Cord Bilirubin Research Articles

The spectrum of ABO hemolytic disease of the newborn infant

A series of 1,704 infants of blood group O mothers have been studied to determine the relation between the degree of red cell sensitization and the cord hemoglobin and bilirubin concentrations. The infants with blood group A or B had significantly higher cord bilirubin and lower cord hemoglobin concentrations than the group O babies. Those infants whose red cells had the greatest evidence of sensitization had the highest bilirubin and lowest hemoglobin levels. The infants in whom no antibody was demonstrable on the red cells or in the red cell eluate also had significantly higher cord bilirubin and lower cord hemoglobin levels than the ABO compatible group; it is suggested that these infants had sufficient erythrocyte sensitization to produce mild hemolysis. ABO incompatibility represents a spectrum of hemolytic disease extending from those in which there is little laboratory evidence of erythrocyte sensitization, but evidence of hemolysis, to severe hemolytic disease in which erythrocyte sensitization is usually easily demonstrable.

Coagulation failure in babies with rhesus isoimmunization.

Serial prospective studies of coagulation status have been undertaken on 73 babies with a positive Coombs test. No abnormalities were detected in the babies with mild haemolytic disease, but seven of the 36 babies with severe haemolytic disease (cord Hb less than 11 g/dl or cord bilirubin greater than 85 mumol/1) showed evidence of transient defibrination 1 d after birth and another six had evidence of coagulation failure at birth with a platelet count of less than 150 x 10(9)/1 and a severe deficiency of multiple coagulation factors. The level of factor II and factor X was less than a fifth of the normal cord blood level in these six babies and the level of I, VII and IX was severely reduced; the factor VIII level was normal or high. Exchange transfusion started within 1 h of birth corrected the immediate factor deficiency in these six babies, but evidence of defibrination then became apparent with afibrinogenaemia, a marked fall in factors II and V, less constant falls in factors VII, IX and X, and a raised fibrin:fibrinogen degradation product level. One of these six babies died with severe pulmonary hypoplasia within an hour of birth; the other five died from haemorrhage into the lung or brain 1 1/2--6 d after birth. The very low vitamin-K dependent factor levels in the cord blood of the babies who died are presumably the result of liver damage in utero, but the subsequent changes are those of a comsumption coagulopathy. Simple screening tests at birth served to indicate which babies were at risk and it is concluded that death due to haemorrhage might be reduced by more intensive factor replacement before there is overt evidence of haemorrhage in these babies.

959 ESTIMATION OF CORD BILIRUBIN AS A MEANS OF SCREENING NEWBORNS AT RISK OF NEONATAL HYPERBILIRUBINEMIA

Cord blood bilirubins were determined in 185 term Rh positive infants with uncomplicated intrapartum courses within 12-24 hours of birth by the method of Melloy-Evelyn. Infants with any manifestations of illness in the first four days of life were excluded. Daily physical examinations were performed on all infants but serial bilirubins were determined only in those who were clinically jaundiced. Healthy non-jaundiced infants were discharged on the fourth day of life. The neonatal courses were subsequently evaluated in terms of the development of pathologic jaundice (>5mg/dl/day or > 12mg/dl), and correlated with the cord bilirubin values. The results indicated that during the first four days of life, infants with cord bilirubin values less than 2.0mg/dl had a benign course whereas those with 2.4mg/dl or greater developed pathologic jaundice requiring investigative and therapeutic intervention. This was particularly impressive in infants with levels ≥ 3.Omg/dl because all such infants required exchange transfusion within 24 hours of birth. There was a statistically significant difference (P<0.05) between the mean cord bilirubin of infants who developed pathologic jaundice requiring phototherapy and/or exchange transfusion (2.85), and those that did not (1.31).These findings suggest that cord bilirubin might be used as a screening tool for pathologic jaundice in the first four days of life, and thereby facilitate early investigative and therapeutic intervention.

