118
January 1977 The Journal o f P E D I A T R 1 C S
Light (phototherapy)-induced riboflavin deficiency in the neonate Phototherapy with blue light decomposes riboflavin, which has a maximum absorption at 450 nm. A study was designed to determine whether riboflavin deficiency developed in neonates who received phototherapy for moderate hyperbilirubinemia. Twenty-one infants with normal erythrocyte glucose-6phosphate dehydrogenase activity were investigated Five infants with moderate hyperbilirubinemia who did not require phototherapy served as the controls. Riboflavin deficiency was determined from the degree o f saturation o f erythrocyte glutathione reductase, a method shown to reflect riboflavin nutritional status in the neonate. Sixteen of 21 infants who were exposed to phototherapy developed riboflavin deficiency; all who had phototherapy for 49 hours or more developed the deficiency. That the concentration of serum bilirubin or the duration of hyperbilirubinemia was not a factor is supported by the fact that none o f the controls became deficient. This observation may have important metabolic and clinical consequences for the neonate.
Donald S, Gromisch, M.D.,* Rafael Lopez, M.D., Harold S. Cole, M.D., and Jack M. Cooperman, Ph.D., N e w Y o r k , N . Y.
PHOTOTHERAPY is widely used for the management of moderate hyperbilirubinemia in the neonate. Its action in reducing serum bilirubin levels is well established/Some controversy, however, exists concerning the safety and possible side effects of this use of phototherapy. ~ In this regard, it has been shown that light may induce physical and metabolic effects in the neonate. :`-=' More recently, the role of the photodynamic action of riboflavin in enhancing bilirubin degradation has been demonstrated by in vitro" and by animal studies/ In addition, the role of light and phototherapy on the products of the activity of some riboflavin coenzymes has been reported/ .... Riboflavin, a light sensitive vitamin, has a maximum absorption spectrum at a wavelength similar to that at which the degradation of bilirubin occurs. Therefore, the possibility of decomposition of this vitamin exists in hyperbilirubinemic neonates undergoing phototherapy. From the Department o f Pediatrics, New York Medical College. *Reprint address: Department of Pediatrics, New York Medical College, 1249 Fifth Ave., New York City, N. Y. 10029.
VoL 90, No. 1, pp. 118-122
We report here our initial observation on the occurrence of riboflavin deficiency in such infants using a new sensitive biochemical assay. PATIENTS AND METHODS The study was designed to evaluate the status of riboflavin in neonates undergoing phototherapy. For this
Abbreviations used activity coefficient AC: EGR: erythrocyte glutathione reductase FAD: flavin adenine dinucleotide NADPH: nicotinamide adenine dinucleotide phosphate (reduced) standard deviation SD: G-6-PD: gtucose-6-phosphate dehydrogenase
purpose, 21 consecutive neonates with moderate hyperbilirubinemia who were to receive phototherapy were chosen. No attempt was made to select on the basis of birth weight or cause of the hyperbilirubinemia. The weight range of these infants was 1,360 to 3,660 gm. Ten weighed less than 2,500 gm.
Volume 90 Number 1
Phototherapy-induced riboflavin deficiency
119
Table I. Data o f 21 hyperbilirubinemic neonates treated with phototherapy
Age at onset of light therapy (hr)
Post therapy
Initial Bilirubin concentration (mg/dO
Sex
Birth weight (gm)
Prematures 1 2 7 10 11 13 14 16 19 20
F F M M M M M F M M
1360 1530 2180 2425 1465 1870 1700 1685 1930 2355
70 43 101 120 48 45 34 120 40 73 Mean 69.4 4- SD 33.3
11.5 9.0 12.5 12.0 9.5 8.0 8.5 11.9 9.4 13.7
1.0 1.0
Full terms 3 4 5 6 8 9 12 15 17 18 21
M M M M F M M M F F M
2500 2635 3360 2725 2660 3265 3205 2935 3660 3330 3030
72 63 62 48 18 48 36 67 23 28 48 Mean 46.5 _+ SD 18.5
12.0 16.0 13.0 12.0 7.0 13.5 13.0 12.7 9.5 10.5 15.0
1.0 1.0
Infant No.
