Outcomes of children diagnosed antenatally with sex chromosome aneuploidies

Non-invasive prenatal testing (NIPT) identifies risk of potential foetal chromosomal anomalies. Sex chromosome aneuploidies (SCA) may be identified on NIPT, with 45,X (Turner Syndrome, TS) and 47,XXY (Klinefelter Syndrome (KS)) being the most common, occurring at a rate of 1/2000 liveborn females and 1/600 liveborn males respectively.1 Wide variation in severity is seen in both KS and TS with a need for lifelong specialist follow-up to ensure appropriate screening, diagnosis and management of potential associations.1 Historically, individuals with SCA were identified due to clinical features, and it is estimated that only 25% of KS males were identified.2 Despite increasing uptake of NIPT screening in Victoria3 there are no data on pregnancy or clinical outcomes of infants identified as being at high-risk of SCA. We aimed to identify the number and clinical characteristics of children with an antenatal diagnosis of KS or TS who were reviewed by an endocrinologist in the first year of life, between 2016 and 2019, compared to the total number of SCA cases confirmed during this period (n = 194).3 All tertiary paediatric endocrinology services (n = 3) and private paediatric endocrinologists (n = 10) in Victoria were approached. Data were available only from two tertiary services (The Royal Children's Hospital and Monash Children's Hospital) and one private endocrinologist due to an inability to accurately identify infants from medical record systems in other settings. We identified 17 infants, 12 with KS and 5 with TS (Table 1), representing <10% of pregnancies with an antenatal diagnosis of a SCA (17/194) for the corresponding time period. NIPT screening is widely offered in Australia via multiple platforms without a framework to systematically record pregnancy/postnatal outcomes. Whilst children with SCA may be managed by other healthcare providers, the discrepancy between the number of confirmed SCA in pregnancy and those seen for specialist care in the first year of life is concerning and may reflect rates of pregnancy termination or a lack of appropriate follow-up. Use of NIPT for SCA screening is a global issue, with the International Society for Prenatal Diagnosis recently calling for 'further studies to evaluate the downstream impacts of offering NIPT for sex chromosome conditions'.4 To provide appropriate counselling to families following a high-risk of SCA being identified on NIPT, accurate long-term outcome data are required. A population-based monitoring and referral process following a prenatal diagnosis of SCA are necessary to expand our understanding when SCA does not present with clinical features in infancy.