Discussion

Discussion
Jaundice is a common clinical problem in the neonatal period. Many neonates develop hyperbilirubinemia that requires intervention. It can progress to severe hyperbilirubinemia, resulting in kernicterus (Bhutani et al., 2004).

In the present study we documented 106 cases of hyperbilirubinemia due to ABO incompatibility between mothers and their babies divided into O-A group about 65 cases and O-B group about 41 cases. Commonly our patients presented within the 2nd day of life 86% compared with patients presented within the 1st day of life that disagree with Pavan Kumar in an Indian study (2012) but has been stated in many studies like Barbara J. et al; 2004 . Our study shows that 9 cases of O-B group (22%) in contrast with 6 cases of OA group (9%) presented in the 1st 24 hours of life which stated in

Most of the patients 78 cases had previous history of jaundice and/or phototherapy and/or exchange transfusion and this result is disagreeing with 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

4 cases presented with G6PD on maternal side whose G6PD enzyme assay was normal. In this study, there were 50 deliveries in which oxytocin were used of those, while of the other 56 deliveries
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without using of oxytocin, which indicated that there isn't statistically significant difference between the two groups. This was in agreement with Oral et al., 2003 disagreeing with keren et al., 2005 and ElShafie et al.,2003 included that the oxytocin exposure as risk factor for hyperbilirubinemia.

D'souza et al, 1979 stated that raised plasma bilirubin levels in cord blood, probably enhanced by breakdown of fetal red cells, appeared to be a dose dependant effect of oxytocin. Also, Buchan, 1979 stated that the vasopressin like action of oxytocin causes osmotic swelling of erythrocytes leading to decreased deformability and hence more rapid destruction with resultant hyperbilirubinemia in the neonates, these studies were done on venous cord blood of 95 healthy newborn infants, 15 were delivered by elective cesarean section, 40 after spontaneous labor and 40 after oxytocin use. There was no significant difference between the first two groups while infants born after oxytocin induced labor showed clear evidence of increased hemolysis with resultant hyperbilirubinemia.

Maisels (1999) stated that there was an association between the use of oxytocin to induce or augment labour and an increased incidence of neonatal hyperbilirubinemia, although the mechanism for this is unclear. Our findings were in accordance with Burgoes et al., 2008 stating that one of the factors associated with decreased likelihood of readmission for jaundice was cesarean section delivery, he found that bilirubin on days 1 and 2 were found to be higher in newborns
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delivered vaginally than caesarian section. As has been suggested neonates are stressed prior to birth and induce conjugative enzymes prior to vaginal delivery. Further newborns delivered by cesarean section are breast-fed relatively infrequently during 1st 48 hours of life than those born by vaginal delivery. Also our findings were in accordance with El-Shafie et al., 2003 stating that normal vaginal delivery was increased risk of hyperbilirubinemia this could be explained by the increased use of oxytocin infusion and the increased incidence of traumatic delivery with in normal delivery than cesarean section delivery. However Olcay et al., 2004 stated that mode of delivery didn't influence levels of bilirubin. Although our study hasnt significant result about maternal oxytocin in delivery but our study agreed with D. P. Davies' 1973 stated in study about 78 neonates provided that infants of mothers whose labor had been induced by amniotomy followed immediately by intravenous oxytocin had mean total bilirubin levels significantly higher (P <005) than did infants whose mothers had had a spontaneous onset of labor and did not require oxytocin. Zarrinkoub F, Beigi A, 2007 found that there were no statistically significant relationships between jaundice and maternal age, parity, mode of delivery, neonatal gender or previous siblings with jaundice (p>0.05). 42 patients (39.6%) cases developed pallor with jaundice and 21 patients (19.8%) developed neurological signs like poor feeding,

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Barbara J. Stoll and Robert M. Kliegman said that ABO incompatibility is the most common cause of hemolytic disease of newborns. KJ Barrington; 2005 stated that Acute encephalopathy which defined as a clinical syndrome, in the presence of severe hyperbilirubinemia, of lethargy, hypotonia and poor suck, which may progress to hypertonia with a high-pitched cry and fever, and eventually to seizures and coma, does not occur in full-term infants whose peak TSB concentration remains below 340 mol/L and is very rare unless the peak TSB concentration exceeds 425 mol/L. Above this level, the risk for toxicity progressively increases. Even with concentrations greater than 500 mol/L, there are still some infants who will escape encephalopathy. All of the reasons for the variable susceptibility of infants are not known; however, dehydration, hyperosmolarity, respiratory distress, hydrops, prematurity, acidosis, hypoalbuminemia, hypoxia and seizures are said to increase the risk of acute encephalopathy in the presence of severe hyperbilirubinemia. In our study there are 10 cases only with sequestrated blood which there's no statistical significant difference between these and others without sequestrated blood regarding mean serum bilirubin level at admission. is in accordance with our study in that sequestrated blood as cephalhematoma, bruises, hematomas, ecchymosis has no statistical significance. S, BRINK et al. 1969 stated that jaundice occurred in the O-B group it tended to be slightly more ever than in the O-A group. This was indicated by the observation that an exchange blood transfusion was