AC
1.0 1.0 1.0 1.07 1.0
1.0 1.0 1.0
1.0
1.0 1.0 1.0 1.0
1.0 1.0
1.0 1.0
Duration of light therapy (hr)
Bilirubin concentration (mg/dl)
48
7.0
72 21 72 52 72 48 60 39 49
7.0 9.4 7.0 8.0 3.7 6.2 5.2 6.8 6.5
24 130 72 28 48 38 48 72 54 58 60
7.2 9.5 9.0 8.0 6.0 9.5 9.0 9.4 7.0 7.4 10.5
AC
1.33 1.58
1.0 1.55 1.33 1.67 1.0
2.0 1.33 1.63 Mean 1.44 -+ SD 0.31 1.33 1.75 1.30
0.92 1.10 1.0 1.43
2.0 1.33
1.37 1.33 Mean 1.35 _+ SD 0.31
AC = Activity coefficient. Five neonates with a weight range of 2,250 to 4,710 gm and serum total biiirubin levels o f 7.9 to I4 mg/dl, who did not receive phototherapy, constituted the control group. All infants were fed Similac liquid or Similac PM 60/40 at concentrations equivalent to 20 calories per ounce. N o n e of the infants received additional vitamins. All infants who received phototherapy were kept undressed in either an open crib or an Isolette; their eyes were shielded. They were continuously exposed to light except during feeding; their positions were changed periodically from prone to supine and vice versa. A bank of eight Westinghouse blue fluorescent bulbs, 20 watts each (No. F20T12B) were kept 56 cm (22 inches) from the skin surface. Bulbs were changed after being used for 200 hours. The infants were protected from ultraviolet irradiation by a Plexiglas shield under the bulbs. The length of phototherapy ranged from 21 to 130 hours. Serum bilirubin values were determined from venous blood by the method of Malloy and Evelyn. ''
Glucose-6-phosphate dehydrogenase was determined in erythrocytes from venous blood by the method o f Motulsky and associates as described by Dacie and Lewis. 12 Erythrocyte glutathione reductase was determined by a modification of the method of Glatzle and associates 13 which has been described in detail? 4 The end point for this method is the decrease in absorbance in optical density units at 340 nm owing to the oxidation of N A D P H by the hemolysate both in absence and presence of flavin adenine dinucleotide. The result, which is a measure of the degree of saturation of the apoenzyme with F A D , is expressed as the activity coefficient. Normal values range from 0.9 to 1.2 for neonates." Venous blood samples for the foregoing determinations were obtained just prior to the initiation and just after cessation of phototherapy. Comparable time intervals were used for obtaining the initial and final blood samples of the five control infants who were not given phototherapy.
12 0
Gromisch et al.
The Journal of Pediatrics January 1977
Table II. Data in five control neonates not exposed to light therapy
Infant
Age at initial bilirubin
Bh~h weight
determinant
No.
Sex
(gm)
(hr)
1 2 3 4 5
F F M M M
4710 3030 2250 3045 3210
48 120 113 108 51
Second
Initial
Bi~rubin value (mg/dl)
9.5
Bilirubin
AC
Time interval (hr)
value (mg/dl)
AC
6.2 8.0 9.0 9.0 9.6
1.0 1.0 1.0 1.0 1.0
11.5 11.5
1.0 1.0
168 72
1.0
112
14.0 7.9
1.0 1.0
72 66
A C = Activity coefficient.
RESULTS All of the neonates in this study had normal erythrocyte G-6-PD activity. In this regard, it has been shown that G-6-PD deficient subjects have elevated EGR activity? ~ The initial AC values in the EGR test for riboflavin deficiency were within normal limits for all infants, both in the experimental group before light therapy and in the control group (Tables I and II). However, the AC values for 16 of 21 infants after phototherapy increased to a range of 1.3 to 2.0, which is indicative of riboflavin deficiency. None of the control group had elevated AC values during the time interval of 66 to 168 hours between initial and second blood samples. Ten of the infants in the experimental group had birth weights under 2,500 gm. Their mean AC values after phototherapy was 1.44 _+ 0.31 SD. Eight of these ten had abnormally elevated AC values indicative of riboflavin deficiency. The mean AC values for the 11 infants weighing 2,500 gm or more at birth was 1.36 _+ 0.31 SD. Eight of these 11 had elevated AC values. The differences between the mean AC values of the premature infants was not statistically different from that of the full-term infants (p > 0.2). These results show that prematurity was not the predisposing factor for the occurrence of riboflavin deficiency in the infants exposed to light. Similarly, the age at which infants were placed under the light did not correlate with the deficiency. All of the infants regardless of birth weight, who were under the lights for more than 48 hours, developed biochemical evidence of riboflavin deficiency. All five of the infants with normal AC values received phototherapy for 48 hours or less (21, 28, 38, 48, and 48 hours) (Fig. 1). A cursory examination of the data in Table I would appear to show that there was a greater drop in serum bilirubin levels after phototherapy in the riboflavin deficient infants than in the nondeficient infants. However, in view of the fact that peak serum bilirubin levels were not
