Introduction. Hemolytic disease of newborn due to ABO incompatibility

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1 Hemolytic disease of newborn due to ABO incompatibility Faris B. AL-Swaf*, Rekan S. Jumaa**, Isam S. Saeed*** *Dept. of pediatrics, Ninava College of Medicine, Mousl University. **Department of pediatrics, College of Medicine, Tikrit University. ***Specialist pediatrician, Ninava health directorate Abstract Hemolytic disease of newborn due to ABO-incompatibility is the most common cause of hemolytic diseases of newborns, its occur due to ABO blood group incompatibility between the mother and infant. The aim of study is to identify the incidence and severity of jaundice in patients with ABO incompatibility. Fifty four babies with ABO incompatibility admitted to Al- Khansah maternity and children teaching hospital (in Mosul were studied between the first of January and end of May 2005). Thirty five were males (68.8%), and 19 cases were females (35.2%), their age was 1-10 days, the majority were fullterms 44 cases (81.5%).and in most of them the weight was> 2.5kg. Family history of jaundice or treatment was negative in (59.2%). Twenty three cases presented during the second and third day of life and jaundice was the hallmark of the disease found in 100% followed by poor feeding, pallor, opisthotonos and hepatosplenomegaly. Serum bilirubin level more than 323 p mol/l (> 19 mg/dl) was in (40.8%) hemoglobin level between g/l was found in (53.7%) reticulocyte count between (5-9%) was found in (63%) and direct Coomb s test was positive in (5.5%) of the patients. Thirty two patients (59.2% ) treated with phototherapy and in most of them 18 patients (56.2%) the duration of phototherapy was hr, while 22 cases (40.8%) were treated by exchange transfusion and in most of them 16 cases the exchange transfusion was done once. Total serum bilirubin was lowered by 25-50% immediately after the exchange transfusion in 13 cases (59%). The prognosis was good for the most of the patients 46 cases (85.3%) and they were discharged well from the hospital. Introduction Hemolytic disease of newborn due to ABO-incompatibility (HDNABO) is the most common cause of hemolytic diseases of the newborns (1). Hemolytic Disease of Newborn (HDN) also called Icterus gravis Neonatorum which was first described by Morgagni in 1761 but only in the last 35 years has it s origin in the blood group incompatibilities between fetus and mother been known (2). A French midwife was the first to report hemolytic disease of the newborn in a set of twins in 1609 (3).HDN-ABO is a form of Isoimmune hemolytic disease of the newborn due to ABO blood group incompatibility between the mother and infant. The anti-a or anti-b antibodies of a mother of blood group O, B or A may cross the placenta and sensitize the RBCs of an A, B, or AB infant (4). In mother with type A and B blood, naturally occurring antibodies are of 1gM class, which do not cross the placenta, where as in type O mother the antibodies are predominantly IgG in nature (cross the placenta) (1). Because A and B antigens are widely expressed in a variety of tissues besides RBCs, only small portion of antibodies crossing the placenta is available to bind to fetal RBCs, in addition, fetal RBCs appear to have less surface expression of A or B antigen, resulting in few reactive siteshence the low incidence of significant hemolysis in affected neonates (5). The infants of type A blood group are generally type Al which is more antigenic than A2. Low antigenicity of the ABO factors in the fetus and newborn infant may account for the low incidence of severe ABO hemolytic disease relative 70

