Early-life stress at the time of the plague in Northern Italy (17th century): The case of two individuals with severe hypoplastic defects from Lazzaretto Vecchio (Venice)

Objectives: This study investigates two cases of severe enamel hypoplasia observed in individuals buried at Lazzaretto Vecchio (Venice, Italy) likely during the 1575–1630 plague outbreak. By integrating histological and geochemical evidence, we assess whether severe hypoplastic defects correspond to alterations in enamel formation dynamics or elemental composition and explore what such patterns may reveal about physiological disruption during crown development. Design: A multi-method approach was applied, including morphological analysis for biological profile reconstruction, enamel histomorphometry and geochemical characterization using Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) and Scanning Electron Microscopy Energy Dispersive X-ray Spectroscopy (SEM-EDS). Results: Daily secretion rates did not differ substantially between stress-associated and physiologically regular enamel incremental markers, indicating that ameloblast activity was not disrupted in terms of secretion rate or overall crown formation time. Spatially-resolved geochemical analyses revealed a magnesium imbalance between pre- and post-hypoplastic enamel regions. This divergence suggests an altered magnesium (Mg) distribution across pre- and post-hypoplastic regions potentially linked to a reduced number of functional ameloblasts available for ion exchange during enamel mineralization. Conclusions: These findings underscore the value of integrating multiple analytical techniques to refine interpretations of developmental stress and to capture physiological variations that remain obscured in single-method approaches.