Darbepoetin Alfa for Late-onset Anemia in Neonates with Rhesus Hemolytic Disease.

Neonates with Rhesus hemolytic disease can present with anemia beyond 1 wk of age due to bone marrow suppression and low erythropoietin secretion. Erythropoietin stimulating agents (ESA) were tried to manage anemia in these neonates. Darbepoetin alfa (DA) is a long-acting ESA used to treat anemia in premature neonates and in children with chronic kidney disease or on cancer chemotherapy. The authors present their experience of using DA to treat late-onset hyporegenerative anemia in 3 neonates with Rhesus isoimmunization. Darbepoetin alfa 4 mcg/kg was given subcutaneously at a 1-2-wk interval to target hemoglobin of 10-12 g/dL. No adverse effects were observed, and the treated infants had a reduced need for the packed red blood cell transfusions.

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International guidelines regarding the role of intravenous immunoglobulin (IVIG) in the management of Rh- and ABO-mediated haemolytic disease of the newborn was drafted by an international panel of experts in the fields of hematology, neonatology, and blood transfusion and was published in British Journal of Haematology on March 16, 2022. The guidelines summarize the evidence-based practice of IVIG in Rh- and ABO-mediated haemolytic disease of the newborn and propose related recommendations. The guidelines recommend that IVIG should not be applied as a routine treatment regimen for Rh- and ABO-mediated haemolytic disease of the newborn in order to reduce exchange transfusion (ET), and the best time to apply IVIG remains unclear in the situations where hyperbilirubinaemia is severe (approaching or exceeding the ET threshold) or ET cannot be implemented. These guidelines are formulated with rigorous methods, but with the lower quality of evidence.

Intravenous immunoglobulin in hemolytic disease of the newborn: A moving target in time.

Background: Alloimmune hemolytic disease of the newborn (AIHDN) results in hemolysis, anemia, hyperbilirubinemia with the potential for brain damage. Intravenous immunoglobulin (IVIG) has been investigated as an alternative low-risk procedure for the treatment of AIHDN in addition to traditional treatment methods such as phototherapy and exchange transfusion (ET). Aim: To evaluate the effectiveness of IVIG therapy in decreasing ET needs based on risk factors and clinical outcomes. Materials and Methods: Charts of neonates born >30 weeks of gestation who underwent phototherapy and were administered IVIG therapy due to AIHDN between January 2013 and July 2018 were retrospectively reviewed. Results: Sixty-three neonates were included in our study. Forty-three of them (68.3) % were full-term infants. ABO incompatibility (n = 33, 52.4%) was the major cause of AIHDN (n = 63). Additional risk factors for jaundice were found to coexist in 95.2% (n = 60) of the infants. Fifteen infants (23.8%) required ET, mostly due to Rh incompatibility (n = 11, 73.3%). Mortality was observed in 3.2% (n = 2) of the patients, 1.6% (n = 1) of whom were related to ET. Serum albumin value was found to be negatively correlated with the requirement for ET (r = 0.713, P < 0.001), whereas serum bilirubin albumin ratio was positively correlated (r = 0.489, _P < 0.001). Nine (14.3%) infants needed a simple transfusion during the hospitalization period, whereas five (7.9%) infants had readmission for simple transfusion after discharge. Apnea was the only complication seen in one (1.6%) patient. Conclusion: IVIG treatment should be considered due to its relative benefits when compared to exchange transfusion. In addition to its safety, it is a less complicated treatment modality with low side effect rates. It may be justified for elective use in neonates suffering from AIHDN, who will require ET with a risk of mortality by decreasing the peak of total serum bilirubin levels.

International guidelines regarding the role of IVIG in the management of Rh- and ABO-mediated haemolytic disease of the newborn.

Haemolytic disease of the newborn (HDN) can be associated with significant morbidity. Prompt treatment with intensive phototherapy (PT) and exchange transfusions (ETs) can dramatically improve outcomes. ET is invasive and associated with risks. Intravenous immunoglobulin (IVIG) may be an alternative therapy to prevent use of ET. An international panel of experts was convened to develop evidence-based recommendations regarding the effectiveness and safety of IVIG to reduce the need for ETs, improve neurocognitive outcomes, reduce bilirubin level, reduce the frequency of red blood cell (RBC) transfusions and severity of anaemia, and/or reduce duration of hospitalization for neonates with Rh or ABO-mediated HDN. We used a systematic approach to search and review the literature and then develop recommendations from published data. These recommendations conclude that IVIG should not be routinely used to treat Rh or ABO antibody-mediated HDN. In situations where hyperbilirubinaemia is severe (and ET is imminent), or when ET is not readily available, the role of IVIG is unclear. High-quality studies are urgently needed to assess the optimal use of IVIG in patients with HDN.

