Evaluation of the effects of phototherapy on cochlear function in newborns.

OBJECTIVE: This study aimed to evaluate any potential effects of phototherapy on cochlear function in newborns using transient evoked otoacoustic emissions (TEOAEs). METHODS AND MATERIALS: Fifty-seven newborns, undergoing phototherapy for hyperbilirubinemia without any other risk factors, and a control group of 53 healthy newborns, were administered the TEOAE test prior to and following phototherapy. In the newborns undergoing phototherapy, otoacoustic emission (OAE) measurements obtained at baseline and following phototherapy were compared. Moreover, pre-phototherapy OAE measurements obtained in the newborns undergoing phototherapy were compared with the OAE measurements of the control group. RESULTS: In newborns undergoing phototherapy, there was no significant difference between pre- and post-phototherapy TEOAE amplitudes, nor in the reproducibility ratios. Similarly, no difference was found in the pre-treatment measurements of amplitude and reproducibility ratios between phototherapy-receiving newborns and controls (p>0.05). CONCLUSION: The normal TEOAE results observed in the newborns undergoing phototherapy suggest that phototherapy does not exert negative effects on the cochlea.

Urinary tract infections in neonates with jaundice in their first two weeks of life.

BACKGROUND: Hyperbilirubinemia is a frequently seen condition in neonates. This study was undertaken to determine the role of urinary tract infections (UTIs) in the etiology of indirect hyperbilirubinemia in neonates with jaundice in their first two weeks of life. METHODS: The study was conducted prospectively. The subjects were neonates aged 4-14 days with hyperbilirubinemia which could not be detected by routine tests and was sufficiently severe to necessitate phototherapy. RESULTS: The study was performed in 104 neonates, of whom 18% (n=19) had UTI. The most frequently identified micro-organism was Escherichia coli (43%). Phototherapy duration and rebound bilirubin level were higher in neonates with UTI (P<0.05). CONCLUSION: UTI should be investigated in neonates with hyperbilirubinemia of unknown etiology in the first two weeks of life.

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.

The influence of phototherapy on serum cytokine concentrations in newborn infants.

We sought to determine cytokine response in term and late preterm newborn infants on phototherapy. Twenty newborn infants with gestational age > or = 35 weeks and birth weight > or = 2000 g in the first week of life had serum interleukin (IL)-6, IL-8, IL-10, IL-1beta, and tumor necrosis factor (TNF)-alpha measured immediately prior to and after 24 hours on phototherapy. Exclusion criteria were newborns with severe congenital malformations, congenital infections, birth asphyxia, sepsis, hemolytic anemia that required blood transfusion, maternal-infant Rh incompatibility and those who required exchange transfusion or intravenous immunoglobulin treatment for hyperbilirubinemia. Median IL-6 concentrations significantly decreased after 24 hours on phototherapy (18.3 pg/mL and 7.85 pg/mL, respectively, p = 0.005). IL-6 concentrations decreased in 17 out of the 20 newborns. There were no statistical differences in IL-8, IL-10, IL-1beta, and TNF-alpha concentrations before and after 24 hours on phototherapy. There was a statistically significant correlation between IL-6 decline and irradiance (r = 0.57, p = 0.009). The finding that serum IL-6 decreases in newborn under phototherapy suggests that phototherapy possibly has an anti-inflammatory effect, although the clinical implications of this study deserve further studies.

Vigintiphobia revisited.

In this review the historical tenets and evidence-based clinical research in support of a bilirubin exchange threshold of >20 mg/dL for the healthy term neonate are revisited. In addition, a hypothesis is ventured that recent cases of kernicterus are related in part to changes in population factors coupled with genetic predispositions that have unmasked an unappreciated potential for marked neonatal hyperbilirubinemia.

Can sunlight replace phototherapy units in the treatment of neonatal jaundice? An in vitro study.

BACKGROUND/AIM: Light can be efficiently used for the treatment of neonatal jaundice. Sunlight, which covers a large portion of the light spectrum including the bilirubin-absorbing range, is abundant in the Middle East. Such advantages prompted the present study to investigate the efficiency of sunlight in isomerizing bilirubin. This may introduce a practical source of light for the treatment of hyperbilirubinic infants in areas where phototherapy units are not available. METHODS: The efficiency of sunlight was quantified by a comparison with a phototherapy unit. Aqueous bilirubin solutions were exposed to periodic sunlight over the entire year and the reduction of bilirubin concentration was monitored spectrophotometrically. Bilirubin solutions were also exposed to a phototherapy unit intensity comparable to that of sunlight (17 cm away from the source). RESULTS: The data indicated that at this comparable light intensity, the phototherapy unit was as effective as sunlight. However, for the treatment of neonatal jaundice, phototherapy units are usually operated at a distance of 50 cm (where the light intensity is six times less than that of sunlight). When this distance was tested, only 16% of bilirubin was isomerized in the first 5 min of exposure. In contrast, about 65% of bilirubin was isomerized when the phototherapy unit was placed at a distance of 17 cm and when the bilirubin solutions were exposed to sunlight for the same time period. The hourly and seasonal changes in sunlight intensity affected the reduction in bilirubin concentration significantly. CONCLUSION: Data revealed that sunlight is almost 6.5 times more effective than a phototherapy unit when operating at the ward geometry after taking isomerization efficiency and area of exposure into consideration. Moreover, sunlight is still more effective during the winter season, when its intensity is lower. Thus, sunlight may be considered an alternative phototherapy source for the treatment of neonatal jaundice, particularly in areas where conventional phototherapy units are unavailable.

