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Efficacy of Double and Triple Phototherapy in Term Newborns With Hyperbilirubinemia: The First Clinical Trial
Pediatr Neonatol 2009;50(6):266−269
O R IGINAL ART ICL E
Efficacy of Double and Triple Phototherapy in Term Newborns With Hyperbilirubinemia: The First Clinical Trial Salma Naderi1*, Fatemeh Safdarian2, Davood Mazloomi3, Elham Bushehri4, Reza Hamidian5 1
Division of Neonatology, Department of Pediatrics, Hormozgan Medical University, Hormozgan, Iran Department of Pediatrics, Hormozgan Medical University, Hormozgan, Iran 3 Specialist in Pediatrics Medicine, Hormozgan, Iran 4 Department of Epidemiology, Hormozgan Medical University, Hormozgan, Iran 5 Cardiovascular Research Center, Tehran University of Medical Sciences, Tehran, Iran 2
Received: Dec 15, 2008 Revised: Jan 27, 2009 Accepted: Mar 6, 2009 KEY WORDS: double phototherapy; efficacy; hyperbilirubinemia; term newborn; triple phototherapy
Background: Icterus is the most common medical problem in neonates and phototherapy is the standard treatment for neonatal hyperbilirubinemia. This study aimed to compare the efficacy and length of hospital stay of double and triple phototherapy in newborns with indirect hyperbilirubinemia. Methods: In a clinical trial, 40 healthy term newborns (gestational age > 37 weeks) with bilirubin ≥ 12 and ≥ 15 mg/dL in the second and third day, respectively, were randomly assigned to triple (n = 20) or double phototherapy (n = 20) groups. Total and direct serum bilirubin were measured at admission, 8, 16, and 24 hours after beginning of phototherapy, and every 12 hours thereafter until discharge (when bilirubin levels reached ≤ 10 mg/dL). Results: There were 21 male (52%) and 19 female (48%) term neonates, with significant difference between patients’ age, weight, and age of icterus. There was no significant difference in the rate of bilirubin decline between the two groups within the first 8, 16 and 24 hours. There was no significant difference in mean length of hospital stay between the two groups. Analysis of complications showed no difference between triple and double groups. Conclusion: Triple phototherapy failed to reduce total serum bilirubin and shorten length of hospitalization more rapidly than double phototherapy.
1. Introduction Icterus is the most common medical problem in neonates.1−3 Around 50−70% of term and 80% of preterm neonates suffer from icterus.1−5 Icterus is also the most common cause of neonate readmission.1,5,6 *Corresponding author. P.O. Box: 13185-1678, Tehran, Iran. E-mail: [email protected] ©2009 Taiwan Pediatric Association
Although it is usually benign in term and preterm neonates,1,3,7,8 severe hyperbilirubinemia is a medical emergency9 because bilirubin is a neurotoxic material3,10 which can lead to neurologic defects even in healthy term neonates.4,7,11 Therefore, management of hyperbilirubinemia in newborns is
Double vs. triple phototherapy still a critical issue. For the past four decades, phototherapy has remained a standard treatment for neonatal hyperbilirubinemia.4−6,12 The effect of phototherapy depends on the intensity of radiation (which in turn depends on the characteristics of radiation, number of radiation sources, and exposed body area) and the distance between the body and the source of radiation.2,4−7 Because of this, several studies have compared the efficacy of single and double phototherapy,10,13 but there is no data comparing double and triple phototherapy. Intensive phototherapy is a method used for the management of neonatal hyperbilirubinemia. The intensive phototherapy devices used included 11 phototherapy lamps, six of which were put above the bassinet, and five below the bassinet. Because devices for intensive phototherapy are rare or unavailable in Iran, some centers use triple phototherapy (adding another phototherapy device to double phototherapy) for intensive phototherapy. The purpose of this study was to compare the benefits, complications, and length of hospitalization for double and triple phototherapy treatment in newborns with indirect hyperbilirubinemia.
