The role of prenatal factors in molar incisor hypomineralization: Could the 2D:4D ratio be a biomarker?

BACKGROUND: Molar incisor hypomineralization (MIH) has a multifactorial, incompletely understood etiology, with prenatal factors increasingly implicated. The second-to-fourth digit length ratio (2D:4D ratio) is an indirect marker of prenatal sex hormone exposure. AIM: To determine whether children with MIH differ from controls in right- and left-hand 2D:4D ratios and whether differences vary by sex. METHODS: This case-control study included 60 children with MIH and 60 age- and sex-matched healthy controls aged 7-12 years. Groups were compared using Welch-corrected and paired-samples t-tests. Binary logistic regression assessed associations between the 2D:4D ratio and MIH, with continuous predictors z-transformed. Sex-stratified comparisons and sex × 2D:4D interaction models were performed as exploratory analyses. RESULTS: Right and left 2D:4D ratios were higher in the MIH group than controls (right: 0.977 ± 0.044 vs. 0.961 ± 0.014, p = 0.006; left: 0.978 ± 0.030 vs. 0.961 ± 0.015, p < 0.001). In logistic regression, each one-standard-deviation increase in the left 2D:4D ratio was associated with higher odds of MIH (OR = 2.29, 95% CI 1.46-3.62, p < 0.001), independently of age and sex. Exploratory sex-stratified analysis indicated that this association was confined to boys (OR = 4.02, 95% CI 1.81-8.92), with no comparable effect in girls (OR = 1.33, 95% CI 0.72-2.46); sex × 2D:4D interactions were significant for both hands. CONCLUSION: Higher 2D:4D ratios, particularly for the left hand, were associated with MIH. The association was concentrated in boys, a pattern compatible with a role for prenatal androgen signaling in enamel maturation. The 2D:4D ratio may be a candidate biomarker, although this sex-specific finding requires confirmation in larger samples.