Phototherapy units in Brazil: are they effective?

The irradiance delivered by a phototherapy unit is an important contributing factor to its efficacy. However, measurement of irradiance during phototherapy requires the use of a photometer which is rarely available in the nurseries of developing countries. We assessed the irradiance of phototherapy units both in the laboratory and in all public hospitals of the City of Rio de Janeiro and found that: a) there is no consensus among companies manufacturing phototherapy units as to the number of fluorescent lights to be used in an equipment since this number varied from 4 to 8, b) over 1/3 of the phototherapy units analysed had 1 or more burnt out lamps, c) the mean irradiance delivered by phototherapy units was 2.36 +/- 0.75 muw/cm2/nm (0.6 to 4.4 muw/cm2/nm) which is considerably lower than the dose currently recommended for clinical efficacy. These results may be relevant to other developing countries where phototherapy meters are seldomly available and irradiance is not routinely measured.

Ultraviolet light burn: a cutaneous complication of visible light phototherapy of neonatal jaundice.

Visible light phototherapy is an easily administered and effective treatment for neonatal indirect hyperbilirubinemia. Reported cutaneous side effects include transient rashes and the uncommon bronze baby syndrome. A more hazardous side effect is ultraviolet burn. Two premature infants developed phototherapy-induced erythema, one associated with a second-degree burn, after exposure to fluorescent daylight bulbs inadvertently used without Plexiglass shields, thus allowing prolonged ultraviolet A (UVA) exposure. Premature infants, especially during the first two weeks of life, may be significantly susceptible to UVA-induced erythema. Plexiglass shields should always be in place during visible light phototherapy, and nursery staff should be made aware of their purpose.

On the efficacy of various irradiation regimens in phototherapy of neonatal hyperbilirubinaemia.

The efficacy of various irradiation regimens in phototherapy of neonatal hyperbilirubinaemia was analysed. One hundred and one newborns were assigned to three groups at random. The best results were achieved when six special blue fluorescent lamps were used and the sides of the incubator were draped with white cloth to reflect the light diffusely. This simple measure increased the therapeutic effect by approx. 35%. Compared to standard phototherapy units equipped with fluorescent lights, a halide lamp was no more effective. The results of the clinical trial confirm the conclusions drawn from measurements, published previously. According to those findings, irradiating large areas of skin as homogeneously as possible should produce optimum results. Using a lamp with a large surface in combination with diffusely reflecting areas should best meet this requirement.

Rapid clearance of a structural isomer of bilirubin during phototherapy.

During phototherapy for neonatal jaundice, bilirubin is converted into a variety of photoproducts. Determination of the relative importance of these photoproducts to the elimination of bilirubin requires knowledge of their rates of excretion. We have measured the rate at which the structural isomer of bilirubin, lumirubin, disappeared from the serum of nine jaundiced premature infants after the cessation of phototherapy. In all patients studied, the decline in serum lumirubin could be approximated by a first-order rate equation with a half-life of 80 to 158 min. This rate of disappearance is much faster than that previously determined for the other major bilirubin photoproducts. In samples of bile aspirated from the duodenum of infants undergoing phototherapy, lumirubin was the principal bilirubin photoproduct found. These results indicate that formation and excretion of lumirubin is an important route for bilirubin elimination during phototherapy.

[Dermatitis solaris in newborn infants following phototherapy with a halogenide radiation unit]. / Dermatitis solaris bei Neugeborenen nach Phototherapie mit einem Halogenidstrahler.

Two cases of dermatitis solaris in newborns after phototherapy with a halide burner gave reason to measure the UV-B radiation emitted by the instrument used. Values between 0.8 microW/cm2 and 1.8 microW/cm2 were found. In small areas under the lamp housing the intensities of the UV-B radiation reached up to 10 microW/cm2. These high intensities are caused by the design of the lamp housing. Especially in connection with aluminium foil used to increase the efficacy of the therapy skin leasons as described may be produced.

