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Pediatrics International (2014) 56, 731–734

doi: 10.1111/ped.12351

Original Article

Problems with using total serum bilirubin as a criterion for phototherapy in extremely low-birthweight infants Kenji Ichinomiya, Fumitaka Inoue, Aya Koizumi, Takahiro Inoue, Toru Fujiu and Kenichi Maruyama Department of Neonatology, Gunma Children’s Medical Center, Gunma, Japan Abstract

Background: Despite the early use of phototherapy and exchange transfusion in premature infants based on total serum bilirubin (TSB), the reemergence of kernicterus has been reported. The aim of this study was to assess the validity of using TSB as the criterion for phototherapy in extremely low-birthweight infants (ELBWI). Methods: We reviewed the medical charts of 43 ELBWI admitted to hospital between January 2009 and December 2010, and analyzed the relationship between TSB and unbound bilirubin (UB). Results: No infant underwent exchange transfusion or developed acute bilirubin encephalopathy. There was a significant correlation between TSB and UB measured immediately before phototherapy during the first 7 days of life (r = 0.657, P < 0.001), but none thereafter (r = 0.120, P = 0.213). Thirty-seven percent of infants who underwent phototherapy during the first 7 days of life had suprathreshold USB but subthreshold TSB, whereas this rose to 97% thereafter. Conclusions: No correlation was observed between TSB and UB in ELBWI after the first 7 days of life, and almost all phototherapy sessions were initiated based on the UB criterion, even though TSB was below the accepted threshold. UB may be high if jaundice is evaluated solely on the basis of TSB.

Key words extremely low-birthweight infant, neonatal hyperbilirubinemia, phototherapy, total serum bilirubin, unbound bilirubin.

Premature infants, especially extremely low-birthweight infants (ELBWI), have a high risk of kernicterus because of the immaturity of the blood–brain barrier, neuronal susceptibility, low bilirubin-binding affinity, and low serum albumin. Unbound bilirubin (UB; bilirubin not bound to albumin) can pass easily through the blood–brain barrier. Therefore, UB reflects bilirubininduced neurotoxicity and is the optimal predictive factor for kernicterus.1,2 In many hospitals, however, the level of total serum bilirubin (TSB), which is easily measured, is used as the criterion for phototherapy and exchange transfusion in neonatal hyperbilirubinemia. Despite the early use of phototherapy and exchange transfusion to treat neonatal hyperbilirubinemia, the reemergence of kernicterus in premature infants has recently been reported.3–7 The purpose of this study was to assess the validity of using TSB as a criterion for phototherapy in ELBWI.

Methods We reviewed the medical charts of ELBWI who were hospitalized until 60 days of age at Gunma Children’s Medical Center between January 2009 and December 2010. We excluded infants with direct hyperbilirubinemia (direct bilirubin >2.0 mg/ dL). In this study, 43 Japanese infants (27 male, 16 female) Correspondence: Kenji Ichinomiya, MD, Department of Neonatology, Gunma Children’s Medical Center, 779 Shimohakoda, Hokkitsu, Shibukawa, Gunma 377-8577, Japan. Email: [email protected] .gunma.jp Received 4 June 2013; revised 12 March 2014; accepted 18 March 2014.

© 2014 Japan Pediatric Society

were enrolled, with a mean (± SD) gestational age of 26.4 ± 2.2 weeks and a mean birthweight of 757.7 ± 123.0 g. TSB and UB and the UB/TSB ratio were measured simultaneously at least once every 12–24 h for the first 7 days of life, and as required thereafter. The infants’ TSB and UB levels were measured at least once a day during phototherapy. Phototherapy was performed for all patients with either an infant phototherapy lamp (PIT-250; Atom Medical, Tokyo, Japan) or the neoBLUE LED Phototherapy System (Natus, San Carlos, CA, USA). The phototherapy sessions were initiated when either TSB or UB exceeded the corresponding thresholds recommended for therapeutic phototherapy for neonatal hyperbilirubinemia in Japan.8 These sessions lasted for at least 24 consecutive hours after they were commenced or recommenced. The TSB thresholds for phototherapy are as follows: ≥5 mg/dL at 120 h. The UB threshold for phototherapy is ≥0.3 μg/mL, irrespective of age. The UB/TSB ratio was not used as a criterion to indicate phototherapy. UB was measured with an automated UB analyzer (Arrows, Osaka, Japan), which uses spectrophotometry and the glucose oxidase–peroxidase method.9 TSB was measured with the bilirubin oxidase method on a clinical biochemistry analyzer (Bio Majesty JCA-BM6050; JEOL, Tokyo, Japan). The study protocol complied with the ethics committee of Gunma Children’s Medical Center. Statistical analysis was performed with Pearson’s correlation coefficient or Student’s t test as appropriate. A two-sided P < 0.05 was considered statistically significant. All results are expressed as mean ± SD.

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Table 1 Subject characteristics

Gestational age (weeks) Birthweight (g) Sex (M/F) 5-min Apgar score

Problems with using total serum bilirubin as a criterion for phototherapy in extremely low-birthweight infants.

Despite the early use of phototherapy and exchange transfusion in premature infants based on total serum bilirubin (TSB), the reemergence of kernicter...
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