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Phototherapy in ABO hemolytic disease of the newborn infant
December, 1971 T h e ]ournal of P E D I A T R I C S
911
Pbototherapy in ABO hemolytic disease of the newborn infa n t Phototherapy for ABO hemolytic disease of the newborn infant usually reduces or prevents a further rise in serum bilirubin levels. In light-treated infants, peak bilirubin concentrations do not occur after the third day of life and exceed 20 rag. per cent in only 10 per cent of the infants. Phototherapy is not indicated for infants with ABO disease of mild onset and severity. In severely affected infants, a trial period of phototherapy is justified but must not exclude consideration of exchange transfusion for control of rapidly rising serum bilirubin levels.
Eugene Kaplan, M.D.,* Fritz Herz, Ph.D., Elsie Scheye, M.D., and Lawrence D. Robinson, Jr., M.D. BALTI]r ORE~ MD.
P rI o T o T I-I E R A V Y is increasingly used in the control of hyperbilirubinemia of prematurity and nonhemolytic disorders of fullterm newborn infants? Light therapy is not very effective in the severe icterus of Rh hemolytic disease of the newborn infant ( H D N ) 3 As Rh disease decreases in frequency following the successful prevention of maternal isoimmunization, pediatricians are giving more attention to ABO-HDN as a factor in the etiology of neonatal jaundice. The effect of light in controlling serum bilirubin levels in ABO-HDN has not been defined with clarity. Thus we have reviewed From the Department of Pediatrics, Sinai Hospital of Baltimore, Inc. Supported by Grant No. HD 01461 of the National Institutes of Health, United States Public Health Service, Bethesda, Maryland, and by a grant from the Baltimore Rh Typing Laboratory, Inc. Presented at the American Pediatric Society, Atlantic City, N. ]., May, 1971. *Address: Sinai Hospital of Baltimore, Inc., Belvedere Ave. at Greenspring, Baltimore, Md. 21215.
a large experience in ABO-HDN and will present our observations of the effect of light therapy in 29 treated infants, against a background of the serum bilirubin course in 150 infants not receiving light therapy. METHODS
ABO-HDN. Approximately 4,000 babies a year are delivered at the Sinai Hospital of Baltimore. Detection of early jaundice and clinical and laboratory evaluation of its etiolSee related article, p. 904. ogy are important aspects of the routine of the newborn nursery. Diagnostic examinations are conducted by a special pediatric laboratory team. Serum bilirubin measurements are performed by a micromodification of the Evelyn Malloy method and are determined at 8 to 12 hour intervals. The data here reported refer only to pre-exchange transfusion bilirubin concentrations. Vol. 79, No. 6, pp. 911-914
9 12
Kaplan et aI.
The Journal of Pediatrics December 1971
Table I. Race and birth weight of infants with ABO hemolytic disease of newborn
Infant s Lighttreated Not treated
No ~
Race Cau- Necasian] l gro
Birth weight ~ 2,500 ~ 2,500 Gin. Gin.
29
I6
13
26
3
29
15
14
27
2
A B O - H D N has been under constant inv e s t i g a t i o n in this nursery for several years?, 4 We define the disease by the following criteria. Obligatory: (1) fetal-maternal ABO incompatibility and (2) clinical icterus within the first 24 hours of life. Expected: (1) indirect serum bilirubin of 10 mg. per cent by 48 hours of age, (2) microspherocytosis, (3) reticulocytosis, (4) positive antiglobulin test (direct or indirect), and (5) reduced red cell acetylcholinesterase activity. The incidence of A B O - H D N has varied from 23 to 34 infants a year. In a continuous period from July, 1964 to January, 1971, the diagnosis was made in 179 infants, corresponding to an incidence of approximately 8/1,000 live births. Infants treated with phototherapy. Phototherapy was introduced into the nursery for control of neonatal hyperbilirubinemia in 1969. T h e selection of infants for phototherapy was made after the detection of early jaundice and the establishment of the etiologic diagnosis. T h e selection was made by different pediatric residents and attending pediatricians, and without uniform protocol. Thus of 58 infants with A B O - H D N (born since phototherapy was instituted), 29 infants were selected for phototherapy, and 29 were not treated. The distribution of the treated and untreated groups with respect to birth weight and race is shown in Table I. The day of life and the serum bilirubin concentration at onset of phototherapy is shown in Table II. Phototherapy is administered by exposing the infant to a bilirubin lamp containing ten 20 watt d~ylight fluorescent bulbs. T h e
Table II. Clinical status and age of infants at beginning of phototherapy Day o[ life
1 Serum bilirubin (rag.%) > 16 12-16 ~12 Type of onset of ABO-HDN: Severe Mild
