Ayyash M, Daviskiba S, Yaquinto A, Roberson J, and Pitts DA. eP446: High rates of ‘atypical’ panorama noninvasive prenatal screening results among consanguineous Arab American women. Genet Med 2022; 24(3):S279-S280.
Genetics in Medicine
Introduction: Panorama is one of the most accurate and commonly used methods of cell free DNA noninvasive prenatal screening (NIPS). The results are reported as either high risk for a specific aneuploidy, high risk due to fetal fraction, insufficient fetal DNA, atypical, high risk, or no results. It is the only form of NIPS that uses a single nucleotide polymorphism (SNP) method, representing genetic changes that are present in over 1% of the general population, to screen for common fetal aneuploidies and microdeletion syndromes. We hypothesize that the SNP method could be leading to the increase in atypical results among women in consanguineous relationships, common amongst Arab Americans, where there is high homogeneity of genetic material. The aim of this study is to explore factors influencing atypical Panorama NIPS results and its association with abnormal fetal outcomes amongst Arab American women.
Methods: A retrospective cohort study was performed by looking at Panorama NIPS performed between September 2018 and January 2021 at a large urban health system in Detroit, Michigan. The records were obtained from Natera, Inc, the clinical genetic testing company for Panorama. Singleton gestations who underwent Panorama screening and had ‘atypical’ results were included. The outcome of interest was fetal anomalies or abnormal genetic outcomes.
Results: A total of 5,886 women underwent Panorama NIPS within the defined time frame and 772 (13.1%) were identified as Arab Americans. Forty-nine (0.79%) women had atypical results, of which 43 were singleton gestations. The mean age was 29.6 ± 5.3 years old. Nineteen women (44.2%) were White, 14 (32.6%) were Arab and 8 (18.6%) were Black. The percentage of Arab American women with atypical results (32.6%) was significantly higher than the overall percentage of Arab American women who ever underwent Panorama testing (13.0%) (p=0.00018). Eight women were in a known consanguineous relationship, all of whom identified as Arab Americans, hence making 57.1% of Arab women with atypical results. The outcomes for all 43 pregnancies showed normal fetal anatomy and no genetic abnormalities. In those who underwent further testing with amniocentesis (14.0%) or MaterniT21 (14.0%), the results were all normal.
Conclusion: We identified a high percentage of Arab American women with atypical results compared to the baseline Arab American women ratio in the population screened. More importantly, we identified a high rate of consanguinity amongst Arab women with atypical results and subsequent normal fetal anatomy suggesting the possible influence of consanguinity on falsely elevated atypical results due to the SNP method used with Panorama testing. Such knowledge might suggest that, for Arab American women, particularly consanguineous couples, Panorama testing may not be the most ideal method for NIPS. This could help reduce unnecessary invasive testing and Maternal Fetal Medicine and genetics consultations.