Maternal Serum Screening for Chromosomal Abnormalities and Neural Tube Defects

Incorporating thyroid markers in Down syndrome screening protocols

“…The standard deviation of TSH in affected pregnancies was estimated to be 0.8 times that in unaffected pregnancies, on the basis of two published studies including a total of 48 Down syndrome cases. This contrasts with the currently used Down syndrome screening markers where the standard deviations in affected pregnancies are either similar to or greater than those in unaffected pregnancies . This could be explained by the square root transformation needed for a Gaussian fit to TSH, whilst the other Down syndrome markers require log transformation.…”

“…Screening for Down syndrome is an established part of prenatal care with most centres now testing in the first trimester of pregnancy. At this time, the protocol with the highest detection rate for a given false positive rate is ultrasound nuchal translucency (NT), maternal serum pregnancy‐associated plasma protein (PAPP)‐A and free β ‐human chorionic gonadotrophin (hCG) (‘combined’ test) . This approach is about to change with the discovery that a single marker, maternal plasma cell‐free cfDNA (cfDNA), has a vastly superior performance to the combined test .…”

“…At this time, the protocol with the highest detection rate for a given false positive rate is ultrasound nuchal translucency (NT), maternal serum pregnancy-associated plasma protein (PAPP)-A and free β-human chorionic gonadotrophin (hCG) ('combined' test). 7 This approach is about to change with the discovery that a single marker, maternal plasma cell-free cfDNA (cfDNA), has a vastly superior performance to the combined test. 8 However, the new marker has a number of limitations including very high costs and the conventional markers have roles beyond aneuploidy.…”

Rethinking second‐trimester Down‐syndrome screening in the cell‐free DNA era

“…In the second trimester, the most common screening test is the ‘quad’ test, which involves assessment of maternal serum levels of α‐fetoprotein (AFP), unconjugated estriol, free β‐hCG and inhibin‐A. Statistical modeling using parameters based on a meta‐analysis and applied to a standardized maternal‐age distribution yielded a predicted viable Down‐syndrome detection rate of 84.5% for a 5% false‐positive rate (FPR) for the combined test performed at 12 weeks' gestation, and a detection rate of 70.8% for 5% FPR for the quad test. Observed detection rates in prospective intervention studies are higher, but they are subject to ‘viability’ bias due to termination of some Down‐syndrome pregnancies that are destined to miscarry.…”

“…Enhancing the quad test with ultrasound markers could in principle achieve equity for women who present late for antenatal screening and cannot resort to cfDNA testing. The addition of ultrasound nuchal skin‐fold, nasal‐bone length and prenasal thickness has a model‐predicted performance comparable to that of the combined test. However, although these markers have been recommended as a ‘useful adjunct’, routine use does not appear to have been introduced widely.…”