1 2 1 3
-5 3
7 3 1
7 3 --
6 2
8 3
-10
individual bulbs are changed after 200 hours of cumulative use. T h e infants are completely undressed, their eyes are carefully shielded, and they are turned over at regular intervals. Phototherapy is continuously applied for periods of 24 hours to as much as 100 hours. Except for occasional large green stools while under the light, no untoward effects have been encountered in the treated infants. RESULTS
Bilirnbin patterns in A B O - H D N . In order to evaluate the effects of phototherapy in A B O - H D N we have analyzed the bilirubin patterns in 150 infants not exposed to the bilirubin lamp. The analysis delineates the serum bilirubin course with respect to the severity of the onset of jaundice, and the intensity and time of the peak concentration. The diagnosis of A B O - H D N is usually made between 8 and 30 hours of life, and follows the clinical recognition of early jaundice and the laboratory examination of the infant's blood. In approximately one third of the infants a severe onset of jaundice is noted, with serum bilirubin increments of 0.5 mg. per cent per hour or more from birth to the time of initial diagnosis. In the remaining two thirds of the infants, a mild onset of jaundice is noted, with serum bilirubin increment of less than 0.5 nag. per cent per hour. (In our experience this frequency is essentially reversed in infants with Rh hemolytic disease of the newborn infant, where ap-
Volume 79 Number 6
Phototherapy in ABO hemolytic disease
PHOTOTHERAPY
ABO
9 13
DISEASE
(Bilirubin Course)
I NO TREATMENT
I1~1
I
TREATMENT
I ' Eii iiii!im,
'
ONSET SEVERE
18
I?iii?iiiiiiiiii iiiiiii iiiil .........,, ,;;i'~';';i:;~:i:; .................................
9 A
decrease
i
i
A
16
ONSET MILD
[
increase
F i g . 1. E f f e c t of p h o t o t h e r a p y o n s e r u m b i l i r u b i n c o u r s e i n A B O h e m o l y t i c d i s e a s e of t h e n e w born infant. Numbers indicate infants in each category.
proximately two thirds of the infants demonstrate a severe onset with respect to bilirubin concentrations.) In the 24 hours or more following the time of diagnosis of ABO-HDN, the serum bilirubin concentration continues to increase in approximately one half of the infants, remains essentially unchanged in about one half, and may infrequently decrease. The maximum level of serum bilirubin is reached on Day 1 in 10 per cent, Day 2 in 30 per cent, Day 3 in 40 per cent, and Days 4 and 5 in 20 per cent of the infants. T h e peak serum bilirubin concentration is 20 mg. per cent or more in approximately 30 per cent, between 16 and 19 rag. per cent in 35 per cent, and less than 16 rag. per cent in 35 per cent of the infants. Results of phototherapy. The effects of phototherapy on the hyperbilirubinemia of A B O - H D N can be demonstrated by comparing the bilirubin course and bilirubin peaks in treated and untreated infants. Thus the bilirubin course in 58 infants in the nursery during the period of optional phototherapy is shown in Fig. 1. The patients are separated as to those with severe onset and mild onset of hyperbilirubinemia. The frequency of the subsequent change in serum bilirubin levels (increase, stationary, or decrease) is compared in both groups of infants. In 11 untreated infants with severe onset the serum bilirubin concentration continued to rise in 8,
remained unchanged in 2, and declined in 1 instance. I n 13 treated infants with severe onset it increased in the 24 hours after start of treatment in 4, remained unchanged in 6, and decreased in 3 infants. In 18 untreated infants with mild onset the serum bilirubin concentration continued to increase in 8 and remained unchanged in the remaining 10 infants. In the 16 treated infants with mild onset it increased in 2, remained unchanged in 7, and decreased in 7 infants. The bilirubin peak in the 29 treated infants differs significantly in time of appearance and level of serum bilirubin concentration from the peak described above in 150 control infants (Fig. 2). Thus in the treated infants, the peak bilirubin level is reached on Day 1 in 10 per cent, Day 2 in 55 per cent, Day 3 in 35 per cent, and in no case after the third day of life. Similarly peak serum bilirubin concentration is 20 mg. per cent or more in only 10 per cent, 16 to 19 rag. per cent in 55 per cent, and less than 16 mg. per cent in 35 per cent of the treated group. No difference in response to phototherapy was observed between Caucasian and Negro infants and infants of different birth weight. During the period of optional phototherapy, exchange transfusions were performed on 9 of 58 infants with hyperbilirubinemia of ABO-HDN. It is of interest that this procedure was elected in 7 of 29 un-
9 14
Kaplan et al.