Correlation of cord bilirubin levels with hyperbilirubinaemia in ABO incompatibility.

We studied 91 offspring of ABO incompatible preganacies and 30 controls resulting from O--O pregnancies to test whether cord bilirubin levels could be used to predict the severity of hyperbilirubinaemia in ABO incompatibility. Blood group, direct Coombs's test, and serum bilirubin estimations were carried out on cord blood, and bilirubin estimations at 12, 24, 36, and 48 hours of life.

Correlation of maternal serum and amniotic fluid bilirubin in gravid patients with sickle cell anemia who were actively hemolyzing

Seven patients with homozygous sickle cell anemia in pregnancy were observed. Simultaneous amniotic fluid biliscan and maternal serum bilirubin values were determined at various intervals from 20 weeks until delivery. The elevation of the biliscan into Zone III (Liley's nomogram) followed the rise in maternal serum bilirubin closely and was related to the time of maternal crisis regardless of time of gestation or labor and delivery. The infants were not affected by the elevated bilirubin, did not contribuse to its elevation, and were found to have normal cord bilirubin levels at birth. Therefore, the findings of a Zone III Liley curve in late pregnancy alone should not prejudice one into performing an unneaessary premature delivery in patients with sickle cell anemia.

Erythroderma and erythroblastosis feralis.

To the Editor.— The appearance of a rash during the course of therapy for neonatal hyperbilirubinemia has been recognized. 1,2 The first report associated a macular erythematous rash to the use of phototherapy for the reduction of serum bilirubin. The second report noted the occurrence of a macular erythematous rash as a possible complication following intensive transfusion therapy for severe hemolytic disease of the newborn. No other references relating hyperbilirubinemia and a macular erythroderma could be found in the available literature. This communication further documents our clinical observations of this peculiar skin reaction in four severely affected erythroblastolic infants, none of which were exposed to bilirubin reduction lamps. Report of Cases.—Case 1.— A 1.9-kg (4 lb 2 oz) male infant was delivered spontaneously at 33 weeks gestation. He had received three intrauterine transfusions beginning at 28 weeks gestation. The total cord bilirubin value was 4.6 mg/100 ml, and the

The Value of Umbilical Cord Blood Bilirubin Measurement in Predicting the Development of Significant Hyperbilirubinemia in Healthy Newborn

The present study was conducted to investigate the predictability of early serumbilirubin levels on the subsequent development of neonatal hyperbilirubinemia. Forthis purpose 84 healthy newborn infants were enrolled and followed up for first 5 daysof life. Study subjects were divided into two groups. Group-I consisted of 71 subjects,who did not develop significant hyperbilirubinemia (bilirubin &lt;17mg/dl); Group-IIconsisted of 13 newborns, who developed significant hyperbilirubinemia (bilirubin &gt;17mg/dl) during the follow up. Of the enrolled subjects, 46 (55%) were male and rest 38(45%) were female; 64 (76%) were term babies and 20 (24%) were pre-term babies.Significantly higher percentage of pre-term babies developed hyperbilirubinemia. ROC(receiver operating characteristic) analysis demonstrates that the critical value ofcord blood bilirubin &gt;2.5mg/dl had the high sensitivity (77%) and specificity (98.6%)to predict the newborn who would develop significant hyperbilirubinemia. At this levelthe negative predictive value was 96% and positive predictive value 91%. In oursetting infants having umbilical cord blood total serum bilirubin (TSB) &gt;2.5 mg/dlshould be followed up strictly either in hospital or as an outpatient department on day5 if practicable. Infants having TSB &lt;2.5mg/dl in cord blood can be discharged early.Key words: Umbilical cord bilirubin; neonatal jaundice; healthy newborn.DOI: 10.3329/bjch.v33i2.5677Bangladesh Journal of Child Health 2009; Vol.33(2): 50-54

The unnecessary exchange transfusion: A study of Rh hemolytic disease of the newborn

The indications for exchange transfusion of infants with Rh hemolytic disease arediscussed. Only infants with either clinical evidence of disease or both a cord hemoglobin below 13.3 Gm. per 100 ml. and a cord bilirubin above 3.5 mg. per 100 ml. received “early” treatment. Immaturity (gestation period less than 37 weeks) acted as bias toward early intervention; otherwise a watch and wait policy was pursued. This did not result in a greater need for repeat transfusions or in an increased incidence of kernicterus. It demonstrated that a considereably greater proportion of these infants than hitherto reported (at least half) are capable of surviving in good health without treatment.