Effect of intravenous immunoglobulins to postpone the gestational age of first intrauterine transfusion in very severe red blood cell alloimmunization: A case-control study.

BACKGROUND: Early intrauterine transfusion (IUT) is associated with a higher risk of fetal loss. Our objective was to evaluate the efficiciency of intravenous immunoglobulins (IVIG) to postpone the gestational age at first IUT beyond 20 weeks of gestation (WG) compared to the previous pregnancy in case of very severe red blood cell (RBC) alloimmunization. STUDY DESIGN AND METHODS: Very severe RBC alloimmunization was defined by a high titer of antibodies and a previous pregnancy complicated by a first IUT before 24 WG and/or perinatal death directly related to alloimmunization. We performed a single-center case-control study. Cases and controls were patients respectively treated with weekly IVIG infusions started before 13 WG, and without. RESULTS: Twenty cases and 21 controls were included. Gestational age (GA) at first IUT was postponed after 20 WG in 18/20 (90 %) of patients treated with IVIG and in 15/21 (71 %) in the control group (p = 0.24). Compared to the previous pregnancy, the GA at first IUT was postponed by a median of 22 [+11; +49] days in the IVIG group and occurred in average 2 days earlier [-17 ; +12] in the non-treated group (p = 0.02). There was no difference between number of IUT and need for exchange-transfusion. IVIG treatment was associated with a significant decrease of antibodies' quantitation. CONCLUSION: In our series, IVIG tends to differ first IUT beyond 20 WG and have a significant effect in postponing the gestational age of the first IUT in patients with very severe RBC alloimmunization.

Hemolytic disease and reticulocytopenia of the newborn attributable to maternal immunoglobulin G anti-M reacting optimally at cold temperatures.

BACKGROUND: Hemolytic disease of the fetus and newborn (HDFN) attributable to anti-M is rare, although case reports implicate anti-M in varying severities of HDFN, including fetal hydrops and intrauterine death. CASE DESCRIPTION: We describe the case of a newborn with HDFN associated with an atypical immunoglobulin (Ig) G anti-M that reacted best at cold temperatures. The maternal antibody detected in pregnancy was not reactive at 37°C, and a direct antiglobulin test (DAT) on red blood cells (RBCs) from the newborn was negative, suggesting an anti-M that should not have been clinically relevant. However, the infant developed hyperbilirubinemia (bilirubin level, 17.6 mg/dL), hemolytic anemia (hemoglobin nadir, 5.5 g/dL), and reticulocytopenia. Laboratory testing demonstrated the presence of an IgG anti-M in maternal and neonatal samples reacting best at 4°C. This passively acquired IgG anti-M provoked hemolytic anemia in the infant and likely suppressed erythropoiesis, resulting in reticulocytopenia with prolonged anemia. He was treated for IgG anti-M HDFN with 10 intravenous Ig infusions and 10 days of oral prednisone followed by a taper. He required seven transfusions with M- RBCs. His hemoglobin level normalized at 3 months of age. Follow-up at 2 years revealed no hematologic or neuro-developmental concerns. CONCLUSION: To our knowledge, this is the second report of HDFN attributable to an IgG anti-M reacting preferentially at cold temperature with no 37°C reactivity. Clinically relevant IgG anti-M may elude standard testing. Early recognition and testing for cold-reacting IgG anti-M should be considered for newborns with hemolysis, a negative DAT, and prolonged anemia.

Single-stranded DNA aptamer targeting and neutralization of anti-D alloantibody: a potential therapeutic strategy for haemolytic diseases caused by Rhesus alloantibody.