2 to the incidence of incompatibility between the blood group of the mother and child. Although antibodies against A and B factors occur without previous immunization (natural antibodies), they are ordinarily present in the 1gM fraction of gamma globulin, which does not cross the placenta. However, univalent, incomplete (albumin active) antibodies to A antigen may be present in the IgG fraction, which does cross the placenta, so O-A isoimmune hemolytic disease may be found in first born infants. Mothers who become immunized against A or B factors from a previous incompatible pregnancy also exhibit IgG antibody. These immune antibodies are the primary mediators in ABO isoimmune disease (1). HDN-ABO may affect a first pregnancy as frequently as a subsequent one and it s not possible to predict ABO hemolytic disease antenatally, even if the blood group set-up is correct. HDN-ABO protects against Rh immunization as naturally occurring anti A and anti B antibodies in the A,B or AB mother destroy incompatible fetal red cells immediately on entering to the maternal circulation (6). For reasons that are unclear B-O incompatibility (mother type O, Baby type B) seems to be in general more severe than A-O incompatibility (7). HDN-ABO can occur if: The mother is O and the fetus is B or A or AB (most common). The mother is A and the fetus is B or AB (uncommon). The mother is B and the fetus is A or AB (uncommon) (8).Sensitization of the mother to fetal antigens may have occurred by previous transfusion, or by conditions of pregnancy that results in transfer of fetal erythrocytes into the maternal, such as first trimester abortion, an ectopic pregnancy, amniocentesis, or even a normal pregnancy. The risk of feto-maternal transfusion is increased by manual extraction of the placenta and by version (external or internal) procedures (9). The aim of study is to identify the incidence and severity of jaundice in patients with ABO incompatibility. Patients and Methods Fifty four babies with hyperbilirubinemia and blood groups A,B and AB Rh +ve whom there mothers were blood group O (45 are Rh +ve and 9 Rh -ve) admitted to the Al -Khansah Maternity and Children Teaching hospital in Mosul were studied between the first of January and the end of May 2005). Clinical information were taken including age, sex, gestational age, birth weight, previous family history of neonatal jaundice, the onset of the jaundice, Feeding of the baby, activity of the baby, fever and any other symptoms. Complete and full examination was done to all the babies looking for the presence of pallor, jaundice, hepatosplenomegaly and any neurological signs like opisthotonos. Blood sample was taken for all the babies and send for blood group and Rh, complete blood picture including reticulocyte count, total serum bilirubin and direct Coomb s test. Blood sample was taken from their mothers and send for identification of blood group and Rh factor, and indirect Coomb s test. All the babies were treated by phototherapy and/or exchange transfusion and most of them did well and discharged in good condition. Results A total 54 patients admitted to hospital and included in present study. Table (1) Shows the age of onset of jaundice in patient with ABOincompatibility, the most common age 71

3 presented with jaundice 1-3 days 23 cases (42.5%) followed by 1 st 24 hours, 19 cases,and then >3days 12 cases. Table (2) Shows the sex distribution of patient, 35, were males while 19, were females. Gestational age of our patients 44 babies were >38weeks while 10 were <38weeks. The weight of patient 39cases were more than 2.5kg, while 15 cases less than 2.5kg. Table(3) shows family history of jaundice and treatment, number of patients with jaundice not required treatment were 10(18.5%), jaundice with phototherapy 8cases,jaundice with phototherapy, and exchange transfusion 4cases, and without previous history were 32 cases. Table (4) shows clinical features at admission to hospital, all patients had jaundice, patients with jaundice and poor feeding were 9 cases. Twenty five patients treated by phototherapy while 20 cases treated by exchange transfusion as shown in table (5). Patients treated by phototherapy were 32,most of them 18 patients the duration of phototherapy was 24-48hr as shown in table (6). Six babies required more than one exchange transfusion, two of them had Rh-ve mother, one of them underwent exchange transfusion twice and the other underwent three times as showen in table (7). Table (8) shows the outcome three patients died ;one had Rhincompatibility in addition to ABOincompatibility, the others two had proved neonatal sepsis, 46 patients discharged well.table (9) shows the main investigations done to the patients with ABO-incompatibility in present study includes, Total serum bilirubin >19mg/dl in 22 cases (40.8%), Hemoglobin level ranged from g/l in 29 cases, regarding Reticulocyte percentage the majority of patients (34 cases) between 5-9.Direct coombs test negative in 51 cases. Discussion Twenty three babies presented with jaundice during the second and third day of life, whereas, (35.2 %) of them presented in the first day of life and 12 cases (22.3%) presented after the third day of life, similar finding was (1,2,4,6,10) reported previously Thirty five were males (64.8%) and nineteen were females (3 5.1%), male infants have consistently higher level of bilirubin than females (11,12). Forty four patients (81.5%) were fullterms and 10 patients (18.5%) were premature, this is in contrast to the fact that the jaundice is observed in approximately 60% of term infants and 80% of preterm infants was reported previously (1). In 15 patients (27.8%), the body weight was less than 2.5 kg while in 39 (72.2%) patient, while (62.9%) was > 2.5. This stands against the fact that small for gestational age babies developed polycythemia (due to fetal hypoxia) which lead to hyperbilirubinemia and this was reported by Robert M. Kliegman (9). Most of the patients 32 cases had no previous history of jaundice and/or phototherapy and/or exchange transfusion and this result is proved by the fact that ABO-incompatibility is presented in approximately 12% of pregnancies, with evidence of fetal sensitization in 3% of live births and fewer than 1% of births are associated with significant hemolysis and,this was reported by Mentzer WC, Glader BE,1998 (10). All the patients (54) cases had the jaundice as the hallmark of the disease and some patients (7) cases(12.9%) developed pallor with jaundice and two patients developed neurological signs like poor feeding (9)cases(16.7%) and opisthotonos 3 cases, Barbara J. Stoll and Robert M. Kliegman said that ABOincompatibility is the most common cause of hemolytic disease of newborns (1).The blood group of (59.2%) was A +ve and it was B +ve in (34.5%)of 72

