Retrospective analysis of HDFN due to ABO incompatibility in a single institution over 6 years.

OBJECTIVES: To study the rate of ABO haemolytic anaemia of fetus and newborn (HDFN) in one institution over 6 years. BACKGROUND: ABO major incompatibility between mothers and their newborns occurs in about 10% of births. So, mothers with an O blood group may form IgG-class antibodies against A and B antigens, which could pass across the placenta and lead to a variable degree of HDFN in the newborn. METHODS: At our institution, we have reviewed data regarding ABO-based HDFN in the last 6 years. RESULTS: We found that, in 28 089 deliveries, an ABO major incompatibility between mothers and newborns occurs in 11% of cases, with 72% of O/A and 28% of O/B incompatibility. In turn, 23% of these newborns had an eluate-confirmed positive direct antiglobulin test [DAT; 74% (511) were due to anti-A and 26% (179) to anti-B], with 1·0% requiring invasive treatments (exchange transfusion or intravenous immunoglobulin). Overall, 2·5% of the total newborns had a positive DAT for an anti-A or anti-B antibody, and 0·11% required invasive treatment in addition to phototherapy for their HDFN. CONCLUSIONS: Serological ABO HDFN is a relatively frequent event when an O-A/O-B incompatibility between mothers and their newborn occurs and, in most cases, translates into a self-limiting disease, with a small number of newborns requiring invasive treatments. The DAT test, although not predictive of disease severity, appears to be a useful tool to monitor babies born from O-A/O-B-incompatible pregnancies and to identify those who may require treatment.

Severe ABO Hemolytic Disease of the Newborn Requiring Exchange Transfusion.

ABO incompatibility (ABOi), the most common cause of hemolytic disease of the newborn (HDN), is nearly always mild and treatable with phototherapy. Reports of ABOi HDN requiring neonatal exchange transfusion are extremely rare since the inception of modern guidelines. Here, a case of ABOi HDN clearly met criteria for exchange transfusion. An O-positive African American mother delivered a B-positive neonate that quickly developed hyperbilirubinemia. The neonatal DAT was positive from anti-B and anti-A,B, and maternal IgG titer was 1024. Double volume exchange transfusion resulted in a favorable outcome. Given early discharge of newborns, further understanding of factors predicting severe disease is needed.

Anti-D in a mother, hemizygous for the variant RHD*DNB gene, associated with hemolytic disease of the fetus and newborn.

BACKGROUND: Individuals with the partial D phenotype when exposed to D+ red blood cells (RBCs) carrying the epitopes they lack may develop anti-D specific for the missing epitopes. DNB is the most common partial D in Caucasians and the clinical significance for anti-D in these individuals is unknown. STUDY DESIGN AND METHODS: This article describes the serologic genotyping results and clinical manifestations in two group D+ babies of a mother presenting as group O, D+ with alloanti-D. RESULTS: The mother was hemizygous for RHD*DNB gene and sequencing confirmed a single-nucleotide change at c.1063G>A. One baby (group A, D+) displayed bilirubinemia at birth with a normal hemoglobin level. Anti-A and anti-D were eluted from the RBCs. For the next ongoing pregnancy, the anti-D titer increased from 32 to 256. On delivery the baby typed group O and anti-D was eluted from the RBCs. This baby at birth exhibited anemia, reticulocytosis, and hyperbilirubinemia requiring intensive phototherapy treatment from Day 0 to Day 9 after birth and was discharged on Day 13. Intravenous immunoglobulin was also administered. Both babies were heterozygous for RHD and RHD*DNB. CONCLUSION: The anti-D produced by this woman with partial D DNB resulted in a case of hemolytic disease of the fetus and newborn (HDFN) requiring intensive treatment in the perinatal period. Anti-D formed by women with the partial D DNB phenotype has the potential to cause HDFN where the fetus is D+. Women carrying RHD*DNB should be offered appropriate prophylactic anti-D and be transfused with D- RBCs if not already alloimmunized.

Red cell alloimmunization in RhD positive pregnant women and neonatal outcome.

The frequency of red blood cell (RBC) alloimmunization in RhD positive pregnant women is not known in our population. We planned to determine its frequency and correlation with neonatal outcome. We included 1000 RhD positive pregnant women: 500 had 'normal pregnancy' (Group I) and another 500 had 'high risk pregnancy' (Group II). ABO and extended Rh phenotyping were done by tube technique, antibody screening and identification by gel technique. For alloimmunized women, the paternal and neonatal ABO and extended Rh typing were done. Neonatal direct antiglobulin test (DAT) was also done and their clinical outcome observed. The frequency of RBC alloimmunization was 0.7% (7/1000) and all these women were from group II (p = 0.015). The alloantibodies were anti-E (85.7%), anti-c (71.4%), anti-Cw (14.3%) and anti-S (14.3%). Also, 6 women had history of transfusion (p < 0.01). Of the 7 neonates born to alloimmunized mothers, 4 (57.14%) had a positive DAT. The mean duration of phototherapy was higher in the DAT positive neonates (p < 0.01) and 2 (50%) required exchange transfusion. Thus, the frequency of alloimmunization was 0.7% in RhD positive pregnant women. High risk pregnancies and antenatal patients having a history of blood transfusion should be considered for regular antibody screening.

CD144+ endothelial microparticles as a marker of endothelial injury in neonatal ABO blood group incompatibility.