2. Methods and Materials 2.1. Study population This study was a clinical trial conducted in a neonatal ward of Bandar Abbas Pediatric Hospital (Bandar Abbas University of Medical Science), in Bandar Abbas, Iran, between January and May 2006. All subjects who met the following inclusion criteria entered to the study: healthy term newborn > 37 weeks, neonatal age > 24 hours, weight > 2500 grams, indirect hyperbilirubinemia, breast-fed, bilirubin levels ≥ 12 and ≥ 15 mg/dL on the 2nd and 3rd day, respectively. Neonates were defined as newborns with a gestational age > 37 weeks with no medical problems and/or hemolysis. Exclusion criteria included infectious, metabolic, or hemolytic diseases (including porphyria, glucose 6-phosphate dehydrogenase deficiency, and ABO alloimmunization), positive Coombs’ test, high reticulocyte count, abnormal peripheral blood smear, occurrence of icterus within the first 24 hours, increased levels of direct serum bilirubin or maternal history of phenobarbital consumption before, during, or after child birth. Also excluded were neonates who were candidates for blood exchange. Using simple randomization (single sequence of random assignment), 40 patients were randomly assigned to triple (n = 20) and double (n = 20) phototherapy groups. Triple and double groups underwent phototherapy using triple and
267 double radiation sources, respectively. All neonates were in bassinets during phototherapy. In double phototherapy (conventional method), two single phototherapy devices were used: one was placed above the bassinet, and the other was placed in line with its length, both with a 25 cm distance from it. In triple phototherapy, in addition to the two previous devices, a third one was placed in the line with width of the bassinette, and with a 35 cm distance from the bed. All phototherapy devices were made by Iran Behkar Medical Industry Co. (Tehran, Iran); fluorescent lamps were made by Royal Philips Electronics, Inc. (Amsterdam, the Netherlands) with 20 W power. The fluorescent lamps were exchanged and used for 500 hours. In each subject, total and direct serum bilirubin were measured at admission, 8, 16, and 24 hours after the beginning of phototherapy and then every 12 hours until discharge from hospital. Bilirubin was measured by the conventional indirect diazo method. Phototherapy was stopped and the newborns was discharged when bilirubin levels decreased to ≤10 mg/dL. A pediatrician visited all subjects once a day to monitor for phototherapy side effects. Recorded data including gender, age and weight, age of occurrence of icterus, bilirubin levels in scheduled time, duration, and phototherapy complications. The study protocol was approved by Institutional Review Board at Bandar Abbas University of Medical Science. Informed consent was obtained from all parents before enrollment in the study.
2.2. Statistical analysis Statistical analysis was conducted using SPSS version 11.5 (SPSS Inc., Chicago, IL, USA). Analysis of variance and independent Student’s t tests (with 95% confidence intervals) were used to compare quantitative data. Statistical significance was defined as p < 0.05.
3. Results There were 21 male (52%) and 19 female (48%) term neonates (a non-significant difference). Patients’ characteristics are shown in Table 1. Insignificant difference between patients’ age, weight, and age of icterus implied that our randomization was suitable and accurate. Comparison of total serum bilirubin in triple and double groups showed no significant differences at the times measured (Table 1). There was no significant difference in the rate of bilirubin decline between the two groups within the first 8, 16, and 24 hours. Thus, both triple and double phototherapy reduced total serum bilirubin in a comparable manner.
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Table 1 Characteristics of neonates in double and triple phototherapy groups Variable Age (d) Weight (g) Age of icterus (d) Total bilirubin at admission (mg/dL) Total bilirubin 8 hr after PT (mg/dL) Total bilirubin 16 hr after PT (mg/dL) Total bilirubin 24 hr after PT (mg/dL) Mean length of hospital stay (hr)
Double phototherapy group (n = 20)*
Triple phototherapy group (n = 20)*
p
6.4 ± 2.4 2916 ± 392 3.4 ± 1.1 16.4 ± 1.3 13.7 ± 1.8 12.2 ± 1.7 10.3 ± 2 34.6 ± 16.5
6.5 ± 2.2 2864 ± 400 3.5 ± 1.1 17 ± 1.3 14 ± 1.7 12.4 ± 1.7 10.9 ± 1 41.5 ± 17.7
0.905 0.681 0.792 0.170 0.590 0.760 0.370 0.211
*Data are presented as mean ± standard deviation. PT = Phototherapy.
