Summary:
This study is a narrative review of observational and experimental evidence that looked at prenatal zinc deficiency as a potential non-genetic contributor to autism spectrum disorder (ASD). ASD is a complex condition influenced by both genetic and environmental factors, particularly during pregnancy. Factors such as maternal infections, toxin exposure, medication use, and nutritional deficiencies may disrupt brain development. This study proposes that disturbances in metal regulation, especially impaired zinc signalling, may represent a mechanism underlying ASD. Zinc is an essential micronutrient involved in DNA synthesis, cell division, and cellular signalling, and is critical for normal neurodevelopment. However, zinc deficiency is common globally, including among pregnant women, due to increased physiological requirements and dietary factors that affect absorption. This study synthesises evidence showing that lower zinc levels are frequently observed in individuals with ASD. Observational studies and meta-analyses report that children with ASD often have reduced zinc concentrations, with some evidence linking lower levels to greater symptom severity. Experimental evidence further supports this association. Animal models demonstrate that prenatal zinc deficiency can disrupt brain development, leading to altered neural structure, impaired synaptic function, and behavioural changes consistent with ASD. Additional mechanisms may include immune dysfunction, oxidative stress, and alterations in the gut-brain axis. Overall, this study suggests that prenatal zinc deficiency may play a key role in ASD by disrupting systems related to brain development. While current human evidence remains associative, these findings highlight zinc as a potential modifiable factor and support further research into its role in prevention and intervention.
Abstract:
Autism spectrum disorder (ASD) is a complex condition influenced by genetic and environmental factors, particularly prenatal ones such as maternal infections, medications, toxins, and nutritional deficiencies. These factors interfere with brain development, leading to the core traits of ASD. Despite extensive research using animal and cell models, few fully replicate the complexity of ASD, highlighting the need to reassess our understanding of its biological processes. Prenatal zinc deficiency has emerged as a significant risk factor, inducing various ASD-related pathologies in studies and potentially uncovering fundamental disrupted biological processes. We propose that a core issue in ASD is metal homeostasis, especially abnormal zinc signaling. This review consolidates current evidence linking zinc to ASD and examines its critical roles in biological functions often affected in individuals with ASD. The findings suggest that prenatal zinc deficiency could reveal the fundamental biological processes disrupted in ASD, which other risk factors might mimic to a lesser extent. Consequently, this narrative review, based on a thorough synthesis of secondary data, provides a critical overview of the growing evidence connecting zinc to ASD while exploring its vital roles in biological functions frequently impaired in affected individuals.
Article Publication Date: 31/01/2026
DOI: 10.1016/j.clnu.2026.106592 External Link
