473 The need for invasive procedure after normal NIPS depends on the type of cardiac malformation

Abstract

To examine the residual risk for clinically significant chromosomal microarray analysis (CMA) results in fetuses with congenital heart defects (CHD) by its various subtypes, after normal non-invasive prenatal screening (NIPS). Using the computerized database of Ministry of Health, we retrieved the reports of all pregnancies undergoing CMA due to CHD through the years 2013-2019. We examined the risk for clinically significant (pathogenic and likely pathogenic) CMA results, compared to a local cohort of pregnancies with normal ultrasound, yielding 1.4% (78/5541) abnormal results. The residual risk for abnormal CMA results was calculated following omission of the common NIPS-detectable anomalies (Trisomy 21/13/18 and sex chromosome aneuploidy). Of the 1,728 fetuses with CHD, 93 (5.4%) yielded clinically significant CMA results – relative risk (RR) 2.7 (95% confidence interval (CI) 2.3-3.1), compared to the control population (Table 1). Interestingly, in two most common isolated cardiac anomalies (627 fetuses with ventricular septal defects (VSD) and 382 with aberrant right subclavian arteries (ARSA)), the risk for abnormal CMA findings was not significantly increased compared to control population (1.9%, RR 1.3 (0.8-2.2), and 1.0%, RR 0.75 (0.3-2.0), respectively). NIPS could theoretically have detected 43.0% of the abnormal results (Figure 1) - 33.3% in isolated and 56.4% in non-isolated CHD, a statistically significant difference (p=0.034). The residual risk for clinically significant CMA findings was highest (approximately 1 in 10) for hypoplastic left heart, Tetralogy of Fallot, transposition of great vessels and aortic coarctation. Residual risk was lowest for pregnancies with VSD (in 1 in 69), and for ARSA (1 in 128). The residual risk for clinically significant CMA results after normal NIPS depends on CHD subtype, and is lowest in fetuses with isolated VSD or ARSA. This information should be taken into an account by the obstetricians and genetic counselors when considering the need for invasive testing.View Large Image Figure ViewerDownload Hi-res image Download (PPT)