Ano-genital distances (AGDs) and penile length (PL) in the first year of life in males: data from the Life-Milch project

Introduction: The Life-Milch project (www.lifemilch.eu) investigates Endocrine Disrupting Chemicals (EDCs) in breast milk, formula milk and urine samples of mothers and infants from 1 to 12 months age. The study evaluates any relationship between growth, adiposity, neurodevelopment to define a risk assessment model in order to prepare health preventive guide lines. AGDs and PL are surrogate biomarkers of foetal androgen action in males, and they can be influenced by exposure to EDCs. Currently, there are few AGD sex-specific references in the first year of life, in males. The aim of this research was to provide AGDs and PL normative data in males. Methods: Data from 356 male infants (physiological pregnancies) were collected at 3 different Italian hospitals from March 2021 to November 2024. Anthropometric measurements, AGDs and PL were registered at 1 (T1), 3 (T2), 6 (T3), and 12 months (T4) of life. AGD1 refers to ano-penile distance and AGD2 to ano-scrotal distance. Trained staff measured AGDs using the TIDES method and an analogical caliper. Correlations among AGDs and anthropometric measurements were evaluated by multivariate analysis. Data were expressed as mean ± 2SD. Results: AGD1 increased from T1 (53±15.0 mm, N=284) to T4 (68±18.2 mm, N=199). AGD2 increased from T1 (30±14.5 mm, N=284) to T3 (35±18.0 mm, N=260). PL was 27.0 ± 13.8 mm at T1 and 28.5 ± 13.0 mm at T4. AGD2 was correlated with PL at T1, T2 and T3 (p<0.001, r:+ 0.47, + 0.40, + 0.28, respectively) and with infant weight at T2 (p<0.001, r:+ 0.30) and T3 (p<0.05, r:+ 0.22). Conclusion: This study presented longitudinal data for AGDs and PL in a large population of male infants, providing a useful instrument for clinical practice and the basis for further studies.