Association of Medication Use with the Development of Enamel Defects in Pregnancy and Childhood: A Critical Review of the Literature

Abstract

Aims: This review critically evaluated the scientific evidence regarding the association between medication exposure during pregnancy or early childhood and the development of Developmental Enamel Defects (DDEs) in children. Study Design: Critical literature review. Methodology: A systematic search was conducted across six databases and the gray literature, following PRISMA guidelines and registered in PROSPERO (CRD420251047079). Observational cohort studies published from 2001 onward were included. Study quality was assessed using the Newcastle-Ottawa Scale (NOS). The search was conducted on May 20, 2025, in the PubMed, Cochrane Library, Web of Science, Scopus, BVS, and Embase databases. A gray literature search was also conducted, analyzing the first 100 references in Google Scholar. Results: Of 1.362 records initially retrieved, 10 cohort studies met the inclusion criteria. No randomized clinical trials were found. The studies investigated various medications, including antibiotics, corticosteroids, asthma drugs, antivirals, bisphosphonates, and vitamin D supplements. While some studies reported associations—particularly with amoxicillin and molar-incisor hypomineralization (MIH)—others found no statistically significant links. NOS scores ranged from 6 to 9 stars, indicating moderate to high methodological quality. Although causal relationships could not be established, observational studies remain a viable approach to investigating drug associations in tooth development. Conclusion: This review found a possible association between medication use and enamel developmental defects, but no causal relationship was established. Further well-designed studies are needed to strengthen the evidence and guide pediatric dentistry practice and policy.