High-Dose Intravenous Gammaglobulin Therapy for Neonatal Immune Haemolytic Jaundice due to Blood Group Incompatibility

ABSTRACT. Three newborn infants who developed hyperbilirubinemia due to blood group incompatibility were treated with high-dose gammaglobulin. Hyperbilirubinemia was caused by Rhesus (Rh) incompatibility (anti-E + anti-c) in Infant 1 and ABO incompatibility (anti-B) in Infants 2 and 3. Hyperbilirubinemia was refractory to conventional phototherapy but responded well to intravenous gammaglobulin (IVGC) at dose of 1 g/kg in all infants. No adverse effects were observed. These findings suggest that high-dose IVGG may be useful in the treatment of hyperbilirubinemia due to isoimmune baemolytic disease resistant to phototherapy.     

Combination of ABO blood group incompatibility and glucose-6-phosphate dehydrogenase deficiency: effect on hemolysis and neonatal hyperbilirubinemia

The incidence (%) of hyperbilirubinemia (serum bilirubin ≥257 μmol/l) was similar in neonates with a combination of ABO incompatibility and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency (45%), with ABO incompatibility (54%) or G-6-PD deficiency (37%), alone (ns). Carboxyhemoglobin values, corrected for inspired CO, were similarly elevated in all three groups (0.87 ± 0.32%, 0.82 ± 0.29%, 0.76 ± 0.18%, respectively, ns), but correlated with bilirubin only in those with ABO incompatibility alone. ABO-incompatible/G-6-PD-deficient neonates, compared with those with either condition alone, are not at increased risk for hemolysis or hyperbilirubinemia.     

Intravenous immune globulin reduces the need for exchange transfusions in Rhesus and AB0 incompatibility

Abstract Aim: To conduct a quality control review of a single institution experience with intravenous immune globulin in the treatment of Rhesus and AB0 incompatibility. Methods: Intravenous immune globulin as treatment for Rhesus and AB0 incompatibility was introduced in our hospital in 1998. We performed a chart review of 176 infants with Rhesus or AB0 incompatibility treated in our hospital between 1993 and 2003, divided into a historical control group (1993-1998) and a treatment group (1999-2003). The project was approved through institutional ethics procedures. Results: The use of exchange transfusion as a therapeutic modality was significantly reduced in the cohort treated with intravenous immune globulin (OR 0.11; 95% CI 0.046-0.26, p < 0.001). We found no difference between the intravenous immune globulin group and the infants receiving only exchange transfusion as far as the duration of phototherapy. Infants with Rhesus incompatibility had a higher need for top-up transfusions than those with AB0 incompatibility. Conclusion: This study supports the evidence from previous studies suggesting that intravenous immune globulin significantly reduces the need for exchange transfusion in infants with Rhesus and AB0 incompatibility.     

Spectrum of neonatal hyperbilirubinemia: an analysis of 454 cases.

A prospective study of 454 newborn babies with pathological hyperbilirubinemia revealed that in about one-third of cases (34.6%), no cause could be identified despite detailed investigations. Nearly three-fifth of infants (62.5%) had hyperbilirubinemia due to hemolytic causes. On the basis of four variables, i.e., peak serum bilirubin level, age of attaining the peak level, age of starting phototherapy and total duration of phototherapy, the cases of hyperbilirubinemia can be categorized into three groups: (a) Group I (mild) included non-hemolytic hyperbilirubinemia, i.e., idiopathic, bacterial infections, intrauterine infections and others, (b) Group II (moderate) comprised of hemolytic as well as non-hemolytic hyperbilirubinemia due to prematurity, administration of oxytocin, bruising/cephalhematoma, and (c) Group III (severe) comprised of hyperbilirubinemia due to hemolysis as a result of blood group incompatibility between the mother and the neonate and G-6-PD deficiency. Sixty six babies required exchange blood transfusion (EBT) and a total of 100 EBTs were performed. Most of the babies (80.3%) requiring exchange blood transfusion belonged to Group III. The most common cause of hemolytic hyperbilirubinemia needing exchange blood transfusion was Rh isoimmunization followed by G-6-PD deficiency and ABO isoimmunization. There was no death attributable to the procedure of exchange blood transfusion.     

High-dose intravenous gammaglobulin therapy for neonatal immune haemolytic jaundice due to blood group incompatibility.

