Benefit versus risk of chromosomal microarray analysis performed in pregnancies with normal and positive prenatal screening results: A retrospective study

Background Most studies on chromosomal microarray analysis (CMA) and amniocentesis risks have not evaluated pregnancies with low risk for genetic diseases; therefore, the efficacy and safety of CMA and amniocentesis in this population are unclear. This study aimed to examine the benefits and risks of prenatal genetic diagnostic tests in pregnancies having low risk for chromosomal diseases. Methods and findings In this retrospective study, we used clinical data from a large database of 30,830 singleton pregnancies at gestational age 16-23 weeks who underwent amniocentesis for karyotyping with or without CMA. We collected socio-demographic, medical and obstetric information, along with prenatal screening, CMA and karyotyping results. Fetal loss events were also analysed. CMA was performed in 5,837 pregnancies with normal karyotype (CMA cohort). In this cohort, 4,174 women had normal prenatal screening results and the risk for identifying genetic abnormalities with >10% risk for intellectual disability by CMA was 1:102, with no significant difference between maternal age groups. The overall post-amniocentesis fetal loss rate was 1:1,401 for the entire cohort (n = 30,830) and 1:1,945 for the CMA cohort (n = 5,837). The main limitation of this study is the relatively short follow-up of 3 weeks, which may not have been sufficient for detecting all fetal loss events. Conclusion The low risk for post-amniocentesis fetal loss, compared to the rate of severe genetic abnormalities detected by CMA, suggests that even pregnant women with normal prenatal screening results should consider amniocentesis with CMA.