The pattern of bilirubin response to phototherapy for neonatal hyperbilirubinaemia.

The pattern of bilirubin response to phototherapy was studied using lamps with an emission spectrum closely similar to the bilirubin absorption spectrum. A dose-response relationship was demonstrated, with increased intensity of phototherapy resulting in greater response; however, the rate of bilirubin decline progressively decreased with increasing radiance till a 'saturation' point was reached, beyond which no further response occurred with further increase in radiance, suggesting a curvilinear relationship of the nature of an asymptotic regression. At the 'saturation' point, a 24-h decline of about 50% was achieved. With extended periods of phototherapy, a gradually decreasing response to phototherapy with declining bilirubin levels was observed, both with maximal or moderate intensity phototherapy; an exponential regression was suggested. At about 5 mg/dl little further decline was observed with continued phototherapy. The rate of the 24-h decline evaluated at 6-h intervals was observed to be proportional to the bilirubin level at the start of the 24-h period.

[Cytogenetic studies of human lymphocytes following blue light irradiation in vitro]. / Zytogenetische Untersuchungen an menschlichen Lymphozyten nach Blaulichtbestrahlung in vitro.

Human lymphocyte cultures were exposed for 0, 2, 4, 6, 8, 10, 12, and 14 h to the rays of the bluelight lamp NC-4400-04 developed by VEB Narva (Berlin) for the phototherapy of icterus neonatorum. The experiments revealed (1) a significant difference in the chromosomal aberration rate between bluelight treated and non-treated cultures and (2) a dependence of the aberration rate on the length of exposure. After the same duration of exposure the individual test series showed a great variation of aberration frequency. Chromatid gaps and breaks, chromosome gaps and breaks, chromatid translocations, and dicentric chromosomes were found to be induced. The majority of aberrations comprised gaps and breaks on the chromatid level.

An evaluation of fluorescent light sources for use in phototherapy of neonatal jaundice.

An evaluation of fluorescent lamps for use in the phototherapy of neonatal jaundice was undertaken by making spectral irradiance measurements of each lamp. Conclusions are drawn on the usefulness of current methods of measuring exposure dose to radiation from the lamps. UV hazards from the lamps are evaluated.

Time-limited phototherapy of term newborns in ABO hemolytic disease and hyperbilirubinaemia.

"Limited" phototherapy was used to treat full term babies with and without ABO-isoimmunization. Serum indirect bilirubin levels calling for irradiation during the first five days of life are summarized in a diagram (Fig. 1). Seperate indications were given for babies with different etiologies of jaundice, maturity (gestational age and birthweight) and indicational levels were correlated with the postnatal age (days and hours) of the infant. After a fall or harmless stagnation of bilirubin levels irradiation was stopped. Clinical assessment of the treatment of 17 babies with ABO-isiommunization, and 16 newborns without it and with hyperbilirubinemia is given in detail. Results were compaired with the outcome of treatment of 44 newborns who received the same care in every respect, but phototherapy. These control cases, selected by pairs, were similar. Exchange transfusion, based on identical indications was necessary in 13 of the 44 babies treated without and only 3 of the 33 infants treated with phototherapy. The billirubin levels of the treated babies were lower during the whole course of the irradiation. The difference in favor of the treated babies was significant on the second and third days of life incases of ABO-hemolytic disease, and from the 4th day of life in cases of hyperbilirubinemia. The values of standard deviations, important in view of the indication for exchange transfusion were also lower in the light treated babies. Successful irradiation required on average of 44 hours (30-72 hours) in cases of ABO-isoimmunization and 40 hours (18-50) in cases of hyperbilirubinemia, respectively. Re-elavation of the bilirubin level after finishing phototherapy was not observed.

Effect of phototherapy on the urinary excretion of tryptophan metabolites in neonatal hyperbilirubinemia.

The 24 hours urinary excretion of tryptophan metabolites after an aminoacid loading (50 mg/Kg body-weight) was studied in a group of hyperbilirubinemic infants with or without light exposure treatment, in comparison to normal newborn babies. Kynurenine was the main metabolite in the urine of the control subjects. In the hyperbilirubinemic infants a high urinary excretion of kynurenine and 3-hydroxyanthranilic acid was observed. In the ones treated with phototherapy these two substances were markedly decreased. Besides 3-hydroxykynurenine was almost always absent. The effect of the light exposure was studied on kynurenine and 3-hydroxykynurenine "in vitro". Kynurenine did not present any photodecomposition. On the contrary, 3-hydroxykynurenine was easily decomposed. This fact can explain the decreased excretion of 3-hydroxykynurenine and 3-hydroxyanthranilic acid observed in urine of hyperbilirubinemic newborn infants treated with phototherapy. The decrease of kynurenine in these infants probably is a consequence of the photodecomposition of 3-hydroxykynurenine.