Three newborn infants who developed hyperbilirubinemia due to blood group incompatibility were treated with high-dose gammaglobulin. Hyperbilirubinemia was caused by Rhesus (Rh) incompatibility (anti-E + anti-c) in Infant 1 and ABO incompatibility (anti-B) in Infants 2 and 3. Hyperbilirubinemia was refractory to conventional phototherapy but responded well to intravenous gammaglobulin (IVGG) at a dose of 1 g/kg in all infants. No adverse effects were observed. These findings suggest that high-dose IVGG may be useful in the treatment of hyperbilirubinemia due to isoimmune haemolytic disease resistant to phototherapy.     

Hemolytic disease of the newborn due to isoimmunization with anti-E antibodies: a case report

Minor blood group hemolytic disease is extremely rare, since the overall potency of minor blood groups in inducing antibodies is significantly lower when compared with that of Rh (D) antigen. We hereby report a very rare case of severe neonatal anti-E hemolytic disease due to E minor blood group incompatibility. A term newborn born to a 27-year-old, gravida 3, para 3 mother was referred due to a high and increasing serum bilirubin level despite phototherapy on the 4th day of life. On admission physical examination was normal except for the jaundice, and results of the laboratory investigation demonstrated a moderate-to-severe anemia (hemoglobin 7.8 g/dl) and a severe hemolytic hyperbilirubinemia (serum total and indirect bilirubin levels 36 mg/ dl and 32.8 mg/dl, respectively; reticulocyte count 15%; and a positive direct antiglobulin test). As there was no apparent cause of the hemolytic disease such as Rh or ABO incompatibilities, further investigation (a positive indirect antiglobulin test and a positive irregular anti-E antibody in both the patient and mother, and minor blood group antigen profiles in family members compatible with E minor blood group isoimmunization) revealed the presence of anti-E hemolytic disease due to E minor blood group incompatibility. Two exchange transfusions with a 12-hour-interval were performed with minor blood group compatible fresh whole blood, and the patient was discharged in a healthy condition on the 10th postnatal day. If the most common causes of severe neonatal hemolytic disease such as Rh and ABO incompatibilities cannot be demonstrated in a newborn with significant hemolytic hyperbilirubinemia, anti-E hemolytic disease should strongly be considered in differential diagnosis. It should be kept in mind that a very severe from of minor group antibody hemolytic disease characterized by anemia and severe hyperbilirubinemia many exchange transfusions may be encountered during the course of the disease.     

Long Duration of Erythrocyte Hypoplasia after Bone Marrow Transplantation

Bone marrow transplantation was performed on a 15 year old girl with chronic myelogenous leukemia. The bone marrow was obtained from her younger sister, who was human leukocyte antigen haplo-identical but major ABO incompatible. As a result, the condition of pure red cell aplasia (PRCA) persisted over a long period of time. In order to overcome major ABO incompatibility, erythrocytes were eliminated from the bone marrow graft before transplantation, and methotrexate and cyclosporine (CsA) were used to prevent graft-versus-host disease (GVHD). Administration of erythropoietin proved ineffective. B19 parvovirus infection could not be detected during that time. Agglutinin titers decreased to less than fourfold in parallel with the recovery of erythrocytes. Reports on similar PRCA have been limited to cases of transplantation with ABO incompatibility and cases where CsA was administered to prevent GVHD. This suggests that ABO incompatibility and CsA might be related to the development of PRCA.     

Haematolytic disease due to ABO incompatibility: Incidence and value of screening in an Asian population

Abstract The population in Singapore is predominantly Asian, with Chinese forming the major ethnic group. The incidence of haemolytic disease of the newborn (HDN) due to Rh incompatibility is very low. The true incidence of HDN due to ABO incompatibility is unknown. Early discharge is practised in Singapore making it important to predict severe HDN due to ABO incompatibility as this would constitute the main cause of haemolysis next to G6PD deficiency. One thousand, six hundred and eight baby-maternal pairs were typed for ABO, Rh, and tested for direct Coombs'test, maternal titre, cord bilirubin and haptoglobin levels. Two hundred and fifty-one were found to be ABO incompatible, with 141 group A and 110 group B babies. The incidence of HDN due to ABO incompatibility was 3.7% of all group O mothers. Coombs'test, maternal antibody titre, cord bilirubin and haptoglobin levels were of low predictive value for severe HDN due to ABO incompatibility. The data further support the notion that it is not cost effective to screen for ABO incompatibility.     

