Impact of Non-invasive Prenatal Testing on genetic counselling, invasive prenatal diagnosis and atypical chromosomal anomalies detection

Abstract

Aneuploidy is one of the known major causes of miscarriage and congenital birth defects. It refers to chromosomal abnormality with chromosome number being different from the usual number for the particular species (Hassold et al. 2001). To estimate the risk of having a baby with chromosomal abnormalities, biochemical markers, such as pregnancy associated plasma protein-A (PAPP-A) and unbound beta human chorionic gonadotrophin (free β-hCG) together with ultrasound measurement of nuchal translucency (NT) of the fetus have been commonly used for prenatal screening of Down syndrome and Edwards syndrome. The detection rate is approximately 90 % with a false positive rate of approximately 5% (Sahota et al. 2010).

The discovery of cell-free fetal DNA in the maternal circulation revolutionized prenatal testing. Cell-free fetal DNA could provide disease related genetic information of the fetus and is available for detection starting from gestation week 10. It has been used as non-invasive prenatal tests (NIPT) to screen for trisomy 21, 18 and 13 of the fetus, other aneuploidies, triploidy, and microdeletions. NIPT carries more than 99% specificity and 98% sensitivity for both T21 and T18 detection, with less than 0.03% of false positive rate (Dan et al. 2012).

The public sector in Macau received government funding to implement NIPT in the general obstetric population at Hospital Conde S. Januário (CHCSJ). NIFTY ™ (Non-Invasive Fetal TrisomY test), provided by BGI Diagnosis Co. Ltd.(BGI), was available for pregnant women in CHCSJ who are at age 35 or above at expected date of confinement from March 2015. This study aims to identify the performance of NIPT in clinical practice, the cost effectiveness and impact on genetic counselling workload as well as the number of invasive tests for the period March 2015 to August 2016. Cost effectiveness was calculated and expressed as incremental cost effectiveness ratio as well as cost per case. Cost of the screening model with NIPT implementation in “high- risk” group at CHCSJ (Macau) was compared with cost of the Tsan Yuk Hospital (TYH) first/second trimester Down syndrome screening model (FTS/STS).

Within the study period, the performance of NIPT was remarkable with 100% detection rate and zero false negative rate. However, the NIPT model did not target atypical chromosome abnormalities detection, hence atypical chromosome abnormalities would be missed. At present the implementation of NIPT in high risk group may not be as cost effective as FTS/STS because of the comparatively high cost of the NIPT test. However, genetic counselling workload and invasive test numbers showed significant reduction. Post-test counselling showed a more significant reduction on workforce. Hence, NIPT is a highly accurate screening test that could achieve high detection of Down syndrome and Edwards syndrome, and at the same time ease manpower shortage at CHCSJ with a predefined budget in the public healthcare system.