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.

Crigler-Najjar Syndrome Type 1: Pathophysiology, Natural History, and Therapeutic Frontier.

BACKGROUND AND AIMS: We describe the pathophysiology, treatment, and outcome of Crigler-Najjar type 1 syndrome (CN1) in 28 UGT1A1 c.222C>A homozygotes followed for 520 aggregate patient-years. APPROACH AND RESULTS: Unbound ("free") bilirubin (Bf ) was measured in patient sera to characterize the binding of unconjugated bilirubin (BT ) to albumin (A) and validate their molar concentration ratio (BT /A) as an index of neurological risk. Two custom phototherapy systems were constructed from affordable materials to provide high irradiance in the outpatient setting; light dose was titrated to keep BT /A at least 30% below intravascular BT binding capacity (i.e., BT /A = 1.0). Categorical clinical outcomes were ascertained by chart review, and a measure (Lf ) was used to quantify liver fibrosis. Unbound bilirubin had a nonlinear relationship to BT (R2  = 0.71) and BT /A (R2  = 0.76), and Bf as a percentage of BT correlated inversely to the bilirubin-albumin equilibrium association binding constant (R2  = 0.69), which varied 10-fold among individuals. In newborns with CN1, unconjugated bilirubin increased 4.3 ± 1.1 mg/dL per day. Four (14%) neonates developed kernicterus between days 14 and 45 postnatal days of life; peak BT  ≥ 30 mg/dL and BT /A ≥ 1.0 mol:mol were equally predictive of perinatal brain injury (sensitivity 100%, specificity 93.3%, positive predictive value 88.0%), and starting phototherapy after age 13 days increased this risk 3.5-fold. Consistent phototherapy with 33-103 µW/cm2 •nm for 9.2 ± 1.1 hours/day kept BT and BT /A within safe limits throughout childhood, but BT increased 0.46 mg/dL per year to reach dangerous concentrations by 18 years of age. Liver transplantation (n = 17) normalized BT and eliminated phototherapy dependence. Liver explants showed fibrosis ranging from mild to severe. CONCLUSION: Seven decades after its discovery, CN1 remains a morbid and potentially fatal disorder.

Making Locally Fabricated Phototherapy Devices Work Better.

BACKGROUND: The efficiency of a phototherapy (PT) device is a function of the irradiance delivered by the device at the surface of the skin. Because cost limits the ability of health care facilities in low- and middle-income countries to procure commercial PT devices, efforts have gone into local fabrication of devices for use in health care facilities in Nigeria. Evaluation of such fabricated devices is yet to be conducted. OBJECTIVE: To identify and document essential features of locally fabricated phototherapy (FPT) devices in use in Nigeria. MATERIALS AND METHODS: A cross sectional survey of locally FPT devices available in health facilities providing newborn health care services was conducted as part of evaluating neonatal jaundice management services in Kaduna State. Each FPT was characterized with respect to mobility/portability, adjustability, lamp type, number and color of lamps used. The irradiance of each device was measured using Model 22 Olympic BiliMeter™ at the facility's traditional PT distance and also at a distance at which optimum irradiance is delivered by the device. RESULTS: A total of 54 PT devices were in use. Thirty-two (59.3%) of these devices were locally fabricated while others were obtained from commercial sources. Of the fabricated devices 22/32 (68.8%) were non-adjustable while the remaining 10 devices were adjustable but with limited adjustability. Only 5/32 (15.6%) of the FPT devices used special blue fluorescent lamps. The majority, 68.8% (22/32) of the FPT devices used ordinary low-intensity blue lamps while the remaining 5/32 (15.6%) devices used white light fluorescent lamps. None of the devices used light emitting diodes as a PT light source. Only three fabricated devices offered irradiance (9.4, 13.6 and 33 µW/cm2/nm) at the facilities' traditional distances for PT. CONCLUSIONS: FPT devices in use in Kaduna, functioned sub-optimally because of technically inadequate designs. The devices will need to be designed to especially enable adjustability to vary distance between device and patient's skin and the use of lamps which offer high irradiance.

