Overview of parental decisions following prenatal diagnosis of sex chromosome aneuploidy in Hong Kong and implication for genetic counselling

Abstract

Objectives With advancement of technology in genetic testing and widespread use of prenatal diagnosis, the prenatal detection of sex chromosome aneuploidies (SCA) is often unavoidable. The genetic counselling as well as the parental decision making are challenging because of phenotypic variability of SCA. The objectives of this study were to analyze the impact of antenatal Down syndrome screening practices on the prenatal detection of SCA, report the pregnancy outcomes, evaluate the parental decisions regarding pregnancies with SCA and provide advice on genetic counselling practice to local health professionals.

Methods A retrospective cohort study identified all patients with sex chromosome aneuploidies (45,X, 47,XXY, 47,XXX, 47,XYY and mosaicism) diagnosed between 1994 and 2014 from eight public hospitals in Hong Kong. Their medical records from eight public hospitals and Genetic Counselling Clinic of Department of Health were retrieved and reviewed.

Results Over a 21-year period, a total 432 cases (0.64%) with sex chromosome aneuploidies were identified in 67681invasive prenatal diagnostic procedures. The annual detection rate of sex chromosome aneuploidies showed an increasing trend, 1.8 to 17.4per1000 prenatal invasive procedures (p<0.0001). After the implementation of universal Down syndrome screening programme in July 2010, the detection rate escalated sharply by almost two fold from 8.7 per 1000 in 2010 to 17.4 per 1000 prenatal invasive diagnostic procedures in 2014. The major cause of increase was contributed by increasing detection of 45,X cases followed by mosaic 45,X cases (p<0.0001 andp=0.002respectively). Turner syndrome was the most commonly diagnosed SCA (43.7%) and its major indication for diagnostic procedure was cystic hygroma and/or fetal hydrops on ultrasonography. After exclusion of affected pregnancies with unknown outcome and termination, the live birth rates of sex chromosome aneuploidies were 21.9%, 100%, 97.2%, 90.5%, and 98.6% for 45,X, 47,XXY, 47,XXX, 47,XYY and mosaicism respectively. The overall termination rate was 55.4%. Pregnancies with ultrasound abnormalities, non-mosaickaryotypes, and with 45,X or 47,XXY karyotypes were associated with higher termination rates than pregnancies with normal ultrasound finding (ultrasound abnormalities vs normal ultrasound finding 91.3% vs 28.1%, p<0.0001 ), mosaic karyotypes (non-mosaic vs mosaic 33.1% vs 19.3%, p=0.025) and 47,XXX, 47,XYY and mosaicism (45,X and 47,XXY vs 47,XXX, 47,XYY and mosaicism 46.3% vs 18.2%, p<0.0001). From multivariate regression analysis on the parental decisions regarding pregnancies with normal ultrasound examination in 228 pregnancies, a higher likelihood to terminate was found in pregnancies affected by 45,X and 47,XXY (adjusted Odds ratio 4.67, 95% confidence interval 2.41-9.02, p<0.0001) and absence of fertility problems (adjusted Odds ratio 5.06, 95% confidence interval 1.08-23.74, p=0.04). Increased maternal age was associated with lower likelihood to terminate (adjusted Odds ratio 0.9, 95% confidence interval 0.82-0.98, p=0.012). There was a trend towards lower termination rate across the time period from36.4% to 23.3% (p=0.1). There was a significant increasing trend of involvement of pediatrician or clinical geneticist in post-diagnosis counselling (p<0.0001). Evaluation of counselling notes showed obstetricians having more directive counselling approach towards continuation of pregnancy than other health professionals (clinical geneticists and pediatricians)(p=0.035).

Conclusion The prenatal detection of SCA is increasing. The type and severity of SCA, fertility problems and maternal age contributed to parental decision making of reproductive choices regarding pregnancies affected by SCA. On the other hand, the content of information given as well as the counselling strategy appeared to be important modifying factors in the parental decision. Structured training and education for health professionals in genetic counselling as well as a multidisciplinary approach in the counselling process can help to improve the quality of genetic counselling in order to support parents in making autonomous informed decisions following the prenatal diagnosis of SCA.