Severe hemolytic disease of the newborn caused by JKb antibody: Two case reports and literature review.

BACKGROUND: JKb antibody rarely causes severe hemolytic disease in the newborn except in 1 case, required blood exchange transfusion but later died of intractable seizure and renal failure. Here we describe 2 cases of JKb-induced severe neonatal jaundice requiring blood exchange transfusion with good neurological outcome. CASE PRESENTATION: Two female Chinese, ethnic Han, term infants with severe jaundice were transferred to us at the age of 5- and 4-day with a total bilirubin of 30.9 and 25.9 mg/dL while reticulocyte counts were 3.2% and 2.2%, respectively. Both infants were not the firstborn to their corresponding mothers. Direct and indirect Coombs' tests were positive, and JKb antibody titers were 1:64 (+) for both mothers. Phototherapy was immediately administered, and a blood exchange transfusion was performed within 5 hours of admission. Magnet resonance image showed no evidence of bilirubin-induced brain damage, and no abnormal neurological finding was detected at 6 months of life. CONCLUSION: JKb antibody-induced hemolytic disease of the newborn usually leads to a benign course, but severe jaundice requiring blood exchange transfusion may occur. Our cases suggest good outcomes can be achieved in this minor blood group-induced hemolytic disease of the newborn if identified and managed early enough.

A Rare Case of Hemolytic Disease of the Fetus and Newborn Caused by Anti-s Antibody in a Chinese Patient.

BACKGROUND: Anti-s is a rare alloantibody, and the reported cases of hemolytic disease of the fetus and newborn (HDFN) caused by anti-s are limited to non-Asian populations. METHODS: Here, we report the case of a Chinese woman with a history of multiple pregnancies who developed an alloantibody with anti-s specificity. RESULTS: Her newborn developed HDFN caused by anti-s but the clinical symptoms were not serious. After supportive treatment and bilirubin light phototherapy, the baby was discharged with a good prognosis. CONCLUSIONS: This is the first reported case of anti-s-induced HDFN in a Chinese patient, highlighting the need for further research in the Asian population.

A case of severe hemolytic disease of newborn due to alloimmunization in primigravida.

Red blood cell (RBC) alloimmunization which is the production of antibodies in response to foreign red cell antigen(s) may occur through exposure to cells or tissues from a genetically different member of same species via transfusion, transplantation or pregnancy. It may cause hemolytic disease of fetus and newborn (HDFN). Usually the incidence of HDFN due to irregular erythrocyte antibody is rare in primigravida. Here we report a primigravida pregnant woman who developed multiple alloantibodies and the neonate developed severe HDFN. A 36-year-old primigravida pregnant woman who had no history of significant medical issues except surgery done for severe endometriosis 1 year back and she had no history of previous blood transfusion presented to us for delivery. The antibody screening came out to be positive with a reaction in cell I and cell II of the antibody screening panel. Further, a mixture of anti D + anti C + anti E alloantibodies were identified using 16 cells panel, select cells and red cell phenotyping. The neonate developed severe HDFN which was managed with phototherapy, exchange transfusion and IvIg. There was no exposure history for sensitization except bleeding in early 2nd trimester. There was a significant discrepancy among mother, father and neonate Rh phenotype which was resolved with clinical history of Invitro fertilization (IVF) with sperm donation. This index case illustrates the need of antibody screening in primigravida antenatal women specially for Rh D negative high risk cases. It also shows importance of Rh Kell typing in sperm donors for future transfusion support of the child.

Neonatal outcomes following intrauterine transfusion for hemolytic disease of the fetus and newborn: a twenty-year service review.