obtained in each case, verification of this awaits further examination. Of 16 deficient infants, six were black and ten were Hispanic. Of the five who were normal after phototherapy, two were black, three were Hispanic. Infants No. 13 and No. 14 (Table I) were fraternal twins born after a 34-week gestation period. Infant No. 13, who underwent phototherapy for 72 hours, developed biochemical evidence of riboflavin deficiency, while the other remained normal in this respect after 48 hours of light therapy. It is of interest that the serum bilirubin levels decreased to a greater extent in the deficient twin. DISCUSSION Sanvordeker and Kostenbauder~ demonstrated by in vitro studies that riboflavin enhanced the photodecomposition of bilirubin, They further demonstrated that serum bilirubin levels decreased more rapidly in Gunn rats injected with riboftavin-5'-phosphate before exposure to light than in controls not given the vitamin.; The probable mechanism involves the reaction of bilirubin with singlet oxygen generated by light-activated riboflavin. Riboflavin has an absorption peak at 450 nm within the range of 425 to 475 rim; this is the spectrum of maximum light emission of the blue fluorescent bulbs used for phototherapy of hyperbilirubinemic infants. During this photodynamic activity, both bilirubin and riboflavin are decomposed. That blood riboflavin may be susceptible to l;~,ht activation may be deduced from the results of studies oy several investigators. It was shown that increased skin and muscle blood flow occurs in hyperbilirubinemic infants undergoing phototherapy? It was further demonstrated that the light used for phototherapy can penetrate the skin layers, including the vascular bed of body integument, permitting photochemical reactions to occur in tissues below the skin. 1'~ Rubaltelli and associates TM presented data which
Volume 90 Number 1
suggested that riboflavin enzymes involved in tryptophan metabolism may be reduced in infants undergoing phototherapy. The present study was designed to determine whether riboflavin deficiency may occur in hyperbilirubinemic neonates undergoing phototherapy. For these purposes, a sensitive and specific biochemical index of riboflavin deficiency was utilized, which involves the measurement of erythrocyte glutathione reductase activity. This method in which the degree of saturation of the apoenzyme with FAD was shown to specifically and accurately reflect the riboflavin nutritional status of the adult '~ and the newborn infant TM was demonstrated to be a better indicator of riboflavin deficiency in the human being than either blood levels or urinary excretion of riboflavin?~Sixteen of the 21 neonates undergoing phototherapy developed abnormally elevated AC values indicative of riboflavin deficiency. The amount of formula consumed was not measured so that the daily riboflavin intake for each infant was not known. It is probable, however, that the infants under 2,500 gm at birth bad smaller body stores and smaller daily intakes of this vitamin than those who weighed 2,500 gm or more at birth. Nevertheless, the distribution of riboflavin deficients and the mean AC values for the premature and term infants were similar. This would indicate that nutritional factors alone could not account for the vitamin deficiency. In this regard, it is of interest that the formula which contained 1 mg of riboflavin per liter was not sufficient to prevent the evidence of riboflavin deficiency in the infants undergoing phototherapy. None of the control infants with comparable degrees of hyperbilirubinemia, but not receiving phototherapy, became deficient during the periods of 66 to 168 hours (between initial and final blood samples). This indicates that elevated plasma bilirubin per se did not cause the riboflavin deficiency. In this regard, a control group of nonjaundiced infants exposed to light was not used because of the possible effects and inherent risks? All of the infants exposed to light for more than 48 hours developed biochemical evidence of riboflavin deficiency and about half of those undergoing phototherapy for 48 hours or less. Of the 12 in the former group, six were premature and six were term infants. From the foregoing data, it is apparent that the prime causative factor for the development of riboflavin deficiency in the infants was the duration of exposure to phototherapy. That metabolic derangements do occur in infants undergoing phototherapy was shown by the studies of Wu and associates ~who demonstrated that such infants do not
Phototherapy4ndueed riboflavin deficiency
12 1
P.i =. ~[
20 19
II--
o
e7
CL
~_
1.6
I"
15
I I
:
9 ~...:
.