We compared length of hospitalization between triple and double groups and found that the minimal and maximal lengths of hospitalization were 16 and 60 hours, respectively, in both groups. Length of hospital stay was not significantly different between the two groups (Table 1). There was no significant difference in the rate of bilirubin reduction between the two groups (p > 0.05). Analysis of complications showed no difference between triple and double groups. In term of complication, loose feces were seen in two newborns in the triple phototherapy group and one newborn in the double phototherapy group. Maculopapular rash was observed in one neonate in the double phototherapy group.
4. Discussion We compared the benefits, complications and length of hospitalization between double and triple phototherapy in term newborns with indirect hyperbilirubinemia. To the authors’ knowledge, this is the first time such a comparison has been made. There was no significant difference in the speed of bilirubin decline and length of hospital stay between the two groups. Kang and Shankaran’s study indicated that double phototherapy more rapidly reduced serum bilirubin concentration, compared with single phototherapy.14 Thus, length of hospitalization of double phototherapy was significantly shorter than that of the single phototherapy. Moreover, the mean of length of hospitalization for double phototherapy (14 ± 6 hours) was markedly shorter than the result in our study. Sarici et al suggested that length of hospitalization was significantly shorter in double phototherapy than single phototherapy.13 Meanwhile, the mean of length of hospitalization for double phototherapy (31.2 ± 8.5 hours) was similar to that of our study. A study by
Nuntnarumit and Naka confirmed the same result,10 and its mean length of hospitalization for double phototherapy (34.9 ± 12.6 hours) was similar to that of our study. Several studies have proved the benefits of double phototherapy in comparison with single phototherapy.5,9,15 In all the above-mentioned studies, double phototherapy was more effective than single phototherapy. This may be related to increased radiation and contact surface. The present study compared the efficacy of double and triple phototherapy methods in order to use examine the use of triple phototherapy as an alternative intensive phototherapy. As there were no similar studies in this field, we cannot directly compare our results with others. The effect of phototherapy is dependent to radiation rate (lamp number), distance from the photo source, contact surface, and photo wavelength. The results of our study (no difference between the two methods) may be explained by the amount of body surface exposed to the photo source (which was the same in two studied methods), and the distance of the device from the body—the distance of the third device was inevitably more than optimal (35 cm), due to space limitations.
4.1. Recommendation Our results suggest that triple phototherapy has no particular benefits compared with double phototherapy, but increases the cost of treatment, expenditure of energy, and, probably, dehydration in newborns. Triple phototherapy is widely used in Iran instead of intensive phototherapy, but the results of the present study do not support such a substitution. We recommend carrying out more detailed studies regarding the benefits and complications of triple phototherapy to help progress towards a more effective instrumental design.
Double vs. triple phototherapy
269
5. Conclusion
6.
Triple phototherapy failed to reduce total serum bilirubin or shorten the length of hospitalization more rapidly than double phototherapy. Thus, it should not be used as a substitution for intensive phototherapy in the treatment of newborn icterus.
7. 8.
9.
Acknowledgments
10.
The authors would like to thank the Farzan Institute for Research and Technology for technical assistance. 11.
References 1. 2. 3.
4.
5.
Greenwald JL. Hyperbilirubinemia in otherwise healthy infants. Am Fam Physician 1988;38:151−8. Porter M, Dennis BL. Hyperbilirubinemia in the term newborn. Am Fam Physician 2002;65:599−606. Stoll BJ, Kliegman RM. Jaundice and hyperbilirubinemia in the newborn. In: Behrman RE, Kliegman RM, Jenson HB, eds. Nelson Textbook of Pediatrics, 17th ed, Chapter 91. Philadelphia: WB Saunders, 2004;592−600. Fetus and Newborn Committee, Canadian Paediatric Society (CPS). Approach to the management of hyperbilirubinemia in term-newborn infants. Paediatr Child Health 1999;4:161−4. Melton K, Akinbi HT. Neonatal jaundice. Strategies to reduce bilirubin-induced complication. Postgrad Med 1999; 106:167−8,171−4,177−8.
