Paediatrica Indonesiana Serological profile and hemolytic disease in [PDF]

Paediatrica Indonesiana July ‡

VOLUME 49

NUMBER 4

Original Article

Serological profile and hemolytic disease in term neonates with ABO incompatibility Desiana Dharmayani, Djajadiman Gatot, Rinawati Rohsiswatmo, Bambang Tridjaja

Abstract Background Hemolytic disease of the newborn (HDN) due to ABO blood type incompatibility is one of the most common cause of neonatal hyperbilirubunemia that potentially leads to ELOLUXELQHQFHSKDORSDWK\'DWDRQ$%2KHPRO\WLFGLVHDVHRIWKH QHZERUQ$%2+'1 HVSHFLDOO\UHJDUGLQJXPELOLFDOFRUGEORRG serological profile, are limited. Objective To identify the serological profile and hemolytic disease in term neonates with ABO incompatibility. Methods 7KLVZDVDFURVVVHFWLRQDOGHVFULSWLYHVWXG\FRQGXFWHG at RSIA Budi Kemuliaan Jakarta. Results :H IRXQG  KHDOWK\ WHUP QHRQDWHV ZLWK $%2 incompatibility, nine of them had positive direct antiglobulin WHVW '$7  UHVXOW DQG  VXEMHFWV KDG D SRVLWLYH UHVXOW RQ '$7 ZLWK HOXWLRQ PHWKRG 7KH KLJKHVW WLWHU RI ,J* ZDV  +\SHUELOLUXELQHPLD ZDV IRXQG LQ    VXEMHFWV DQG $%2+'1 ZDV GLDJQRVHG LQ    VXEMHFWV :LWKLQ WKH positive DAT group, eight out of nine subjects had suffered IURP K\SHUELOLUXELQHPLD DQG $%2+'1 0HDQZKLOH ZLWKLQ WKH SRVLWLYH'$7 ZLWK HOXWLRQ PHWKRG JURXS  VXEMHFWVKDG VXIIHUHGIURPK\SHUELOLUXELQHPLDZLWKRIWKHPKDYLQJ$%2 +'1%DVHGRQWKHFKLVTXDUHDQDO\VLVWKRVHZLWKSRVLWLYH'$7 ZLWKHOXWLRQPHWKRGKDGWLPHVKLJKHUULVNRIVXIIHULQJIURP $%2+'1)XUWKHUPRUHWKHUHZDVDWLPHVKLJKHUULVNRI sufferring from hyperbilirubinemia. Conclusion In healthy term neonates with ABO incompatibility, WKHLQFLGHQFHRI$%2+'1LV'$7VHURORJLFDOH[DPLQDWLRQ with elution method is better than DAT in assessing risk IRU K\SHUELOLUXELQHPLD DQG $%2+'1 [Paediatr Indones. 2009;49:219-23].

I

n the last decade, discharging healthy term neonates earlier from hospital is a common practice due to medical and socioeconomic reasons. Several studies show that neonates GLVFKDUJHG LQ OHVV WKDQ  KRXUV RI DJH DUH VLJQLILFDQWO\ EHLQJ UHKRVSLWDOL]HG PRUH RIWHQ WKDQ WKRVH GLVFKDUJHG DW PRUH WKDQ  KRXUV RI DJH Hyperbilirubinemia is reported as the most common cause of rehospitalization during the early neonatal period. ABO incompatibility is one of the cause of hemolytic disease in newborns (HDN) that has been one of the most common risk factor of neonatal hyperbilirubinemia. Term neonates with ABO LQFRPSDWLELOLW\ KDYH D  WLPHV KLJKHU ULVN RI suffering from hyperbilirubinemia on the first day. This condition potentially leads to hyperbilirubinemia encephalopathy. (VWDEOLVKLQJ GLDJQRVLV RI $%2+'1 LV QRW easy because there is no specific diagnosis. Diagnosis RI$%2+'1LVXVXDOO\SUHVXPSWLYHZKHQ$RU% EORRGW\SHQHRQDWHZKRLVERUQIURPDPRWKHUZLWK2

)URP WKH 'HSDUWPHQW RI &KLOG +HDOWK 0HGLFDO 6FKRRO 8QLYHUVLW\ RI ,QGRQHVLD&LSWR0DQJXQNXVXPR+RVSLWDO-DNDUWD,QGRQHVLD

Keywords: ABO incompatibility, hyperbilirubinemia, DAT

5HSULQW UHTXHVW WR 'HVLDQD 'KDUPD\DQL 0' 'HSDUWPHQW RI &KLOG +HDOWK0HGLFDO6FKRRO8QLYHUVLW\RI,QGRQHVLD&LSWR0DQJXQNXVXPR +RVSLWDO-O6DOHPED-DNDUWD,QGRQHVLD7HO )D[

