzed. The mean gestational age and birth weight were 36 +/- 1.3 weeks and 2837 +/- 403 grams respectively. Twenty-seven infants (75%) received between 2 and 8 intravascular intrauterine blood transfusions. Fourteen infants (39%) required simple packed red blood cell transfusions and 11 infants (31%) required exchange blood transfusion in the immediate postnatal period. Thirty infants (83%) developed late anemia and required blood transfusions at a mean postnatal age of 43.3 +/- 15.7 days. Sixty-four percent of infants who had exchange blood transfusions did not develop late anemia, while 92% of infants who did not require exchange blood transfusion developed late anemia, and the difference was statistically significant (P = 0.035). Serum erythropoietin levels were determined in 8 infants immediately before simple transfusion for late anemia. The media serum erythropoietin level was 21.2 mU/ml, ranging between less than 10 to 114.2 mU/ml. We conclude that late hyporegenerative anemia is common among Rh isoimmunized infants, regardless of the intravascular intrauterine transfusion. Exchange blood transfusion was associated with less occurrence of late anemia.

The impact of phototherapy in the management of neonatal hyperbilirubinemia: comparison of historical cohorts

To quantitatively assess the impact of phototherapy (PT) in the prevention of kernicterus we calculated the rate of exchange transfusion (ET) in two large historical cohorts of Greek neonates (birthweight > or = 2.5 kg), one before (period I: 1957-61) and one after (period II: 1980-92) the introduction of PT. Overall, the introduction of PT was associated with a reduction of the rate of ET from 0.43% in period I to 0.05% in period II. The reduction was observed in all etiological categories but was more marked in the ABO-incompatible group. With an estimated rate of kernicterus without treatment of 0.085% (excluding rhesus hemolytic disease of the newborn and prematurity) we estimated that 4.2 and 0.36 infants were treated by ET for each spared kernicterus in periods I and II, respectively. Finally, in period II 185 infants were treated with PT or PT and ET for each spared kernicterus.

High dosage immunoglobulin therapy in Rhesus incompatibility

From September 1992 to the end of August 1993 we treated fourteen children who suffered from rhesus hemolytic disease with high-dose intravenous immune globulin G. Eleven patients did not require an exchange transfusion, three needed an exchange transfusion despite immune globulin therapy. Although an exchange transfusion cannot be avoided in all patients, this new method is an important addition to the currently available possibilities of treatment. It is without adverse side effects and helps to lower the number of exchange transfusions.

Rhesus hemolytic disease in the fetus and newborn as a risk factor for schizophrenia in male adults

Rhesus hemolytic disease in the fetus and newborn as a risk factor for schizophrenia in male adults

Single-cell analysis of the RhD blood type for use in preimplantation diagnosis in the prevention of severe hemolytic disease of the newborn

OBJECTIVE: Our purpose was to develop a molecular assay to determine the fetal RhD blood type on single diploid cells, including blastomeres. STUDY DESIGN: Polymerase chain reaction amplification of a 99 bp deoxyribonucleic acid fragment of the RhD gene or a 113 bp fragment from the RhCE gene was performed from 20 venous blood samples and 20 amniotic fluid samples and from 60 single-cultured lymphoblasts and 12 media blanks mixed in a blinded fashion. This reaction was similarly tested after whole-genome amplification on 10 lymphoblasts and seven human blastomeres. RESULTS: Deoxyribonucleic acid amplification was successful and correct from all genomic deoxyribonucleic acid samples. Ninety-seven percent of single cells amplified: correct diagnosis was made in 96%. Five blastomeres successfully amplified. No media blanks produced amplified, contaminating deoxyribonucleic acid. CONCLUSIONS: The RhD blood type can be determined reliably from single cells and can be used for preimplantation genetic diagnosis for the prevention of rhesus hemolytic disease.