The Rh problem in obstetrics and a new concept of its management using amniocentesis and spectrophotometric scanning of amniotic fluid

1. Amniocentesis has been performed on more than 900 occasions in a group of over 300 Rh-immunized pregnant women without a major mishap to either the fetus or the mother. A detailed account of the antepartum management of these cases and the clinical outcome in 245 completed pregnancies is presented. The total perinatal loss (stillbirths and neonatal deaths) due to hemolytic disease was 8 per cent of the total 245 immunized pregnancies, and 9 per cent of the total number of affected Rh-positive infants (211 pregnancies). The previous perinatal mortality rate from hemolytic disease at this hospital was 30 per cent of the total number of affected Rh-positive infants. In addition, only one first affected baby was lost in this study as a result of hemolytic disease, and no unnecessary inductions of premature labor nor cesarean sections were performed to deliver unaffected infants.2. In the antepartum management of a Rh-immunized pregnancy, the spectrophotometric scanning of the amniotic fluid appears to be the most clinically useful procedure. However, it is suggested that the true value of this procedure can only be realized by repeating the test at biweekly intervals (or sometimes at weekly intervals); in order to minimize the risk of amniocentesis, the placenta should be localized by both the radioisotope and thermograph methods.3. The physical characteristics and the clinical interpretation of the spectrophotometric tracings has been discussed in detail.4. There appears to be a better correlation between the spectrophotometric tracings within 10 days of delivery and the clinical condition of the infant at birth, as assessed by the Apgar score and the presence or absence of circulatory failure, than with the level of cord hemoglobin and cord bilirubin, etc. It is suggested that the standard evaluation of the severity of hemolytic disease of the newborn should be revised to include the general condition (as assessed by recent amniotic fluid analysis) of the infant.5. The principal value of amniocentesis and spectrophotometry is to determine the fetal outcome (survival or death) and not the level of hemoglobin at birth.

Erythroblastosis Foetalis A Survey of 491 Consecutive Cases of Rh‐Immunization in Pregnancy Part II. Liveborn Affected by Erythroblastosis Foetalis1

SummaryIn the 10‐year period 1951–1961 the offspring of 491 consecutive Rh‐immunized pregnancies representative of a region of West Norway were born in one Maternity Hospital and the liveborn were cared for in one Children's Hospital. The stillbirth rate was 6.3% and the neonatal mortality 4.3%. The nperinatal mortality is thus 10.6%. Details concerning the stillbirths have been published in Part I [5].All the liveborn have been studied as regards the maternal incomplete antibody titre in pregnancy, the cord bilirubin, haemoglobin at birth and need for treatment (single or multiple exchange transfusions).A special study has been made of the newborns who died of haemolytic disease. Severe anaemia with circulatory failure was the most important cause of death. Unexplainable deaths in connection with exchange transfusion in severely ill in fants with haemolytic disease also play a major role. All deaths occurred in the first 48 hours of life.Late anaemia and the necessity for simple blood transfusions very rarely occurred. No complications with kernicterus were seen.Adequate supervision in pregnancy, reference of selected Rh‐immunized women to a Maternity Hospital in due time, delivery in a special unit and immediate supervision and treatment of the affected newborn in a hospital with adequate facilities and experienced staff are of definitive importance in the management of erythroblastosis foetalis.