0
"
z I,-,r
(n
14 13
[
L=J
12
I
In
o
January 1977 The Journal o f P E D I A T R 1 C S
Light (phototherapy)-induced riboflavin deficiency in the neonate Phototherapy with blue light decomposes riboflavin, which has a maximum absorption at 450 nm. A study was designed to determine whether riboflavin deficiency developed in neonates who received phototherapy for moderate hyperbilirubinemia. Twenty-one infants with normal erythrocyte glucose-6phosphate dehydrogenase activity were investigated Five infants with moderate hyperbilirubinemia who did not require phototherapy served as the controls. Riboflavin deficiency was determined from the degree o f saturation o f erythrocyte glutathione reductase, a method shown to reflect riboflavin nutritional status in the neonate. Sixteen of 21 infants who were exposed to phototherapy developed riboflavin deficiency; all who had phototherapy for 49 hours or more developed the deficiency. That the concentration of serum bilirubin or the duration of hyperbilirubinemia was not a factor is supported by the fact that none o f the controls became deficient. This observation may have important metabolic and clinical consequences for the neonate.
Donald S, Gromisch, M.D.,* Rafael Lopez, M.D., Harold S. Cole, M.D., and Jack M. Cooperman, Ph.D., N e w Y o r k , N . Y.
PHOTOTHERAPY is widely used for the management of moderate hyperbilirubinemia in the neonate. Its action in reducing serum bilirubin levels is well established/Some controversy, however, exists concerning the safety and possible side effects of this use of phototherapy. ~ In this regard, it has been shown that light may induce physical and metabolic effects in the neonate. :`-=' More recently, the role of the photodynamic action of riboflavin in enhancing bilirubin degradation has been demonstrated by in vitro" and by animal studies/ In addition, the role of light and phototherapy on the products of the activity of some riboflavin coenzymes has been reported/ .... Riboflavin, a light sensitive vitamin, has a maximum absorption spectrum at a wavelength similar to that at which the degradation of bilirubin occurs. Therefore, the possibility of decomposition of this vitamin exists in hyperbilirubinemic neonates undergoing phototherapy. From the Department o f Pediatrics, New York Medical College. *Reprint address: Department of Pediatrics, New York Medical College, 1249 Fifth Ave., New York City, N. Y. 10029.
VoL 90, No. 1, pp. 118-122
We report here our initial observation on the occurrence of riboflavin deficiency in such infants using a new sensitive biochemical assay. PATIENTS AND METHODS The study was designed to evaluate the status of riboflavin in neonates undergoing phototherapy. For this
Abbreviations used activity coefficient AC: EGR: erythrocyte glutathione reductase FAD: flavin adenine dinucleotide NADPH: nicotinamide adenine dinucleotide phosphate (reduced) standard deviation SD: G-6-PD: gtucose-6-phosphate dehydrogenase
purpose, 21 consecutive neonates with moderate hyperbilirubinemia who were to receive phototherapy were chosen. No attempt was made to select on the basis of birth weight or cause of the hyperbilirubinemia. The weight range of these infants was 1,360 to 3,660 gm. Ten weighed less than 2,500 gm.
Volume 90 Number 1
Phototherapy-induced riboflavin deficiency
119
Table I. Data o f 21 hyperbilirubinemic neonates treated with phototherapy
Age at onset of light therapy (hr)
Post therapy
Initial Bilirubin concentration (mg/dO
Sex
Birth weight (gm)
Prematures 1 2 7 10 11 13 14 16 19 20
F F M M M M M F M M
1360 1530 2180 2425 1465 1870 1700 1685 1930 2355
70 43 101 120 48 45 34 120 40 73 Mean 69.4 4- SD 33.3
11.5 9.0 12.5 12.0 9.5 8.0 8.5 11.9 9.4 13.7
1.0 1.0
Full terms 3 4 5 6 8 9 12 15 17 18 21
M M M M F M M M F F M
2500 2635 3360 2725 2660 3265 3205 2935 3660 3330 3030
72 63 62 48 18 48 36 67 23 28 48 Mean 46.5 _+ SD 18.5
12.0 16.0 13.0 12.0 7.0 13.5 13.0 12.7 9.5 10.5 15.0
1.0 1.0
Infant No.
