Reference values for the external genitalia of full-term and pre-term female neonates

Abstract

Background and objectivesIdentifying virilisation of the genitalia in female newborns early during the neonatal period is important to diagnose pathologies. However, there is no clear threshold for clitoromegaly or for the anogenital ratio. The objective of this study was to define reference values for the external genitalia of full-term and pre-term female neonates.DesignThis was a prospective study of all females born in the study centre between May 2014 and July 2016. Clitoral length and anogenital ratio were measured in 619 newborns with a gestational age of 24+2 to 41+3 weeks during their first 3 days of life. Associations between the values at day 3 and gestational age, birth weight and other newborn characteristics were examined by linear regression.ResultsThe mean clitoral length at day 3 of life was 3.69±1.53 mm (n=551; 95th percentile, 6.5 mm; maximum, 8 mm), and the mean anogenital ratio was 0.42±0.09 (95th percentile, 0.58). There was no significant variation with gestational age or birth weight, and no significant difference between the results at day 0 and day 3.ConclusionThese results suggest that clitoromegaly can be defined as a clitoral length >6.5 mm. Values ≥8 mm should prompt further investigations. An anogenital ratio >0.6 should be considered a sign of virilisation. Since clitoral size does not vary with gestational age or birth weight, clitoromegaly should not be attributed to prematurity.

Clitoromegaly in Premature Infants: Is It Truly Pathologic?

“…This timing was consistent with the timing of consults (CA=1-3 months) for our study patients. If true clitoromegaly is present at birth, an evaluation may be warranted as noted by Castets et al [62]. However, the authors' suggestion that clitoral size remains stable after 24 weeks GA is debatable.…”

Society for Endocrinology UK Guidance on the initial evaluation of a suspected difference or disorder of sex development (Revised 2021)

“…This will avoid unnecessary detailed investigations of boys with isolated glandular or mid‐shaft hypospadias and boys with unilateral inguinal testis. In newborn girls, the length of the clitoris does not seem to be dependent on gestation and a newborn with a length greater than 8mm requires further evaluation 40 . Micropenis is defined as a stretched penile length of less than 2.5SD from the mean and based on contemporary studies from a wide range of countries, a stretched penile length of less than 2cm would represent a reasonable cut off for micropenis in the newborn 34,41–45 .…”

The role of androgens in clitorophallus development and possible applications to transgender patients

“…The size can vary at time of birth from 3.7 to 7.7 mm in length, depending on features of the population studied including race and gestational age. [27][28][29][30][31][32][33][34] The length of a clitorophallus of a patient born with functional testes and AR is typically 3.5 cm, with a urethra on the ventral aspect. 35 Micropenis is a term used for a clitorophallus that is considered >2.5 standard deviations (SD) smaller than a fully virialized clitorophallus but that still typically has a ventral urethra.…”

“…The clitorophallus of a neonate with functional ovaries and no androgenic exposure in utero is typically the smallest, with a separate urethra. The size can vary at time of birth from 3.7 to 7.7 mm in length, depending on features of the population studied including race and gestational age 27‐34 . The length of a clitorophallus of a patient born with functional testes and AR is typically 3.5 cm, with a urethra on the ventral aspect 35 .…”

“…However, the results are controversial. For example, some researchers have reported that SARS-CoV-2 was not detected in the male reproductive tract, [25][26][27][28][29][30][31][32][33][34] while others reported that SARS-CoV-2 RNA was found in the semen or testes of COVID-19 patients. 35,36 There are also unknown factors regarding COVID-19 and male reproduction.…”