The Journal o[ Pediatrics December 197l
PHOTOTHERAPY
ABO
(Bilirubin
DISEASE
Peak)
- loo7~ 4;5 3
<1
~ 16
(A) DAY (B) (C) t,4g.7o (D) Fig. 2. Effect of phototherapy on serum bilirubin peak in Ago hemolytic disease of the newborn infant. Day refers to days of llfe and rag.% to peak bilirubin concentration. A and C indicate untreated infants; B and D indicate light-treated infants. treated infants, and in 2 of 29 infants under phototherapy. DISCUSSION Our observations serve to clarify the proper use of phototherapy in the management of hyperbilirubinemia due to ABO-HDN. In most infants, the disease is relatively mild in onset, in subsequent course, and in the degree and duration of hyperbilirubinemia. While phototherapy is shown to effectively reduce or prevent further increase in serum bilirubin levels in mildly affected infants, the application of this form of therapy does not seem indicated, in view of the benign nature of the illness and the uncertainty at this time of undesired late effects of phototherapy. In the most severely affected infants, because of the rapid increment, serum bilirubin concentrations may approach 20 rag. per cent before 30 hours of life. While phototherapy might be tried in such infants, a period of 24 hours of treatment may be needed for significant effect on the serum bilirubin.
A continued bilirubin rise during this trial period might suggest that exchange transfusion is the preferred mode of management. In somewhat less severely affected infants a 24 hour trial of phototherapy could result in a distinct leveling off or decrease in the bilirubin concentration. In these infants phototherapy would be useful, and the reduced need for exchange transfusions would justify the potential risk of light therapy. REFERENCES
1. Behrman, R. E., and Hsla, D. Y. Y.: Summary of a symposium on phototherapy for hyperbilirubinemia, J. PEmATR. 75: 718, 1969. 2. Sisson, T. R. C., Kendall, N., Davies, R., Berger, D., Bunyavlroch, E., and Knutson, S.: Photoblologlc aspects of hyperbillrubinemia, Pediatr. Res. 3: 380, 1969. 3. Kaplan, E., Herz, F., and Hsu, K. S.: Erythrocyte acetyleholinesterase activity in ABO hemolytic disease of the newborn, Pediatrics 33: 205, 1964. 4. IZ_ramer,L. I.: Advancement of dermal icterus in the jaundiced newborn, Am. J. Dis. Child. 118: 454, 1969.
911
Pbototherapy in ABO hemolytic disease of the newborn infa n t Phototherapy for ABO hemolytic disease of the newborn infant usually reduces or prevents a further rise in serum bilirubin levels. In light-treated infants, peak bilirubin concentrations do not occur after the third day of life and exceed 20 rag. per cent in only 10 per cent of the infants. Phototherapy is not indicated for infants with ABO disease of mild onset and severity. In severely affected infants, a trial period of phototherapy is justified but must not exclude consideration of exchange transfusion for control of rapidly rising serum bilirubin levels.
Eugene Kaplan, M.D.,* Fritz Herz, Ph.D., Elsie Scheye, M.D., and Lawrence D. Robinson, Jr., M.D. BALTI]r ORE~ MD.
P rI o T o T I-I E R A V Y is increasingly used in the control of hyperbilirubinemia of prematurity and nonhemolytic disorders of fullterm newborn infants? Light therapy is not very effective in the severe icterus of Rh hemolytic disease of the newborn infant ( H D N ) 3 As Rh disease decreases in frequency following the successful prevention of maternal isoimmunization, pediatricians are giving more attention to ABO-HDN as a factor in the etiology of neonatal jaundice. The effect of light in controlling serum bilirubin levels in ABO-HDN has not been defined with clarity. Thus we have reviewed From the Department of Pediatrics, Sinai Hospital of Baltimore, Inc. Supported by Grant No. HD 01461 of the National Institutes of Health, United States Public Health Service, Bethesda, Maryland, and by a grant from the Baltimore Rh Typing Laboratory, Inc. Presented at the American Pediatric Society, Atlantic City, N. ]., May, 1971. *Address: Sinai Hospital of Baltimore, Inc., Belvedere Ave. at Greenspring, Baltimore, Md. 21215.
a large experience in ABO-HDN and will present our observations of the effect of light therapy in 29 treated infants, against a background of the serum bilirubin course in 150 infants not receiving light therapy. METHODS
ABO-HDN. Approximately 4,000 babies a year are delivered at the Sinai Hospital of Baltimore. Detection of early jaundice and clinical and laboratory evaluation of its etiolSee related article, p. 904. ogy are important aspects of the routine of the newborn nursery. Diagnostic examinations are conducted by a special pediatric laboratory team. Serum bilirubin measurements are performed by a micromodification of the Evelyn Malloy method and are determined at 8 to 12 hour intervals. The data here reported refer only to pre-exchange transfusion bilirubin concentrations. Vol. 79, No. 6, pp. 911-914
9 12
Kaplan et aI.