AC
1.0 1.0 1.0 1.07 1.0
1.0 1.0 1.0
1.0
1.0 1.0 1.0 1.0
1.0 1.0
1.0 1.0
Duration of light therapy (hr)
Bilirubin concentration (mg/dl)
48
7.0
72 21 72 52 72 48 60 39 49
7.0 9.4 7.0 8.0 3.7 6.2 5.2 6.8 6.5
24 130 72 28 48 38 48 72 54 58 60
7.2 9.5 9.0 8.0 6.0 9.5 9.0 9.4 7.0 7.4 10.5
AC
1.33 1.58
1.0 1.55 1.33 1.67 1.0
2.0 1.33 1.63 Mean 1.44 -+ SD 0.31 1.33 1.75 1.30
0.92 1.10 1.0 1.43
2.0 1.33
1.37 1.33 Mean 1.35 _+ SD 0.31
AC = Activity coefficient. Five neonates with a weight range of 2,250 to 4,710 gm and serum total biiirubin levels o f 7.9 to I4 mg/dl, who did not receive phototherapy, constituted the control group. All infants were fed Similac liquid or Similac PM 60/40 at concentrations equivalent to 20 calories per ounce. N o n e of the infants received additional vitamins. All infants who received phototherapy were kept undressed in either an open crib or an Isolette; their eyes were shielded. They were continuously exposed to light except during feeding; their positions were changed periodically from prone to supine and vice versa. A bank of eight Westinghouse blue fluorescent bulbs, 20 watts each (No. F20T12B) were kept 56 cm (22 inches) from the skin surface. Bulbs were changed after being used for 200 hours. The infants were protected from ultraviolet irradiation by a Plexiglas shield under the bulbs. The length of phototherapy ranged from 21 to 130 hours. Serum bilirubin values were determined from venous blood by the method of Malloy and Evelyn. ''
Glucose-6-phosphate dehydrogenase was determined in erythrocytes from venous blood by the method o f Motulsky and associates as described by Dacie and Lewis. 12 Erythrocyte glutathione reductase was determined by a modification of the method of Glatzle and associates 13 which has been described in detail? 4 The end point for this method is the decrease in absorbance in optical density units at 340 nm owing to the oxidation of N A D P H by the hemolysate both in absence and presence of flavin adenine dinucleotide. The result, which is a measure of the degree of saturation of the apoenzyme with F A D , is expressed as the activity coefficient. Normal values range from 0.9 to 1.2 for neonates." Venous blood samples for the foregoing determinations were obtained just prior to the initiation and just after cessation of phototherapy. Comparable time intervals were used for obtaining the initial and final blood samples of the five control infants who were not given phototherapy.
12 0
Gromisch et al.
The Journal of Pediatrics January 1977
Table II. Data in five control neonates not exposed to light therapy
Infant
Age at initial bilirubin
Bh~h weight
determinant
No.
Sex
(gm)
(hr)
1 2 3 4 5
F F M M M
4710 3030 2250 3045 3210
48 120 113 108 51
Second
Initial
Bi~rubin value (mg/dl)
9.5
Bilirubin
AC
Time interval (hr)
value (mg/dl)
AC
6.2 8.0 9.0 9.0 9.6
1.0 1.0 1.0 1.0 1.0
11.5 11.5
1.0 1.0
168 72
1.0
112
14.0 7.9
1.0 1.0
72 66
A C = Activity coefficient.
RESULTS All of the neonates in this study had normal erythrocyte G-6-PD activity. In this regard, it has been shown that G-6-PD deficient subjects have elevated EGR activity? ~ The initial AC values in the EGR test for riboflavin deficiency were within normal limits for all infants, both in the experimental group before light therapy and in the control group (Tables I and II). However, the AC values for 16 of 21 infants after phototherapy increased to a range of 1.3 to 2.0, which is indicative of riboflavin deficiency. None of the control group had elevated AC values during the time interval of 66 to 168 hours between initial and second blood samples. Ten of the infants in the experimental group had birth weights under 2,500 gm. Their mean AC values after phototherapy was 1.44 _+ 0.31 SD. Eight of these ten had abnormally elevated AC values indicative of riboflavin deficiency. The mean AC values for the 11 infants weighing 2,500 gm or more at birth was 1.36 _+ 0.31 SD. Eight of these 11 had elevated AC values. The differences between the mean AC values of the premature infants was not statistically different from that of the full-term infants (p > 0.2). These results show that prematurity was not the predisposing factor for the occurrence of riboflavin deficiency in the infants exposed to light. Similarly, the age at which infants were placed under the light did not correlate with the deficiency. All of the infants regardless of birth weight, who were under the lights for more than 48 hours, developed biochemical evidence of riboflavin deficiency. All five of the infants with normal AC values received phototherapy for 48 hours or less (21, 28, 38, 48, and 48 hours) (Fig. 1). A cursory examination of the data in Table I would appear to show that there was a greater drop in serum bilirubin levels after phototherapy in the riboflavin deficient infants than in the nondeficient infants. However, in view of the fact that peak serum bilirubin levels were not
