Action spectrum of phototherapy in hyperbilirubinemic neonates.

BACKGROUND: Phototherapy with blue light matching plasma absorption spectrum of the bilirubin-albumin complex with peak at 460 nm is standard treatment of neonatal hyperbilirubinemia. AIM: To demonstrate clinically the action (efficacy) spectrum of phototherapy in hyperbilirubinemic neonates, through determination of the fraction of total serum bilirubin (TSB) decreased by phototherapy with peak emission wavelengths ≥478 nm (blue-green) compared with that of light of 459/452 nm (blue). METHODS: TSB values were compiled from three earlier trials, in which hyperbilirubinemic neonates were randomized to receive 24 h of either blue-green light (478/490/497 nm) (intervention groups) or blue light (459/452/459 nm) (control groups) with equal irradiance and exposed body surface areas. Ratios (efficacy) between the decrease in TSB between intervention and control groups were calculated and graphed versus peak wavelengths, demonstrating the course of the action spectrum. RESULTS: Calculated efficacy ratios were 1.31, 1.18, and 1.04 for light with peak wavelengths of 478, 490, and 497 nm, respectively. The action spectrum increases from 452/459 to maximum at 478 nm, from where it decreases to 1.18 and finally to 1.04. CONCLUSION: For optimal phototherapeutic treatment, neonates need to be exposed to light with peak wavelength some 20 nm longer than is presently used. IMPACT: The action (efficacy) spectrum of phototherapy for hyperbilirubinemic neonates has its peak wavelength at 478 nm. The peak wavelength of this action spectrum is 20 nm longer than the wavelength presently believed to be most efficient. The peak is also different from the peak found in vitro. For optimal phototherapeutic effect, neonates need to be treated with light of wavelengths some 20 nm longer than are presently used.

Effect of blue LED phototherapy centered at 478 nm versus 459 nm in hyperbilirubinemic neonates: a randomized study.

BACKGROUND: Treatment of choice for hyperbilirubinemic neonates is blue light matching the absorption spectrum of bilirubin-albumin in vitro with maximum absorption at 459 nm. Blue LED light centered at 478 nm was hypothesized as being more efficient than that centered at 459 nm. This study compares the bilirubin-reducing effect of the two light qualities with equal irradiance in a randomized nonblinded clinical trial. METHODS: Inclusion criteria were healthy hyperbilirubinemic neonates with gestational age ≥33 weeks. Forty-nine neonates included in each group received phototherapy from above for 24 h. Mean irradiances were 9.2 × 1015 and 9.0 × 1015 photons/cm2/s for the 478 and 459 nm groups, respectively. RESULTS: Mean [95% CI] decreases in total serum bilirubin were 150 [141, 158] and 120 [111, 130] µmol/L for the 478 and 459 nm groups, respectively; mean difference was 29 [17, 42] µmol/L. Mean [95% CI] percentage decreases in bilirubin were 54.8% [52.5, 57.0] and 41.8% [39.3, 44.3]; mean difference was 12.9 [9.6, 16.3] percentage points. After adjustment this difference was 13.4 [10.2, 16.7] percentage points. All differences were highly statistically significant (P < 0.001). CONCLUSION: Blue LED light centered at 478 nm had a greater bilirubin-reducing effect than that centered at 459 nm with equal irradiance quantified as photon fluence rate. IMPACT: Blue LED light centered at 478 nm had a greater in vivo bilirubin-reducing effect than blue LED light centered at 459 nm with equal irradiance quantified as photon fluence rate in the treatment of hyperbilirubinemic late preterm or term neonates. LED light centered at 478 nm might reduce the duration of phototherapy compared to LED light centered at 459 nm as the same effect can be obtained while exposing the infants to fewer photons. Blue light matching the absorption spectrum of the bilirubin-albumin complex in vitro with peak absorption at 459 nm is used worldwide as it is considered to be the most effective light for phototherapy of jaundiced neonates. This study showed that blue LED light centered at 478 nm had a greater bilirubin-reducing effect than blue LED light centered at 459 nm. Therefore, blue LED light centered at 478 nm should be used instead of blue light centered at 459 nm. By this, the risk of potential side effects might be minimized, and the duration of phototherapy potentially reduced.

Prediction of ABO hemolytic disease of the newborn using pre- and perinatal quantification of maternal anti-A/anti-B IgG titer.