Sixty years of phototherapy for neonatal jaundice - from serendipitous observation to standardized treatment and rescue for millions.

A breakthrough discovery 60 years ago by Cremer et al. has since changed the way we treat infants with hyperbilirubinemia and saved the lives of millions from death and disabilities. "Photobiology" has evolved by inquiry of diverse light sources: fluorescent tubes (wavelength range of 400-520 nm; halogen spotlights that emit circular footprints of light; fiberoptic pads/blankets (mostly, 400-550 nm range) that can be placed in direct contact with skin; and the current narrow-band blue light-emitting diode (LED) light (450-470 nm), which overlaps the peak absorption wavelength (458 nm) for bilirubin photoisomerization. Excessive bombardment with photons has raised concerns for oxidative stress in very low birthweight versus term infants treated aggressively with phototherapy. Increased emphasis on prescribing phototherapy as a "drug" that is dosed cautiously and judiciously is needed. In this historical review, we chronicled the basic to the neurotoxic components of severe neonatal hyperbilirubinemia and the use of standardized interventions.

The effect of light wavelength on in vitro bilirubin photodegradation and photoisomer production.

BACKGROUND: The action spectrum for bilirubin photodegradation has been intensively studied. However, questions still remain regarding which light wavelength most efficiently photodegrades bilirubin. In this study, we determined the in vitro effects of different irradiation wavelength ranges on bilirubin photodegradation. METHODS: In our in vitro method, normalized absolute irradiance levels of 4.2 × 1015 photons/cm2/s from light-emitting diodes (ranging from 390-530 nm) and 10-nm band-pass filters were used to irradiate bilirubin solutions (25 mg/dL in 4% human serum albumin). Bilirubin and its major photoisomer concentrations were determined; the half-life time of bilirubin (t1/2) was calculated for each wavelength range, and the spectral characteristics for bilirubin photodegradation products were obtained for key wavelengths. RESULTS: The in vitro photodegradation of bilirubin at 37 °C decreased linearly as the wavelength was increased from 390 to 500 nm with t1/2 decreasing from 63 to 17 min, respectively. At 460 ± 10 nm, a significantly lower rate of photodegradation and thus higher t1/2 (31 min) than that at 500 nm (17 min) was demonstrated. CONCLUSION: In our system, the optimum bilirubin photodegradation and lumirubin production rates occurred between 490 and 500 nm. Spectra shapes were remarkably similar, suggesting that lumirubin production was the major process of bilirubin photodegradation.

Filtered sunlight versus intensive electric powered phototherapy in moderate-to-severe neonatal hyperbilirubinaemia: a randomised controlled non-inferiority trial.