BACKGROUND: ABO antigens are expressed on the surfaces of red blood cells and the vascular endothelium. We studied circulating endothelial microparticles (EMP) in ABO haemolytic disease of the newborn (ABO HDN) as a marker of endothelial activation to test a hypothesis of possible endothelial injury in neonates with ABO HDN, and its relation with the occurrence and severity of haemolysis. MATERIAL AND METHODS: Forty-five neonates with ABO HDN were compared with 20 neonates with Rhesus incompatibility (Rh HDN; haemolytic controls) and 20 healthy neonates with matched mother and infant blood groups (healthy controls). Laboratory investigations were done for markers of haemolysis and von Willebrand factor antigen (vWF Ag). EMP (CD144(+)) levels were measured before and after therapy (exchange transfusion and/or phototherapy). RESULTS: vWF Ag and pre-therapy EMP levels were higher in infants with ABO HDN or Rh HDN than in healthy controls, and were significantly higher in babies with ABO HDN than in those with Rh HDN (p<0.05). In ABO HDN, pre-therapy EMP levels were higher in patients with severe hyperbilirubinaemia than in those with mild and moderate disease or those with Rh HDN (p<0.001). Post-therapy EMP levels were lower than pre-therapy levels in both the ABO HDN and Rh HDN groups; however, the decline in EMP levels was particularly evident after exchange transfusion in ABO neonates with severe hyperbilirubinaemia (p<0.001). Multiple regression analysis revealed that the concentrations of haemoglobin, lactate dehydrogenase and indirect bilirubin were independently correlated with pre-therapy EMP levels in ABO HDN. DISCUSSION: Elevated EMP levels in ABO HDN may reflect an IgG-mediated endothelial injury parallel to the IgG-mediated erythrocyte destruction and could serve as a surrogate marker of vascular dysfunction and disease severity in neonates with this condition.

Hour-specific bilirubin nomogram in infants with ABO incompatibility and direct Coombs-positive results.

OBJECTIVE: To determine the usefulness of the hour-specific Bhutani et al bilirubin nomogram when applied to infants with Coombs-positive test results. DESIGN: Retrospective chart review. SETTING: Term nursery and neonatal intensive care unit of a university-affiliated hospital. PATIENTS: All infants with A+ or B+ blood type born in our center from September 1, 2006, through August 31, 2008, to mothers with O+ blood. OUTCOMES: Proportion of infants with Coombs-positive results from the nomogram zones who required phototherapy and comparison of the percentage of infants with Coombs-positive results in each zone with the percentage of those with Coombs-negative results in each zone. RESULTS: A total of 240 infants with Coombs-positive and 460 with Coombs-negative results having a gestational age of 35 weeks or older were evaluated. Sensitivity and specificity of data for infants with direct Coombs-positive results in zone 4 (high risk; 74.2% and 97.1%) and those for infants in zones 3 (high-intermediate risk) and 4 combined (96.7% and 83.7%) compared favorably with the data from the Bhutani et al cohort, which had direct Coombs-negative results (54.0% and 96.2% for zone 4; 90.5% and 84.7% for zones 3 and 4 combined). The likelihood ratio for infants with direct Coombs-positive results in zone 4, 25.8 (95% confidence interval, 11.4-58.4), was twice that of the Bhutani et al cohort, 14.1 (11.0-18.1). The nomogram performed well in directing the timing of bilirubin level follow-up. All infants in zones 3 and 4 with Coombs-positive results were followed up after hospital discharge. None required an exchange transfusion or developed bilirubin encephalopathy. CONCLUSIONS: The Bhutani et al bilirubin nomogram reliably identified infants at gestational age of older than 35 weeks with direct Coombs-positive results who were at risk for significant hyperbilirubinemia and directed the timing of follow-up for these infants. This finding has direct clinical applicability to the health care professional practicing in the newborn nursery.

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

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.

Severe hemolytic disease of the newborn in a group B African-American infant delivered by a group O mother.

Maternal-fetal ABO incompatibility is a common hematological problem affecting the newborn. In general, hemolysis is minimal and the clinical course is relatively benign, rarely causing the escalating levels of hyperbilirubinemia and significant anemia commonly associated with Rh hemolytic disease of the newborn (HDN). The incidence of HDN ranges from one in 150 births to 1:3000 births, depending on the degree of anemia and level of serum bilirubin. The etiology of ABO hemolytic disease of the newborn (ABO-HDN) is complex because anti-A and anti-B antibodies are composed mainly of IgM. Since only IgG antibodies cross the placenta, those pregnant women with high levels of IgG anti-A,B, anti-A, or anti-B with an ABO incompatible fetus will be the ones to give birth to an infant with ABO-HDN. We describe a case of a B/Rh positive term newborn born to an O/Rh negative African-American mother demonstrating aggressive hemolysis and a robust response of the bone marrow. This case was successfully managed with phototherapy and simple RBC transfusion without the need for exchange transfusion.

Readmission for newborn jaundice: the value of the Coombs' test in predicting the need for phototherapy.

Current practice at our hospital is to perform a direct antiglobulin test (DAT) on cord blood samples of all infants born to blood type O or Rh-negative mothers. Measurement of serum total bilirubin (STB) level and follow-up after discharge are at the discretion of the individual physician. The purposes of the present study were, first, to determine the clinical utility of performing a routine DAT and, second, to define the clinical characteristics of infants readmitted to the hospital for phototherapy. The study was done over a 1-year period extending from January 1 to December 31, 2000. A retrospective review of the DAT results of all infants born to type O or Rh-negative mothers was conducted. The 2 groups of infants included those who had a positive cord blood DAT and were treated with phototherapy and those who needed readmission to the hospital for phototherapy. We found that routine DAT testing of cord blood from term nonjaundiced infants born to O positive mothers is not necessary. Infants with 2 or more risk factors for jaundice irrespective of the results of the DAT are at an increased risk for needing readmission for phototherapy.