Serum bilirubin levels in the newborn infant

Summary 1.Cord bilirubin levels of full-term“compatible”, full-term “incompatible”, and premature infants are essentially the same. The average cord bilirubin level of infants with erythroblastosis is more than double that of infants without erythroblastosis and a level above 5 mg. per cent is strongly suggestive of this disease. 2.Normal infants usually show a rise of bilirubin during the first day of life, but infants with erythroblastosis show a marked elevation during this period. 3.Normal full-term infants reachtheir peak elevation of bilirubin at about two days of life, whereas the peak bilirubin of premature infants is attained on the fourth day of life, on the average. The peak elevation of bilirubin of premature infants not only occurs later than that of full-term infants, but reaches higher levels, confirming the clinical impression that physiological jaundice is more severe and more prolonged in the premature infant than in the full-term infant. 4.In this series, infants with erythroblastosis,treated by exchange transfusion, have their bilirubin peak during the second day of life, on the average. Exchange transfusion greatly modifies the bilirubinemia in these infants. A level of serum bilirubin above 10 mg. per cent during the first twenty-four hours of life, or the appearance of skin icterus during this period, must be considered due to erythroblastosis until proved otherwise. 5.Determinations of the level ofserum bilirubin during the first two days of life are of great diagnostic value with respect to erythroblastosis, particularly in cases caused by ABO incompatibility. They are of even greater value as a therapeutic guide in the use of replacement transfusion. Summary 1.Cord bilirubin levels of full-term“compatible”, full-term “incompatible”, and premature infants are essentially the same. The average cord bilirubin level of infants with erythroblastosis is more than double that of infants without erythroblastosis and a level above 5 mg. per cent is strongly suggestive of this disease. 2.Normal infants usually show a rise of bilirubin during the first day of life, but infants with erythroblastosis show a marked elevation during this period. 3.Normal full-term infants reachtheir peak elevation of bilirubin at about two days of life, whereas the peak bilirubin of premature infants is attained on the fourth day of life, on the average. The peak elevation of bilirubin of premature infants not only occurs later than that of full-term infants, but reaches higher levels, confirming the clinical impression that physiological jaundice is more severe and more prolonged in the premature infant than in the full-term infant. 4.In this series, infants with erythroblastosis,treated by exchange transfusion, have their bilirubin peak during the second day of life, on the average. Exchange transfusion greatly modifies the bilirubinemia in these infants. A level of serum bilirubin above 10 mg. per cent during the first twenty-four hours of life, or the appearance of skin icterus during this period, must be considered due to erythroblastosis until proved otherwise. 5.Determinations of the level ofserum bilirubin during the first two days of life are of great diagnostic value with respect to erythroblastosis, particularly in cases caused by ABO incompatibility. They are of even greater value as a therapeutic guide in the use of replacement transfusion.

A Method of Measuring the Severity of a Series of Cases of Hemolytic Disease of the Newborn

1. The hemoglobin concentration in the cord blood of infants affected with hemolytic disease is very closely related to their chance of survival. If the hemoglobin concentration is plotted against the chance of survival, a sigmoid curve is obtained. Probit analysis can be applied and the results of treatment can then be summarized in terms of the severity of the cases treated. For example, in the present series the cord hemoglobin concentration corresponding to a 50 per cent chance of survival was 8.09 Gm./100 ml.2. Application of probit analysis makes it possible to compare results obtained in different centers, for due allowance is made for any difference in severity in the cases included in the different series.3. In the present series, despite uniform treatment (exchange transfusion), over-all mortality fell from 37 percent in 1947 and 1948 to 3 per cent in 1950. It is shown that this can be entirely explained by a decrease in the number of severely affected infants.4. Predictions of survival based on the cord hemoglobin concentration and cord bilirubin concentration combined are not significantly better than predictions based on cord hemoglobin concentration alone.5. Infants with positive direct Coombs tests whose cord hemoglobin concentrations exceed 15.5 Gm./100 ml. have some risk (approximately 1 in 12) of developing kernicterus, if untreated.