BACKGROUND: Kernicterus resulting from severe neonatal hyperbilirubinaemia is a leading cause of preventable deaths and disabilities in low-income and middle-income countries, partly because high-quality intensive phototherapy is unavailable. Previously, we showed that filtered-sunlight phototherapy (FSPT) was efficacious and safe for treatment of mild-to-moderate neonatal hyperbilirubinaemia. We aimed to extend these studies to infants with moderate-to-severe hyperbilirubinaemia. METHODS: We did a prospective, randomised controlled non-inferiority trial in Ogbomoso, Nigeria-a simulated rural setting. Near-term or term infants aged 14 days or younger who were of 35 weeks or more gestational age and with total serum bilirubin concentrations at or above the recommended age-dependent treatment levels for high-risk neonates were randomly assigned (1:1) to either FSPT or intensive electric phototherapy (IEPT). Randomisation was computer-generated, and neither clinicians nor the parents or guardians of participants were masked to group allocation. FSPT was delivered in a transparent polycarbonate room lined with commercial tinting films that transmitted effective phototherapeutic light, blocked ultraviolet light, and reduced infrared radiation. The primary outcome was efficacy, which was based on assessable treatment days only (ie, those on which at least 4 h of phototherapy was delivered) and defined as a rate of increase in total serum bilirubin concentrations of less than 3·4 µmol/L/h in infants aged 72 h or younger, or a decrease in total serum bilirubin concentrations in those older than 72 h. Safety was defined as no sustained hypothermia, hyperthermia, dehydration, or sunburn and was based on all treatment days. Analysis was by intention to treat with a non-inferiority margin of 10%. FINDINGS: Between July 31, 2015, and April 30, 2017, 174 neonates were enrolled and randomly assigned: 87 to FSPT and 87 to IEPT. Neonates in the FSPT group received 215 days of phototherapy, 82 (38%) of which were not assessable. Neonates in the IEPT group received 219 treatment days of phototherapy, 67 (31%) of which were not assessable. Median irradiance was 37·3 µW/cm2/nm (IQR 21·4-56·4) in the FSPT group and 50·4 µW/cm2/nm (44·5-66·2) in the IEPT group. FSPT was efficacious on 116 (87·2%) of 133 treatment days; IEPT was efficacious on 135 (88·8%) of 152 treatment days (mean difference -1·6%, 95% CI -9·9 to 6·7; p=0·8165). Because the CI did not extend below -10%, we concluded that FSPT was not inferior to IEPT. Treatment was safe for all neonates. INTERPRETATION: FSPT is safe and no less efficacious than IEPT for treatment of moderate-to-severe neonatal hyperbilirubinaemia in near-term and term infants. FUNDING: Thrasher Research Fund and National Center for Advancing Translational Sciences.

Variation in the Phototherapy Practices and Irradiance of Devices in a Major Metropolitan Area.

BACKGROUND: Phototherapy (PT) is widely used to prevent and treat severe hyperbilirubinemia and its associated risks for both acute and chronic bilirubin encephalopathy. Intensive PT, recommended for inpatient treatment of hyperbilirubinemia in term and near-term infants, is defined as having a spectral irradiance of ≥30 µW/cm2/nm. OBJECTIVES: We aimed to assess local PT practices by measuring the irradiance of PT devices in local neonatal intensive care units and newborn nurseries. METHODS: The irradiance footprint, including maximum irradiance at the center of the footprint, of 39 PT devices in 7 area hospitals was measured according to current practice in these facilities. RESULTS: The mean ± SD (range) footprint irradiance was 20.7 ± 5.8 (8.8-29.4) µW/cm2/nm. The mean ± SD maximum irradiance at the footprint center for all devices at a mean clinically used treatment distance of 33.1 ± 9.3 (25.5-60.0) cm was 27.8 ± 7.0 (14.7-42.0) µW/cm2/nm. Sixty-two percent of the devices did not meet the minimum recommended spectral irradiance for intensive PT. For the sites without irradiance-based protocols, the maximum irradiance of the devices (n = 33) at the treatment distances was 25.8 ± 6.1 µW/cm2/nm. CONCLUSIONS: Despite established PT guidelines, local protocols and practices vary. Based on an assessment of 7 local hospitals, intensive PT was suboptimal for 62% of devices. Straightforward changes, such as decreasing the distance between an infant and the light source and establishing a consistent irradiance-based protocol, could substantially improve the quality of the intervention.

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 × 10(15) and 5.1 × 10(15) photons/cm(2)/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.

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 × 10(15) and 5.1 × 10(15) photons/cm(2)/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.

The effect of hematocrit on in vitro bilirubin photoalteration.

