InABO hemolytic disease of the newborn (also known as ABO HDN) maternalIgGantibodies with specificity for theABO blood group system pass through theplacenta to thefetal circulation where they can causehemolysis of fetalred blood cells which can lead to fetalanemia andHDN. In contrast toRh disease, about half of the cases of ABO HDN occur in a firstborn baby and ABO HDN does not become more severe after further pregnancies.[citation needed]
The ABO blood group system is the best known surface antigen system, expressed on a wide variety of human cells. ForCaucasian populations about one fifth of all pregnancies have ABO incompatibility between the fetus and the mother, but only a very small minority develop symptomatic ABO HDN.[1] The latter typically only occurs in mothers of blood group O due to an increased chance of the antibodies against A and B antigens being of the IgG subclass, as opposed to the more common IgM subclass which is unable to cross the placenta.[2]
Although very uncommon, cases of ABO HDN have been reported in infants born to mothers with blood groups A[3][4] and B.[5]
Anti-A and anti-B antibodies are usuallyIgM and do not pass through the placenta, but some mothers "naturally" haveIgG anti-A or IgG anti-B antibodies, which can pass through the placenta. Exposure to A-antigens and B-antigens, which are both widespread in nature, usually leads to the production of IgM anti-A and IgM anti-B antibodies but occasionally IgG antibodies are produced.[citation needed]
Fetal-maternal transfusion
Some mothers may be sensitized by fetal-maternal transfusion of ABO incompatible red blood and produce immune IgG antibodies against the antigen they do not have and their baby does. For example, when a mother of genotype OO (blood group O) carries a fetus of genotype AO (blood group A) she may produce IgG anti-A antibodies. The father will either have blood group A, with genotype AA or AO or, more rarely, have blood group AB, with genotype AB.[citation needed]
Blood transfusion
It would be very rare for ABO sensitization to be due to therapeuticblood transfusion as a great deal of effort and checking is done to ensure that blood is ABO compatible between the recipient and the donor.[citation needed]
In about a third of all ABO incompatible pregnancies maternal IgG anti-A or IgG anti-B antibodies pass through the placenta to the fetal circulation leading to a weakly positivedirect Coombs test for the neonate's blood.[citation needed] However, ABO HDN is generally mild and short-lived and only occasionally severe because:
IgG anti-A (or IgG anti-B) antibodies that enter the fetal circulation from the mother find A (or B) antigens on many different fetal cell types, leaving fewer antibodies available for binding onto fetal red blood cells.[15]
FetalRBC surface A and Bantigens are not fully developed during gestation and so there are a smaller number of antigenic sites on fetal RBCs.[15]
Routineantenatal antibody screening blood tests (indirect Coombs test) do not screen for ABO HDN.[citation needed] If IgG anti-A or IgG anti-B antibodies are found in the pregnant woman's blood, they are not reported with the test results, because they do not correlate well with ABO HDN.[citation needed] Diagnosis is usually made by investigation of a newborn baby who has developedjaundice during the first week of life.
Testing
Coombs - after birth, the newborn will have a direct Coombs test run to confirm antibodies attached to the infant's red blood cells. This test is run from cord blood.[6] In some cases, the direct Coombs will be negative but severe, even fatal HDN can occur.[16] An indirect Coombs needs to be run in cases of anti-C,[17] anti-c,[17] or anti-M presence. In case of anti-M detection, it is also recommended to perform antigen testing to rule out the presence of HDN.[18]
Hgb - the infant's hemoglobin should be tested from cord blood.[6]
Reticulocyte count - Reticulocytes are elevated when the infant is producing more blood to combat anemia.[6] A rise in the reticulocyte count can mean that an infant may not need additional transfusions.[19] Low reticulocyte count is observed in infants treated with IUT and in those with HDN from anti-Kell[17]
Neutrophils - as Neutropenia is one of the complications of HDN, the neutrophil count should be checked.[10][11]
Thrombocytes - as thrombocytopenia is one of the complications of HDN, the thrombocyte count should be checked.[10]
