ESPE Abstracts

Background: The anogenital distance (AGD) is a well-known measure in rodents used to distinguish male and female pubs. Likewise, AGD display sex-specific differences in humans. It is considered a postnatal readout of early androgen exposure in fetal life. Thus, in postnatal life AGD is longer in boys than in girls, reduced in infants born with cryptorchidism and hypospadias as well as in boys exposed to anti-androgenic agents in fetal life. However, little is known on the development of this sex-specific measure during human fetal and postnatal life.

Aim: The aim of this study is to describe fetal AGD in males and females, and to evaluate if fetal AGD correlates with infant AGD.

Methods: The Copenhagen Analgesic Study (COPANA) (ClinicalTrials.gov NCT04369222) is a prospective cohort study evaluating prenatal exposure of mild analgesics on gonadal function in infants. AGD was measured from the center of the anus to the posterior base of the scrotum (AGDas), and the posterior converge of the fourchette (AGDaf) in males and females, respectively. Fetal AGD was measured by transabdominal ultrasound in the axial plane at gestational week (GW) 29-34 in healthy, singleton fetuses who were subsequently born AGA. Infant AGD was subsequently measured during minipuberty (median age 3.8 months (males) and 4.2 months (females)) with TIDES method. All fetal ultrasound scans were performed by a single sonographer while 6 examiners performed the infant examinations. Three repeated measurements were assessed, and the average was used.

Results: AGD was available in 571/590 (97%) fetuses (275 males) and 588/590 (99%) infants (287 males). AGD was completely separated between sexes with male AGD significantly longer than female AGD as early as the third trimester of pregnancy continuing into infancy: fetal male AGDas median (IQR) 21.3 mm (18.9-23.5), female fetal AGDaf; 12.8 mm (11.1-14.2), P=0.001 (Mann Whitney U (MWU); male infant AGDas 31.8 mm (28.1-36.1), female infant AGDaf 15.7 mm (13.5-17.77), P=0.001. Fetal AGD adjusted for birthweight were positively correlated with AGD in infancy adjusted for body mass index for both male and females (Spearman’s r= 0.24 (P=0.001), and r= 0.14 (P=0.021), respectively).

Conclusions: AGD is sexually dimorphic as early as GW 29 and the separation continues during infancy. We found a positive correlation between fetal and postnatal AGD in both sexes, however strongest for male infants. Future studies will unravel fetal AGD as a new marker of androgen exposure during early fetal life.