BACKGROUND: Hemolysis in fetus/newborns is often caused by maternal antibodies. There are currently no established screening procedures for maternal ABO antibodies harmful to fetus/newborn. We investigated the clinical significance, and predictive value of maternal anti-A/B titer for hyperbilirubinemia in ABO-incompatible newborns. METHODS: We conducted a case-control study of blood group O mothers and their ABO-compatible (O) vs. -incompatible (A/B) newborns receiving phototherapy, and of ABO-incompatible newborns receiving phototherapy vs. no phototherapy. Newborn data and treatment modalities were recorded, and total serum bilirubin and hemoglobin were measured. Maternal anti-A/B immunoglobulin-γ (IgG) titers were measured prenatally and perinatally, and negative and positive predictive values (NPV, PPV) were calculated to assess the risk of developing hyperbilirubinemia requiring phototherapy. RESULTS: We found a significantly higher maternal IgG antibody titer in the case group (p < 0.001). Maternal anti-A/B titers at first trimester had modest predictive values: NPV = 0.82 and PPV = 0.65 for neonatal hyperbilirubinemia; titers at birth improved the predictive values: NPV = 0.93 and PPV = 0.73. Newborn hemoglobin was significantly lower in incompatibles compared to compatibles (p = 0.034). Furthermore, increased anti-A/B IgG production during pregnancy was associated with hyperbilirubinemia and hemolysis in incompatible newborns. CONCLUSIONS: There was a significant association between maternal anti-A/B IgG titer and hyperbilirubinemia requiring treatment. IMPACT: Maternal anti-A/B IgG titer in the first trimester and at birth is predictive of hemolytic disease of the ABO-incompatible newborn. Increased IgG anti-A/B production throughout pregnancy in mothers to ABO-incompatible newborns developing hyperbilirubinemia contrasts a constant or reduced production in mothers to newborns not developing hyperbilirubinemia. Screening tools available in most immunohematology laboratories can identify clinically important IgG anti-A/B. Use of maternal samples taken at birth yielded NPV = 0.93 and PPV = 0.73.

A greater awareness of children with glucose-6-phosphate dehydrogenase deficiency is imperative in western countries.

AIM: This national retrospective Danish study described the characteristics of children diagnosed with glucose-6-phosphate dehydrogenase (G6PD) deficiency, an inherited X-linked recessive disorder that often affects children of Middle Eastern descent. METHODS: We studied children born between 1 January 2000 and 31 December 2017 and diagnosed with G6PD deficiency. They were identified from the Danish National Hospital Discharge Register and the Danish Database of Extreme Neonatal Hyperbilirubinaemia. RESULTS: There were 113 children diagnosed with G6PD deficiency, 67% were of Middle Eastern descent and they were frequently diagnosed before the onset of symptoms, based on known heredity. Of the 67 infants born in Denmark, 10% had extreme neonatal hyperbilirubinaemia and one developed kernicterus spectrum disorder, as did one child born in the Middle East. Most (61%) of the 33 children with jaundice received phototherapy, 12% had exchange transfusions and 18% received whole blood transfusions. After the neonatal period, 23% of the cohort had blood transfusions and 4% needed intensive care for acute haemolytic anaemia. The incidence of G6PD deficiency appeared to be severely underestimated. CONCLUSION: Many families from countries where G6PD deficiency is endemic move to Denmark and other Western countries. Greater awareness is essential to avoid chronic and potentially lethal, consequences.

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.

The effectiveness of phototherapy using blue-green light for neonatal hyperbilirubinemia - Danish clinical trials.

The effectiveness of phototherapy for neonatal hyperbilirubinemia based on Danish clinical trials is presented. Randomized controlled trials on the quality of light showed that blue-green fluorescent light (peak emission at 490 nm) was more efficient than blue fluorescent light (peak emission at 452 nm); blue-green light-emitting diode (LED) light (peak emission at 478 nm) was more efficient than blue LED light (peak emission at 459 nm); and blue-green LED light (peak emission at 497 nm) was equivalent to blue LED light (peak emission at 459 nm). Bilirubin-reducing effects correlated with irradiance, dependent on hemoglobin concentration, and independent of rotating infants. Phototherapy from both above and below was more efficient than therapy applied only from above at high levels of irradiance. In conclusion, we estimate and recommend the use of blue-green LED light (peak emission at 480 nm) rather than blue light (peak emission at 460 nm) for treating of neonatal hyperbilirubinemia.