BACKGROUND: Rhesus (Rh) D antigen is the most important antigen in the Rh blood group system because of its strong immunogenicity. When RhD-negative individuals are exposed to RhD-positive blood, they may produce anti-D alloantibody, potentially resulting in delayed haemolytic transfusion reactions and Rh haemolytic disease of the foetus and newborn, which are difficult to treat. Inhibition of the binding of anti-D antibody with RhD antigens on the surface of red blood cells may effectively prevent immune haemolytic diseases. MATERIALS AND METHODS: In this study, single-stranded (ss) DNA aptamers, specifically binding to anti-D antibodies, were selected via systematic evolution of ligands by exponential enrichment (SELEX) technology. After 14 rounds of selection, the purified ssDNA was sequenced using a Personal Genome Machine system. Haemagglutination inhibition assays were performed to screen aptamers for biological activity in terms of blocking antigen-antibody reactions: the affinity and specificity of the aptamers were also determined. RESULTS: In addition to high specificity, the aptamers which were selected showed high affinity for anti-D antibodies with dissociation constant (Kd) values ranging from 51.46±14.90 to 543.30±92.59 nM. By the combined use of specific ssDNA aptamer 7 and auxiliary ssDNA aptamer 2, anti-D could be effectively neutralised at low concentrations of the aptamers. DISCUSSION: Our results demonstrate that ssDNA aptamers may be a novel, promising strategy for the treatment of delayed haemolytic transfusion reactions and Rh haemolytic disease of the foetus and newborn.

Intravenous immunoglobulin in the management of a rare cause of hemolytic disease of the newborn: Anti-SARA antibodies.

Hemolytic disease of newborn (HDN) is a condition that develops in a fetus, when the IgG molecules produced by the mother pass through the placenta and attack the fetal red blood cells. HDN can occur due to Rh and ABO incompatibilities between the mother and the fetus as well as due to other allo-immune antibodies belonging to Kell (K and k), Duffy (Fya), Kidd (Jka and Jkb), and MNS (M, N, S, and s) systems. Role of intravenous immunoglobulin in management of HDN is not clear.SARA red blood cell antigen, first discovered in 1990 is a low frequency antigen. We report, a multiparous female whose pregnancy was complicated by HDN due to anti-SARA antibodies requiring both exchange transfusion and intravenous immunoglobulin. The response was sustained after intravenous immunoglobulin (IVIG) rather than after exchange transfusion.

Use of intravenous immunoglobulin in neonates at a tertiary academic hospital: a retrospective 11-year study.

BACKGROUND: Intravenous immunoglobulin (IVIG) is used to treat a variety of diseases in the neonatal intensive care unit (NICU). Although audits have reported on the spectrum of IVIG use in adults, the indications and utilization in neonates has not been investigated. The objectives of this study were to describe the usage pattern of and indications for IVIG in a tertiary care NICU. STUDY DESIGN AND METHODS: A retrospective chart review was performed of all neonates who received IVIG in the NICU from January 2003 to December 2013. Data collected included patient demographic features, antenatal maternal details, neonatal laboratory results, treatment details, adverse events, and patient outcome. RESULTS: Thirty-seven neonates received IVIG over the 11-year period. Twenty-three (67%) were treated for hemolytic disease of the newborn (HDN); 13 treatments were ABO related, six were anti-D related, and four were for clinically significant antibodies. Fourteen (33%) were treated for non-HDN causes, including eight for septic neonates, two for neonates with necrotizing enterocolitis, two for neonates with a clinically significant antibody but without evidence of hemolysis, and two for neonates with glucose 6-phosphate dehydrogenase deficiency. A complete hemolytic workup was not performed consistently before the receipt of IVIG. CONCLUSIONS: This novel assessment of IVIG use in the NICU revealed the spectrum of disease for which IVIG is ordered. This study also found that key diagnostic tests needed to confirm an immune etiology for idiopathic jaundice are not performed routinely before IVIG receipt. Neonatal transfusion-related databases are needed to carry out pragmatic clinical trials to establish better evidence-based guidelines for IVIG therapy in the NICU.

Enfermedad hemolítica perinatal causada por anticuerpos anti-M y tratada con inmunoglobulinas intravenosas fetales / Hemolytic disease of the fetus due to anti-M antibodies treated with fetal intravenous immunoglobulin therapy

Presentamos el caso de una mujer de 28 años, con 2 abortos tardíos previos causados por anticuerpos anti-M. En la actual gestación es tratada desde la semana 23 hasta la semana 34 con inmunoglobulinas intravenosas fetales, con resultado satisfactorio. Aunque no hay estudios randomizados y controlados que indiquen que las inmunoglobulinas fetales son efectivas en el manejo de la isoinmunización, pequeñas series de casos sugieren resultados prometedores (AU)

We present the case of a 28-year-old woman with two prior late miscarriages caused by anti-M antibodies, leading to alloimmunization of her previous pregnancies. During this pregnancy, she was successfully treated with intravenous immunoglobulins administered from the 23th to the 34th week of pregnancy. There are no randomized trials to indicate whether the antenatal use of intravenous immunoglobulin is effective in the management of fetal red blood cell alloimmunization. Several case series suggest a beneficial role in preventing severe fetal anemia (AU)

Intravenous immunoglobulin in isoimmune haemolytic disease of newborn: an updated systematic review and meta-analysis.

