Errors in Antenatal Genetic Diagnosis and Wrongful Therapeutic Abortion

In November 2018 a 39 year old IVF patient of mine received terrible news that her Non Invasive Prenatal Test at 11 weeks was positive for Trisomy 13.

Patau syndrome is associated with severe intellectual disability and a range of physical defects including heart abnormalities, cleft lip, microphthalmia, brain and spinal anomalies. Only 10% or less of such infants survive until the second year of life. 

Needless to say many mothers would request a therapeutic abortion when given that diagnosis and this was certainly an option for my patient.

Some wise advice was given to me by a geneticist who recommended that the NIPT diagnosis be confirmed by genetic amniocentesis. That took another 5 weeks of agonising wait for the patient however the result showed a NORMAL karyotype. Thankfully I was spared the embarrassment of terminating a eukaryotic fetus. 

In May this year a Dublin woman was not so lucky when she had a termination for a trisomy 18 (Edwards syndrome) at the National Maternity Hospital - normally a very conservative obstetric hospital. It was thought the baby had Trisomy18, also known as Edwards Syndrome, but a series of genetic tests later found that that was not the case.

Edward syndrome is due to Trisomy 18 and is associated with intrauterine growth restriction, congenital heart disease, a small, abnormally shaped head; a small jaw and mouth; and clenched fists with overlapping fingers. It is associated with stillbirth. Some survive and in Ireland there are teenagers living with the disorder.

In an interview with RTE news radio on 17 May 2019 the Master of the Rotunda Hospital in Dublin (my alma mater) explained that NIPT tests should be confirmed by CVS or genetic amniocentesis. Prof Fergal Malone also noted that the karyotype may differ between fetus and placenta.

Accuracy of NIPT tests for Trisomies

1. 82% of T21 positive results will have Down Sydndrome
2. 49% of T18 positive results will have Edward syndrome
3. 37% of T13 positive results will have Patau syndrome

This means that all NIPT positive trisomy findings  should be confirmed either by CVS or genetic amniocentesis.

Trisomy 13 occurs in about 1 in 16,000 newborns

Trisomy 18 occurs in about 1 in 5,000 live-born infants

Further Reading:

1. Taylor-Phillips S, Freeman K, Geppert J, et al Accuracy of non-invasive prenatal testing using cell-free DNA for detection of Down, Edwards and Patau syndromes: a systematic review and meta-analysis BMJ Open 2016;6:e010002. doi: 10.1136/bmjopen-2015-010002
2. Mersy E, Smits LJ, van Winden LA, et al. Non-invasive detection of fetal trisomy 21: systemat ic  review and report of quality and outcomes of diagnostic accuracy studies performed be tween 1997 and 2012. Hum Reprod Update 2013;19:31829. doi:10.1093/humupd/dmt001
3. Verweij EJ, van den Oever JM, de Boer MA, et al. Diagnostic accuracy of non-invasive detec tion of fetal trisomy 21 in maternal blood: a systematic review. Fetal Diagn T her 2012;31:81 6. doi:10.1159/000333060