The Journal of Pediatrics December 1971
Table I. Race and birth weight of infants with ABO hemolytic disease of newborn
Infant s Lighttreated Not treated
No ~
Race Cau- Necasian] l gro
Birth weight ~ 2,500 ~ 2,500 Gin. Gin.
29
I6
13
26
3
29
15
14
27
2
A B O - H D N has been under constant inv e s t i g a t i o n in this nursery for several years?, 4 We define the disease by the following criteria. Obligatory: (1) fetal-maternal ABO incompatibility and (2) clinical icterus within the first 24 hours of life. Expected: (1) indirect serum bilirubin of 10 mg. per cent by 48 hours of age, (2) microspherocytosis, (3) reticulocytosis, (4) positive antiglobulin test (direct or indirect), and (5) reduced red cell acetylcholinesterase activity. The incidence of A B O - H D N has varied from 23 to 34 infants a year. In a continuous period from July, 1964 to January, 1971, the diagnosis was made in 179 infants, corresponding to an incidence of approximately 8/1,000 live births. Infants treated with phototherapy. Phototherapy was introduced into the nursery for control of neonatal hyperbilirubinemia in 1969. T h e selection of infants for phototherapy was made after the detection of early jaundice and the establishment of the etiologic diagnosis. T h e selection was made by different pediatric residents and attending pediatricians, and without uniform protocol. Thus of 58 infants with A B O - H D N (born since phototherapy was instituted), 29 infants were selected for phototherapy, and 29 were not treated. The distribution of the treated and untreated groups with respect to birth weight and race is shown in Table I. The day of life and the serum bilirubin concentration at onset of phototherapy is shown in Table II. Phototherapy is administered by exposing the infant to a bilirubin lamp containing ten 20 watt d~ylight fluorescent bulbs. T h e
Table II. Clinical status and age of infants at beginning of phototherapy Day o[ life
1 Serum bilirubin (rag.%) > 16 12-16 ~12 Type of onset of ABO-HDN: Severe Mild
1 2 1 3
-5 3
7 3 1
7 3 --
6 2
8 3
-10
individual bulbs are changed after 200 hours of cumulative use. T h e infants are completely undressed, their eyes are carefully shielded, and they are turned over at regular intervals. Phototherapy is continuously applied for periods of 24 hours to as much as 100 hours. Except for occasional large green stools while under the light, no untoward effects have been encountered in the treated infants. RESULTS
Bilirnbin patterns in A B O - H D N . In order to evaluate the effects of phototherapy in A B O - H D N we have analyzed the bilirubin patterns in 150 infants not exposed to the bilirubin lamp. The analysis delineates the serum bilirubin course with respect to the severity of the onset of jaundice, and the intensity and time of the peak concentration. The diagnosis of A B O - H D N is usually made between 8 and 30 hours of life, and follows the clinical recognition of early jaundice and the laboratory examination of the infant's blood. In approximately one third of the infants a severe onset of jaundice is noted, with serum bilirubin increments of 0.5 mg. per cent per hour or more from birth to the time of initial diagnosis. In the remaining two thirds of the infants, a mild onset of jaundice is noted, with serum bilirubin increment of less than 0.5 nag. per cent per hour. (In our experience this frequency is essentially reversed in infants with Rh hemolytic disease of the newborn infant, where ap-
Volume 79 Number 6
Phototherapy in ABO hemolytic disease
PHOTOTHERAPY
ABO
9 13
DISEASE
(Bilirubin Course)
I NO TREATMENT
I1~1
I
TREATMENT
I ' Eii iiii!im,
'
ONSET SEVERE
18
I?iii?iiiiiiiiii iiiiiii iiiil .........,, ,;;i'~';';i:;~:i:; .................................
