Long-term Hazards of Neonatal Blue-Light Phototherapy

J. Oláh; E. Tóth-Molnár; L. Kemény; Z. Csoma

Disclosures

The British Journal of Dermatology. 2013;169(2):243-249. 

In This Article

Abstract and Introduction

Abstract

Blue-light phototherapy has been an essential therapeutic tool in the management of neonatal jaundice for decades. Rarely, it is accompanied by acute dermatological and systemic side-effects, but fortunately these are reversible and can be adequately and promptly treated in routine neonatal practice. In contrast, much less is known about the potential long-term side-effects of neonatal blue-light phototherapy (NBLP). Many of the data that are currently available on how NBLP influences melanocytic naevus (MN) development are controversial. The results of recent well-designed epidemiological surveys suggest that NBLP could well be a risk factor for MN formation, and highlight the need for additional in vivo and in vitro studies. NBLP is at present the mainstay of treatment for neonatal jaundice, but in the future greater consideration should be given to its long-term side-effects when phototherapy is indicated. It is relevant to emphasize the importance of appropriately restricted and adequate clinical guidelines, and strict monitoring of the management of hyperbilirubinaemia, in order to avoid the unnecessary overtreatment of newborn infants.

Introduction

Neonatal blue-light phototherapy (NBLP) has been an essential therapeutic tool in the management of neonatal jaundice for decades (Fig. 1). Millions of full-term and preterm infants have received this very effective, simple and safe therapy to reduce the concentration of serum bilirubin. NBLP may be accompanied by acute dermatological and systemic side-effects, but fortunately these are reversible, and can be adequately and promptly treated in routine neonatal practice. Thanks to the restricted treatment protocols, the prevalence of short-term adverse events is currently very low. These minor and transient complications include skin burns, erythematous skin rash, purpuric and bullous eruptions, retinal damage, thermoregulatory instability, irritability, loose stools, dehydration, feeding difficulties and the 'bronze-baby' syndrome.[1–3] Chen et al.[4] have reported significant alterations in circadian gene expression and melatonin secretion among neonates receiving NBLP, resulting in changes in circadian rhythm and behaviour.

Figure 1.

Neonatal blue-light phototherapy.

In contrast, much less is known about the potential long-term side-effects of NBLP. It should be recalled that the wavelengths of blue light (BL) and ultraviolet (UV) radiation are adjacent, and their biological effects might therefore partially overlap. Moreover, the traditional and widely used BL lamps emit a minor UVA radiation component in addition to the therapeutic blue wavelengths (Fig. 2).[5] The erythema and tanning of the newborn skin observed after phototherapy might be due to this small amount of UV irradiation.[6] UV irradiation has profound immunosuppressive and immunomodulatory effects; it induces melanocyte proliferation and plays an important role in naevogenesis. Visible light has similar physiological effects to those of UV radiation, as it induces the production of reactive oxygen species and increases the release of proinflammatory cytokines.[7] Visible light can penetrate deeper into the skin than can UV irradiation, and may possibly give rise to significant biological effects on the epidermal and dermal cells. Similarly to UV radiation, BL may exert cytotoxic effects, inducing significant oxidative stress, DNA damage and sister chromatid exchange, and may also influence the immune system.[8–11] Aspberg et al.[10] reported a possible association between neonatal phototherapy and asthma in hospitalized children, as a long-term consequence of the influence of phototherapy on the immature immune system.

Figure 2.

Emission spectrum of the commonly used, traditional blue-light lamp with Plexiglas cover between the fluorescent bulbs and the infant. According to measurements, the emission spectrum of the blue-light lamps used in Hungary is between 370 nm and 600 nm, with a maximum at 450 nm. Approximately 0·3% of the output comprises ultraviolet (UV) A radiation. Our measurements were made with a QE6500 spectrophotometer (Ocean Optics, Dunedin, FL, U.S.A.) at the exact position of the infants, and suggest that a minor component of UVA radiation can transmit through the Plexiglas cover.

Immediate adverse effects of NBLP on the neonatal eye are well known in clinical practice: accidental exposure can cause periocular skin erythema, bacterial infection and photokeratitis. This latter damage of the corneal epithelium is a consequence of direct exposure of the anterior surface of the eye. Retinal photodamage was investigated in primates in one study by Messner et al.[12] Newborn monkeys were continuously exposed to high-intensity fluorescent light. The animals could open and close their eyelids as desired during the exposure. The newborn primate retina was damaged in a progressive manner. Morphological retinal damage could be proven as early as after 12 h of exposure (the shortest interval examined). With increasing periods of exposure, the retinal damage became more extensive.[12]

The long-term effects have been only poorly investigated. In a group of 4-year-old children who participated in NBLP, Dobson et al.[13] did not observe any ophthalmological changes, including a lack of electroretinographic alterations. The possibility of an association between ocular and cutaneous melanocytes follows from the fact that uveal melanocytes and melanocytes of the conjunctiva and the skin all originate in the neural crest and migrate to their respective sites during embryological development. These morphologically similar dendritic melanocytes, which reside in the skin, conjunctiva, iris, ciliary body and choroid, may give rise to naevi or melanomas at these respective sites.[14,15] As far as we are aware, our 2011 article provided the first literature survey of ocular pigmented alterations in patients treated with NBLP during the early neonatal period.[16]

As some attempts have been made in the past few years to investigate the possible long-term impacts of NBLP concerning the development of melanocytic naevus (MN), in this review article we set out to assess the available dermatological and ophthalmological evidence.

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