12.
13.
14.
15.
Dennery PA, Seidman DS, Stevenson DK. Neonatal hyperbilirubinemia. N Engl J Med 2001;344:581−90. Agarwal R, Deorari AK. Unconjugated hyperbilirubinemia in newborns: current perspective. Indian Pediatr 2002;39:30−40. American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004;114:297−316. Steffensrud S. Hyperbilirubinemia in term and near term infants: kernicterus on the rise? Newborn Infant Nurs Rev 2004;4:191−200. Nuntnarumit P, Naka C. Comparison of the effectiveness between the adapted-double phototherapy versus conventional-single phototherapy. J Med Assoc Thai 2002;85 (Suppl 4):1159−66. Provisional Committee for Quality Improvement and Subcommittee on Hyperbilirubinemia, American Academy of Pediatrics. Practice parameter: management of hyperbilirubinemia in the healthy term newborn. Pediatrics 1994;94:558−65. Suchonska B, Wielgos M, Bobrowska K, Marionowski L. Concentration of bilirubin in the umbilical blood as an indicator of hyperbilirubinemia in newborns. Ginekol Pol 2004; 75:749−53. [In Polish] Sarici SU, Alpay F, Unay B, Ozcan O, Gökcay E. Double versus single phototherapy in term newborns with significant hyperbilirubinemia. J Trop Pediatr 2000;46:36−9. Kang JH, Shankaran S. Double phototherapy with high irradiance compared with single phototherapy in neonates with hyperbilirubinemia. Am J Perinatol 1995;12:178−80. Tan KL. Efficacy of bidirectional fiber-optic phototherapy for neonatal hyperbilirubinemia. Pediatrics 1997;99:E13.
O R IGINAL ART ICL E
Efficacy of Double and Triple Phototherapy in Term Newborns With Hyperbilirubinemia: The First Clinical Trial Salma Naderi1*, Fatemeh Safdarian2, Davood Mazloomi3, Elham Bushehri4, Reza Hamidian5 1
Division of Neonatology, Department of Pediatrics, Hormozgan Medical University, Hormozgan, Iran Department of Pediatrics, Hormozgan Medical University, Hormozgan, Iran 3 Specialist in Pediatrics Medicine, Hormozgan, Iran 4 Department of Epidemiology, Hormozgan Medical University, Hormozgan, Iran 5 Cardiovascular Research Center, Tehran University of Medical Sciences, Tehran, Iran 2
Received: Dec 15, 2008 Revised: Jan 27, 2009 Accepted: Mar 6, 2009 KEY WORDS: double phototherapy; efficacy; hyperbilirubinemia; term newborn; triple phototherapy
Background: Icterus is the most common medical problem in neonates and phototherapy is the standard treatment for neonatal hyperbilirubinemia. This study aimed to compare the efficacy and length of hospital stay of double and triple phototherapy in newborns with indirect hyperbilirubinemia. Methods: In a clinical trial, 40 healthy term newborns (gestational age > 37 weeks) with bilirubin ≥ 12 and ≥ 15 mg/dL in the second and third day, respectively, were randomly assigned to triple (n = 20) or double phototherapy (n = 20) groups. Total and direct serum bilirubin were measured at admission, 8, 16, and 24 hours after beginning of phototherapy, and every 12 hours thereafter until discharge (when bilirubin levels reached ≤ 10 mg/dL). Results: There were 21 male (52%) and 19 female (48%) term neonates, with significant difference between patients’ age, weight, and age of icterus. There was no significant difference in the rate of bilirubin decline between the two groups within the first 8, 16 and 24 hours. There was no significant difference in mean length of hospital stay between the two groups. Analysis of complications showed no difference between triple and double groups. Conclusion: Triple phototherapy failed to reduce total serum bilirubin and shorten length of hospitalization more rapidly than double phototherapy.