BACKGROUND: Intravenous immunoglobulin (IVIg) is used in neonates with isoimmune haemolytic disease to prevent exchange transfusion (ET). However, studies supporting IVIg had methodological issues. OBJECTIVE: To update the systematic review of efficacy and safety of IVIg in neonates with isoimmune haemolytic disease. METHODS: MEDLINE, Embase databases and Cochrane Central Register of Controlled Trials (Cochrane Library) were searched (from inception to May 2013) for randomised or quasi-randomised controlled trials comparing IVIg with placebo/controls in neonates with isoimmune haemolytic disease without any language restriction. Three investigators assessed methodological quality of included trials. Meta-analyses were performed using random effect model and risk ratio (RR)/risk difference (RD) and mean difference with 95% CI calculated. MAIN RESULTS: Twelve studies were included, ten trials (n=463) of Rh isoimmunisation and five trials (n=350) of ABO isoimmunisation (three studies had both population). Significant variations in risk of bias precluded an overall meta-analysis of Rh isoimmunisation. Studies with high risk of bias showed that IVIg reduced the rate of ET in Rh isoimmunisation (RR 0.23, 95% CI 0.13 to 0.40), whereas studies with low risk of bias that also used prophylactic phototherapy did not show statistically significant difference (RR 0.82, 95% CI 0.53 to 1.26). For ABO isoimmunisation, only studies with high risk of bias were available and meta-analysis revealed efficacy of IVIg in reducing ET (RR 0.31, 95% CI 0.18 to 0.55). CONCLUSIONS: Efficacy of IVIg is not conclusive in Rh haemolytic disease of newborn with studies with low risk of bias indicating no benefit and studies with high risk of bias suggesting benefit. Role of IVIg in ABO disease is not clear as studies that showed a benefit had high risk of bias.

Uso posnatal de altas dosis de gamma globulina EV en el tratamiento de la enfermedad hemolítica RH / Postnatal use of high doses of EV gammaglobulin in the treatment of hemolytic disease RH

El uso posnatal de altas dosis de inmunoglobulina endovenosa (IgGEV) aparece promisorio, en los escasos trabajos publicados, en reducir la necesidad de exsanguinotransfusiones (EXT) en el recién nacido (RN) con enfermedad hemolítica RH (EHRH). Objetivo: Evaluar la eficacia de la IgGEV para moderar la severidad de la hemólisis: necesidad de EXT, tiempo de luminoterapia (LMT) y número de transfusiones (T) en el RN con EHRH. Diseño: Ensayo clínico controlado y randomizado. Lugar de estudio: Hospital Materno Infantil “Ramón Sardá”. Población y métodos: Todos los RN con EHRH [Coombs directa (+)], fueron estratificados en 3 grados (leve, moderado y severo) según la severidad de la hemólisis evaluada intraútero. Solicitado el consentimiento informado a los padres, los RN de cada grado se randomizaron en: Grupo tratado: recibió IgGEV (500mg/kg/día por tres días, la primera dosis antes de las 2 horas posnatales) más LMT, y grupo control: solo LMT. Las variables estudiadas fueron: mínimo hematocrito (Hto), bilirrubina (Bi) máxima, n° de EXT y/o T, LMT (hs), internación (días) y tiempo hasta la EXT. Resultados: Entre febrero/99 y mayo/00 fueron enrolados 46 RN (grado leve: 24 y grado moderado-severo (gM-S): 22). 23 RN pertenecieron al grupo tratado y 23 al control. Ambos grupos fueron comparables en sexo, peso, EG y Hto, Bi, Hb y prot. totales de cordón. No se observaron diferencias significativas excepto en n° de EXT. De los 23 RN tratados, 5 requirieron EXT (21.74%) cuando su bilirrubina alcanzó el nivel establecido en las guías del hospital; 18 de los 23 RN controles requirieron EXT (78,26%), Chi2 0.0011. El número necesario a tratar (NNT) fue 1,8 para prevenir una EXT. La probabilidad de sufrir EXT es significativamente menor en un paciente tratado que en un control, en cualquier momento del período de estudio (Log Rank test p= 0,0024). Conclusiones: Estos resultados apoyan el beneficio clínico de tratar con IgGEV a los RN con incompatibilidad RH.

