Pernille Kure Vandborg

Relation between serum bilirubin levels ≥450 μmol/L and bilirubin encephalopathy; a Danish population-based study

Aim:  Describe the relation between levels of total serum bilirubin (TsB) ≥450 μmol/L and acute intermediate, acute advanced and chronic bilirubin encephalopathy.

Dose-Response Relationship of Phototherapy for Hyperbilirubinemia

BACKGROUND AND OBJECTIVE: Using light-emitting diodes during conventional phototherapy, it is possible to reduce the distance from light source to infant, thus increasing light irradiance. The objective of this study was to search for a “saturation point” (ie, an irradiation level above which there is no further decrease in total serum bilirubin [TsB]). This was a prospective randomized study performed in the NICU of Aalborg Hospital, Denmark. METHODS: One hundred fifty-one infants (gestational age ≥33 weeks) with uncomplicated hyperbilirubinemia were randomized to 1 of 4 distances from the phototherapy device to the mattress (20, 29, 38, and 47 cm). TsB was measured before and after 24 hours of phototherapy and irradiance every eighth hour. Main outcome was 24-hour decrease of TsB expressed in percent, (∆ TsB0–24, difference between TsB0 and TsB24 [%]). RESULTS: A highly significant linear relation was seen between light irradiance and ∆ TsB0–24 (%) (P < .001): when the irradiance increased from 20 to 55 μW/cm2/nm, ∆ TsB0–24 (%) increased from approximately 30% to 50%. In addition, smooth regression showed no tendency for ∆ TsB0–24 (%) to level off as irradiance increased. ∆ TsB0–24 (%) was negatively correlated to birth weight and positively to formula volume. Average weight gain during phototherapy was 1%, independent of light irradiance. CONCLUSIONS: By using light-emitting diodes, we found a linear relation between light irradiance in the range of 20 to 55 μW/cm2/nm and a decrease in TsB after 24 hours of therapy, with no evidence of a saturation point.

Follow-up of Neonates With Total Serum Bilirubin Levels ≥25 mg/dL: A Danish Population-Based Study

OBJECTIVE: To study if severe hyperbilirubinemia in infants with no or minor neurologic symptoms in the neonatal period affects children’s development at the age of 1 to 5 years. METHODS: Controlled descriptive follow-up study of a national cohort of Danish children. The exposed group consisted of all live-born infants in Denmark from 2004 to 2007 with a gestational age ≥35 weeks and severe hyperbilirubinemia in the neonatal period, defined as at least 1 measure of total serum bilirubin level ≥25 mg/dL during the first 3 weeks of life. The exposed group of 206 children was matched with a control group of 208 children. The Ages and Stages Questionnaire (ASQ), a method of evaluating the child’s development, was filled in by parents. Main outcome measure was effect size of ASQ total score. Statistical analyses comprised a matched analysis of 102 pairs and a nonmatched regression analysis of all participants. RESULTS: The response rate was 79% (n = 162 of 206) in the study group and 70% (n = 146 of 208) in the control group. Neither the matched nor the nonmatched analysis showed any statistically significant differences between the groups; the effect size of the total score was 0.04 (−0.24 to 0.32) and −0.04 (−0.26 to 0.19), respectively. CONCLUSIONS: Using the parent-completed ASQ, we found no evidence of developmental delay in children aged between 1 and 5 years with severe neonatal hyperbilirubinemia compared with a matched control group.

Comparison of the transcutaneous bilirubinometers BiliCheck and Minolta JM-103 in preterm neonates

Aim:  To investigate the trueness and uncertainty of two transcutaneous bilirubinometers BiliCheck and Minolta JM‐103 in preterm infants; establish cut‐off values for the transcutaneous bilirubin (TcB) level, indicating the need for total serum bilirubin (TsB) measurement; and estimate how many blood samples could be saved.

Effect of phototherapy with turquoise vs. blue LED light of equal irradiance in jaundiced neonates

Background:Blue light with peak emission around 460 nm is the preferred treatment of neonatal hyperbilirubinemia. However, studies using fluorescent light tubes have suggested that turquoise light with peak emission at 490 nm may be more efficient. At present, the predominant light source for phototherapy is light emitting diodes (LEDs). Hence, the aim of this study was to compare the bilirubin-reducing effect in jaundiced neonates treated either with turquoise or with blue LED light with peak emission at 497 or 459 nm, respectively, with equal irradiance on the infants.Methods:Infants with gestational age ≥33 wk and uncomplicated hyperbilirubinemia were randomized to either turquoise or blue LED light and were treated for 24 h. The mean irradiance footprint at skin level was 5.2 × 1015 and 5.1 × 1015 photons/cm2/s, respectively.Results:Forty-six infants received turquoise light and 45 received blue light. The median (95% confidence interval) decrease of total serum bilirubin was 35.3% (32.5; 37.3) and 33.1% (27.1; 36.8) for infants treated with turquoise and blue lights, respectively. The difference was nonsignificant (P = 0.53). The decrease was positively correlated to postnatal age and negatively to birth weight.Conclusion:Using LED light of equal irradiance, turquoise and blue lights had equal bilirubin-reducing effect on hyperbilirubinemia of neonates.

Follow‐up of extreme neonatal hyperbilirubinaemia in 5‐ to 10‐year‐old children: a Danish population‐based study

To investigate whether infants with neonatal hyperbilirubinaemia but without intermediate or advanced bilirubin encephalopathy develop long‐term sequelae, with impairment of motor development, executive function, or hearing.