1. Introduction Icterus is the most common medical problem in neonates.1−3 Around 50−70% of term and 80% of preterm neonates suffer from icterus.1−5 Icterus is also the most common cause of neonate readmission.1,5,6 *Corresponding author. P.O. Box: 13185-1678, Tehran, Iran. E-mail: [email protected] ©2009 Taiwan Pediatric Association
Although it is usually benign in term and preterm neonates,1,3,7,8 severe hyperbilirubinemia is a medical emergency9 because bilirubin is a neurotoxic material3,10 which can lead to neurologic defects even in healthy term neonates.4,7,11 Therefore, management of hyperbilirubinemia in newborns is
Double vs. triple phototherapy still a critical issue. For the past four decades, phototherapy has remained a standard treatment for neonatal hyperbilirubinemia.4−6,12 The effect of phototherapy depends on the intensity of radiation (which in turn depends on the characteristics of radiation, number of radiation sources, and exposed body area) and the distance between the body and the source of radiation.2,4−7 Because of this, several studies have compared the efficacy of single and double phototherapy,10,13 but there is no data comparing double and triple phototherapy. Intensive phototherapy is a method used for the management of neonatal hyperbilirubinemia. The intensive phototherapy devices used included 11 phototherapy lamps, six of which were put above the bassinet, and five below the bassinet. Because devices for intensive phototherapy are rare or unavailable in Iran, some centers use triple phototherapy (adding another phototherapy device to double phototherapy) for intensive phototherapy. The purpose of this study was to compare the benefits, complications, and length of hospitalization for double and triple phototherapy treatment in newborns with indirect hyperbilirubinemia.
2. Methods and Materials 2.1. Study population This study was a clinical trial conducted in a neonatal ward of Bandar Abbas Pediatric Hospital (Bandar Abbas University of Medical Science), in Bandar Abbas, Iran, between January and May 2006. All subjects who met the following inclusion criteria entered to the study: healthy term newborn > 37 weeks, neonatal age > 24 hours, weight > 2500 grams, indirect hyperbilirubinemia, breast-fed, bilirubin levels ≥ 12 and ≥ 15 mg/dL on the 2nd and 3rd day, respectively. Neonates were defined as newborns with a gestational age > 37 weeks with no medical problems and/or hemolysis. Exclusion criteria included infectious, metabolic, or hemolytic diseases (including porphyria, glucose 6-phosphate dehydrogenase deficiency, and ABO alloimmunization), positive Coombs’ test, high reticulocyte count, abnormal peripheral blood smear, occurrence of icterus within the first 24 hours, increased levels of direct serum bilirubin or maternal history of phenobarbital consumption before, during, or after child birth. Also excluded were neonates who were candidates for blood exchange. Using simple randomization (single sequence of random assignment), 40 patients were randomly assigned to triple (n = 20) and double (n = 20) phototherapy groups. Triple and double groups underwent phototherapy using triple and
267 double radiation sources, respectively. All neonates were in bassinets during phototherapy. In double phototherapy (conventional method), two single phototherapy devices were used: one was placed above the bassinet, and the other was placed in line with its length, both with a 25 cm distance from it. In triple phototherapy, in addition to the two previous devices, a third one was placed in the line with width of the bassinette, and with a 35 cm distance from the bed. All phototherapy devices were made by Iran Behkar Medical Industry Co. (Tehran, Iran); fluorescent lamps were made by Royal Philips Electronics, Inc. (Amsterdam, the Netherlands) with 20 W power. The fluorescent lamps were exchanged and used for 500 hours. In each subject, total and direct serum bilirubin were measured at admission, 8, 16, and 24 hours after the beginning of phototherapy and then every 12 hours until discharge from hospital. Bilirubin was measured by the conventional indirect diazo method. Phototherapy was stopped and the newborns was discharged when bilirubin levels decreased to ≤10 mg/dL. A pediatrician visited all subjects once a day to monitor for phototherapy side effects. Recorded data including gender, age and weight, age of occurrence of icterus, bilirubin levels in scheduled time, duration, and phototherapy complications. The study protocol was approved by Institutional Review Board at Bandar Abbas University of Medical Science. Informed consent was obtained from all parents before enrollment in the study.