obtained in each case, verification of this awaits further examination. Of 16 deficient infants, six were black and ten were Hispanic. Of the five who were normal after phototherapy, two were black, three were Hispanic. Infants No. 13 and No. 14 (Table I) were fraternal twins born after a 34-week gestation period. Infant No. 13, who underwent phototherapy for 72 hours, developed biochemical evidence of riboflavin deficiency, while the other remained normal in this respect after 48 hours of light therapy. It is of interest that the serum bilirubin levels decreased to a greater extent in the deficient twin. DISCUSSION Sanvordeker and Kostenbauder~ demonstrated by in vitro studies that riboflavin enhanced the photodecomposition of bilirubin, They further demonstrated that serum bilirubin levels decreased more rapidly in Gunn rats injected with riboftavin-5'-phosphate before exposure to light than in controls not given the vitamin.; The probable mechanism involves the reaction of bilirubin with singlet oxygen generated by light-activated riboflavin. Riboflavin has an absorption peak at 450 nm within the range of 425 to 475 rim; this is the spectrum of maximum light emission of the blue fluorescent bulbs used for phototherapy of hyperbilirubinemic infants. During this photodynamic activity, both bilirubin and riboflavin are decomposed. That blood riboflavin may be susceptible to l;~,ht activation may be deduced from the results of studies oy several investigators. It was shown that increased skin and muscle blood flow occurs in hyperbilirubinemic infants undergoing phototherapy? It was further demonstrated that the light used for phototherapy can penetrate the skin layers, including the vascular bed of body integument, permitting photochemical reactions to occur in tissues below the skin. 1'~ Rubaltelli and associates TM presented data which
Volume 90 Number 1
suggested that riboflavin enzymes involved in tryptophan metabolism may be reduced in infants undergoing phototherapy. The present study was designed to determine whether riboflavin deficiency may occur in hyperbilirubinemic neonates undergoing phototherapy. For these purposes, a sensitive and specific biochemical index of riboflavin deficiency was utilized, which involves the measurement of erythrocyte glutathione reductase activity. This method in which the degree of saturation of the apoenzyme with FAD was shown to specifically and accurately reflect the riboflavin nutritional status of the adult '~ and the newborn infant TM was demonstrated to be a better indicator of riboflavin deficiency in the human being than either blood levels or urinary excretion of riboflavin?~Sixteen of the 21 neonates undergoing phototherapy developed abnormally elevated AC values indicative of riboflavin deficiency. The amount of formula consumed was not measured so that the daily riboflavin intake for each infant was not known. It is probable, however, that the infants under 2,500 gm at birth bad smaller body stores and smaller daily intakes of this vitamin than those who weighed 2,500 gm or more at birth. Nevertheless, the distribution of riboflavin deficients and the mean AC values for the premature and term infants were similar. This would indicate that nutritional factors alone could not account for the vitamin deficiency. In this regard, it is of interest that the formula which contained 1 mg of riboflavin per liter was not sufficient to prevent the evidence of riboflavin deficiency in the infants undergoing phototherapy. None of the control infants with comparable degrees of hyperbilirubinemia, but not receiving phototherapy, became deficient during the periods of 66 to 168 hours (between initial and final blood samples). This indicates that elevated plasma bilirubin per se did not cause the riboflavin deficiency. In this regard, a control group of nonjaundiced infants exposed to light was not used because of the possible effects and inherent risks? All of the infants exposed to light for more than 48 hours developed biochemical evidence of riboflavin deficiency and about half of those undergoing phototherapy for 48 hours or less. Of the 12 in the former group, six were premature and six were term infants. From the foregoing data, it is apparent that the prime causative factor for the development of riboflavin deficiency in the infants was the duration of exposure to phototherapy. That metabolic derangements do occur in infants undergoing phototherapy was shown by the studies of Wu and associates ~who demonstrated that such infants do not
Phototherapy4ndueed riboflavin deficiency
12 1
P.i =. ~[
20 19
II--
o
e7
CL
~_
1.6
I"
15
I I
:
9 ~...:
.
0
"
z I,-,r
(n
14 13
[
L=J
12
I
In
o