OBJECTIVE: The primary objective was to explore perinatal and neonatal outcomes amongst infants who received intrauterine transfusion (IUT) for the management of hemolytic disease of the fetus and newborn (HDFN). The secondary objective was to evaluate the role of key investigations in the fetus at risk of HDFN and assess the relationship with neonatal outcomes. We hypothesized that middle cerebral artery peak systolic velocity (MCA-PSV) and corresponding multiples of the median (MoM) would be predictive of neonatal course. METHODS: This was a retrospective observational study conducted at a tertiary center in the United Kingdom between January 2000 and August 2020. Trust approval was obtained to conduct this service review. Pregnancies requiring IUT for HDFN were identified using the fetal medicine department database. Inclusion criteria were infants who received IUT for HDFN. 67 pregnancies were eligible for inclusion in the study with 156 IUT events. Data were extracted using healthcare records. Statistical analysis was performed using SPSS version 28.0, data were assessed for normality and Spearman's correlation analysis was performed with p values < .05 considered significant. RESULTS: 67 pregnancies were included in the study which led to the live birth of 68 infants (one twin pregnancy). There were no fetal deaths following IUT. There was one neonatal death due to extreme prematurity following spontaneous vaginal delivery at 23 + 4 weeks gestation, occurring three days following IUT. 97% of infants required admission to the neonatal intensive care unit and 88% required phototherapy. 25% of infants required readmission for red blood cell transfusion due to anemia. There was a significant correlation between maternal anti-D antibody levels and length of neonatal admission r = 0.477, p = .014. MCA-PSV and MoM measured prior to the last IUT had a significant positive correlation with the duration of phototherapy: r = 0.527 (p < .001) and r = 0.313 (p < .05) respectively. Linear regression analysis demonstrated a significant positive relationship between MCA-PSV and corresponding MoM recorded prior to the last IUT with r2= 0.177 (p = .003) and r2= 0.101 (p = .029). CONCLUSION: HDFN is an important cause of fetal anemia associated with significant neonatal morbidity. MCA-PSV and MoM may be predictive of neonatal phototherapy requirements. The predictive value of MCA-PSV appears to be dependent on the timing of measurement during the antenatal period and more research is needed. Multicentre collaboration is required to generate a reliable large-scale database to further delineate the value of MCA-PSV and MoM and predict neonatal outcomes in cases of HDFN requiring IUT. This data would assist clinicians in antenatal planning and enable more informed counseling of parents in the antenatal period.

Neonatal hemolytic disease due to anti-Diegoa antibody: a case report.

BACKGROUND: The Diegoa antigen commonly occurs in certain Asian and South American Indian populations. In general, hemolysis caused by anti-Diegoa antigen is not severe, and exchange transfusion is rarely needed. Here, we report a neonate with moderate hemolytic disease caused by anti-Diegoa antigen in the Baoji area of China. CASE PRESENTATION: A 39-week gestation male newborn of Han nationality was delivered by second cesarean section because of scarred uterus. The newborn's birth weight was 3700 g with an Apgar score of 9. Four hours after delivery, transcutaneous bilirubin test revealed a level of 17 mg/dl. After 23 hours, the neonate developed anemia and hyperbilirubinemia. Bacterium, virus and other pathogens, as well as tests for arcuate and glucose-6-phosphate dehydrogenase, were all negative. Direct antiglobulin test of the neonate was positive. Diegoa antigens of the baby and his father were positive, while his mother was negative. The newborn was successfully cured with phototherapy and one-dose intravenous injection of human albumin. CONCLUSIONS: It is important to consider and test for the anti-Diegoa antibody in cases of hemolytic disease of the newborn of the Han ethnicities of China.

Hemolytic Disease of the Fetus and Newborn Caused by Anti-Group A IgG From a Group B Mother.

ABO incompatibility has emerged as the premier reason for hemolytic disease of the fetus and newborn (HDFN). It always occurs in the offspring of blood group O mother. We present a rare case that the fetus of group A got HDFN caused by the anti-group A immunoglobulin G from a group B mother. The direct Coombs test of the fetus blood was negative, but the indirect Coombs test on A1 standard blood cells was strong positive (4+). The acid release test of antibody on the membrane of red blood cells to A1 standard blood cells was also strong positive (4+). Bilirubin of the fetus reached the threshold of exchange transfusion, but she just received 4 days' phototherapy and 2.2 g albumin intravenous injection, with no packed blood cells transfusion, because her family refused, and came to a favorable outcome. This case reminds us not to ignore the possibility of HDFN in offspring of mothers with non-O blood group.