ENDOGENOUS FORMATION OF CARBON MONOXIDE IN NEWBORN INFANTS III. ABO Incompatibility

The carboxyhaemoglobin (COHb) concentration in blood, which is assumed to reflect the degree of haemoglobin catabolism, was determined in 62 newborn infants selected because of significant jaundice associated with ABO incompatibility, and in 46 infants with ABO incompatibility, selected without regard to the degree of bilirubinaemia. Furthermore, the COHb level was determined in 46 icteric infants without haemolytic disease, and in 61 infants of ABO homospecific pregnancies, selected without regard to their bilirubin level. In infants with ABO incompatibility increased COHb concentrations were found not only in infants with unequivocal signs of haemolytic disease but also in infants with a clinical picture indistinguishable from physiological jaundice. During the first days the relation between COHb and bilirubin in infants with ABO incompatibility was the same, whether the infants were selected because of significant jaundice or irrespective of the degree of bilirubinaemia. This indicates a common pathogenesis of the bilirubinaemia in the two groups. The COHb and bilirubin levels in infants of ABO heterospecific pregnancies and in infants of ABO homospecific pregnancies, selected without regard to the degree of bilirubinaemia, were compared. It is concluded that the COHb level probably is a more sensitive indicator of haemolysis than the bilirubin concentration. Increased COHb concentrations were also found in icteric infants without blood group incompatibility, but the relation between COHb and bilirubin indicates that in ABO incompatibility increased haemolysis is of greater importance in the pathogenesis of the jaundice.     

Trends in neonatal exchange transfusions at Yodogawa Christian Hospital

A review was conducted to determine the trends in exchange transfusion (ET) of newborn infants at the Yodogawa Christian Hospital during the past 18 years. At that hospital in 1957, the first ET was performed on a term infant with severe hemolytic jaundice caused by rhesus factor (Rh) incompatibility. By 1989, ET had been performed in more than 1400 newborn infants. These cases of newborns who had had ET were retrospectively reviewed, with a focus on every 3 year period from 1974 to 1992. The total number of infants requiring ET noticeably decreased from 68 cases (14.0% of total admissions) in 1974 to 19 cases (6.1% of total admissions) in 1992. (X², P < 0.001) There were three major significant changes in ET during those years. The first was a change in the subjects for ET. The incidence of ET for term infants showed a marked decrease, while the incidence of ET for preterm infants, especially for very low birthweight (VLBW) infants (< 1500 g), noticeably increased. The second was a change in indications for ET. There was a marked decrease in the need for ET as a result of hyperbilirubinemia, while the incidence of ET because of other etiologies, such as septicemia and/or disseminated intravascular coagulopathy, noticeably increased. The third was a change in the technical methods of ET. Now at the Yodogawa Christian Hospital, 100% of the infants are given ET with an automated peripheral two-site method, instead of the Diamond method. Although ET might still be a useful treatment for severe hyperbilirubinemia and other acute problems, the total number of ET noticeably decreased in accord with a decrease in the number of severe hyperbilirubinemia in term newborns. On the other hand, the incidence of ET in preterm infants increased relatively, accompanied by an increase in the survival of VLBW infants. The automated two-site method is the preferred technique for ET at the Yodogawa Christian Hospital, rather than the Diamond method. Further changes in ET might occur in accord with new alternative measures in future.     

Neonatal jaundice due to ABO incompatibility in Sri Lankan

A prospective study was carried out on 101 neonates with jaundice due to ABO incompatibility. The direct Coomb’s test was weakly positive in 4 cases. The indirect Coomb’s test using the eluate was positive in 8 cases. In the maternal blood either IgG anti-A or anti-B haemolysin was present in high titre in every case. Phototherapy was given when the indirect serum bilirubin level exceeded 9 mg/dl. Exchange transfusion was done in 39 cases, 9 babies requiring multiple exchanges. There were 2 deaths.     

Exchange Transfusion with Fresh Heparinized Blood is a Safe Procedure

1069 newborns were subjected to exchange transfusion with fresh heparinized blood in the years 1968, 1971, 1974, 1977 and 1981. There were 258 infants with Rh disease, 328 with hyperbilirubinemia with ABO incompatibility, 436 with hyperbilirubinemia without ABO incompatibility and 47 infants without hyperbilirubinemia or evidence of hemolytic disease. The total annual number of infants decreased gradually from 279 in 1968 to 130 in 1981. A total of 48 infants of the 1069 newborns died during neonatal period but the death was possibly related to exchange transfusion in four of them. There were serious complications in 14 infants during and in only five infants after the procedure. Morbidity related to exchange transfusion was the highest among newborns with serious basic disease. Using the presented bilirubin nomograms and fresh heparinized blood we have not found that the hazards of exchange transfusion would have overgone the risks of hyperbilirubinemia.     