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 (HbO 2), deoxygenated hemoglobin (HbR), and total hemoglobin (Hb tot =HbO 2 + 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 Hb tot × 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. (J P EDIATR 1994;125:617-21)

Causes and Clinical Consequences of Rhesus (D) Haemolytic Disease of the Newborn

Causes and Clinical Consequences of Rhesus (D) Haemolytic Disease of the Newborn

Causes and clinical consequences of Rhesus (D) haemolytic disease of the newborn: a study of a Scottish population, 1985-1990.

To identify the reasons behind failures to prevent the development of Rhesus (D) haemolytic disease of the newborn. Retrospective analysis of the case records of all pregnancies that resulted in the birth of an infant with a positive direct antiglobulin test on the cord red cells born to Rh(D) negative women between 1 April 1985 and 31 March 1990. Obstetric units in the South East Scotland region and the South East Scotland Regional Blood Transfusion Service Antenatal Laboratory. The causes and clinical consequences of maternal immunisation to the Rhesus (D) antigen. Between 1985 and 1990, 80 pregnancies resulted in the birth of an infant sensitised with anti-D on the cord red cells. There were no deaths due to haemolytic disease, but considerable resources were deployed in obstetric and neonatal care for these pregnancies. Sufficient data were available to categorise the cause of maternal immunisation in 70 pregnancies. Seven cases were due to immunisation by pregnancy before 1970. Sixty-three cases could be attributed to failure of the Rhesus programme: 10 cases (16%) were due to failure to implement the programme adequately, the other 53 cases (84%) were due to failure of the current guidelines to provide adequate protection. Late immunisation in an uncomplicated pregnancy was the single commonest identifiable cause. It is likely that substantial further reductions in Rhesus (D) immunisation and haemolytic disease of the newborn will require changes in the Rhesus prevention programme. In particular the role of antenatal prophylaxis requires detailed consideration.

Developmental outcome after intravascular intrauterine transfusion for rhesus haemolytic disease.

The development outcome of 16 infants who had rhesus disease was assessed at 18 months. Eight had received intravascular intrauterine transfusion and eight postnatal exchange transfusions. There was no difference in developmental outcome and neither group was different from the population as a whole.

Antenatal diagnosis and outcome in hydrops fetalis

The records of 15 cases of hydrops fetalis consecutively delivered at our institution were reviewed to determine the accuracy of antenatal diagnosis and whether antenatal diagnostic techniques yielded information useful in predicting outcome. All 15 cases were detected antenatally, five were due to rhesus haemolytic disease and 10 were non-immune hydrops. All the infants required active resuscitation. Ten infants eventually died, two had immune hydrops fetalis and 8 non-immune hydrops. Seven infants had pleural effusions, all had been detected antenatally. The presence of pleural effusions did not influence mortality. All structural abnormalities were accurately detected in those patients seen prior to labour and there were no survivors in the group of infants so affected. We conclude that the mortality of non-immune hydrops fetalis remains high and that antenatal diagnosis of this condition is accurate and provides useful prognostic information.

Effect of an Exchange Transfusion on Plasma Antioxidants in the Newborn

The effect of an exchange transfusion on antioxidants in the plasma of newborns with rhesus hemolytic disease was studied. The antioxidant concentrations in donor blood were similar to normal adult values except for the lower vitamin C concentrations. Exchange transfusion decreased the newborns' iron and ferritin levels and increased their ceruloplasmin and transferrin (primary antioxidants) concentrations and latent iron-binding capacity. The changes in secondary antioxidant concentrations were variable; uric acid and thiols were stable, vitamin C and bilirubin fell, and vitamin E rose. The total peroxyl-radical trapping capacity of the secondary antioxidants did not change significantly. The fall in levels of thiobarbituric acid reactive substances, an index of lipid peroxidation, was related to the lower levels present in the donor blood. Exchange transfusion rapidly produced variable changes in the concentrations of prooxidant and antioxidant substances in plasma and may thus influence free radical metabolism in the newborn.