Paediatr Indones, Vol. 49, No. 4, July 2009‡219

Desiana Dharmayani et al: Serological profile and hemolytic disease in ABO incompatibility

EORRGW\SHVXIIHUVIURPMDXQGLFHLQWKHILUVWKRXUVRI life.+LVWRU\RIK\SHUELOLUXELQHPLDRU$%2+'1 in siblings can also support the diagnosis.5,15 Data about ABO incompatibility, especially regarding to VHURORJLFDOSURILOHRI$%2+'1LQ,QGRQHVLDLVVWLOO limited. The objective of this study was to identify the profile of antiglobulin test'$7 DQWL$DQGDQWL% immunoglobulin titer, and hemolytic disease in term neonates with ABO incompatibility.

Methods 7KLVZDVDFURVVVHFWLRQDOGHVFULSWLYHVWXG\FRQGXFWHG at the delivery rooms of RSIA Budi Kemuliaan Jakarta, GXULQJ 2FWREHU WR 1RYHPEHU  6XEMHFWV ZHUH recruited consecutively. We included healthy term neonates without any signs of infection or syndrome, $ RU % EORRGW\SH DQG ERUQ IURP D PRWKHU ZLWK 2 EORRGW\SH ZLWKRXW UKHVXV LQFRPSDWLELOLW\ :H H[FOXGHG VPDOOIRUDJH  QHRQDWHV PRWKHUV ZLWK VHYHUH DQHPLD DQGRU LQWUDODERXU LQIHFWLRQ DQG mothers with a history of particular drug consumption FKORUDPSKHQLFROVDOLF\OLFDFHW\ODQGDQWLPDODULDO drugs). Umbilical cord blood specimen from neonates was taken and collected in a EDTA tube, underwent '$7 DQG '$7 ZLWK HOXWLRQ PHWKRG DQG DQWL$ DQG DQWL% LPPXQRJOREXOLQ* WLWHU LQ &HQWUDO 5HG &URVV &5&  ODERUDWRU\ $W WKH DJH RI  KRXUV peripheral blood was taken from the heel and underwent hemoglobin, hematocrit, bilirubin, and peripheral blood examination to see the percentage of reticulocyte and microspherocyte. 'LDJQRVLV RI $%2+'1 LV HVWDEOLVKHG LI there was hemolytic condition, indicated by hyperbilirubinemia (total bilirubin >5 mg/dl), MDXQGLFHLQWKHILUVWKRXUVRIOLIHLQQHRQDWHVZLWK ABO incompatibility without rhesus incompatibility, SUHVHQFHRIUHWLFXORF\WRVLVUHWLFXORF\WH! DQG microspherocyte in peripheral blood smear, and can be supported by positive DAT. Data about sex, gestational age, birth weight, APGAR score, birth method, maternal age, primi/ PXOWLJUDYLGDH[LVWHQFHRISUHHFFODPSWLDDQGKLVWRU\ of jaundice in siblings, were taken from each case. 6WDWLVWLFDODQDO\VLVZDVGRQHXVLQJ6366DQG(SL Info 6.

220‡Paediatr Indones, Vol. 49, No. 4, July 2009

Results )URPQHRQDWHVERUQIURPPRWKHUVZLWK2EORRG W\SH  XPELOLFDO FRUG EORRG VDPSOHV KDG EHHQ VXFFHVVIXOO\FROOHFWHGZLWK RIWKHPKDYLQJ $RU%EORRGW\SH7KHUHZHUHRQO\VXEMHFWVWKDW completed all examinations required and became subjects of this study. &KDUDFWHULVWLFV RI VXEMHFWV ZKR IXOILOOHG WKH criteria for this research were listed in Table 1. +LVWRU\ RI MDXQGLFH LQ VLEOLQJV ZDV IRXQG LQ  FDVHV ZLWK  RI WKHP VXIIHULQJ IURP $%2+'1

Table 1. Characteristics of subjects with ABO incompatibility pregnancy (n=68) Characteristics Sex Male Female Birth weight 4.6 Microspherocyte Yes No Bilirubin level (mg/dl)  ŭ >5 Direct antiglobulin test (DAT) Direct (+)/(-) Elution method (+)/(-)

n(%) 31(46) 37(54) 9(13)   65(96) 3(4)    5(7)/0(0)    28(41) 10(15) 1(2) 29(43) 38(56) 30(44) 10(15) 58(85) 18(27) 44(65) 6(9)   49(72) 43(63) 25(37)   38(56) 9(13)/59(87) 38(56)/30(44)

