The “ExternalGenitaliaScore” to Describe External Genitalia in Male and Female Infants. A Europeanmulticenter Validation Study

Background: The “External Masculinization Score”(EMS) is an objective method of scoring undervirilized genitalia in infants but may require further adaptation to capture the appearance of the genitalia more comprehensively across the phenotypic spectrum. Objective: To develop and validate a non-binary, standardized score that describes the range of appearance of external genitalia. Method: The external genitalia score (EGS), designed by WG1 of COST Action BM1303 assesses the same anatomical landmarks (urethral meatus, location of gonads, size of genital tubercle, labioscrotal fusion) as EMS, using a gradual scale from female to male (range 0-12), and a vocabulary suitable for both sexes. Intraand inter-observer variability were studied in infants with typical (n=35) and atypical (n=74) genitalia. In a subsequent multicenter validation study, cross-sectional data were obtained in 378 fullterm, 163 preterm babies and 308 infants up to 24 months with equal sex distributions, and in 74 babies with atypical genitalia (46,XY: n=69; 46,XX: n=5). EGS was compared to Prader Score (PS) and EMS. Following anogenital distances (AGD) were measured: AGDas: anus to posterior base of scrotum, AGDap: to anterior base of penis, AGDaf: to fourchette, AGDac: to anterior base of clitoris. Results: Inter-observer reproducibility of EGS in typical and atypical genitalia is excellent, being 1 and 0,98 respectively (95%RI 0,97-0,99). Median (10th - 90thcentile) EGS in male premature (>33 weeks) and full-term babies up to 24 months is 12 (11-12); in preterm males < 33 weeks, it is 11 (10,5-12). Median EGS in female premature and full-term babies up to 24 months is 0 (0-0). In male and female infants with variant genital development, median EGS is 9,7 (6,5-11,9), and median EMS is 9 (4,1-12). In babies with typical genitalia, median (10th - 90thcentile; SD) AGDas/ap in males is 0,49 (0,39-0,61; 0.09), in females AGDaf/ac is 0,40 (0,31-0,48;0,07). In babies who have 46,XY DSD, median (10th - 90thcentile;SD) AGDas/ap is 0,43 (0,28-0,57; 0.11). AGDas/ap in males with typical genitalia is significantly different from AGDas/ap in 46,XY DSD (t= 1,9, p=0,05). In babies with 46,XY DSD, AGD-ratio correlates positively with EGS (Spearman’s r=0,33, p< 0,05) and with EMS (r=0,42, p<0,05). Conclusion: EGS provides an alternative to EMS as a non-binary and reproducible tool to describe the range of external genitalia in premature and term infants up to 24 months. The AGD-ratio, a measure of prenatal androgen exposure, correlates with EGS in male infants.