BACKGROUND: Phototherapy using light in the spectral range of 410-500 nm, which overlaps the absorption of bilirubin, is the common treatment for neonatal hyperbilirubinemia. Hemoglobin (Hb) absorbs light strongly throughout this same range and thus can compete with bilirubin for this light and consequently reduce the efficacy of phototherapy. Here, we determined the effect of hematocrit (Hct) on in vitro bilirubin photoalteration using narrow-band blue (450 nm) light-emitting diodes (LEDs). METHODS: Suspensions with Hcts from 0 to 80% and 16 ± 1 mg/dl bilirubin were prepared by mixing red blood cells (RBCs), bilirubin (30 mg/dl) in 4% human serum albumin, and normal saline. Aliquots of each suspension were exposed to blue light at equal irradiances. Before and after 60 min of exposure, bilirubin levels in supernatants (n = 46) were measured using a diazo-dye method. RESULTS: Bilirubin photoalteration steeply decreased by ~60% as Hct increased from 0 to 10%. Over the clinically relevant range of 30-70% Hct, the decrease was significant, but less drastic, exhibiting a quasi-linear dependence on Hct. CONCLUSION: Bilirubin photoalteration under blue light in vitro is significantly reduced as Hct increases. Clinical studies are warranted to confirm these in vitro observations that Hct can affect the efficacy of phototherapy.

A Randomized Trial of Phototherapy with Filtered Sunlight in African Neonates.

BACKGROUND: Sequelae of severe neonatal hyperbilirubinemia constitute a substantial disease burden in areas where effective conventional phototherapy is unavailable. We previously found that the use of filtered sunlight for the purpose of phototherapy is a safe and efficacious method for reducing total bilirubin. However, its relative safety and efficacy as compared with conventional phototherapy are unknown. METHODS: We conducted a randomized, controlled noninferiority trial in which filtered sunlight was compared with conventional phototherapy for the treatment of hyperbilirubinemia in term and late-preterm neonates in a large, urban Nigerian maternity hospital. The primary end point was efficacy, which was defined as a rate of increase in total serum bilirubin of less than 0.2 mg per deciliter per hour for infants up to 72 hours of age or a decrease in total serum bilirubin for infants older than 72 hours of age who received at least 5 hours of phototherapy; we prespecified a noninferiority margin of 10% for the difference in efficacy rates between groups. The need for an exchange transfusion was a secondary end point. We also assessed safety, which was defined as the absence of the need to withdraw therapy because of hyperthermia, hypothermia, dehydration, or sunburn. RESULTS: We enrolled 447 infants and randomly assigned 224 to filtered sunlight and 223 to conventional phototherapy. Filtered sunlight was efficacious on 93% of treatment days that could be evaluated, as compared with 90% for conventional phototherapy, and had a higher mean level of irradiance (40 vs. 17 µW per square centimeter per nanometer, P<0.001). Temperatures higher than 38.0°C occurred in 5% of the infants receiving filtered sunlight and in 1% of those receiving conventional phototherapy (P<0.001), but no infant met the criteria for withdrawal from the study for reasons of safety or required an exchange transfusion. CONCLUSIONS: Filtered sunlight was noninferior to conventional phototherapy for the treatment of neonatal hyperbilirubinemia and did not result in any study withdrawals for reasons of safety. (Funded by the Thrasher Research Fund, Salt Lake City, and the National Center for Advancing Translational Sciences of the National Institutes of Health; Clinical Trials.gov number, NCT01434810.).

Safety and efficacy of filtered sunlight in treatment of jaundice in African neonates.

OBJECTIVES: Evaluate safety and efficacy of filtered-sunlight phototherapy (FS-PT). METHODS: Term/late preterm infants #14 days old with clinically significant jaundice, assessed by total bilirubin (TB) levels, were recruited from a maternity hospital in Lagos, Nigeria. Sunlight was filtered with commercial window-tinting films that remove most UV and significant levels of infrared light and transmit effective levels of therapeutic blue light. After placing infants under an FS-PT canopy, hourly measurements of axillary temperatures, monitoring for sunburn, dehydration, and irradiances of filtered sunlight were performed. Treatment was deemed safe and efficacious if infants were able to stay in FS-PT for $5 hours and rate of rise of TB was ,0.2 mg/dL/h for infants #72 hours of age or TB decreased for infants .72 hours of age. RESULTS: A total of 227 infants received 258 days of FS-PT. No infant developed sunburn or dehydration. On 85 (33%) of 258 treatment days, infants were removed briefly from FS-PT due to minor temperature-related adverse events. No infant met study exit criteria. FS-PT was efficacious in 92% (181/197) of evaluable treatment days. Mean 6 SD TB change was ­0.06 6 0.19 mg/dL/h. The mean 6 SD (range) irradiance of FS-PT was 38 6 22 (2­115) mW/cm2/nm, measured by the BiliBlanket Meter II. CONCLUSIONS: With appropriate monitoring, filtered sunlight is a novel, practical, and inexpensive method of PT that potentially offers safe and efficacious treatment strategy for management of neonatal jaundice in tropical countries where conventional PT treatment is not available.