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required in 12 out of the 36 jaundiced cases in the O-B group, whereas it was needed in only 24 of the 80 O-A jaundiced cases which agree with our study. In accordance with our study, Shu-Huey et al; 2012 stated that Mean Hb and RBC for the AO group were higher and nucleated RBC ratios were lower than for the BO group; however, these differences were also not statistically significant. Interestingly, the mean Hct value of the BO group was significantly lower than that of the AO group (p = 0.04). 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 Tikrit Medical Journal 2009; 15(2):70-78 Faris B. alswaf et al; 2009 stated that main investigations done to the patients with ABO-incompatibility includes, Total serum bilirubin >19mg/dl in 22 cases (40.8%), Hemoglobin level ranged from 100140g/l in 29 cases, regarding Reticulocyte percentage the majority of patients (34 cases) between 5-9.Direct coombs test negative in 51 cases. Michael Kaplan, MB, ChB et al; 2010 stated that Hb values were somewhat lower for the O-B neonates, the difference between these and the O-A group was not significant (17.0 3.1 g/dL vs. 17.7 2.8 g/dL, p=0.2).
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A slight increase in reticulocytes is acommon feature in HDN due to ABO incompitability according to Rosenfield 1955. In the series of fairly severe cases collected by Crawford and co-workers 1953, the reticulocyte count exceeded 15% in 6 out of 11 cases. **** Mollison's blood transfusion in clinical medicine Book Author(s) Klein, Harvey G., Anstee, David J., Mollison, P. L., Mollison, P. L. Date 2005 Publisher Blackwell Pub Place of Publication Malden, Mass, Oxford Edition11th ed ISBN-10 0632064544 ISBN-13 9780632064540 Web address http://www.loc.gov/catdir/toc/ecip0512/2005012 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). Faris B. alswaf et al; 2009 stated that Thirty two patients (59.2%) treated with phototherapy and in most of them ,18 patients(56.2%) the duration of phototherapy was 24-48 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.

**** Immunology of Pregnancy and Cancer Valentin I. Govallo, M.D; 1993 had a study about 85 women with ABO-sensitization but only 31 cases had ABO-HDN. Most cases had jaundice but 8 cases only had exchange transfusion. Nine of the women only (29%) had spontaneous abortions.

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Ehealth me site 2012 agreed with us that nitrifurantoin had no significance to lead into neonatal jaundice.

Ziprin et al; 2005 in an analysis of their 2 cases of ABO-HDN and 6 other cases in the literature, made the observation that severe hemolysis usually involves both the anti-B antibody as well as black mothers. Peevy KJ, Wiseman HJ's study1987 confirmed the increased incidence of ABO-HDN in black infants with blood type B, but showed no increase in the severity of the disease. In spite of Redman M, Malde R, Contreras M.' study 1990 that showed increased incidence of ABO-HDN in black and blood group B infants is believed to result from environmental factors rather than genetic factors . Interestingly, the severe hemolysis seen in the present case also involves both the black ethnic background and the presence of anti-B maternal antibodies. *****Ziprin JH, Payne E, Hamidi J, Roberts I, Regan F. ABO incompatibility due to immunoglobulin G anti-B antibodies presenting with severe fetal anemia. Transfus Med 2005;15:57-60. *****Peevy KJ, Wiseman HJ. ABO hemolytic disease of the newborn: evaluation of management and identification of racial and antigenic factors. Pediatrics 1978;61:475478. *****Redman M, Malde R, Contreras M. Comparison of IgM and IgG anti-A and anti-B levels in Asian, Caucasian and Negro donors in North West Thames Region. Vox Sang 1990;59:89-91. Stiller RJ Herzlinger R et al; 1996 stated that ABO incompatibility is the most common maternal-fetal blood group incompatibility and the most common cause of hemolytic disease of the newborn (HDN). ABO incompatibility is more often seen in newborns who have type A
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blood because of the higher frequency of type A compared to type B in most populations. ****Stiller RJ Herzlinger R, Siegel S et.al. Fetal ascites associated with ABO incompatibility:case report and review of the literature. Am J Obstet Gynecol 1996 175(S) 1371-1372 McDonnell M, Hannam,S, Devane SP. Hydrops fetalis due to ABO incompatibility. Arch Dis Child Fetal neonatal Ed 1998 78: F 220221

