Mechanism-based Safety Stratification of Esthetic Dermatologic Interventions during Pregnancy: A Systematic Review of Energy-based Devices, Injectables, and Regenerative Therapies

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Women of reproductive age are requesting esthetic dermatologic procedures more frequently, but their safety during pregnancy is still uncertain and somewhat inconsistently interpreted. Due to ethical concerns of direct experimentation in pregnant populations, clinical practice is largely guided by precaution and indirect evidence. This review aimed at summarizing the literature to date and, more importantly, at reorganizing it from a mechanism-based perspective instead of continuing using the traditional “safe” versus “unsafe” dichotomy. Using PRISMA-guided selection, 1360 records were systematically retrieved from the major databases, resulting in 39 studies meeting predetermined inclusion criteria. Topical agents, energy-based devices, injectables, as well as new regenerative therapies were included in these studies. In the literature reviewed, a clear trend emerged: decreasing risk was not so much determined by the name of the intervention but rather by mechanisms of tissue interaction, systemic absorption potential, and biological signaling modalities. Superficial interventions with little systemic exposure – such as photoprotection and selective topical agents – also exhibit consistently positive safety profiles. In contrast, deeper tissue penetration and/or biologically active compounds such as botulinum toxin, dermal fillers, and more recent regenerative approaches (e.g., platelet-rich plasma or exosomes) fall into a grey area of limited and frequent circumstantial evidence. Although a lack of reported adverse fetal outcomes across various domains may suggest safety, this is primarily due to methodological and ethical limitations. Collectively, these findings justify a cautious, mechanism-informed approach to clinical decision-making. This proposed stratification framework, which may help clinicians manage complex situations and thus identify future research priorities in the form of well-designed observational studies and registries, is also designed to draw attention to contexts where such approaches are urgently required.