Delayed cord clamping in Rh-alloimmunised infants: a randomised controlled trial.

Despite advancement in medical care, Rh alloimmunisation remains a major cause of neonatal hyperbilirubinaemia, neuro-morbidity, and late-onset anaemia. Delayed cord clamping (DCC), a standard care now-a-days, is yet not performed in Rh-alloimmunised infants due to paucity of evidence. Hence, we randomised these infants of 28- to 41-week gestation to delayed cord clamping (N = 36) or early cord clamping (N = 34) groups. The primary outcome variable was venous packed cell volume (PCV) at 2 h of birth. The secondary outcomes were incidence of double volume exchange transfusion (DVET) and partial exchange transfusion (PET), duration of phototherapy (PT), functional echocardiography (parameters measured: superior vena cava flow, M-mode fractional shortening, left ventricular output, myocardial perfusion index, and inferior vena cava collapsibility) during hospital stay, and blood transfusion (BT) until 14 weeks of life. Neonates were managed as per unit protocol. The baseline characteristics of enrolled infants were comparable between the groups. The median (IQR) gestation and mean (SD) birth weight of enrolled infants were 35 (33-37) weeks and 2440 (542) g, respectively. The DCC group had a higher mean PCV at 2 h of life (48.4 ± 9.2 vs. 43.5 ± 8.7, mean difference 4.9% (95% CI 0.6-9.1), p = 0.03). However, incidence of DVET and PET, duration of PT, echocardiography parameters, and BT until 14 weeks of postnatal age were similar between the groups.Conclusion: DCC in Rh-alloimmunised infants improved PCV at 2 h of age without significant adverse effects.Trial registration: Clinical Trial Registry of India (CTRI), Ref/2016/11/012572 http://ctri.nic.in/Clinicaltrials, date of trial registration 19.12.2016, date of first patient enrolment 1 January 2017.What is Known:•Delayed cord clamping improves haematocrit, results in better haemodynamic stability, and decreases the need of transfusion in early infancy.•However, due to lack of evidence, potential risk of hyperbilirubinaemia, and exacerbation of anaemia (following delayed cord clamping), early cord clamping is the usual norm in Rh-alloimmunised infantsinfants.What is New:•Delayed cord clamping in Rh-alloimmunised infants improves haematocrit at 2 h of life without any increase in incidence of serious adverse effects.

A young woman with a transfusion-related pregnancy complication. / En ung kvinne med transfusjonsutløst svangerskapskomplikasjon.

BACKGROUND: Individuals with the K0 phenotype are extremely rare. They may develop anti-Ku antibodies, which react with all antigens of the Kell blood group system, thereby leading to haemolytic transfusion reactions and haemolytic disease of the fetus and newborn. CASE PRESENTATION: A primigravida who was transfused with one unit of red blood cells due to iron deficiency anaemia developed anti-Ku antibodies. The pregnancy was closely monitored by ultrasound and antibody titres. Maternal autologous blood collection was performed twice during the last trimester as back-up in case of maternal peripartum bleeding, and a few frozen K0 red blood cell units were provided in case of severe fetal anaemia. At gestational week 36+6, labour was induced due to increasing antibody titres and high blood velocities in the fetal middle cerebral artery during systole. The woman was delivered vaginally without need for transfusion. The infant was diagnosed with haemolytic disease of the fetus and newborn and treated with phototherapy, repeated infusions of intravenous immunoglobulin and iron supplements until normalisation of haemoglobin at three months of age. INTERPRETATION: Iron deficiency anaemia should be treated primarily with iron supplementation before considering blood transfusions, which pose the risk of developing alloantibodies that can cause transfusion complications and haemolytic disease of the fetus and newborn.

Atypical erythroblastosis in a patient with Diamond-Blackfan anemia who developed del(20q) myelodysplasia.