Ferritin - because most infants affected by HDN have iron overload, ferritin levels must be measured before giving the infant any additional iron.[12]
Newborn Screening Tests - Transfusion with donor blood during pregnancy or shortly after birth can affect the results of the Newborn Screening Tests. It is recommended to wait and retest 10–12 months after the last transfusion. In some cases, DNA testing from saliva can be used to rule out certain conditions.[citation needed]
The antibodies in ABO HDN causeanemia due to destruction of fetal red blood cells andjaundice due to the rise in blood levels ofbilirubin a by-product ofhemoglobin break down. If the anemia is severe, it can be treated with a blood transfusion, however this is rarely needed. On the other hand, neonates have underdeveloped livers that are unable to process large amounts of bilirubin and a poorly developedblood–brain barrier that is unable to block bilirubin from entering the brain. This can result inkernicterus if left unchecked. If the bilirubin level is sufficiently high as to cause worry, it can be lowered viaphototherapy in the first instance or anexchange transfusion if severely elevated.[citation needed]
Phototherapy - Phototherapy is used for cord bilirubin of 3 or higher. Some doctors use it at lower levels while awaiting lab results.[20]
IVIG - Intravenous Immunoglobulin therapy (IVIG) has been used to successfully treat many cases of HDN. It has been used not only on anti-D, but on anti-E as well.[21] IVIG can be used to reduce the need for exchange transfusion and to shorten the length of phototherapy.[22] The AAP recommends "In isoimmune hemolytic disease, administration of intravenous γ-globulin (0.5-1 g/kg over 2 hours) is recommended if the TSB is rising despite intensive phototherapy or the TSB level is within 2 to 3 mg/dL (34-51 μmol/L) of the exchange level . If necessary, this dose can be repeated in 12 hours (evidence quality B: benefits exceed harms). Intravenous γ-globulin has been shown to reduce the need for exchange transfusions in Rh and ABO hemolytic disease."[20]
Exchange transfusion - Exchange transfusion is used when bilirubin reaches either the high or medium risk lines on the normogram provided by the American Academy of Pediatrics (Figure 4).[20] Cord bilirubin >4 is also indicative of the need for exchange transfusion.[23]
^Dean, Laura (2005),"The ABO blood group",Blood Groups and Red Cell Antigens [Internet], National Center for Biotechnology Information (US), retrieved2025-06-12
^Wang, Michael; Hays, Taru; Ambruso, Dan R.; Silliman, Christopher C.; Dickey, William C. (2005). "Hemolytic disease of the newborn caused by a high titer anti-group B IgG from a group a mother".Pediatric Blood & Cancer.45 (6):861–2.doi:10.1002/pbc.20503.PMID16007582.S2CID44546304.
^Haque, K. M.; Rahman, M (2000). "An unusual case of ABO-haemolytic disease of the newborn".Bangladesh Medical Research Council Bulletin.26 (2):61–4.PMID11508073.
^Shapiro, Steven M (2004). "Definition of the Clinical Spectrum of Kernicterus and Bilirubin-Induced Neurologic Dysfunction (BIND)".Journal of Perinatology.25 (1):54–9.doi:10.1038/sj.jp.7211157.PMID15578034.S2CID19663259.
^Lande, Lottie (1948). "Clinical signs and development of survivors of kernicterus due to Rh sensitization".The Journal of Pediatrics.32 (6):693–705.doi:10.1016/S0022-3476(48)80225-8.PMID18866937.
^abcdKoenig, J. M.; Christensen, R. D. (1989). "Neutropenia and thrombocytopenia in infants with Rh hemolytic disease".The Journal of Pediatrics.114 (4 Pt 1):625–31.doi:10.1016/s0022-3476(89)80709-7.PMID2494315.
^abRath, M. E. A.; Smits-Wintjens, V. E. H. J.; Oepkes, D.; Walther, F. J.; Lopriore, E. (2013). "Iron status in infants with alloimmune haemolytic disease in the first three months of life".Vox Sanguinis.105 (4):328–33.doi:10.1111/vox.12061.PMID23802744.S2CID24789324.
^Al-Alaiyan, S.; Al Omran, A. (1999). "Late hyporegenerative anemia in neonates with rhesus hemolytic disease".Journal of Perinatal Medicine.27 (2):112–5.doi:10.1515/JPM.1999.014.PMID10379500.S2CID32155893.
^Heddle, N. M.; Wentworth, P.; Anderson, D. R.; Emmerson, D.; Kelton, J. G.; Blajchman, M. A. (1995). "Three examples of Rh haemolytic disease of the newborn with a negative direct antiglobulin test".Transfusion Medicine.5 (2):113–6.doi:10.1111/j.1365-3148.1995.tb00197.x.PMID7655573.S2CID21936425.