Desiana Dharmayani et al: Serological profile and hemolytic disease in ABO incompatibility

Two mothers have history of blood transfusion, HLJKWPRWKHUVKDYHKLVWRU\RISUHHFODPSVLDDQG mothers are multiparous. Incidence of hemolytic disease in this study ZDV IURPVXEMHFWV7KHKLJKHVWWLWHURI DQWL$DQGDQWL%,J*ZDV'LVWULEXWLRQRI'$7 and DAT with elution method on the occurence of $%2+'1DQGK\SHUELOLUXELQHPLDLVOLVWHGLQTable 2 and Table 3. Table 2. Distribution of DAT and DAT with elution method on ABO-HDN DAT Direct Positive Negative Elution method Positive Negative

ABO-HDN(%)

NonABO-HDN(%)

8(12) 20(29)

1(2) 39(57)

23(33) 5(7)

15(22) 25(37)

Table 3. Distribution of DAT results on hyperbilirubinemia in term neonates with ABO incompatibility DAT Direct Positive Negative Elution method Positive Negative

Hyperbilirubinemia (%)

Non Hyperbilirubinemia (%)

8 (12) 21 (31)

1 (2) 38 (56)

24 (35) 6 (9)

14 (21) 24 (35)

Statistical analysis showed that groups with SRVLWLYH '$7 KDG D UHODWLYH ULVN 55  RI   &,WR3 WRVXIIHUIURP$%2+'1 7KLVJURXSDOVRKDG55RI&,WR3  WRVXIIHUIURPK\SHUELOLUXELQHPLDZKLOHWKRVH with positive DAT using elution method had RR of &,WR3 

Discussions Pregnancy with ABO incompatibility was accounted IRUIURPDOOSUHJQDQFLHVIn this study, there ZDV    QHRQDWHV ZLWK $%2 LQFRPSDWLELOLW\ IURP  PRWKHUV ZLWK 2 EORRG W\SH 7KLV UHVXOW is smaller in comparison to the study by Kadri16 at WKH VDPH SODFH LQ  7KH DFWXDO SUHYDOHQFH RI pregnancy with ABO incompatibility could not be FDOFXODWHG EHFDXVH WKHUH ZHUH  QHRQDWHV IURP

mothers with O blood type that had not undergone blood type examinations. Most neonates were born through ceasarian section. This condition can be explained by the fact that RSIA Budi Kemuliaan is a referral hospital with high number of ceasarian section. According to Sarici et al, history of jaundice in siblings was a good predictor of significant hyperbilirubinemia and VHYHUH $%2+'1 ,Q WKLV VWXG\  VXEMHFWV KDG KLVWRU\RIMDXQGLFHLQVLEOLQJVDQGRIWKHPZHUHDOVR KDYLQJ$%2+'1.DW]et al15 UHSRUWHGWKDWIURP QHRQDWHVZLWKKLVWRU\RI$%2+'1LQVLEOLQJV RIWKHPKDG$%2+'1ZLWKQHRQDWHVQHHGLQJ phototherapy. Most of the subjects in this study had normal hemoglobin levels. This is in accordance with literature, that anemia in neonates with ABO incompatibility rarely occurs and was usually slight.6,14 Reticulocytosis happen as an erythropoietin activity response to compensate a hemolytic condition. Normal levels of reticulocyte in term neonates ranged EHWZHHQ In this study, reticulocytosis was IRXQGLQFDVHVIRXQGWREHPXFKKLJKHUWKDQWKH study by Iskandar9FDVHV 7KLVGLIIHUHQFHZDV SUREDEO\GXHWRWKHKLJKHUFXWRIIRIUHWLFXORF\WRVLV XVHGLQWKHVWXG\E\,VNDQGDU!  Microspherocyte is the most commonly found feature in ABO incompatibility.14 Pathogenesis of microspherocyte was predicted due to the decrease of erythrocyte surface caused by antibody phagocytosis on erythrocyte and erythrocyte membrane by macrophage.6 0LFURVSKHURF\WH ZDV IRXQG LQ  of cases in this study, in accordance with a previous VWXG\ 9 In this study, positive results in DAT was UHYHDOHGLQFDVHV7KLVQXPEHUZDVVPDOOHUWKDQ RWKHUOLWHUDWXUHZKLFKVKRZSRVLWLYHUHVXOWVLQ FDVHV however the method used in the previous studies was not explained. Positive results in DAT with HOXWLRQPHWKRGZDVUHYHDOHGLQFDVHVLQUDQJHRI FDVHVLQSUHYLRXVVWXGLHV The large discrepancy between percentages in DAT group and DAT with elution method group maybe due to the field range of neonatal red blood cell antigen which is less than in adults. Besides that, the small amount of antibody molecule would also influence the result of DAT, which is relatively smaller than common literature.

