| BackgroundsHemolytic disease of the newborn (HDN) is a situation in which transplacental passage of maternal antibodies results in immune hemolysis of fetal/neonatal red cells. The implicated antibodies could be naturally occurring (anti A, anti B) or immune antibodies which develop following a sensitizing event like transfusion or pregnancy. HDN is mainly caused by ABO and Rhesus D incompatibility, in which red cells in the fetus or neonate are destroyed by the serum antibodies derived from the mother by placental transport. HDN may cause hyperbilirubinemia and anemia, then further develop into encephalopathy, or even fatal kernicterus if undiagnosed or neglected. ABO hemolytic disease of the newborn (ABO HDN), which maternal anti-A or anti-B antibodies acts on neonatal erythrocytes, is the most common cause of HDN in China. In some western countries, due to the administration of Rh IG to Rh (D) negative women during pregnancy and D positive infants shortly after given birth by Rh (D) negative mother, the incidence of Rh D HDN had been greatly reduced. Therefore, ABO incompatibility is also becoming the single largest cause of HDN in these countries.The incidence of ABO HDN, according to previous reports, varies among different racial populations, regions and sanitary condition. A higher incidence and severity were observed among Africans, Arabs, and Latin Americans, and relatively lower in Caucasians. In Asia, the incidence of ABO HDN is not more study. In Indian, the incidence of ABO incompatibility is15-20%, and among them,10%will develop into HDN. In Singapore, the incidence of ABO incompatibility is15.69%, the incidence of ABO HDN is3.7%. In our China the incidence of ABO incompatibility generally believed to be20-25%, but the incidence of ABO HDN have been variable, ranged from2%-4%. Given the exact incidence of ABO hemolytic disease of the Chinese people clearly outstanding, in order to improve the understanding of ABO hemolytic disease and severe ABO hemolytic disease of early prediction of conduct, it is necessary to ABO HDN incidence and characteristics make a thorough investigation.It was generally considered the lower expression of A and B antigens on fetal red cells minimizes the feto-maternal incompatibility and hence ABO HDN was generally mild. But nowadays more reports had shown that the disease is not always benign and may require active management. Besides, due to the changes in China’s medical, economic, and social conditions happened in recent years, more newborns are discharged24-48hours after the delivery, during when the ABO HDN infants’ jaundice is about to appear. This increasing missed diagnosis rate led to a series of severe cases that needed exchange transfusion.So far, most of the studies were focused on the factors that may aggravate ABO hemolytic on pathogenesis, such as maternal antibody concentration, antibody subclass, antibody glycosylation, antibody specificity, Fc receptor polymorphisms, etc., but most of them remained controversy. Moreover, advanced lab tests of ABO HDN require particular and expensive equipments, which made it harder to promote in community hospital. Several cord blood parameters and first-day bilirubin level have been studied in an attempt to anticipate the clinical course of a newborn with ABO HDN, however, due to the different racial populations, regions and sanitary condition, it may not for us. Our object of this study is to calculate the current incidence of ABO HDN in our region and to find out early prediction of the disease severity by analyze common clinical parameters.C-reactive protein (C-reactive protein CRP) is an acute phase protein when, normally a very small amount of serum CRP levels. Inflammatory reaction or (and) under stress, a sharp rise in serum CRP hours or1-2days several times, or even a hundred times, the clinical judgment of infection has been used as an early indicator. When CRP is an acute inflammatory mediators produced by the induction phase protein synthesized by the liver, with the activation of complement, promoting phagocytic cells of the immune function, regulation of immune processes and defensive infectious diseases. In clinical, we found that some children with ABO HDN slightly elevated CRP, but no obvious symptoms of infection, this phenomenon cannot be excluded because the infection is often troubled by the use of antibiotics in clinical decision-making. Whether CRP is ABO HDN reaction severity index, has not been reported. In conclution, the aim of the present study:1. To calculate the incidence of ABO HDN in our region and prospectively determine the ability to predict significant hyperbilirubinemia and severe hemolytic disease in relatively healthy full-term newborns with ABO HDN based on common clinical parameters.2. To investigate the characteristics of C-reactive protein (CRP) and Procalcitonin (PCT) in neonates with ABO hemolytic disease of newborn (ABO HDN) who were suffered from infection disease or not.Methods1. Incidence of ABO HDN1.1The object of studyFrom January2009to December2013, all the blood-type-O mothers’babies born in Nanfang Hospital were enrolled in our study.1.2experimental methodCord blood of these babies were obtained then tested with direct antiglobulin test (DAT), antibody release test and free antibody test.1.3Diagnostic criteriaABO HDN was diagnosed when1) infants of type A or B born to a mother of type O,2) Positive results in