Treatment of neonatal jaundice with filtered sunlight in Nigerian neonates: study protocol of a non-inferiority, randomized controlled trial.

BACKGROUND: Severe neonatal jaundice and its progression to kernicterus is a leading cause of death and disability among newborns in poorly-resourced countries, particularly in sub-Saharan Africa. The standard treatment for jaundice using conventional phototherapy (CPT) with electric artificial blue light sources is often hampered by the lack of (functional) CPT devices due either to financial constraints or erratic electrical power. In an attempt to make phototherapy (PT) more readily available for the treatment of pathologic jaundice in underserved tropical regions, we set out to test the hypothesis that filtered sunlight phototherapy (FS-PT), in which potentially harmful ultraviolet and infrared rays are appropriately screened, will be as efficacious as CPT. METHODS/DESIGN: This prospective, non-blinded randomized controlled non-inferiority trial seeks to enroll infants with elevated total serum/plasma bilirubin (TSB, defined as 3 mg/dl below the level recommended by the American Academy of Pediatrics for high-risk infants requiring PT) who will be randomly and equally assigned to receive FS-PT or CPT for a total of 616 days at an inner-city maternity hospital in Lagos, Nigeria. Two FS-PT canopies with pre-tested films will be used. One canopy with a film that transmits roughly 33% blue light (wavelength range: 400 to 520 nm) will be used during sunny periods of a day. Another canopy with a film that transmits about 79% blue light will be used during overcast periods of the day. The infants will be moved from one canopy to the other as needed during the day with the goal of keeping the blue light irradiance level above 8 µW/cm²/nm. PRIMARY OUTCOME: FS-PT will be as efficacious as CPT in reducing the rate of rise in bilirubin levels. Secondary outcome: The number of infants requiring exchange transfusion under FS-PT will not be more than those under CPT. CONCLUSION: This novel study offers the prospect of an effective treatment for infants at risk of severe neonatal jaundice and avoidable exchange transfusion in poorly-resourced settings without access to (reliable) CPT in the tropics. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01434810.

Evaluation of window-tinting films for sunlight phototherapy.

We evaluated nine semi-transparent plastic window-tinting films for their ability to block ultraviolet A (UVA) and infrared (IR) radiation and transmit therapeutic blue light (400-520 nm) for treating jaundiced newborns. For indoor testing, three light sources (TL/52 special blue fluorescent, Black Light UVA and IR heat lamps) were positioned above each film and measured successively using a thermocouple thermometer, UVA radiometer and blue light irradiance meter, placed below each film. For outdoor testing, the same setup was used with the sun at zenith and a cloudless sky. Compared with unfiltered radiation, blue light transmission through films ranged from 24 to 83%, UVA transmission was 0.1-7.1% and reductions in IR heat were 6-12°C and 5-10°C for heat lamp and sun, respectively. The data suggest that most of the relatively low-cost window-tinting films tested can effectively reduce sunlight UV and IR and offer a range of significant attenuations of therapeutic blue light.

Phototherapy device effectiveness in Nigeria: irradiance assessment and potential for improvement.