Paediatr Indones, Vol. 49, No. 4, July 2009‡221

Desiana Dharmayani et al: Serological profile and hemolytic disease in ABO incompatibility

7KH KLJKHVW WLWHU RI DQWL$ DQG DQWL% ,J* LQ WKLVVWXG\ZDV7KLVLVVPDOOHUWKDQLQWKHVWXG\ E\ .DGUL ZKLFK VWDWHG KLJKHVW WLWHU RI  +LJK titer IgG in neonates had positive correlation with high maternal IgG titer, and numbers of mothers with high titer of IgG was higher in groups of mother with placenta inflammation.16 In this study, the presence of intralabour infection signs was regarded as an exclusion criteria, therefore resulting in a lower titer RIDQWL$DQGDQWL%,J* 7HUPQHRQDWHVZLWK$%2LQFRPSDWLELOLW\KDG WLPHVKLJKHUULVNWRVXIIHUIURPK\SHUELOLUXELQHPLD on the first day of life.In this study, hyperbilirubinemia LQWKHILUVWKRXUVRIOLIHRFFXUUHGLQRIFDVHV DQGKHPRO\WLFGLVHDVHLQFDVHV7KLVLQFLGHQFHLV higher than in Iskandar’s study9 which reported an LQFLGHQFHRIFDVHVRXWRIQHRQDWHV DQG Sarici ZLWK  FDVHV  RXW RI  QHRQDWHV  &DQWD\XGDUHSRUWHG WKDWQHRQDWHVKDG VXIIHUHGIURP$%2+'17KLVGLIIHUHQFHZDVSUREDEO\ due to the different diagnosis criteria used. In this study, neonates with positive result RI '$7 KDG D  WLPHV KLJKHU ULVN WR VXIIHU IURP $%2+'1 PHDQZKLOH QHRQDWHV ZLWK SRVLWLYH UHVXOW RI '$7 XVLQJ HOXWLRQ PHWKRG KDG  WLPHV a higher risk. Maissels stated that neonates from ABO incompatibility pregnancy with positive DAT KDG D  WLPHV KLJKHU ULVN WR VXIIHU IURP PRGHUDWH K\SHUELOLUXELQHPLD WRWDO ELOLUXELQ ! PJG/  compared to those without ABO incompatibility. 1HRQDWHV ZLWK SRVLWLYH '$7 DOVR KDG  times higher risk to suffer from hyperbilirubinemia, meanwhile those with positive DAT using elution PHWKRG KDG  WLPHV KLJKHU ULVN WR VXIIHU IURP hyperbilirubinemia. Quinn et alstated that positive DAT with or without elution method is useful in predicting the occurence of jaundice, but is not able to predict the severity of jaundice. 7KLV VWXG\ ZDV GHVLJQHG DV D FURVVVHFWLRQDO descriptive study, but with some limitations in assessing correlation between variables. By adjusting the power of the study, analysis on some variables was done with this limited data. We suggest further analytical studies with higher numbers of samples and using control to assess corelation between several parameters related to LQFLGHQFHRI$%2+'1 In conclusion, term neonates with ABO LQFRPSDWLELOLW\LQWKLVVWXG\KDGKLJKHVWWLWHURIDQWL$

222‡Paediatr Indones, Vol. 49, No. 4, July 2009

DQGDQWL%,J*SRVLWLYHUHVXOWRI'$7LQ cases, and positive result of DAT with elution method LQFDVHV7KHLQFLGHQFHRI$%2+'1LQWKLV VWXG\ZDV'$7ZLWKHOXWLRQPHWKRGLVEHWWHU than DAT in assessing the risk of hyperbilirubinemia DQG$%2+'1

References 1. 





5. 6.





9.



11.



Maissels MJ, Kring E. Length of stay, jaundice, and hospital UHDGPLVVLRQ3HGLDWULFV /HH .6 3HUOPDQ 0 %DOODQW\QH 0 $VVRFLDWLRQ EHWZHHQ duration of neonatal hospital stay and readmission rate. J 3HGLDWU 6RVNROQH(/6FKXPDNHU5)\RFN&FLWHG$SULO@ Available from: http://pedsinreview.aappublications.org

Paediatr Indones, Vol. 49, No. 4, July 2009‡223