DAT or antibody release test and3) hyperbilirubinemia and (or) anemia (Hb≤170g/L)and (or) hemolysis (reticulocyte percentage≥6%)2. The risk factors of serious ABO HDN2.1The object of study From January2012to October2013, all ABO HDN infants in Nanfang Hospital were enrolled in our study. Excluded premature and high-risk infants (asphyxia or glucose-6-phosphate dehydrogenase existed, or neonatal infection).2.2MethodNewborns with ABO HDN were followed prospectively with perinatal characteristics of mothers and infants and common laboratory indicators. TSB was prospectively obtained within the first24hours of life, and repeated twice daily for the next3days. The infants were assigned into hyperbilirubinemia group (cord bilirubin levels≥4mg/dL or serum total bilirubin levels of≥11.5mg/dL and an increase in serum total bilirubin concentration of^0.5mg/dL/h in the first24hours,≥15mg/dL on day2,≥17.5mg/dL on day3, and≥20mg/dL on days4and5) and non-hyperbilirubinemia group2.3Statistical methodsStatistic analysis was performed using the SPSS13.0. Measurement data were analyzed with the independent sample t test and enumeration data were analyzed with chi-square tests. For statistical hypothesis testing, the level of significance was0.05. When p<0.05, this data will be included in the regression model. The predictive value (for identifying newborns that subsequently develop hyperbilirubinemia) was determined based on the variables found to have a significant independent effect in the multiple regression models. 3. The clinical significance of CRP in ABO hemolytic disease of newborn3.1The object of studyThe full term infants with ABO HDN admitted to our department from Jan.2012to Oct.2013were assigned into infection group and non-infection group prospectively,3.2MethodCompared the clinical general data, CRP and PCT value in the first day and third day stay in hospital3.3Statistical methodsStatistic analysis was performed using the SPSS13.0. Measurement data were analyzed with the independent sample t test and enumeration data were analyzed with chi-square tests. Area under the curve is calculated by ROC curve, sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and accuracy.Results1.Incidence of ABO HDNDuring the study period,16092infants were born,2116infants were ABO (O-A and O-B) incompatibility, the incidence of ABO incompatibility was13.15%, and233were diagnosed ABO HDN, having met the criteria mentioned previously, the incidence of the disease was1.45%, and the incidence of ABO HDN among ABO incompatibility was11.01%. The incidence of DAT+is7.18%, and the incidence amomg ABO HDN is65.24%.2. The risk factors of serious ABO HDN 2.1There were significant differences between the newborns who did and the newborns who did not develop significant hyperbilirubinemia with respect to NEU (14.38±4.76vs12.56±4.71), Hb (143.32±26.66vs162.27±23.600), HCT(0.41±0.09vs0.47±0.06), reticulocyte percentage (9.75±4.19vs5.98±1.95) TSB level (213.52±75.96vs99.72±42.68).2.2The reticulocyte percentage, TSB level considered in the regression model to predict significant hyperbilirubinemia.2.3The regression model to predict significant hyperbilirubinemia sensitivity is94.85%, specificity is73.68%, positive likelihood ratio is5.15%, negative likelihood ratio is26.32%. The reticulocyte percentage to predict significant hyperbilirubinemia sensitivity is55.67%, specificity is71.05%, positive likelihood ratio is44.33%, negative likelihood ratio is28.95%.3. The clinical significance of CRP in ABO hemolytic disease of newborn3.1CRP and PCT values in the first day and third day in hospital were significantly higher in infection group than in non-infection group CRP-1.40(0.20,6.95) vs0.30(0.10,1.50)/Day1,12.70(2.70,34.50) vs1.80(0.90,4.30)/Day3; PCT-1.05(0.42,10.05) vs0.43(0.15,1.48)/Dayl,3.21(0.95,7.80) vs0.37(0.21,0.68)/Day3, p<0.05.3.2The detection rates of the abnormal value of CRP in non-infection group and infection group were62.5%(5/8);18.58(21/113); PCT:75%(6/8);0.88%(1/113) respectively. The abnormal value of CRP in infection group was significantly higher than non-infection group (29.57±18.43vs11.00±7.20, P<0.05).3.3In non-infection group, the CRP value in infants with hyperbilirubinemia was higher than that in infants without hyperbilirubinemia1.90(0.50,5.00) vs0.20(0.10,1.15), p<0.05.3.4Diagnosing infection, the sensitivity, specificity and accuracy of PCT were better than CRP (0.793vs0.690;0.994vs0.811;0.978vs0.802respectively).3.5EOS count in infection group was less than in non-infection group (0.23±0.13vs0.36±0.24, P<0.05), parity in infection group was low than in non-infection group (1.28±0.53vs1.55±0.71, P<0.05).Conclusions1.The study nearly five years of large sample research in the region for the first time concluded the incidence of the incidence of ABO incompatibility was13.15%, and233were diagnosed ABO HDN, having met the criteria mentioned previously, the incidence of the disease was1.45%, and the incidence of ABO HDN among ABO incompatibility was11.01%. The incidence of DAT+is7.18%, and the incidence amomg ABO HDN is65.24%.2. The present study confirms reticulocyte percentage, TSB level considered could predict significant hyperbilirubinemia in ABO HDN.3. As an infection marker, PCT has more advantages than CRP. The value of CRP increased slightly in some of ABO HDN infants without infection, and it could be considered as a predictor of subsequent hyperbilirubinemia. |
