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

Neonatal Blue-Light Phototherapy and Cutaneous Melanocytic Naevus

In the first study in the literature, Bauer et al.[17] conducted a cross-sectional study on 1812 white children aged 2–7 years. A notably high number (n = 333) of the children had received NBLP. It was concluded from both bivariate and multivariate analyses that NBLP was not associated with an increased risk of the development of MN; the untreated and the treated children exhibited the same median number of MNs.[17]

In a prospective case–control study, Matichard et al.[18] found that intensive NBLP was a strong risk factor for the development of naevi in childhood. They compared the naevus count in two groups of 8–9-year-old children, one group consisting of 18 subjects treated with intensive NBLP in the first few days of life, and the control group consisting of 40 untreated children. The number of naevi measuring ≥ 2 mm was significantly higher in the exposed group. When the analysis was limited to naevi measuring 2–5 mm, the difference proved to be even more significant. Conversely, the association between NBLP and the total naevus count was not significant for naevi < 2 mm or > 5 mm in size. However, the relatively small groups limited the power of the results.[18]

In the multicentre study by Mahé et al.[19] on a homogeneous population of 9-year-old children, NBLP was not associated with an increase in the number of naevi, irrespective of their location or size. In total, 180 of the 828 children studied had received phototherapy. Naevi measuring < 2 mm, 2–5 mm and > 5 mm were counted separately, and the evaluation was blinded for the history of NBLP.

Our own initial study revealed a significantly higher prevalence of clinically atypical MNs (CAMNs) among schoolchildren aged 14–18 years who had received NBLP. In total, 747 schoolchildren were investigated to determine the prevalence of common MN (CMN) and CAMN. Data were recorded with regard to the neonatal history, such as prematurity, neonatal jaundice and NBLP; 44·6% of the children had received NBLP. The prevalence of dysplastic naevi was 19·1% in the untreated group and 25·2% in the treated group. NBLP resulted in a relative risk of 1·32 for the development of CAMN. The prevalence of CMN was quite similar in the treated and the untreated children, but the exposed subjects were somewhat more likely to exhibit multiple moles.[20]

It is worthy of mention that NBLP has been utilized for the treatment of neonatal jaundice in Hungary since 1968. We therefore considered the question of whether there was a difference in the prevalence of CAMN between those born before or after the introduction of NBLP. In 2006, in the course of an employment screening programme, 618 healthy, unselected subjects underwent whole-body skin examinations. We found that the prevalence of CAMN was significantly higher among those born in or after 1968 than among those born before 1968. The prevalence of CAMN in the two groups was 36·3% and 21·2%, respectively.[21]

Nevertheless, it is important to bear in mind the possibility that the increasing prevalence of MN among white populations in recent decades might be explained in part by the increased UV exposure due to climatic changes, the depletion of the protective ozone layer and the changes in sunbathing habits and sun-protection methods.

The striking results mentioned above led us to investigate the impact of NBLP on MN development in a more homogeneous population, where the role of environmental factors appears to be more similar. We examined monozygotic and dizygotic twins, where one of the twins had received phototherapy for neonatal jaundice, whereas the other had not. Fifty-eight pairs of twins (15 monozygotic and 43 dizygotic) and one set of triplets, of white origin, aged 3–30 years, were included in the study.[16] Univariate analysis revealed that NBLP was associated with a significantly higher prevalence of both CMN and CAMN in the examined twin pairs (Fig. 3). When the analysis was focused separately on the monozygotic and dizygotic twin pairs, a statistically significant difference in the number of naevi was still observed between the exposed and nonexposed subjects in the case of the monozygotic twins. For the dizygotic twin pairs, the number of CMNs and the overall number of MNs differed in a statistically significant manner between the treated and untreated twin members. Multivariate linear regression analysis demonstrated that the number of MNs was also significantly and independently associated with a history of NBLP. A standardized questionnaire was used to assess the data relating to constitutional or sun exposure and other variables. These factors proved to be very consistent in the examined monozygotic twin pairs. The phenotypic characteristics of the dizygotic twins did differ to some extent, but the environmental impacts were very similar until adulthood.[16]

Figure 3.

Difference in the number of melanocytic naevi in a monozygotic twin pair. The twin on the right-hand side, who received blue-light phototherapy, demonstrates a significantly higher naevus count than that of the sibling on the left-hand side, who did not receive neonatal phototherapy.

Various epidemiological data indicate that the presence of large numbers of CMNs and CAMNs is the most important independent phenotypic risk factor for the development of malignant melanoma in fair-skinned populations, and our results therefore raise the question of whether NBLP could also be a risk factor for melanoma. A preliminary case–control study suggested that there was no significant risk of the development of childhood malignant melanoma after NBLP.[22] Melanoma was not observed either in the NBLP-exposed subjects or in the control groups in our surveys, but the follow-up period was relatively short.