2.2. Statistical analysis Statistical analysis was conducted using SPSS version 11.5 (SPSS Inc., Chicago, IL, USA). Analysis of variance and independent Student’s t tests (with 95% confidence intervals) were used to compare quantitative data. Statistical significance was defined as p < 0.05.
3. Results There were 21 male (52%) and 19 female (48%) term neonates (a non-significant difference). Patients’ characteristics are shown in Table 1. Insignificant difference between patients’ age, weight, and age of icterus implied that our randomization was suitable and accurate. Comparison of total serum bilirubin in triple and double groups showed no significant differences at the times measured (Table 1). There was no significant difference in the rate of bilirubin decline between the two groups within the first 8, 16, and 24 hours. Thus, both triple and double phototherapy reduced total serum bilirubin in a comparable manner.
268
S. Naderi et al
Table 1 Characteristics of neonates in double and triple phototherapy groups Variable Age (d) Weight (g) Age of icterus (d) Total bilirubin at admission (mg/dL) Total bilirubin 8 hr after PT (mg/dL) Total bilirubin 16 hr after PT (mg/dL) Total bilirubin 24 hr after PT (mg/dL) Mean length of hospital stay (hr)
Double phototherapy group (n = 20)*
Triple phototherapy group (n = 20)*
p
6.4 ± 2.4 2916 ± 392 3.4 ± 1.1 16.4 ± 1.3 13.7 ± 1.8 12.2 ± 1.7 10.3 ± 2 34.6 ± 16.5
6.5 ± 2.2 2864 ± 400 3.5 ± 1.1 17 ± 1.3 14 ± 1.7 12.4 ± 1.7 10.9 ± 1 41.5 ± 17.7
0.905 0.681 0.792 0.170 0.590 0.760 0.370 0.211
*Data are presented as mean ± standard deviation. PT = Phototherapy.
We compared length of hospitalization between triple and double groups and found that the minimal and maximal lengths of hospitalization were 16 and 60 hours, respectively, in both groups. Length of hospital stay was not significantly different between the two groups (Table 1). There was no significant difference in the rate of bilirubin reduction between the two groups (p > 0.05). Analysis of complications showed no difference between triple and double groups. In term of complication, loose feces were seen in two newborns in the triple phototherapy group and one newborn in the double phototherapy group. Maculopapular rash was observed in one neonate in the double phototherapy group.
4. Discussion We compared the benefits, complications and length of hospitalization between double and triple phototherapy in term newborns with indirect hyperbilirubinemia. To the authors’ knowledge, this is the first time such a comparison has been made. There was no significant difference in the speed of bilirubin decline and length of hospital stay between the two groups. Kang and Shankaran’s study indicated that double phototherapy more rapidly reduced serum bilirubin concentration, compared with single phototherapy.14 Thus, length of hospitalization of double phototherapy was significantly shorter than that of the single phototherapy. Moreover, the mean of length of hospitalization for double phototherapy (14 ± 6 hours) was markedly shorter than the result in our study. Sarici et al suggested that length of hospitalization was significantly shorter in double phototherapy than single phototherapy.13 Meanwhile, the mean of length of hospitalization for double phototherapy (31.2 ± 8.5 hours) was similar to that of our study. A study by
Nuntnarumit and Naka confirmed the same result,10 and its mean length of hospitalization for double phototherapy (34.9 ± 12.6 hours) was similar to that of our study. Several studies have proved the benefits of double phototherapy in comparison with single phototherapy.5,9,15 In all the above-mentioned studies, double phototherapy was more effective than single phototherapy. This may be related to increased radiation and contact surface. The present study compared the efficacy of double and triple phototherapy methods in order to use examine the use of triple phototherapy as an alternative intensive phototherapy. As there were no similar studies in this field, we cannot directly compare our results with others. The effect of phototherapy is dependent to radiation rate (lamp number), distance from the photo source, contact surface, and photo wavelength. The results of our study (no difference between the two methods) may be explained by the amount of body surface exposed to the photo source (which was the same in two studied methods), and the distance of the device from the body—the distance of the third device was inevitably more than optimal (35 cm), due to space limitations.
