A Nationwide Study of the Prevalence and Initial Management of Atypical Genitalia in the Newborn in Scotland

Abstract

Provision of optimum healthcare for infants with atypical genitalia requires a clear understanding of the occurrence of this condition. The objective of this study was to determine the prevalence of atypical genitalia and its initial management. A prospective, electronic survey of clinicians within managed clinical networks in Scotland was undertaken between 2013 and 2019. Notification from clinicians was sought for term neonates requiring specialist input for atypical genitalia. Additional information was also sought from the 4 regional genetics laboratories that provided details for neonates who had an urgent karyotype performed for atypical genitalia or sex determination. In total, the study identified 171 term infants who required some investigation for atypical genitalia in the neonatal period, providing a birth prevalence of 1:1,881 term births. Of the 171 infants, 97 (57%) had specialist input over the first 3 months of life, providing a birth prevalence of 1:3,318 term births that received specialist input for atypical genitalia. A total of 92 of these 97 cases had complete 3-month follow-up data, 62 (67%) presented within 24 h of birth, and age at presentation ranged from birth to 28 days. Age at sex assignment ranged from birth to 14 days, and in 63 cases (68%), sex assignment occurred at birth. Thus, the birth prevalence of a case of atypical genitalia where sex assignment was reported to be delayed beyond birth was estimated at 1:11,097 births. In 1 case sex was re-assigned at 3 months. Atypical genitalia requiring specialist input within the first month of life are rare in term newborns, and in only a third of these cases, sex assignment is delayed beyond birth. This study provides new clinical benchmarks for comparing and improving the delivery of care in centres that manage these conditions.

A Single-Center, Observational Study of 607 Children and Young People Presenting With Differences of Sex Development (DSD)

“…Previously, Thyen et al [ 9 ] have suggested a birth prevalence of 1:5000 in Germany, which is similar to our data. In contrast, Rodie et al [ 10 ] have recently reported a birth prevalence of children requiring specialist assessment for atypical genitalia of 1:3318 in Scotland, although 68% of these children were assigned at birth before the results of more detailed investigations, so more complex DSD may have a similar prevalence to in our study. Specifically focusing on CAH, national registry data from the British Paediatric Surveillance unit (August 2007-August 2009) suggested an overall CAH incidence of 1 in 18 000 children (1 in 13 000-15 000 in many countries), and that three-quarters of girls present in the newborn period with genital changes [ 11 ].…”

The Use of Genetics for Reaching a Diagnosis in XY DSD

“…Atypical genitalia at birth are the most common manifestation of DSD occurring in approximately 1 in 300 births [Ahmed et al, 2004]. However, genitalia that are sufficiently atypical to require any investigations during early infancy are rarer with a birth prevalence of about 1 in 1,200 in term infants [Rodie et al, 2022]. In addition, three-quarters of cases of atypical genitalia that present with a hypospadias have a 46,XY karyotype and are raised as boys [Ahmed et al, 2004;Rodie et al, 2022].…”

“…However, genitalia that are sufficiently atypical to require any investigations during early infancy are rarer with a birth prevalence of about 1 in 1,200 in term infants [Rodie et al, 2022]. In addition, three-quarters of cases of atypical genitalia that present with a hypospadias have a 46,XY karyotype and are raised as boys [Ahmed et al, 2004;Rodie et al, 2022]. A substantial proportion of these boys will be profoundly undermasculinised, and at least 20-25% may not have a satisfactory outcome [Al-Juraibah et al, 2019;Tack et al, 2020].…”

Update on the management of a newborn with a suspected difference of sex development

“…The newborn with atypical genitalia requiring specialist input occurs in approximately 1 in 3000 term births 18. In these cases, sex assignment of the affected child should not just be based on a simple extrapolation of future gender role behaviour from the appearance of the genitalia at birth, but on the best prognosis for future psychosocial and psychosexual function, taking into account the clinical presentation of the child, details of the clinical syndrome, likelihood of fertility as well as the possible effects of prenatal steroid exposure.…”

“…The family may also wish to wait until sex of rearing is known before they name the baby or announce the birth to others. In most cases, a decision can be reached within 2–3 working days 18 28. There remains significant social stigma around DSD conditions and parents may find it difficult to talk about this diagnosis with others, particularly in the initial days 25.…”