Illuminating Connections: Exploring the Dynamic Relationship Between Phototherapy and the Skin.

The neonatal period represents a critical window for skin barrier maturation, microbial colonization, and immune development. As such, early-life exposures may exert lasting effects on dermatologic and systemic health. A common early-life exposure is blue light phototherapy (BLP), a life-saving treatment for neonatal hyperbilirubinemia. Although BLP is traditionally regarded as a localized, superficial intervention, emerging evidence suggests that it is a biologically active exposure that directly interacts with developing skin, thereby influencing barrier integrity, the developing microbiome, and immune signaling. As an active immune organ, neonatal skin has been proposed to engage in dynamic crosstalk with the nervous, gut, and endocrine systems. Therefore, BLP may act systemically by modulating these interconnections. These effects raise concerns about the potential long-term impact of BLP during this critical developmental period. The development of immune-mediated conditions, such as atopic dermatitis (AD), is of particular interest as they are hypothesized to engage in these cross-system networks. This review examines the multifactorial relationship between BLP and neonatal skin development, highlighting BLP as an active exposure that may interact with developing skin, microbiome, and immune system, while emphasizing the need for longitudinal studies to clarify long-term clinical implications.