Ethical considerations when offering noninvasive prenatal testing

Abstract

Technology in the prenatal setting is advancing at an exceptional rate, and these advancements will likely result in major changes to current pregnancy screening and testing paradigms. In Australia, prenatal testing is increasingly becoming a routine part of antenatal care and pregnant women are offered an assortment of screening and diagnostic tests, which give them information about their fetus, and can identify potential anomalies before it is born. In Victoria (Australia), each year approximately 4% of babies will be born with a birth defect or fetal abnormality many of which are diagnosed in uterus. Greater than 97% of women in Victoria have at least one or more ultrasounds during pregnancy and greater than 80% of pregnant women take up screening for Down syndrome, with the majority having First Trimester Combined Screening (FTCS). FTCS combines maternal serum analytes — pregnancy associated plasma protein-A (PAAP-A) and beta human chorionic gonadotrophin (free β-hCG) — with results from the nuchal translucency ultrasound to give a risk figure for Down syndrome and Trisomy 18. Approximately 5% of women will receive a false positive result from FTCS, meaning they screen positive for Down syndrome or Trisomy 18 and do not have an affected pregnancy. Women who are considered to be “increased risk” either because of a screening result or ultrasound finding are offered invasive diagnostic testing whereby a fetal sample is obtained via chorionic villus sampling (CVS) or amniocentesis and sent for conventional or molecular karyotyping (microarray). These tests carry a miscarriage risk of up to 1% above the background rate of miscarriage. There has been increasing demand for a safe and reliable alternative to invasive diagnostic testing and very recently, noninvasive prenatal testing (NIPT) has become commercially available to women in America (2012), Australia and many other countries, including Brazil (2013). NIPT is an advanced screening test, which relies on the fact that small fragments of cell-free fetal DNA and RNA circulate in maternal serum. In the first and second trimesters of pregnancy, approximately 6–10% of total cell free DNA (cfDNA) circulating in maternal serum is thought to be fetal in origin; this fetal fraction rises to 10–20% in the third trimester. Using massively parallel sequencing technology, scientists can sequence cfDNA fragments in maternal plasma and detect specific chromosome aneuploidies such as trisomies 21, 13 and 18, much earlier in pregnancy than has previously been possible,