9 A
decrease
i
i
A
16
ONSET MILD
[
increase
F i g . 1. E f f e c t of p h o t o t h e r a p y o n s e r u m b i l i r u b i n c o u r s e i n A B O h e m o l y t i c d i s e a s e of t h e n e w born infant. Numbers indicate infants in each category.
proximately two thirds of the infants demonstrate a severe onset with respect to bilirubin concentrations.) In the 24 hours or more following the time of diagnosis of ABO-HDN, the serum bilirubin concentration continues to increase in approximately one half of the infants, remains essentially unchanged in about one half, and may infrequently decrease. The maximum level of serum bilirubin is reached on Day 1 in 10 per cent, Day 2 in 30 per cent, Day 3 in 40 per cent, and Days 4 and 5 in 20 per cent of the infants. T h e peak serum bilirubin concentration is 20 mg. per cent or more in approximately 30 per cent, between 16 and 19 rag. per cent in 35 per cent, and less than 16 rag. per cent in 35 per cent of the infants. Results of phototherapy. The effects of phototherapy on the hyperbilirubinemia of A B O - H D N can be demonstrated by comparing the bilirubin course and bilirubin peaks in treated and untreated infants. Thus the bilirubin course in 58 infants in the nursery during the period of optional phototherapy is shown in Fig. 1. The patients are separated as to those with severe onset and mild onset of hyperbilirubinemia. The frequency of the subsequent change in serum bilirubin levels (increase, stationary, or decrease) is compared in both groups of infants. In 11 untreated infants with severe onset the serum bilirubin concentration continued to rise in 8,
remained unchanged in 2, and declined in 1 instance. I n 13 treated infants with severe onset it increased in the 24 hours after start of treatment in 4, remained unchanged in 6, and decreased in 3 infants. In 18 untreated infants with mild onset the serum bilirubin concentration continued to increase in 8 and remained unchanged in the remaining 10 infants. In the 16 treated infants with mild onset it increased in 2, remained unchanged in 7, and decreased in 7 infants. The bilirubin peak in the 29 treated infants differs significantly in time of appearance and level of serum bilirubin concentration from the peak described above in 150 control infants (Fig. 2). Thus in the treated infants, the peak bilirubin level is reached on Day 1 in 10 per cent, Day 2 in 55 per cent, Day 3 in 35 per cent, and in no case after the third day of life. Similarly peak serum bilirubin concentration is 20 mg. per cent or more in only 10 per cent, 16 to 19 rag. per cent in 55 per cent, and less than 16 mg. per cent in 35 per cent of the treated group. No difference in response to phototherapy was observed between Caucasian and Negro infants and infants of different birth weight. During the period of optional phototherapy, exchange transfusions were performed on 9 of 58 infants with hyperbilirubinemia of ABO-HDN. It is of interest that this procedure was elected in 7 of 29 un-
9 14
Kaplan et al.
The Journal o[ Pediatrics December 197l
PHOTOTHERAPY
ABO
(Bilirubin
DISEASE
Peak)
- loo7~ 4;5 3
<1
~ 16
(A) DAY (B) (C) t,4g.7o (D) Fig. 2. Effect of phototherapy on serum bilirubin peak in Ago hemolytic disease of the newborn infant. Day refers to days of llfe and rag.% to peak bilirubin concentration. A and C indicate untreated infants; B and D indicate light-treated infants. treated infants, and in 2 of 29 infants under phototherapy. DISCUSSION Our observations serve to clarify the proper use of phototherapy in the management of hyperbilirubinemia due to ABO-HDN. In most infants, the disease is relatively mild in onset, in subsequent course, and in the degree and duration of hyperbilirubinemia. While phototherapy is shown to effectively reduce or prevent further increase in serum bilirubin levels in mildly affected infants, the application of this form of therapy does not seem indicated, in view of the benign nature of the illness and the uncertainty at this time of undesired late effects of phototherapy. In the most severely affected infants, because of the rapid increment, serum bilirubin concentrations may approach 20 rag. per cent before 30 hours of life. While phototherapy might be tried in such infants, a period of 24 hours of treatment may be needed for significant effect on the serum bilirubin.
A continued bilirubin rise during this trial period might suggest that exchange transfusion is the preferred mode of management. In somewhat less severely affected infants a 24 hour trial of phototherapy could result in a distinct leveling off or decrease in the bilirubin concentration. In these infants phototherapy would be useful, and the reduced need for exchange transfusions would justify the potential risk of light therapy. REFERENCES
1. Behrman, R. E., and Hsla, D. Y. Y.: Summary of a symposium on phototherapy for hyperbilirubinemia, J. PEmATR. 75: 718, 1969. 2. Sisson, T. R. C., Kendall, N., Davies, R., Berger, D., Bunyavlroch, E., and Knutson, S.: Photoblologlc aspects of hyperbillrubinemia, Pediatr. Res. 3: 380, 1969. 3. Kaplan, E., Herz, F., and Hsu, K. S.: Erythrocyte acetyleholinesterase activity in ABO hemolytic disease of the newborn, Pediatrics 33: 205, 1964. 4. IZ_ramer,L. I.: Advancement of dermal icterus in the jaundiced newborn, Am. J. Dis. Child. 118: 454, 1969.