Prenatal diagnosis for chromosomal abnormality: Time to change the Israeli policy

Down syndrome is the most common serious chromosomal abnormality among live births. Safe, inexpensive, and accurate prenatal screening, with a high detection rate (DR) and low false positive rate (FPR) is needed for prevention. Second trimester screening, based on three maternal serum markers (free bHCG, uE3, AFP) has a 59-75% DR with a 5% FPR. The addition of Inhibin-A to this panel (Quadruple test), increases DR to 70-85%. First trimester screening combining two serum markers (free bHCG, PAPP-A), with ultrasound nuchal translucency (NT) has a 80-90% DR, allows reassurance or early diagnosis and pregnancy termination in a relatively simple and safe technique. Testing sequentially in both trimesters (NT, PAPP-A, then Quadruple markers), but withholding results until all markers are measured, allows a 92-94% DR with a low FPR, although the clinical and human advantages of early testing are lost. Three alternative approaches are presented in this review, which achieve a high DR and low FPR without this disadvantage. Based on recently published data, we propose a change in the current policy practiced in Israel whereby women above 35 are referred for invasive prenatal diagnosis paid by the government. Instead, awareness of modern screening methods should be enhanced and invasive diagnosis only offered to women whose risk based on screening exceeds an agreed cut-off. This would achieve better and safer prevention acceptable to a wide spectrum of ethnicities, religions and cultures in Israeli society, at a reasonable cost to the public health system in Israel.