Phenobarbitone in Rh hemolytic disease of the newborn: a randomized double-blinded placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy of prophylactic oral phenobarbitone (PB) in neonates with Rh hemolytic disease of the newborn. STUDY DESIGN: In this double-blind randomized trial conducted in a tertiary care unit, we randomly allocated neonates with Rh hemolytic disease of the newborn born at or after 32 weeks' gestation to PB (10 mg/kg/day on day 1 followed by 5 mg/kg/day on days 2-5) (n = 23) or oral glucose (n = 21). The primary outcome was the duration of phototherapy. RESULTS: Baseline variables were comparable. There was no difference in the median duration of phototherapy [54 (range: 0-180) vs. 35 h (0-127); p = 0.39] and in the incidences of failure of phototherapy or significant rebounds of serum bilirubin. However, the proportion of infants with cholestasis was significantly lower in the PB group (0 vs. 19%; p = 0.04). CONCLUSIONS: PB does not reduce duration of phototherapy or its episodes. Its potential to reduce cholestasis needs validation in larger studies.

Use of intravenous immunoglobulin in neonates with haemolytic disease and immune thrombocytopenia.

BACKGROUND/AIM: Intravenous immunoglobulin is a blood product made of human polyclonal immunoglobulin G. The mode of action of intravenous immunoglobulin is very complex. It is indicated in treatment of neonatal immune thrombocytopenia and haemolytic disease of the newborn. The aim of the study was to present our experience in the use of intravenous immunoglobulin in a group of term neonates. METHODS: We analysed all relevant clinical and laboratory data of 23 neonates who recieved intravenous immunoglobulin during their hospitalization in Neonatal Intensive Care Unit of Mother and Child Health Care Institute over a five year period, from 2006. to 2010. RESULTS: There were 11 patients with haemolytic disease of the newborn and 12 neonates with immune thrombocytopenia. All of them recieved 1-2 g/kg intravenous immunoglobulin in the course of their treatment. There was no adverse effects of intravenous immunoglobulin use. The use of intravenous immunoglobulin led to an increase in platelet number in thrombocytopenic patients, whereas in those with haemolytic disease serum bilirubin level decreased significantly, so that some patients whose bilirubin level was very close to the exchange transfusion criterion, avoided this procedure. CONCLUSION: The use of intravenous immunoglobulin was shown to be an effective treatment in reducing the need for exchange transfusion, duration of phototherapy and the length of hospital stay in neonates with haemolytic disease. When used in treatment of neonatal immune thrombocytopenia, it leads to an increase in the platelet number, thus decreasing the risk of serious complications of thrombocytopenia.

Tin-mesoporphyrin in the treatment of refractory hyperbilirubinemia due to Rh incompatibility.

We describe the use of tin-mesoporphyrin (SnMP) in the treatment of an infant with Rh hemolytic disease. The infant's hyperbilirubinemia responded to phototherapy but every time the phototherapy was discontinued, the serum bilirubin rebounded and repeat phototherapy was necessary. A single intramuscular dose of SnMP on day 18 eliminated the need for further phototherapy and allowed us to discharge this infant.

Hematological morbidity and management in neonates with hemolytic disease due to red cell alloimmunization.

Treatment of severe anemia with intrauterine red cell transfusions in fetuses with red cell alloimmunization has led to a dramatic increase in perinatal survival. Due to this increased survival focus is nowadays shifting towards improving postnatal treatment options. Phototherapy, exchange transfusions and intravenous immunoglobulin are used to treat hyperbilirubinemia and prevent kernicterus. Postnatal treatment of anemia consists of top-up transfusions, supplements to support erythropoiesis such as folic acid and iron, and occasionally erythropoietin treatment. In addition to anemia, other hematological complications such as thrombocytopenia, coagulation disturbances, leucopenia and iron overload have been reported. This review focuses on the hematological morbidity in neonates with red cell alloimmunization and summarizes the current evidence on management options.

Single versus multiple dose intravenous immunoglobulin in combination with LED phototherapy in the treatment of ABO hemolytic disease in neonates.