Diamond-Blackfan anemia (DBA) is a congenital red cell aplasia arising from ribosomal protein (RP) defects. Affected patients present with neonatal anemia, occasional dysmorphism, and cancer predisposition. An anemic newborn was diagnosed with DBA due to RPL5 mutation (c.473_474del, p.K158SfsX26). Refractory anemia required regular transfusions and iron chelation therapy. Pancytopenia occurred at age 16 years. Bone-marrow studies showed myelodysplasia, erythroblastosis, and clonal evolution of del(20)(q11.2q13.3). Severe anemia required transfusions. Del(20q), including the L3MBTL1 gene, is reported to be relevant to the hematological phenotype of Shwachman-Diamond syndrome. A combined defect of RPL5 and L3MBTL1 may contribute to the aberrant erythropoiesis in the present case.

Prevalence of positive direct antiglobulin test and clinical outcomes in Surinamese newborns from D-negative women.

BACKGROUND: In low-resource countries, screening for D antibodies to detect pregnancies at risk for hemolytic disease of the newborn is not routine practice. Retrospective data showed that 5.5% of Surinamese newborns of D-negative women had a positive direct antiglobulin test (DAT), indicating the presence of maternal antibodies against fetal antigens. Here, the frequency and clinical relevance of DAT positivity is evaluated. STUDY DESIGN AND METHODS: Between April 2015 and June 2016, an observational, multicenter cohort study was undertaken among Surinamese newborns born to D-negative women. In newborns, the DAT was performed, and clinical outcomes between DAT-negative and DAT-positive newborns were compared. RESULTS: Of the 232 evaluable newborns, 19 (8.2%) had a positive DAT, of which 11 of 15 antibody-tested newborns had D antibodies. DAT-positive newborns had lower hemoglobin levels (p = 0.02) and a trend toward higher bilirubin concentrations (p = 0.09) in the first days of life compared with DAT-negative newborns. DAT-positive newborns were admitted more frequently (p = 0.02), needed phototherapy treatment almost four times as often as DAT-negative newborns (26% vs. 7%; p = 0.008), and therapy took 2 days longer (p = 0.01). Exchange transfusions were performed in two newborns with D antibodies, both complicated with sepsis. The hospital stay was 2.5 days longer for DAT-positive newborns (p = 0.007). Overall, the prevalence of hemolytic disease of the newborn requiring treatment was 2.2% among the whole cohort of newborns. CONCLUSION: We found a high prevalence of DAT positivity with substantial need for hyperbilirubinemia treatment in newborns in Suriname. These results stress the necessity for better management procedures in D-negative women.

Indication of Mild Hemolytic Reaction Among Preterm Infants With ABO Incompatibility.

BACKGROUND: Among term infants, ABO incompatibility is a leading cause of hemolytic disease and neonatal jaundice. With respect to preterm infants, data are lacking. OBJECTIVE: To evaluate the incidence and severity of ABO incompatibility hemolytic disease among preterm infants with respect to hemolytic and jaundice parameters. DESIGN: Clinical and laboratory data were collected retrospectively from the medical records of 118 ABO-incompatible preterms born at gestational age (GA) 29-34 weeks, as well as 118 controls matched for GA, birth weight, and multiplicity. All infants were born at the Sheba Medical Center Tel-Hashomer between 2009 and 2012. RESULTS: The study and control groups were similar on all maternal and neonatal outcome parameters. No differences between the groups were recorded throughout hospitalization regarding hematocrit levels or the need for blood transfusion. Bilirubin levels were higher among the study (ABO-incompatible) group during the first 10 days of life; however, no significant differences were found regarding the need for phototherapy. Upon evaluating subgroups divided by GA, we found no differences on any hematological and jaundice factors among preterms of 29-31 weeks, whereas among preterms of 32-34 weeks higher positive direct antiglobulin test (DAT) results (7% vs. 0% in the control, P = 0.014) as well as higher bilirubin levels were documented. CONCLUSIONS: Among ABO-incompatible preterm infants with GA 29-34 weeks, there is no evidence of significant hemolytic reaction derived from placental transfer of antibodies. With increasing GA, antibody transfer becomes more significant, resulting in more positive DAT results and greater incidence of neonatal jaundice.

Non-specific red cell reactivity in an obstetric population.

