Single nucleotide polymorphism array versus karyotype for prenatal diagnosis in fetuses with abnormal ultrasound: A systematic review and meta-analysis

Objective: To estimate the incremental yield of single nucleotide polymorphism (SNP) array over karyotype and to assess the diagnostic accuracy of SNP array as a stand-alone test versus SNP array with karyotype in detecting chromosomal abnormalities for prenatal diagnosis in women with an abnormal fetal ultrasound. Study design: Studies in which SNP array and karyotype had been used for diagnosing chromosomal aberrations in fetuses with abnormal ultrasound findings were included. A systematic search of relevant studies published in the English language in EMBASE, PubMed, CENTRAL, CDSR (Cochrane database of systematic reviews), SCOPUS and Web of science between 1996 and May 2020 was performed. Primary outcome was incremental yield of SNP array over karyotype (number of patients with abnormalities detected by SNP array over number of patients with normal karyotype). Other outcomes included diagnostic accuracy of SNP array alone versus SNP array and karyotype for prenatal diagnosis. Pooled sensitivities, specificities, and their 95% confidence intervals (CI) were presented. Result(s): Seven studies were included. The incremental yield of SNP array over karyotype was 8% (95% Confidence interval, CI 4-12%) while incremental yield of karyotype over SNP array in foetus with abnormal ultrasound was 0% (95% CI 0-1%). The agreement between SNP array and karyotype was 92%. The variant of unknown significance rates ranged between 4 and 8 %. The pooled sensitivity and specificity of SNP array versus SNP array and karyotype was 0.97 (95% CI 0.92-0.99) and 1.00 (95% CI1.00-1.00), respectively. Conclusion(s): SNP array provides additional information on chromosomal abnormalities over and above conventional karyotype. When used as a stand-alone test, SNP array performs favourably as a diagnostic modality when compared against SNP array and karyotype for prenatal diagnosis with an abnormal fetal ultrasound.

Automated summary

This study evaluated the incremental yield and diagnostic accuracy of SNP array compared to karyotype analysis in detecting chromosomal abnormalities for prenatal diagnosis. The results showed that SNP array had a higher incremental yield and accuracy compared to karyotype analysis. When used as a stand-alone test, SNP array performed favorably in prenatal diagnosis compared to SNP array combined with karyotype analysis.