4 the babies and this is consistent with the studies of john a. Ozolek, Jon F. Watchko and Francis Mimouni in 1993 (10), and supported by the fact found by Dean Edell (10). The hemoglobin level was g/l in 53.7% of the patients at admission, while the reticulocyte count was (5-9%)in 63% of the patients and, so this means that ABO-compatibility is a mild disease and this is supported by the fact that hemolysis develops in only 10% of ABO-compatibility and this was found by Barbara J. Stoll and Robert M. Kliegman (1). Total serum bilirubin was more than (19 mg/dl) in 40.8% of the patients. So that ABO-incompatibility is an important cause of hyperbilirubinemia, this is consistent with the study done by Tariq Al-Shujairi in 2001 (14). Barbara J. Stoll and Robert M. Kliegman (1) concluded that Jaundice is the only clinical manifestation of ABO-incompatibility. Direct combs test was positive in three patients only and this test is a qualitative one so, a positive results does not suggest the amount of antibody or the degree of hemolysis, Maisels MJ (13), but Barbara J. Stoll and Robert M. Kliegman (1) said that direct Coomb s test is weakly to moderately positive in ABO incompatibility. Indirect Coomb s test was negative in all the mothers of the patients and this means that this test is a weak marker for hemolysis, this was proved by Swinhoe D,J. et. al. In 1990 (15). Thirty two patients (59.2%) treated with phototherapy and in most of them,18 patients(56.2%) the duration of phototherapy was hr, while 22 cases (40.8%) were treated by exchange transfusion and in most of them 16 cases (72.2%) the exchange transfusion was done just once and the total serum bilirubin was lowered by 25-50% immediately after the exchange transfusion in 13 cases out of 22. These results indicate that phototherapy is an important and effective measure in the treatment of hyperbilirubinemia and also the exchange transfusion was effective for reducing the neonatal jaundice and these results are supported by the fact that the need for exchange transfusion decreases due to phototherapy, but when there is an indication for exchange transfusion, phototherapy should not be used as a substitute, however, phototherapy may reduce the need for repeated exchange transfusion in infants with hemolysis and this was reported by previous study (1) and this results was also found by Maurer H.M. et. al in his study on efficacy of phototherapy as a substitute for exchange transfusion particularly in severe hemolysis. They were nine babies with Rhve mothers, seven babies has been treated with phototherapy alone and just two required exchange transfusion and this means that ABO-incompatibility is protective against Rhesus hemolytic disease of newborn and this is supported by the fact that ABO incompatibility between the mother and fetus protects against Rh immunization as naturally occurring anti A and anti B antibodies in A, B or AB mother destroy incompatible fetal red cells immediately on entering to the maternal circulation, and this fact was found by Mclntosh N. (6). Also Bowman J. M. in 1986 found that ABO-incompatibility should not be taken into account when making a decision for management of Rhesus hemolytic disease for newborn and ABO incompatibility does not ameliorate the severity of erythroblastosis fetalis after Rhesus immunization has developed (16). We recommend to educate people through mass media about jaundice in newborn baby in order to seek early medical advice so that diagnosis and prompt treatment can be instituted to prevent dangerous sequelae. 73