OBJECTIVE: To examine non-specific red cell reactivity (NSR) on antibody (Ab) screening of obstetric inpatients. METHODS: Observational study of 5438 obstetric inpatients (2009-2013). Ab-positive patients were identified and their records reviewed for NSR, other antibodies, transfusion reactions or hemolytic disease of the fetus/newborn (HDFN). Evaluation of NSR frequency by test era assessed the impact of an institutional change to solid-phase screening in 2011. RESULTS: Of obstetric inpatients, 5.3% had at least one positive Ab screen; 1.6% had NSR. Of NSR-positive patients, 16.7% had identifiable Abs that pre-dated NSR; 25% had concurrent Abs and 8.5% had subsequent Ab identification. In 49.1%, NSR resolved during follow-up. The frequency of NSR was higher after the change to solid-phase Ab screening, but specific Ab frequency was similar in both testing periods. No transfusion reactions or cases of HDFN were noted in this cohort. CONCLUSIONS: NSR is found in 1-2% of obstetrical inpatients at our institution, and has more than doubled since the initiation of solid-phase screening. Although likely clinically insignificant by itself, NSR is commonly found in relation to other red cell Abs and may precede their development.

Clinically significant hemolytic disease of the newborn secondary to passive transfer of anti-D from maternal RhIG.

BACKGROUND: RhIG is used worldwide to reduce the incidence of alloimmunization to D during pregnancy. We report a case of clinically significant neonatal hemolysis mediated by maternally administered RhIG. CASE REPORT: A 25-year-old, O-, primigravid mother with a negative antenatal antibody screen delivered a 6-lb 4-oz, blood group A, D+ baby girl at 36.5 weeks' gestation. Prenatal care included a dose of intramuscular RhIG at 28 weeks' gestation. At delivery, the newborn was markedly jaundiced with a total bilirubin of 6.3 mg/dL, which reached more than 20 mg/dL after 6 days. The newborn's lactate dehydrogenase (LDH) was 485 U/L (normal, <226 U/L) and further laboratory studies revealed reticulocytosis (17.2%; normal range, 0.36%-1.9%) and a hemoglobin (Hb) of 14.3 g/dL (normal for age range, 13.4-19.8 g/dL) that decreased to 11.5 g/dL (normal for age range, 13.5-22.6 g/dL) by Day-of-life 7. Although the maternal antibody screen was negative, the newborn's direct antiglobulin test (DAT) was positive for immunoglobulin (Ig)G, with an anti-D identified by elution studies. The possibility of hemolytic disease of the newborn (HDN) due to anti-A was considered, but ultimately ruled out by the absence of anti-A1 in the eluate. The newborn's hyperbilirubinemia was adequately managed with phototherapy. Analysis of the mother's plasma 10 days postpartum revealed an anti-D titer of 8. Two months after birth, the child's laboratory studies, DAT, antibody screen, and peripheral smear were unremarkable. CONCLUSION: In the context of neonatal anemia, elevated LDH, and reticulocytosis, a positive IgG DAT with anti-D identified in the eluate suggests RhIG-mediated HDN. This appears to be a rarely reported event.

Hemolytic disease of the fetus and newborn caused by anti-Lan.

BACKGROUND: Antibodies to the high-incidence red blood cell (RBC) antigen Lan (Langereis) are typically immunoglobulin G and have been shown to fix complement and cause hemolysis of Lan antigen-positive RBCs. Only three cases of hemolytic disease of the fetus and newborn (HDFN) have been reported involving anti-Lan and all have been characterized as "mild." CASE REPORT: A 26-year-old Hispanic female presented in her fifth pregnancy for routine obstetric care. Due to progressively rising anti-Lan titers, middle cerebral artery (MCA) Dopplers were performed. At 32 weeks of gestation, the antibody titer had reached 128; the MCA Doppler indicated that fetal anemia was severe. An intrauterine transfusion with Lan antigen-negative RBCs was performed and a viable infant was delivered 25 days later. DISCUSSION: Three cases of HDFN associated with anti-Lan have been previously reported. While these cases have been associated with somewhat variable serologic findings, none have resulted in fetal demise or severe symptomatology requiring pre- or postnatal intervention other than routine phototherapy. The current report, however, suggests that in some instances anti-Lan can result in a more severe form of HDFN requiring more aggressive prenatal therapy. CONCLUSION: In spite of previous case reports suggesting that anti-Lan is associated with relatively mild HDFN, this case suggests that in some instances, this antibody can cause severe HDFN requiring prenatal intervention.

