Kuwait Medical Association Updates in Medicine Obstetrics and

Kuwait Medical Association Updates in Medicine Obstetrics and Gynecology Non-invasive Prenatal Testing March 18 th 2016 Dr. Shakir Bahzad, MD, FRCPC Kuwait Medical Genetics Center Kuwait Cancer Control Center sbahzad@moh. gov. kw

Disclosure: • Nothing to disclose.

Outlines: • What is Non-Invasive Prenatal Screening (NIPS)? • To use or not to use NIPS? That is the question!

Part 1: NIPS = Non-Invasive Prenatal Screening NIPT = Non-Invasive Prenatal Testing NIPD = Non-Invasive Prenatal Diagnosis (please don’t use this one!) “ … is a screening test that utilizes bioinformatic algorithms and next generation sequencing of fragments of cf. DNA in maternal serum to determine the probability of certain chromosome conditions in a pregnancy. ” http: //nsgc. org/page/non-invasive-prenatal-testing-healthcare-providers • Not to be confused with “Preimplantation Genetic Screening” (PGS)!

http: //ftp. cdc. gov/pub/CLIAC_meeting_presentations/pdf/Addenda/cliac 1115/10_Bellcross_Genetics_NIPS_CLIAC_Nov 2015. pdf

http: //www. tmrblog. com/2015/05/global-non-invasive-prenatal-testing. html

• Pre- and post-test genetics counseling. • 10 -11 weeks of gestation • U/S (singleton) • High risk women only • Looking for Fetal aneuploidy (T 21, T 18, T 13, X and Y aneuploidy)

• • • Bambni. Test Harmony informa. Seq Materni. T 21 PLUS NIFTY Panorama Prena. Test verifi Visibili. T i. Gene. Screen Counsyl Others

SNPs: Single Nucleotide Polymorphism http: //www. panoramatest. com. hk/snp-testing-next-generation-of-NIPT

Schematic illustration of the procedural framework for using massively parallel genomic sequencing for the noninvasive prenatal detection of fetal chromosomal aneuploidy. Rossa W. K. Chiu et al. PNAS 2008; 105: 20458 -20463 © 2008 by National Academy of Sciences

Part 2: How good is NIPS? Biochemical Screening http: //geneticcounseling. info/#4

NIPS http: //www. panoramatest. com/en/healthcare-provider/our-science

In reality …. . http: //nsgc. org/page/non-invasive-prenatal-testing-healthcare-providers

Wang et al. Genet Med 2005; 17: 234

http: //www. mombaby. org/nips_calculator. html

ACOG states that DNA-based screening tests may be performed only on women who are at increased risk of having a fetus with aneuploidy. Among the indications listed for women considered to be at increase risk are: http: //www. acog. org/Resources_And_Publications/Committee_Opinions/Committee_on_Genetics/Noninvasive_Prenatal_Testing_for_Fetal_Aneuploidy

Pre-test counseling for cf. DNA should include: - All genetic screening is optional and may be declined. - cf. DNA appears to be the most accurate screening test for trisomy 21. - False positive and false negative results do occur with cf. DNA. - Patients who desire definitive information about chromosome conditions in their pregnancy should be offered the option of amniocentesis or CVS. - Confirmatory diagnostic testing is recommended for abnormal cf. DNA results. - A negative cf. DNA result indicates a decreased risk and does not definitively rule out chromosome conditions. - cf. DNA screening may not yield a result (inconclusive), which may indicate an increased risk for a chromosome condition. - cf. DNA does not evaluate for all chromosome conditions. - Limitations of the test are explained.

General limitations from ACOG:

False Negative NIPS: - Too little fetal DNA (usually reported as failed) - Mosaicism confined to the fetus. False positive NIPS: - Placental mosaicism - Vanishing twin - Maternal sex chromosome abnormality - Neoplasia – apoptosis of cancer cells, aneuploidy common

http: //ftp. cdc. gov/pub/CLIAC_meeting_presentations/pdf/Addenda/cliac 1115/10_Bellcross_Genetics_NIPS_CLIAC_Nov 2015. pdf

Post-test Counseling: - If a positive NIPT result: - Remember False Positives occur - What is the PPV for this patient? - Refer for genetic counseling - Always offer invasive testing for confirmation - If parents decline invasive testing, postnatal confirmation should be completed - If a Negative NIPT result: - Remember False Negatives occur – especially in higher risk pregnancies - Always offer invasive testing if parents want to “know for sure”

Take-home Message!

Norton ME, et al. NEJM, epub 4/1/15

http: //ftp. cdc. gov/pub/CLIAC_meeting_presentations/pdf/Addenda/cliac 1115/10_Bellcross_Genetics_NIPS_CLIAC_Nov 2015. pdf