4.1. Recommendation Our results suggest that triple phototherapy has no particular benefits compared with double phototherapy, but increases the cost of treatment, expenditure of energy, and, probably, dehydration in newborns. Triple phototherapy is widely used in Iran instead of intensive phototherapy, but the results of the present study do not support such a substitution. We recommend carrying out more detailed studies regarding the benefits and complications of triple phototherapy to help progress towards a more effective instrumental design.
Double vs. triple phototherapy
269
5. Conclusion
6.
Triple phototherapy failed to reduce total serum bilirubin or shorten the length of hospitalization more rapidly than double phototherapy. Thus, it should not be used as a substitution for intensive phototherapy in the treatment of newborn icterus.
7. 8.
9.
Acknowledgments
10.
The authors would like to thank the Farzan Institute for Research and Technology for technical assistance. 11.
References 1. 2. 3.
4.
5.
Greenwald JL. Hyperbilirubinemia in otherwise healthy infants. Am Fam Physician 1988;38:151−8. Porter M, Dennis BL. Hyperbilirubinemia in the term newborn. Am Fam Physician 2002;65:599−606. Stoll BJ, Kliegman RM. Jaundice and hyperbilirubinemia in the newborn. In: Behrman RE, Kliegman RM, Jenson HB, eds. Nelson Textbook of Pediatrics, 17th ed, Chapter 91. Philadelphia: WB Saunders, 2004;592−600. Fetus and Newborn Committee, Canadian Paediatric Society (CPS). Approach to the management of hyperbilirubinemia in term-newborn infants. Paediatr Child Health 1999;4:161−4. Melton K, Akinbi HT. Neonatal jaundice. Strategies to reduce bilirubin-induced complication. Postgrad Med 1999; 106:167−8,171−4,177−8.
12.
13.
14.
15.
Dennery PA, Seidman DS, Stevenson DK. Neonatal hyperbilirubinemia. N Engl J Med 2001;344:581−90. Agarwal R, Deorari AK. Unconjugated hyperbilirubinemia in newborns: current perspective. Indian Pediatr 2002;39:30−40. American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004;114:297−316. Steffensrud S. Hyperbilirubinemia in term and near term infants: kernicterus on the rise? Newborn Infant Nurs Rev 2004;4:191−200. Nuntnarumit P, Naka C. Comparison of the effectiveness between the adapted-double phototherapy versus conventional-single phototherapy. J Med Assoc Thai 2002;85 (Suppl 4):1159−66. Provisional Committee for Quality Improvement and Subcommittee on Hyperbilirubinemia, American Academy of Pediatrics. Practice parameter: management of hyperbilirubinemia in the healthy term newborn. Pediatrics 1994;94:558−65. Suchonska B, Wielgos M, Bobrowska K, Marionowski L. Concentration of bilirubin in the umbilical blood as an indicator of hyperbilirubinemia in newborns. Ginekol Pol 2004; 75:749−53. [In Polish] Sarici SU, Alpay F, Unay B, Ozcan O, Gökcay E. Double versus single phototherapy in term newborns with significant hyperbilirubinemia. J Trop Pediatr 2000;46:36−9. Kang JH, Shankaran S. Double phototherapy with high irradiance compared with single phototherapy in neonates with hyperbilirubinemia. Am J Perinatol 1995;12:178−80. Tan KL. Efficacy of bidirectional fiber-optic phototherapy for neonatal hyperbilirubinemia. Pediatrics 1997;99:E13.