This study investigated the effectiveness of simple-to-implement adjustments of phototherapy devices on irradiance levels in a cross-section of Nigerian hospitals. A total of 76 phototherapy devices were evaluated in 16 hospitals while adjustments were implemented for a subset of 25 devices for which consent was obtained. The mean irradiance level was 7.6 ± 5.9 µW/cm(2)/nm for all devices prior to adjustments. The average irradiance level improved from 9.0 µW/cm(2)/nm to 27.3 µW/cm(2)/nm for the adjusted group (n = 25) compared with 6.8 ± 5.4 µW/cm(2)/nm for the unadjusted group (n = 51). Simple, inexpensive adjustments to phototherapy devices with sub-optimal irradiance levels can significantly improve their effectiveness to acceptable international standards and should be widely promoted in resource-constrained settings.

High variability and low irradiance of phototherapy devices in Dutch NICUs.

OBJECTIVE: To evaluate phototherapy practices by measuring the irradiance levels of phototherapy (PT) devices. DESIGN: Prospective study. SETTING: Tertiary neonatal intensive care units. PATIENTS: None. INTERVENTIONS: Irradiance levels of PT devices used in the 10 Dutch Neonatal Intensive Care Units (NICUs) were measured according to the local PT practice patterns. The irradiance levels of all overhead and fibre-optic PT devices were measured with a radiometer using an infant silhouette model. RESULTS: Eight different PT devices were used in the 10 NICUs; five were overhead devices and three fibre-optic pads. The median (range) irradiance level for overhead PT devices was 9.7 (4.3-32.6) µW/cm(2)/nm and for fibre-optic pads 6.8 (0.8-15.6) µW/cm(2)/nm. Approximately 50% of PT devices failed to meet the minimal recommended irradiance level of 10 µW/cm(2)/nm. Maximal irradiance levels for overhead PT spot lights were inversely related to the distance between device and infant model (R2=0.33). The distances ranged from 37 cm to 65 cm. CONCLUSIONS: PT devices in the Dutch NICUs show considerable variability with often too low irradiance levels. These results indicate that suboptimal PT is frequently applied and may even be ineffective towards reducing total serum bilirubin levels. These results underline the need for greater awareness among all healthcare workers towards the requirements for effective PT including measurements of irradiance and distance.

Effect of light exposure on metalloporphyrin-treated newborn mice.

BACKGROUND: Neonatal hyperbilirubinemia arises from increased bilirubin production and decreased bilirubin elimination. Although phototherapy safely and effectively reduces bilirubin levels, recent evidence shows that it has adverse effects. Therefore, alternative treatments are warranted. Metalloporphyrins, competitive inhibitors of heme oxygenase (HO), the rate-limiting enzyme in bilirubin production, effectively reduce bilirubin formation; however, many are photoreactive. Here, we investigated possible photosensitizing effects of chromium mesoporphyrin (CrMP) and zinc deuteroporphyrin bis-glycol (ZnBG). METHODS AND RESULTS: Administration of CrMP or ZnBG to 3-d-old mouse pups (3.75-30.0 µmol/kg intraperitoneally) and exposure to cool white (F20T12CW) and blue (TL20W/52) fluorescent lights (+L) for 3 h, resulted in a dose-dependent mortality (50% lethal dose (LD50) = 21.5 and 19.5 µmol/kg, respectively). In contrast to ZnBG, there was no significant difference in survival between the CrMP+L and CrMP groups. Following 30 µmol/kg ZnBG+L, we found significant weight loss, decreased liver antioxidant capacities, and increased aspartate aminotransaminase levels. At 6-d post-light exposure, ZnBG+L-treated pups showed gross and histologic skin changes at doses >7.5 µmol/kg. No lethality was observed following treatment with 30 µmol ZnBG/kg plus exposure to blue light-emitting diodes. Phototoxicity of ZnBG was dependent on light source, emission spectrum, and irradiance. CONCLUSION: Low doses of ZnBG (<3.75 µmol/kg) retained maximal HO inhibitory potency without photosensitizing effects, and therefore are potentially useful in treating neonatal hyperbilirubinemia.