Exchange transfusion with fresh heparinized blood is a safe procedure. Experiences from 1 069 newborns

1 069 newborns were subjected to exchange transfusion with fresh heparinized blood in the years 1968, 1971, 1974, 1977 and 1981. There were 258 infants with Rh disease, 328 with hyperbilirubinemia with ABO incompatibility, 436 with hyperbilirubinemia without ABO incompatibility and 47 infants without hyperbilirubinemia or evidence of hemolytic disease. The total annual number of infants decreased gradually from 279 in 1968 to 130 in 1981. A total of 48 infants of the 1 069 newborns died during neonatal period but the death was possibly related to exchange transfusion in four of them. There were serious complications in 14 infants during and in only five infants after the procedure. Morbidity related to exchange transfusion was the highest among newborns with serious basic disease. Using the presented bilirubin nomograms and fresh heparinized blood we have not found that the hazards of exchange transfusion would have overgone the risks of hyperbilirubinemia.     

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目的研究葡萄糖6磷酸脱氢酶(G6PD)缺乏的新生儿高胆红素血症发生率及发病特点。方法对近5年来中山市陈星海医院产科分娩的足月健康新生儿脐带血进行G6PD定量测定,对G6PD活性缺乏的患儿,按性别和酶活性缺乏的程度分组调查其高胆红素血症的发生率及发病时间。结果(1)418例G6PD活性缺乏的患儿共发生高胆红素血症82例,占19.62%。(2)在G6PD活性缺乏的患儿中,男性酶的活性极显著低于女性(P<0.01);高胆红素血症的发生率男性极显著高于女性(P<0.01);酶活性缺乏程度不同的3组患儿高胆红素血症发生率有显著差别(P<0.05);G6PD活性缺乏的患儿发生高胆红素血症的时间主要在出生后的1周内。结论在新生儿期,G6PD活性缺乏的患儿高胆红素血症的发生率较高,发病具有男性多于女性、酶活性缺乏程度越重高胆红素血症的发生率越高的特点,患儿发生高胆红素血症的高峰时间在出生后的2～4d。     

Mortality of exchange transfusion and risks associated with hyperbilirubinemia

Summary The mortality of exchange transfusions and risks associated with hyperbilirubinemia experienced with 202 exchange transfusions performed on 143 newborn infants, have been reviewed. A large proportion of the infants belonged to the groups with ABO or no incompatibility. In view of the high risk of kernicterus in severe hyperbilirubinemia, exchange transfusion should be attempted even in the face of poor general condition in such cases. From the Department of Pediatrics, Faculty of Medicine, Pahlavi University, Shiraz, Iran.     

足月儿高胆红素血症482例相关因素分析

目的 探讨足月儿高胆红素血症(简称高胆)的相关因素以及高胆程度.方法 对2001年7月-2006年7月收治的高胆足月儿482例进行分析.结果 482例高胆患儿中,早发型母乳性黄疸178例(36.9%,其中70.3%为剖宫产),迟发型母乳性黄疸125例(25.9%),ABO血型不合溶血60例(12.5%),围产相关因素54例(11.2%),感染相关因素49例(10.2%),其他16例(3.3%).以溶血者总血清胆红素最高(351.0±188.1)μmol/L.482例高胆患儿中轻、中、重度分别占42.5%、36.3%和21.2%.重度高胆中早发型母乳性黄疸31例(30.4%),ABO溶血20例(19.6%),迟发型母乳性黄疸25例(24.5%).482例中核黄疸4例,1例为严重酸中毒、脱水,3例为ABO溶血.结论 母乳性黄疸为住院足月儿高胆的主要原因,剖宫产可能与早发型母乳性黄疸有关;ABO溶血是导致患儿核黄疸的主要原因.     

新生儿MN血型不合溶血病3例报道暨文献复习

目的总结新生儿MN血型不合溶血病的临床特点、诊治经验及发病机理。方法报告我科近年诊治的3例新生儿MN血型不合溶血病,复习我科曾报道的另外2例,并通过中国知网、万方数据库和维普中文期刊数据库,检索国内近24年来报告的所有病例报告,对患儿的临床表现和实验室检查进行总结分析。结果包括本文报道的3例,国内共报道31例新生儿MN血型不合溶血病,MN型25例,M型6例;直接抗人球蛋白试验阳性13例,抗体释放试验阳性17例,患儿血型抗体IgG抗M型阳性28例;母亲血型抗体IgG抗M型阳性30例,IgM抗M阳性16例。31例患儿中6例（19．4％）为第1胎发病,贫血发生率67．7％,其中重度贫血发生率29．0％,重度高胆红素血症发生率22．6％;较多患儿需要换血（29．0％）和输血（45．2％）;病死率9．7％。结论新生儿MN血型不合溶血病容易出现黄疸、贫血,可导致患儿急性死亡。光疗、输注丙种球蛋白、白蛋白等治疗效果良好,严重病例需要换血、输血治疗。为了提高MN溶血病的诊断率,应检测孕妇MN血型及抗M抗体效价。     

