Prenatal hormonal signature (2D:4D) and dental maturation in childhood: a prospective study

The second-to-fourth digit ratio (2D:4D) is a stable anthropometric marker thought to reflect prenatal androgen-estrogen balance. Although 2D:4D has been linked to developmental timing, its association with dental maturation remains unclear. This study evaluated whether 2D:4D relates to dental development in children and assessed its potential as a complementary biomarker.

In this study, 300 healthy children (150 girls, 150 boys; 6-12 years) were enrolled. Bilateral 2D:4D was measured with digital calipers (0.01 mm accuracy). Dental age was determined from panoramic radiographs using Demirjian's method. Analyses included t-tests/ANOVA, Pearson correlations, and multiple linear regression with chronological age, sex, body mass index (BMI), and 2D:4D as covariates. Hand-specific and sex-stratified comparisons were pre-specified; multiple testing was controlled using the Benjamini-Hochberg false-discovery rate (FDR) procedure, with significance set at q < 0.05 (false discovery rate-adjusted p-value).

Mean chronological age was 9.10 ± 1.99 years, dental age 9.09 ± 2.03 years, and BMI 16.51 ± 1.89 kg/m². 2D:4D showed clear sex differences (higher in girls, p < 0.001). Chronological and dental ages were strongly correlated (r = 0.976, p < 0.001). In the overall sample, dental age correlated weakly with 2D:4D (right: r = 0.155, p = 0.007; left: r = 0.135, p = 0.019). Sex-stratified analyses indicated a positive but non-significant trend in girls (right: r = 0.135, p = 0.099; left: r = 0.110, p = 0.181) and no association in boys (all p > 0.05). In multivariable models, chronological age was the strongest predictor (p < 0.001); 2D:4D contributed independently (β = 0.12-0.16, p < 0.001), while BMI was not significant.

2D:4D shows a weak association with dental maturation at the population level. Within-sex analyses reveal a non-significant positive trend in girls and no association in boys. As a simple, non-invasive measure, 2D:4D may provide supportive information alongside radiographic methods; confirmation in larger, longitudinal, sex-specific cohorts is warranted.