Long-term Hazards of Neonatal Blue-Light Phototherapy

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


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

In This Article


As with many of the findings of pivotal importance in medical science, the recognition of the beneficial effect of natural light on neonatal jaundice was serendipitous.[53] Phototherapy is now widely and successfully applied to the treatment of neonatal jaundice in order to reduce the plasma bilirubin concentration and hence to prevent the need for exchange transfusion. Bilirubin absorbs light most strongly in the blue region of the spectrum (425–475 nm). The absorption of light by dermal and subcutaneous bilirubin induces various photochemical reactions, and the toxic, native, unconjugated bilirubin is converted to less toxic, water-soluble photoisomers, which are excreted in the bile and urine without requiring conjugation. Commonly used phototherapy units include daylight, cool-white, green, blue or 'special blue' fluorescent tubes. Other units involve tungsten–halogen lamps, high-intensity gallium nitride light-emitting diodes or fibre-optic systems.[54] When the total serum bilirubin level approaches the range in which intensive phototherapy is recommended, it is particularly important to use lamps with the clinically most effective blue emission spectrum. The American Academy of Pediatrics currently recommends the application of special blue fluorescent lamps or light-emitting diode lights.[55]

A large number of term and preterm infants are treated with phototherapy worldwide. The considerable variations between international and national guidelines often result in the overuse of phototherapy.[56] It is relevant to clarify the potential prompt and long-term hazards of this widely accepted and used therapeutic modality as there is a growing body of evidence that phototherapy can potentially exert various effects on neonates, because of the unique physiological and pharmacological characteristics of this population.

In this review article we have attempted, as far as possible, to survey the results of previous clinical studies relating to the effects of NBLP on naevus development. In four of the six studies, an association was found between NBLP and naevus development,[16,18,20,21] whereas the other two studies did not confirm this.[17,19] It is rather difficult to compare the outcomes of these six surveys for several reasons. The sizes of the study populations differed significantly from each other: some studies involved large populations,[17–19] and others much smaller populations with less statistical power.[18] Similarly, the age of the population is another important factor in an interpretation of the results. One of the major limitations of some of the investigations was the relatively young age of their study populations.[17–19] As adolescence and young adulthood are critical periods as concerns the development of MN, it appears essential to focus separately on these age groups, too.

It appears doubtful to make use of recollected anamnestic data regarding the neonatal history of the subjects. It is unacceptable simply to rely on data obtained from interviews with the parents without utilization of the official neonatal medical charts. The treatments had often occurred years or even decades before the clinical surveys, and after such a long time it is not always easy to reconstruct exactly the phototherapeutic modalities applied, e.g. the dose and intensity of NBLP, which can significantly influence the potential long-term side-effects.

Most studies to date have investigated the effects of NBLP on full-term infants. Certain clinical observations point to the possibility of different effects of NBLP on full-term and preterm infants; the potential minor complications of phototherapy, such as dehydration, temperature instability and electrolyte imbalance are generally fairly benign in mature neonates, but they can be much more serious in low-birthweight infants.[57,58] In their multicentre, randomized trial, Morris et al.[59] found an increase in mortality rate in extremely low-birthweight infants (< 750 g) who received aggressive phototherapy. Phototherapy may significantly affect the haemodynamics of various organs, increase the cerebral and peripheral blood flow, enhance transepidermal water loss, decrease the cardiac output and the renal and mesenteric blood flows, and cause reopening of the ductus arteriosus in preterm infants by modifying the blood endothelin and nitric oxide levels.[57,60] NBLP can induce a higher frequency of sister chromatid exchanges in the peripheral lymphocytes of preterm icteric neonates,[61,62] and also lead to oxidative stress.[8] The antioxidant defence capacity of low-birthweight, immature infants is considerably lower than that of term neonates. In preterm infants, the thickness of the stratum corneum is significantly reduced, and the production of melanin in the immature melanocytes is deficient, resulting in a limited photoprotective capacity. In view of the special characteristics of their skin, preterm infants may be particularly sensitive to intensive phototherapy, and it appears advisable to investigate the MN count of this special study population, too.

In conclusion, many of the data that are currently available on how NBLP influences naevus 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 the treatment of neonatal jaundice, and has proved to be an essential and generally safe modality for the prevention of bilirubin encephalopathy, 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.