Exchange transfusion in infants with extreme hyperbilirubinemia: an experience from a developing country

OBJECTIVE: To determine the clinical and epidemiological features of infants with extreme hyperbilirubinemia who require exchange transfusion (ET). STUDY DESIGN: Term and near-term infants admitted to a paediatric hospital over a 5-year period in La Paz, Bolivia, were included in the study if they met the following criteria: age less than 30 days; total serum bilirubin (TSB) levels > or =428 micromol/L (> or =25 mg/dL) on admission and if they had undergone an ET. RESULTS: Fifty-six infants were identified during the study period. Most of them were exclusively breastfed (98.2%). Median age at admission was 7 days. Weight loss of more than 12% since birth, as well as dehydration, was registered in more than one-third of cases. Extreme hyperbilirubinemia was considered as secondary to increased enterohepatic circulation (EHC) in most cases (73%). The mean TSB level on admission was 531.8 micromol/L (31.1 mg/dL). Fifteen infants (26.8%) showed signs of acute bilirubin encephalopathy (ABE). Early ABE was reversible after ET in most cases but all infants with advanced ABE developed severe kernicteric sequelae. Nine patients (16.1%) developed adverse events attributable to ET. CONCLUSIONS: Dehydration and weight loss in breastfed infants appeared to be an important factor associated with extreme hyperbilirubinemia and secondary brain damage during the first week of life. This may well be avoided if signs of ABE and its associated conditions are identified appropriately by follow-up programmes.     

Early prediction of neonatal hyperbilirubinemia

The study aim was to predict, using serum bilirubin, level measured 18 to 24 hours (SB, 18–24) after birth, the occurrence of peak serum bilirubin level >15 mg/dL (hyperbilirubinemia) or the requirement of phototherapy, any time from the second to fifth postnatal day. The study was conducted on a prospective cohort of 274 neonates born in north India. The main outcome measures were (a) hyperbilirubinemia and (b) phototherapy. Serum bilirubin level was estimated at 18–24 hours of age and then daily from second to fifth postnatal day. Exclusion criteria were Rh incompatibility, asphyxia and life threatening congenital malformations; and neonates of women with gestational diabetes or history intake of drugs affecting the fetal liver. Hyperbilirubinemia was found in 12.8%; and 19.3% neonates received phototherapy. Dichotomous SB 18–24, using a cut-off of >3.99 mg/dL, as the “prediction test” had the following sensitivity and specificity for predicting (a) hyperbilirubinemia: 67% and 67%, respectively, and (b) the treatment with phototherapy: 64% and 68%, respectively. We concluded that by using SB 18–24 as the “prediction test”, approximately two-thirds of neonates were test negative and had about one in ten chances of re-admission for treatment of hyperbilirubinemia, if discharged. After further validation, our results will be of benefit to neonates delivered in developing countries.     

Genetic polymorphisms in Thai neonates with hyperbilirubinemia

Aim:  Polymorphisms of the UGT1A1 gene, SLCO1B1 gene and GST gene have been associated with significant hyperbilirubinemia. We would like to determine whether the variation of UGT1A1 gene, SLCO1B1 gene and GST gene may play a significant role in neonatal hyperbilirubinemia in Thai infants.
Methods:  Ninety-one study subjects (hyperbilirubinemic group) and 86 control subjects were studied.
Results:  The cause of neonatal hyperbilirubinemia could not be identified in 64 infants (70.3%), ABO blood group incompatibility in 14.3% and Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency in 8.8%. In the hyperbilirubinemic group, 23 of 91 (25.3%) infants demonstrated variant of UGT1A1 at nucleotides (nt) 211 as compared to 6 of 86 (7%) in the control group (p = 0.001). There were no significant differences between groups in the variants UGT1A1 at nt 686, SLCO1B1 gene at nt 388, 463 and the GST gene. Male infants with G-6-PD deficiency were associated with hyperbilirubinemia (21.2% vs. 4.8% in the control group) with an odds ratio (OR) of 5.37 (p =0.02). The relationship between G-6-PD and variant in UGT1A1 gene at nt 211 could not be determined.
Conclusion:  Thai infants with variant in the UGT1A1 at nt 211 or with G-6-PD deficiency are at higher risk for developing neonatal hyperbilirubinemia.