Intravenous immunoglobulin (IVIG) has been found to decrease hemolysis in neonatal jaundice due to blood group incompatibility, but a consensus on its usage has not been reached. We conducted a study to compare single versus multiple dose of IVIG in combination with light emitting diode (LED) phototherapy in patients with neonatal jaundice secondary to ABO blood incompatibility, and compared the efficacy of these treatments with that in a group of patients who received LED phototherapy solely. Thirty-nine term neonates with ABO blood group incompatibility were enrolled in the study. Group I received one dose of IVIG (1 g/kg) and LED phototherapy, and group II two doses of IVIG (1 g/kg) and LED phototherapy, whereas group III received LED phototherapy only. In group I, exchange transfusion was performed in one patient (6%) and in group II in one patient (10%). In the control group, none of the patients required exchange transfusion. Duration of LED phototherapy was 4.3 ± 0.7 days in group I + II (IVIG group), 3.9 ± 0.6 days in group III (P = 0.06). Lowest hematocrit level in group I + II was 35.0 ± 7.8 and group III was 38.9 ± 4.2, this was statistically significant (P = 0.034). IVIG therapy, single or multiple, did not affect exchange transfusion, need of erythrocyte transfusion and hospitalization time when used in combination with LED phototherapy in the treatment of ABO hemolytic jaundice in neonates.

Intravenous immunoglobulin in neonates with rhesus hemolytic disease: a randomized controlled trial.

BACKGROUND: Despite limited data, international guidelines recommend the use of intravenous immunoglobulin (IVIg) in neonates with rhesus hemolytic disease. OBJECTIVE: We tested whether prophylactic use of IVIg reduces the need for exchange transfusions in neonates with rhesus hemolytic disease. DESIGN AND SETTING: We performed a randomized, double-blind, placebo-controlled trial in neonates with rhesus hemolytic disease. After stratification for treatment with intrauterine transfusion, neonates were randomly assigned for IVIg (0.75 g/kg) or placebo (5% glucose). The primary outcome was the rate of exchange transfusions. Secondary outcomes were duration of phototherapy, maximum bilirubin levels, and the need of top-up red-cell transfusions. RESULTS: Eighty infants were included in the study, 53 of whom (66%) were treated with intrauterine transfusion(s). There was no difference in the rate of exchange transfusions between the IVIg and placebo groups (7 of 41 [17%] vs 6 of 39 [15%]; P = .99) and in the number of exchange transfusions per patient (median [range]: 0 [0-2] vs 0 [0-2]; P = .90) or in duration of phototherapy (4.7 [1.8] vs 5.1 [2.1] days; P = .34), maximum bilirubin levels (14.8 [4.7] vs 14.1 [4.9] mg/dL; P = .52), and proportion of neonates who required top-up red-cell transfusions (34 of 41 [83%] vs 34 of 39 [87%]; P = .76). CONCLUSIONS: Prophylactic IVIg does not reduce the need for exchange transfusion or the rates of other adverse neonatal outcomes. Our findings do not support the use of IVIg in neonates with rhesus hemolytic disease.

Early intravenous immunoglobin (two-dose regimen) in the management of severe Rh hemolytic disease of newborn--a prospective randomized controlled trial.

Phototherapy is the standard treatment in moderately severe hemolytic disease of newborn (HDN), whereas exchange transfusion (ET) is the second line in progressive cases. Intravenous immunoglobin (IVIG) has been suggested to decrease the need for ET. We aimed at assessing the efficacy of early two-dose regimens of IVIG to avoid unnecessary ET in severe Rh HDN. The study included 90 full-term neonates with Rh incompatibility unmodified by antenatal treatment and not eligible for early ET and which were randomly assigned into one of three groups: group (I), treated by conventional method; groups IIa and IIb received IVIG once at 12 h postnatal age if PT was indicated, in a dose of 0.5 and 1 g/kg, respectively. Analysis revealed 11 neonates (22%) in the conventional group and 2 (5%) in the intervention group who administered low-dose IVIG at 12 h, while none in group IIb required exchange transfusion (p = 0.03). Mean bilirubin levels were significantly lower during the first 96 h in the intervention group compared to the conventional group (p < 0.0001). Shorter duration of phototherapy (52.8 ± 12.39 h) and hospital stay (3.25 ± 0.71 days) in the IVIG group compared to conventional group (84 ± 12.12 h and 4.72 ± 0.78 days, p < 0.0001, respectively) were observed. We conclude that IVIG administration at 12 h was effective in the treatment of severe Rh HDN; the low-dose IVIG (0.5 g/kg) was as effective as high dose (1 g/kg) in reducing the duration of phototherapy and hospital stay, but less effective in avoiding exchange transfusion.