Successful management of severe hemolytic disease of the fetus due to anti-Jsb using intrauterine transfusions with serial maternal blood donations: a case report and a review of the literature.

BACKGROUND: The management of pregnant women with anti-Jsb is challenging due to the paucity of antigen-negative blood for fetal and neonatal transfusion. CASE REPORT: A 29-year-old woman with anti-Jsb was referred for assessment of recurrent fetal losses. With the presence of the sister as a historically matched donor, she was planned for active surveillance for fetal anemia during pregnancy. STUDY DESIGN AND METHODS: The fetus remained well until 21 weeks of gestation when signs of fetal anemia and early hydrops fetalis were noted. Anti-Jsb titer was at 128. The sister's red blood cells (RBCs) were cross-match incompatible. Urgent intrauterine transfusion (IUT) was performed with washed irradiated maternal RBCs, donated after cessation of heparin. The mother was given intravenous iron (IV-Fe) and continued on weekly recombinant human erythropoietin (rHu-EPO). RESULTS: Repeated IUTs were needed every 1 to 3 weeks. Throughout a 7-week period, three maternal donations were performed with total donated whole blood volume of 1250 mL, supporting four IUTs. At 29 weeks of gestation, the procedure was complicated by umbilical cord hematoma necessitating urgent cesarean section. A male newborn was delivered, transfused at birth, and subsequently treated with phototherapy and five top-up transfusions. CONCLUSION: This case represents a successful example of managing hemolytic disease of the fetus due to a rare antibody using maternal blood. It also supports previous data on safety of maternal donations during pregnancy and the use of combination of rHu-EPO and IV-Fe as a supportive measure.

Postnatal outcome in neonates with severe Rhesus c compared to rhesus D hemolytic disease.

BACKGROUND: Neonates with Rhesus c (Rh c) hemolytic disease of the fetus and newborn (HDFN) are often managed in the same way as neonates with Rhesus D (Rh D) HDFN, although evidence to support this policy is limited. The objective of this study was to evaluate neonatal outcome in severe Rh c HDFN compared to Rh D HDFN. STUDY DESIGN AND METHODS: A retrospective study of (near-)term neonates with severe Rh c (n = 22) and Rh D HDFN (n = 103; without additional antibodies) admitted to the Leiden University Medical Center between January 2000 and October 2011 was conducted. The need for intrauterine transfusions (IUTs), phototherapy, exchange transfusions (ETs), and top-up transfusions up to 3 months of age were recorded and compared between both groups. RESULTS: Although there was a trend for a slightly more severe antenatal course for Rh D HDFN reflected by an earlier need for and higher number of IUTs (median [interquartile range], 2 [1.5-4] vs. 2 [1-2] in Rh c HDFN; p = 0.070), no significant differences were found for the postnatal course between Rh c and Rh D group in days of phototherapy (mean, Days 4.8 and 4.6, respectively; p = 0.569), need for ET (50% vs. 44%, respectively; p = 0.589), and top-up transfusions (62% vs. 78%, respectively; p = 0.128). CONCLUSION: Postnatal outcome in neonates with severe Rh c HDFN is similar compared to neonates with severe Rh D hemolytic disease in terms of days of phototherapy, need for ET, and need for top-up transfusions. These results justify a similar postnatal management of neonates with Rh D and Rh c HDFN.

The efficacy of the use of intravenous human immunoglobulin in Brazilian newborns with rhesus hemolytic disease: a randomized double-blind trial.