Eugene Kaplan et al; 1971 stated that In hyperbilirubinemia of ABO hemolytic disease of newborn (ABO-HBN), phototherapy is less effective in lowering bilirubin concentrations than in hyperbilirubinemia of prematurity or nonhemolytic disorders of newborns. Nevertheless, phototherapy does alter patterns of serum bilirubin in ABO-HDN, as seen in a comparison of 29 treated infants with 144 untreated infants. In ABO-HDN, recognizable patterns of serum bilirubin result from variations in the severity of onset in the 1st day of life, and in the time, extent, and duration of maximum serum bilirubin concentrations. A severe onset is seen in of infants with ABO-HDN, serum bilirubin increasing at a rate of 0.5 mg/hr or greater. Peak bilirubin levels are noted on day 1 (10% of infants), day 2 (30%), day 3 (40%) and day 4 or 5 (20%). The peak bilirubin concentration is less than 16 mg% in of the infants; between 16 and 19 mg% in and exceeds 20 mg% in the remaining . In of infants the maximum bilirubin concentration remains unchanged for at least 24 hrs. before decreasing. On phototherapy, the bilirubin levels in 20% of infants with ABOHDN continue to rise, remain unchanged in 40% and decrease in 40%. Light is least effective in infants with severe onset during the 1st day of life. However, in no infant on phototherapy does bilirubin reach its peak after the 3rd day of life and the maximum bilirubin concentration exceeds 20 mg% in only 10% of treated infants. Pediatric Research (1971) 5, 407407; doi:10.1203/00006450197108000-00150 Phototherapy in ABO hemolytic disease of newborn Eugene Kaplan, Fritz Herz, Elsie Scheye and Lawrence Robinson Jr. 1Sinai Hosp. of Baltimore, Inc., Baltimore, Md.
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ISSN: 0031-3998 EISSN: 1530-0447 2012 International Pediatric Research Foundation, Inc.

{{{{Several investigators were unable to show any difference in clinical severity between O-A and O-B hemolytic disease of the newborn, although in the former report there was a trend towards performing exchange transfusion during the first 24 hours more frequently in O-B compared with O-A infants (2830). Similarly, a retrospective analysis of ABO hemolytic disease did not find significant relationships between the infants blood type and clinical outcome (31). Sisson (32) and Kaplan (33) reported no significant differences in severity or response to therapy between the two blood types. An infant whose blood group was A was as likely to be affected by ABO hemolytic disease as a blood group B infant (34). However, Bakkeheim et al found a significantly increased rate of invasive treatments, including intravenous immune globulin therapy and exchange transfusion, in O-B infants compared with O-A (35). Two studies documented a higher need for exchange transfusion in O-B neonates than in O-A (36, 37).}}}}}

((((mean daily serum total billirubin concentration reduction (56.49-/+24.05 micromol/L) in treatment group were lower than those in the control group (P<0.01). The jaundice resolution time (23.51-/ +11.19 h) and the phototherapy time (3.01-/+0.89 h) for billirubinemia treatment in treatment group were shorter than those in the control group (P<0.01). The patients in the the treatment group had higher hemoglobin level after treatment (15.59-/+2.01 g/L) than those of the control group (P<0.01).))))) Koura, H.M et al; 2009 stated that There was no significant statistical difference between (Group I treated cases ) and (Group II untreated cases) in (TSB) level on admission (p>0.05); while after 24 and 48 hours of therapy the (TSB) level was significantly lower in the treated group (Group I) than the control group (Group II) where the p value was 0.000 and 0.001 respectively. Regarding the duration of phototherapy the difference was not statistically significant (p>0.05) in both groups where in the patient group the mean duration was

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(85.0724.33 hours) and in the control group the mean duration was (96.3320.48 hours).
Table 2: Total serum bilirubin (TSB) in Group I and Group II 24 hours and 48 hours from therapy. TSB(mg/dl) Group I Group II - test P value On admission 13.6-31. 1 14.00-30.90 -------------------------------------------------------------------------------------------------------------------18.7474.474 21.4585.346 1.506 0.143 24 hours 10.80-25.00 15.12-29.90 -------------------------------------------------------------------------------------------------------------------15.8333.736 22.5274.380 -4.503 0.000* 48 hours 6.70-29.10 15.70-30.00 -------------------------------------------------------------------------------------------------------------------13.1205.293 18.8793.409 -3.543 0.001* *P>0.001 is highly significant .

Journal of Applied Sciences Research, 5(11): 1923-1928, 2009 2009, INSInet Publication Corresponding Author: Koura, H.M., Pediatrics department, National Research Centre (NRC), El-Tahrir Street, Dokki., Egypt. Book name: Role of Intravenous Immunoglobulins in Decreasing the Need for Exchange Transfusion in Neonates with Isoimmune Haemolytic Jaundice Koura H.M., Ezz el din Z.M., Ibrahim N.2 1 1 A., 2Motawie A.A., 2Saleh M.E. 1Pediatric Department, Faculty of medicine, Cairo University 2Pediatric Department, National Research Centre, Cairo Egypt

Alpay 1999 also found statistical significant in ttt of ABO HDN with phototherapy or IVIG on his study on 116 cases. http://www.health.gov.nl.ca/health/bloodservices/pdf/ivig_hem atology_guideline.pdf
Helen M. Sowers, M.A., CLS showed that frequently abo HDN

occur in first pregnancy as well as Handbook of Pediatric Transfusion Medicine by Christopher D. Hillyer,Ronald G. Strauss,Naomi L. C. Luban
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