Early formation of bilirubin isomers during phototherapy for neonatal jaundice: effects of single vs. double fluorescent lamps vs. photodiodes

Abstract

Background:In neonatal jaundice, phototherapy converts bilirubin to more polar photoisomers which can be excreted without conjugation. We measured changes in the concentration of bilirubin Z,E-photoisomer during the first 4 h of intensive phototherapy using single fluorescent lights as a reference, compared to double fluorescent lights, and a single unit of photodiodes. Methods: Neonates (N = 42; birth weight: 1,200-4,690 g; gestational age: 28-42 wk) were studied during phototherapy. Infants were randomized to: (i) single, or (ii) double fluorescent phototherapy; or (iii) single unit photodiodes. Irradiance was measured. Serum bilirubin (by cooximetry) and Z,E bilirubin (by high-pressure liquid chromatography) were measured at 0,15, 30, 60, 120, and 240 min after the start of phototherapy. Data were analyzed with a linear mixed model. results: There was a highly significant increase of Z,E-bilirubin over time (P < 0.0001), starting at 15 min. Photoisomers reached ~25% of total bilirubin concentration after 4 h. However, there were no significant differences between the three randomized groups in spite of significantly higher irradiance using double fluorescent lights vs. single fluorescent or photodiodes. conclusion: Formation of bilirubin photoisomers is rapid, and occurs early during intensive phototherapy for neonatal jaundice. The rate and level of photoisomerization was not influenced by irradiance and light source. P hototherapy is the standard treatment for hyperbilirubinemia in newborns, and is administered to prevent kernicterus and other sequelae of bilirubin neurotoxicity (1).It is effective and considered safe. However, a recent report suggests that "aggressive" phototherapy in the smallest infants of birth weight 501-750 g may be associated with increased risk of death (2).When native bilirubin IXα (Z,Z) in neonates is exposed to light, a rapid photochemical reaction produces water-soluble configurational (4Z,15E; 4E,15Z; 4E,15E) and structural (Z-lumirubin; E-lumirubin) isomers (3,4). Photooxidation may also occur (5,6). Due to increased polarity, these isomers can be excreted in bile and urine, bypassing the need for conjugation. It has recently been suggested that these isomers, because of their polarity, should be less able to cross the bloodbrain barrier (1,7). If this is correct, photoisomer formation might be directly neuroprotective, irrespective of the effect on excretion. Experimental data suggest that bilirubin photoisomers are less toxic than the native IX α (Z,Z), but there are methodological weaknesses in these studies (1). Thus, experimental proof of the hypothesized direct neuroprotective effects of photoisomerization is still needed. Both different light qualities and variable light irradiance are commonly employed in practical phototherapy. Herein we have investigated whether such factors may impact on photoisomer formation.The common light sources used in phototherapy are either fluorescent, or tungsten-halogen lamps with wide emission spectrum, or light-emitting diodes (LEDs) wi...

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

“…After 24 h of phototherapy, the percentage of Z,E-bilirubin to total bilirubin isomers was higher for infants treated with light centered at 459 nm than for those treated with light centered at 497 nm (23% vs. 14%), and thus also the percentage of total bilirubin isomers formed during treatment to total bilirubin isomers was highest for the infants treated with light centered at 459 nm (26% vs. 18%) ( Table 3). This is in agreement with previous in vitro studies, which showed that after equilibrium between Z,Z-and Z,Eisomers is reached, the percentage of Z,E-bilirubin decreases with longer wavelengths (4,16).This observation has also been confirmed in earlier clinical studies, where the reported percentages of Z,E-bilirubin to total bilirubin isomers were: 24% to 27% (10,13,14), 16% (10) and 9% (14) in children exposed to light of wavelengths ~460, 490, and 528 nm, respectively.…”

“…The concentration of Z,E-bilirubin increases until equilibrium with Z,Z-bilirubin is reached, which occurs after approximately 4-6 h of exposure to light (13)(14)(15). Thereafter, the percentage of Z,E-bilirubin to the sum of Z,Z-and Z,E-bilirubin only depends on the emission spectrum of the light (15).…”

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

“…From a theoretical perspective, there is increasing, although indirect, evidence that isomerization of bilirubin in vivo primarily occurs in the skin capillary circulation (10,11). Our findings support this understanding.…”

Uniform national guidelines do not prevent wide variations in the clinical application of phototherapy for neonatal jaundice

“…However, it has also been shown that routinely alternating the infant's position during phototherapy does not increase the effect of phototherapy, presumably because it happens in the capillary circulation near the skin's surface . This was compatible with studies that showed that formation of bilirubin photoisomers was detectable within a few minutes of turning on phototherapy lights, long before diffusion from the skin tissue could have occurred .…”