Etiology of Hypomineralized Second Primary Molars: A Systematic Review

ABSTRACT Objectives Hypomineralized Second Primary Molars (HSPM) are qualitative enamel defects that typically involve one to four second primary molars. Although widely investigated, their etiology remains unclear. This review synthesizes current evidence on potential etiological factors. Materials and Methods The design of this systematic review complied with the 2020 PRISMA guidelines. The research was conducted using five databases. Study quality and bias were assessed using the Newcastle‐Ottawa Scale. Results Nine articles met the inclusion criteria, underscoring the limited evidence base. Prenatal factors were most frequently associated with HSPM, particularly epigenetic markers in blood (DNA hypermethylation and hypomethylation, p < 0.05), maternal smoking ( p = 0.001), and maternal illness ( p < 0.001). Though effect sizes varied, and methodological heterogeneity limited comparability. Perinatal factors such as preterm birth ( p = 0.024) and delivery complications ( p = 0.032) were also reported, but evidence was less robust and often confounded by small sample sizes. Postnatal factors, including recurrent childhood illnesses (asthma, otitis media, episodes of fever, and eczema) were significantly linked to HSPM, yet causality remains uncertain given the dependence on retrospective designs and parent‐reported data. Conclusions Current evidence suggests that HSPM is likely multifactorial with contributions from prenatal, perinatal, and postnatal exposures. However, the overall level of evidence is moderate, constrained by small study numbers, variable quality, low response rate, and the retrospective nature of the studies. Stronger conclusions will require large‐scale, prospective studies with standardized diagnostic criteria and rigorous control of bias.