Extreme Neonatal Hyperbilirubinemia and a Specific Genotype: A Population-Based Case-Control Study

OBJECTIVES: Extreme hyperbilirubinemia (plasma bilirubin ≥24.5 mg/dL) is an important risk factor for severe bilirubin encephalopathy. Several risk factors for hyperbilirubinemia are known, but in a large number of patients, a causal factor is never established. UGT1A1 is the rate-limiting enzyme in bilirubin’s metabolism. The genotype of Gilbert syndrome, the UGT1A1*28 allele, causes markedly reduced activity of this enzyme, but its association with neonatal hyperbilirubinemia is uncertain and its relationship with extreme hyperbilirubinemia has not been studied. We examined whether the UGT1A1*28 allele is associated with extreme hyperbilirubinemia. METHODS: The UGT1A1*28 allele was assessed in a case-control study of 231 white infants who had extreme hyperbilirubinemia in Denmark from 2000 to 2007 and 432 white controls. Cases were identified in the Danish Extreme Hyperbilirubinemia Database that covers the entire population. Genotypes were obtained through the Danish Neonatal Screening Biobank. Subgroup analysis was done for AB0 incompatible cases. RESULTS: No association was found between the UGT1A1*28 allele and extreme hyperbilirubinemia. With the common genotype as reference, the odds ratio of extreme hyperbilirubinemia was 0.87 (range, 0.68–1.13) for UGT1A1*28 heterozygotes and 0.77 (range, 0.46–1.27) for homozygotes. Also, no association was found for AB0 incompatible cases. CONCLUSIONS: The UGT1A1*28 allele was not associated with risk for extreme hyperbilirubinemia in this study.

Bilirubin isomer distribution in jaundiced neonates during phototherapy with LED light centered at 497 nm (turquoise) vs. 459 nm (blue).

Background:Phototherapy using blue light is the treatment of choice worldwide for neonatal hyperbilirubinemia. However, treatment with turquoise light may be a desirable alternative. Therefore, the aim of this randomized, controlled study was to compare the bilirubin isomer distribution in serum of jaundiced neonates after 24 h of therapy with narrow-band (LED) light centered at 497 nm (turquoise) vs. 459 nm (blue), of essentially equal irradiance.Materials:Eighty-three neonates (≥33 wk gestational age) with uncomplicated hyperbilirubinemia were included in the study. Forty neonates were exposed to light centered at 497 nm and 43 infants with light centered at 459 nm. Irradiances were 5.2 × 1015 and 5.1 × 1015 photons/cm2/s, respectively.Results:After 24 h of treatment no significant differences in serum concentrations of total bilirubin isomers and Z,Z-bilirubin were observed between the 2 groups. Interestingly, concentrations of Z,E-bilirubin, and thus also total bilirubin isomers formed during therapy, were highest for infants receiving light centered at 459 nm, while the concentration of E,Z-bilirubin was highest for those receiving light centered at 497 nm. No significant difference was found between concentrations of E,Z-lumirubin.Conclusion:Therapy with LED light centered at 497 nm vs. 459 nm, applied with equal irradiance on the infants, resulted in a different distribution of bilirubin isomers in serum.

Double versus single intensive phototherapy with LEDs in treatment of neonatal hyperbilirubinemia

Objective:We investigate whether double phototherapy reduces total serum bilirubin concentration faster than single light during intensive phototherapy with high levels of irradiance using light-emitting diodes.Study Design:Eighty-three infants with gestational age ⩾33 weeks and uncomplicated hyperbilirubinemia were randomized to either double (n=41) or single phototherapy (n=42) for 24 h. The mean irradiance was 64.8 μW cm−2 nm−1 from above and 39 μW cm−2 nm−1 from below.Results:The percentage decreases of total serum bilirubin after 12 h of double vs single phototherapy were (mean (95% confidence interval (CI))) 39% (37 to 42) vs 30% (27 to 32), respectively (P<0.001). After 24 h, the decreases were 58% (56 to 61) vs 47% (44 to 50), respectively (P<0.001). The results were still significant after adjustment for confounding. The only side effect was loose stools.Conclusion:Even with intensive phototherapy increasing spectral power by increasing the irradiated body surface area, the efficacy of phototherapy is improved.

The impact of hemoglobin on the efficacy of phototherapy in hyperbilirubinemic infants

BackgroundPhototherapy is the routine treatment for neonatal hyperbilirubinemia. Absorption of light in the skin transforms the native Z,Z-bilirubin to photobilirubins. This study investigates whether the hemoglobin concentration has an impact on efficacy of phototherapy, expressed by the decline of total serum bilirubin concentration (TsB).MethodsA trial was conducted on 93 infants, gestational age ≥33 weeks, with uncomplicated hyperbilirubinemia. The infants were treated with conventional phototherapy using LED light for 24 h. The median light irradiance was 66.8 μW/cm2/nm.ResultsThe median decrease in TsB after 24 h was 121 (57–199) μmol/l; the median hemoglobin was 12.0 (7.0–14.7) mmol/l. There was a significant effect of hemoglobin concentration on the decrease in TsB of −3.61 μmol/mmol hemoglobin (P=0.022), after adjusting for initial TsB and postnatal age. That is, assuming the same initial TsB and postnatal age, for each mmol/l increase in hemoglobin, the decrease in TsB was 3.61 μmol/l smaller. In our hemoglobin range, the decrease in TsB is reduced by 28 μmol/l (23%).ConclusionIncreasing hemoglobin levels led to a decrease in the efficacy of phototherapy. Our data provide additional support for the conclusion that the transformation of bilirubin to photobilirubins takes place mainly in the superficial capillaries of the skin.