BACKGROUND: The purpose of this study was to evaluate the efficacy of intravenous human immunoglobulin (IVIG) in the presence of high-intensity phototherapy in decreasing the need for exchange transfusion in newborns with rhesus hemolytic disease. STUDY DESIGN AND METHODS: We performed a randomized, double-blind, placebo-controlled trial. The trial included D+ newborns born at 32 weeks of gestational age or later with a positive direct antiglobulin test and whose mothers were Rh-alloimmunized and did or did not receive intrauterine transfusion. The newborns were randomly assigned to receive either IVIG at a dose of 500 mg/kg or placebo (saline solution, 10 mL/kg) during the first 6 hours of life. The primary outcome was the need for exchange transfusion. The criteria for exchange transfusion were total serum bilirubin (TSB) level at or above 340 µmol/L (20 mg/dL) or increasing by 8.5 µmol/L/hr (0.5 mg/dL/hr) despite intensive phototherapy. RESULTS: The trial included 92 newborns. There was no difference in the rate of exchange transfusion between groups: 6 of 46 (13%) in the IVIG group versus 7 of 46 (15.2%) in the placebo group (p = 0.765). There were no significant differences between groups with respect to their need for exchange transfusion, phototherapy time, peak bilirubin, or length of hospital stay. There were no adverse events related to the drug or the form of administration. CONCLUSION: Nonspecific human immunoglobulin was not effective in preventing the need for exchange transfusion in neonates with rhesus hemolytic disease.

Cholestasis in neonates with red cell alloimmune hemolytic disease: incidence, risk factors and outcome.

BACKGROUND: Etiology of cholestatic liver disease in neonates with hemolytic disease of the newborn (HDN) has been associated with iron overload due to intrauterine red cell transfusions (IUTs). Data on the incidence and severity of cholestasis in neonates with HDN are scarce, and little is known about pathogenesis, risk factors, neonatal management and outcome. OBJECTIVE: To evaluate incidence, risk factors, management and outcome of cholestasis in neonates with red cell alloimmune hemolytic disease. METHODS: All (near-) term neonates with HDN due to red cell alloimmunization admitted to our center between January 2000 and July 2010 were included in this observational study. Liver function tests (including conjugated bilirubin) were routinely performed in the neonatal period. We recorded the presence of cholestasis, investigated several potential risk factors and evaluated the management and outcome in affected neonates. RESULTS: A total of 313 infants with red cell alloimmune hemolytic disease treated with or without IUTs were included. The incidence of cholestasis was 13% (41/313). Two risk factors were independently associated with cholestasis: treatment with at least one IUT (OR 5.81, 95% CI 1.70-19.80, p = 0.005) and rhesus D type of alloimmunization (OR 4.66, 95% CI 1.05-20.57, p = 0.042). Additional diagnostic tests to investigate possible causes of cholestasis were all negative. In 5 infants (12%), supportive medical and nutritional therapy was started, and one neonate required iron chelation therapy. CONCLUSION: Cholestasis occurs in 13% of neonates with HDN due to red cell alloimmunization, and it is independently associated with IUT treatment and rhesus D type of alloimmunization.

Exchange transfusions and top-up transfusions in neonates with Kell haemolytic disease compared to Rh D haemolytic disease.

OBJECTIVE: To evaluate neonatal outcome in Kell haemolytic disease compared to Rh D haemolytic disease. STUDY DESIGN: Retrospective study of all (near)-term neonates with Kell (n=34) and Rh D haemolytic disease (n=157) admitted to our centre between January 2000 and December 2008. We recorded the need for exchange transfusion and top-up transfusions up to 3 months of age. RESULTS: Neonates in the Kell group required less days of phototherapy than neonates in the Rh D group [2.4 vs. 4.1 days, respectively (P<0.01)]. The percentage of neonates requiring an exchange transfusion was lower in the Kell group than in the Rh D group [6% (2/34) and 62% (98/157), respectively (P<0.01)]. The percentage of neonates in the Kell group and Rh D group requiring a top-up transfusion was 62% (21/34) and 72% (113/157), respectively (P=0.20). The median number of top-up transfusions per neonate in the Kell group and Rh D group was 1 [interquartile range (IQR) 0-2] and 2(IQR 0-2), respectively (P=0.07). CONCLUSION: Neonates with Kell haemolytic disease require less phototherapy and less exchange transfusions compared to neonates with Rh D haemolytic disease, but an equal number of top-up transfusions.