Serum unbound bilirubin as a predictor for clinical kernicterus in extremely low birth weight infants at a late age in the neonatal intensive care unit

Morioka, Ichiro; Nakamura, Hajime; Koda, Tsubasa; Sakai, Hitomi; Kurokawa, Daisuke; Yonetani, Masahiko; Morisawa, Takeshi; Katayama, Yoshinori; Wada, Hiroshi; Funato, Masahisa; Takatera, Akihiro; Okumura, Akihisa; Sato, Itsuko; Iijima, Kazumoto

doi:10.1016/j.braindev.2015.01.001

Cited by 34 publications

(36 citation statements)

References 23 publications

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“…Unfortunately, it is not routinely measured in the USA because of lack of commercially available assay methods but is available in other countries, such as Japan. (7, 8)…”

mentioning

confidence: 99%

Effects of Soybean Lipid Infusion on Unbound Free Fatty Acids and Unbound Bilirubin in Preterm Infants

Hegyi

Kleinfeld

Huber

et al. 2017

The Journal of Pediatrics

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Objective To assess the effects of a soybean lipid emulsion infusions on levels of unbound (free) bilirubin (Bf) and unbound free fatty acids (FFAu) as well as changes in Bf and total serum bilirubin (TSB) during phototherapy in preterm infants. Study design Ninety-seven preterm infants (birthweight: 500-2000g; gestational age: 23- 34 weeks) were enrolled to investigate the effect of 0, 1, 2 and 3 g/kg/day of Intralipid (IL) infusion on Bf and FFAu. Pre- and post-phototherapy total serum bilirubin (TSB), FFAu and Bf were also analyzed in 91 infants to assess the effects of phototherapy. FFAu levels were measured using the fluorescent probe ADIFAB2 and Bf by the fluorescent Bf sensor BL22P1B11-Rh during IL infusion and at start and end of phototherapy. TSB and plasma albumin were measured by the diazo and Bromcresol Green techniques, respectively. Bilirubin-albumin dissociation constants (Kd) were calculated based on Bf and plasma albumin. Results Bf and FFAu increased with increasing IL dosage across all gestational ages. TSB and Bf were significantly correlated when infants received 0 or 1 g/kg/day of IL, but not at higher IL doses (2 and 3 g/kg/day). Although phototherapy effectively reduced both TSB and Bf in the total phototherapy group (by 32% and 12%, respectively), it reduced TSB, but not Bf, in infants below 28 weeks of gestation. Conclusions Increasing IL doses result in increasing FFAu levels, which are associated with increased Bf independent of TSB. In extremely preterm infants (<28 weeks gestation), phototherapy effectively reduces TSB but not Bf.

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“…Unfortunately, it is not routinely measured in the USA because of lack of commercially available assay methods but is available in other countries, such as Japan. (7, 8)…”

mentioning

confidence: 99%

Effects of Soybean Lipid Infusion on Unbound Free Fatty Acids and Unbound Bilirubin in Preterm Infants

Hegyi

Kleinfeld

Huber

et al. 2017

The Journal of Pediatrics

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“…Preterm infants are particularly vulnerable to bilirubin neurotoxicity due to immaturity of the blood–brain barrier, liver function, and other organ function. Chronic bilirubin encephalopathy or kernicterus can occur even in a low TSB environment in preterm infants, compared with term infants . Therefore, the TSB and UB treatment initiation criteria for preterm infants were set at lower levels than for those in term infants (Table ) …”

Section: Why Has Chronic Bilirubin Encephalopathy Occurred In Japan?mentioning

confidence: 99%

“…Second, because the 1992 Kobe University treatment criteria did not target preterm infants, specifically extremely preterm infants, there are no treatment criteria values for infants ≥1 week of age. As aforementioned, preterm infants should be managed for hyperbilirubinemia and treated for as long as needed during their neonatal care unit stay, because half of extremely preterm children who developed chronic bilirubin encephalopathy had peak TSB after 4 weeks of age (maximum, 12 weeks of age) . Therefore, treatment criteria values until discharge from the neonatal care unit are required.…”

Section: Why Should the 1992 Kobe University Treatment Criteria Be Rementioning

confidence: 99%

Hyperbilirubinemia in preterm infants in Japan: New treatment criteria

Morioka

2018

Pediatrics International

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In 1992, Kobe University proposed treatment criteria for hyperbilirubinemia in newborns using total serum bilirubin and serum unbound bilirubin reference values. In the last decade, chronic bilirubin encephalopathy has been found to develop in preterm infants in Japan because it can now be clinically diagnosed based on an abnormal signal of the globus pallidus on T2-weighted magnetic resonance imaging and abnormal auditory brainstem response with or without apparent hearing loss, along with physical findings of kinetic disorders with athetosis. We therefore revised the Kobe University treatment criteria for preterm hyperbilirubinemic infants in 2017. The three revised points are as follows: (i) newborns are classified under gestational age at birth or corrected gestational age, not birthweight; (ii) three treatment options were created: standard phototherapy, intensive phototherapy, and albumin therapy and/or exchange blood transfusion; and (iii) initiation of standard phototherapy, intensive phototherapy, and albumin therapy and/or exchange blood transfusion is decided based on the total serum bilirubin and serum unbound bilirubin reference values for gestational weeks at birth at <7 days of age, and on the reference values for corrected gestational age at ≥7 days of age. Studies are needed to establish whether chronic bilirubin encephalopathy can be prevented using the 2017 revised Kobe University treatment criteria for preterm infants in Japan.

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“…[8] In addition, preterm infants may exhibit clinical evidence of kernicterus at normal or marginally elevated TB levels. [9,10] Damage to the auditory system has long-reaching consequences for affected children, as language development is intricately tied to auditory function, and even mild-to-moderate hearing loss can significantly impact a child’s quality of speech acquisition. [11]…”

Section: Introductionmentioning

confidence: 99%

Bilirubin-Induced Audiologic Injury in Preterm Infants

Olds

Oghalai

2016

Clinics in Perinatology

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While hyperbilirubinemia is extremely common among neonates and is usually mild and transient, it sometimes leads to bilirubin-induced neurologic damage (BIND). The auditory pathway is highly sensitive to the effects of elevated total serum/plasma bilirubin (TB) levels, with damage manifesting clinically as auditory neuropathy spectrum disorder (ANSD). Compared to full-term neonates, preterm neonates are more susceptible to BIND and suffer adverse effects at lower TB levels with worse long-term outcomes. Furthermore, while standardized guidelines for management of hyperbilirubinemia exist for term and late-preterm neonates, similar guidelines exist for neonates less than 35 wks gestational age (GA) are limited.

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Serum unbound bilirubin as a predictor for clinical kernicterus in extremely low birth weight infants at a late age in the neonatal intensive care unit

Cited by 34 publications

References 23 publications

Effects of Soybean Lipid Infusion on Unbound Free Fatty Acids and Unbound Bilirubin in Preterm Infants

Effects of Soybean Lipid Infusion on Unbound Free Fatty Acids and Unbound Bilirubin in Preterm Infants

Hyperbilirubinemia in preterm infants in Japan: New treatment criteria

Bilirubin-Induced Audiologic Injury in Preterm Infants

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