Non‐invasive prenatal diagnosis: improved detection rates

In the Prenatal Diagnosis special issue of July 2010, a good prediction was made by the author (Dennis Lo, 2010) on non-invasive methods of diagnosis of fetal anomalies. Non-invasive prenatal diagnoses are useful in the detection of fetal genetic abnormalities, aneuploidies and high-risk pregnancy. Fetal DNA analysis in maternal plasma using single molecule analysis method, no doubt, will definitely improve in diagnostics by 2020 but not to an extent to replace maternal serum screening and ultrasound as primary modalities to detect fetal abnormalities. In developing countries, the cost, availability and technical expertise about the new procedure make it less useful. There are well established traditional non-invasive antenatal tests. Maternal serum screening is well accepted worldwide in many countries, especially for neural tube defects (NTDs) and Down syndrome. The combined screening tests during the first trimester have a detection rate for Down syndrome up to 89% with a false positive rate of 5%. Combined screening in the second trimester for women older than 35 years is 90%, but the false positive rate is 16 to 22%, while the detection rate of trisomy 18 is 90% for all ages with a false positive rate of 2%. When both firstand second-trimester testing is combined, detection rates were improved to 92 to 96% with false positive rates of 5% (Anderson and Brown, 2009). Integrated screening, using both first trimester and second trimester analytes, is being followed at many fetal medicine units or prenatal tertiary care centres. The additional advantages of triple screening include incidental detection of abnormalities other than trisomies, like triploidy, triple X syndrome, Smith–Lemli– Opitz syndrome (SLOS) and X-linked ichthyosis (XLI, steroid sulfatase deficiency). In triploidy and triple X cases, the triple test may show increased risk for Down syndrome and/or Edward syndrome. The unconjugated estriol levels are especially low in maternal serum in cases of SLOS and XLI (Shackleton et al., 2007). Steroid ratios like dehydro-estriol/estriol (DHE3/E3) can also be used in the second trimester screening for SLOS. These however require further validation in maternal urine and serum. The association of increased nuchal fold thickness (NFT) with aneuploidy is well known but NFT may also be increased in some other disorders such as osteogenesis imperfecta, Perlman syndrome and cardiac defects/renal anomalies (Bilardo et al., 2007). Chromosomal soft markers like choroid plexus cyst, echogenic cardiac foci and fetal echogenic bowel, etc also give clues to diagnosis of chromosomal disorders (Beke et al., 2008). With the introduction of 3D and 4D fetal ultrasound scanning, anatomical assessment, morphometry and volumetry, as well as functional assessment of the infant are more clearly delineated and can identify fetal anomalies at the earliest (Yagel et al., 2009). Abdominal wall abnormalities, placental abnormalities, congenital cardiac defects and other defects like fetal demise can also be detected on follow-up ultrasound in maternal serum screening positive cases (Kazerouni et al., 2010). Thus, newer techniques like tests on fetal cells in maternal circulation should be used in conjunction with updated versions of traditional non-invasive methods to improve diagnostic accuracy.