5 References 1. Barbara J. Stoll and Robert M. Kliegman. The Fetus and the Neonatal Infant. In: Behrman RE, Kliegman RM, Jensen HB and eds. Nelson Textbook of Pediatrics. 17 th ed. Philadilphia, WB saunders Co. 2004; Vulliamy D.G. Haemorrhage and Jaundice. In: The Newborn child. 4 th.ed. Hong Kong Pa: Churchill living stone 1977; Bowman J. The management of hemolytic disease in the fetus and newborn. Semin perinatol Feb. 21(1); Edward wasserman, Lawrence B. Slobody. Diseases of the newborn. In: Survey of clinical pediatrics. 6 th.ed. Tokyo - Japan. Mc Graw Hill Koga Kusha, Ltd. 1974; Wagle S. MD. Clinical Assistant professor, Department of pediatrics, Division of Neonatology. University of Mississippi Medical center, Prashant G Deshpande, MD. Consulting staff, Depart. Of. Ped., Hope children s Hospital. Hernolytic Diseases of newborn. Last updated. March, 14, Mclntosh N. The newborn. In: Forfar and Arneil s Textbook of pediatrics. 5 th ed. U.K. pa. churchilllivingstone, London; 1998; Hull.J.W. ABO incomputability. In: General Health Encyclopedia 2002; Dean Edell: ABO. incompatibility. In: General Health Encyclopedia. Adam. Corn ; Robert M. Kliegman. Fetal and Neonatal Medicine. In: Richard E. Behrman, Robert M. kliegman. Nelson Essentials of Pediatrics. 4 th. ed. USA. Pa: W.B. 10. Mentzer WC, Glader BE: Erythrocyte disorders in infancy. In: Taeusch HW, Ballard RA, eds. Avery s diseases of the newborn. 7 th ed - Philadelphia, pa. WB saunders. 1998; John A. Ozolek, Jon F. Watchko, Francis Mimounia prevalence and lack of clinical significance of blood group incompatibility in mothers with blood type A or B the Journal of pediatrics, Pennsylvania. July 1994; 125(1) Shelley C. Springer, MD, MBA, MSC, Neonatologist; Medical Director of Pediatric Transport Team, Assistant professor of pediatrics, Depart. Of ped., Gundersen Lutheran Hospital, a member of the American Academy of pediatrics. And south Carolina Medical Association.. Kernicterus last updated. Feb. 14, Maisels MJ. Jaundice In: Avery, Fletcher, eds. Neonatology, pathophsiology and Management of the newborn 5 th ed. Philadelphia pa. lippincott; 1999; Tariq Abadi AL-Shujairi. In: Profile of management of indirect - reacting neonatal hyperbilirubinemia Iraq, 2001; Swinhoe D., Gilmore. D, McNay. M and Whittlem Rh hemolytic disease: continuing problem of management Arch - Dis - Child, 1990 Apr,65(4): Bowman J.M. Fetomaternal ABO incompatibility and erytheroblastosis fetalis. VOX Song.1986; 50(2):

6 Table (1): The age of onset of jaundice in patient with ABO-incompatibility. Age Case % 1 st 24 hr days >3 days Total % Table (2): Sex, Gestational age, Birth weight distribution of patients with ABOincompatibility.. No. % Male % Female % >38 wk * % <38 wks * % <2.5 ** % >2.5 ** % * Gestational age ** Birth weight 75

7 Table(3): Family history of jaundice and its treatment. Family history of jaundice No. % Jaundice not required treatment Jaundice +Phototherapy Jaundice + Phototherapy + Exchange transfusion non Total Table(4): General condition of neonate at admission time Clinical Features No. =54 % Jaundice Jaundice + poor feeding Jaundice + pallor Jaundice + Opisthotonos Jaundice + Hepatosplenomegaly Table(5): Treatment methods to the patient with ABO-incompatibility Phototherapy Exchange transfusion No. (%) No. (%) Rh +ve mother 25 (46.2) 20 (37) Rh ve mother 7 (12.9) 2 (3.7) Total No. 32 (59.2) 22 (40.8) 76

8 Table(6): Duration of phototherapy in hours. Hour No (%) > Total Table(7): Frequency of exchange transfusions. frequency No. % once Twice Trice Total % Table(8): Outcome (condition on discharge). No. % Well Kernicturous Death Total

9 Table(9): Investigations to the patients with ABO-incompatibility No. % <170(<10mg) * % (10-19) * % >323 (>19) * % <100 ** 2 3.7% ** % ** % 5-9 *** % *** % >14 *** 3 5.5% Positive **** Negative **** * TSB levels in µmol/l (mg/dl) ** Hb.(g/L) *** Reticulocyte% **** Direct coombs test 78