Prenatal Screening & Testing

Prenatal Screening & Testing25 November 2015Rels 300 / Nurs 330

1Prenatal Screening vs. Prenatal DiagnosisScreening:aim is to identify women who have increased risk factors (larger than the general population of pregnant women) for having a child with a congenital anomalybecause women over 35 years of age at delivery have a statistically higher risk for fetal chromosome problems, maternal age is a risk factor that suggests screeningDiagnostic tests:In contrast to screening tests, diagnostic testing identifies specific indicators of fetal abnormalities2300/330 - applebyPrenatal Diagnosis and Medical GeneticsMount Sinai HospitalJoseph and Wolf Lebovic Health ComplexToronto, Ontariohttp://www.mountsinai.on.ca/care/pdmg 3300/330 - appleby

Maternal Serum Screening (MSS)blood analysis is routinely offered to pregnant women between the 15th & 18th weeks of pregnancymeasures the levels of certain hormonal substances present in a woman's blood during pregnancyhormones may be elevated or below average levels abnormal levels can indicate the possibility of a neural tube defect (NTD) such as spina bifida, or anencephaly; or chromosomal disorders such as Down SyndromeMSS is not a diagnostic test4300/330 - appleby5TrisomiesGenetic chromosomal disordersTrisomy 21 also known as Down Syndrome3 copies of chromosome 21 are presentrange of developmental delays; common physical characteristics: heart disease, leukemia, early dementia, etc.Trisomy 18 also known as Edwards Syndrome3 copies of chromosome 18 are presentsevere intellectual and physical disabilities heart, kidney, intestinal, esophageal, and irregular physical structuressome still-born; others die soon after birth; few survive childhoodTrisomy 13 also known as Patau Syndrome3 copies of chromosome 13 are presentabnormal brain structure; heart and kidney defects; wide-spread physical abnormalities; some still-born; others die soon after birth300/330 - appleby

prenatal testing56Neural Tube DefectsSpina bifidaopening in the bones around the spinal cordoften not covered by skinAnencephaly brain and skull do not develop completelybrain may be absent, or only brain stem may be presentincompatible with continued life babies may be stillborn, or die within hours or daysOne to two babies out of 1,000 are born with a neural tube defectnot linked to maternal age

300/330 - appleby7MSS sensitivityHow accurate is it? Analysis of maternal serum, performed between 16 & 18 weeks detects 85% of fetuses with open spina bifida95% of fetuses with anencephaly60% to 70% for Trisomy 18 and Trisomy 21This means comparable rates of results are false positives, or false negatives.If pregnant women go on to have more invasive fetal testing (which is diagnostic and has a greater reliability), this introduces risks for the fetus300/330 - appleby Ultrasound

confirms the gestational age of the fetusconfirms single or multiple pregnancydetermines the nuchal translucency measurement (thick skin fold at nape of neck which may indicate Downs or congenital heart defects)screening measure, not diagnostic (40%-70% detection rate)detailed ultrasound at 18 weeks can give information on fetal anatomy and growth; detect cardiac activity structural abnormalities such as spina bifida can be detectednot all structural abnormalities can be detected by ultrasound8Ultrasound imaging is non-invasive and has no known accompanying fetal risks.

300/330 - applebyMarch 2009 GUIDELINES FOR ULTRASOUND AS PART OF ROUTINE PRENATAL CARE (SOGC)Following discussion and results of previous studies, the SOGC recommends:Routine diagnostic prenatal ultrasound at 18 to 22 weeks gestation should be offered to each pregnant womanWomen should be informed of the limitations of accurate diagnosis: detection rates vary from 25% to 71%, and partly depend on ultrasonographer and the equipment used; may suggest further investigation for anomaliesNo evidence that ultrasound poses any fetal risksIf abnormalities detected, refer for counsellingCurrently, average of 2.1 ultrasound scans per delivery in Canada9300/330 - applebyAmniocentesis Suspended in the fluid are fetal cells, which are grown in the lab. About two weeks after the sample is drawn, chromosomes from the cells are checked for abnormalities. 10Amniocentesis is often offered to women 35 and older.genetic diagnostic testsecond trimester (15 16 weeks)fine needle is inserted through the abdomen and into the uterus 20 milliliters of amniotic fluid removed

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Risks of Amniocentesis

11MiscarriageWith no amniocentesis, natural rate of miscarriage after 16 weeks is about 3%. With amniocentesis, the additional risk is about 0.5% (1/200), making the total risk about 3.5%.Leakage of amniotic fluid, spotting or cramping during the first 12 hours following amniocentesis InfectionInfection following the procedure is extremely rare (1-2 in 3000); may develop fever, have chills, cramps or bleedingInjury to Fetusvery small risk of the needle touching the fetus; no injuries reported300/330 - applebyChorionic Villus Sampling (CVS) performed for the same reasons as amniocentesischorionic villus sampling is generally done during the first trimester (10-13 weeks), giving results much earlier than amniocentesis2 forms:a thin tube, called a catheter, is inserted through the cervix and, under the guidance of ultrasound, is used to extract a small sample of the placentaor, a needle can be inserted through the abdomen to sample the placenta (rather than the amniotic fluid)With chorionic villus sampling, the sac enclosing the fetus is not disturbed. 12300/330 - applebyRisks of CVSMiscarriagenatural pregnancy loss at 10 weeks is about 4%additional loss due to CVS is about 1%; total loss rate risk is about 5%Injury to Fetus1992 WHO report - no significant incidence of limb abnormalities in women having CVS compared with the general population when the CVS is performed by experienced physicians at 10 weeks of pregnancy or laterSpotting or crampingSome patients have some spotting or bleeding following the procedure. InfectionInfection following the procedure is extremely rare300/330 - appleby1314Cordocentesis (percutaneous umbilical blood sampling)Only done in high-risk pregnancies3% risk for miscarriage with procedureNeed for rapid chromosomal analysisUmbilical cord contains fetal blood samples which are analyzedPerformed beyond 16 weeksHighly accurate results300/330 - appleby15PRENATAL DIAGNOSIS and AGE2 to 3% of babies born have some type of major birth defectrisk of some problems, due to abnormal separation of genetic material (chromosomes), increases with the mothers age. about 50% of chromosomal anomalies involve Down Syndrome (Trisomy 21)other 50% of chromosomal anomalies are caused by a variety of problems (e.g. deletions, translocations, damage)any other chromosomal problems result in a severely affected baby or one which does not survive even to delivery (e.g. Trisomy 13, 18)incidence of Down Syndrome and other chromosomal problems increases with ageat 35 years the risk of a chromosomal anomaly is about 1:200 300/330 - appleby300/330 - appleby16Test/ProcedureFirst Trimester Screening (FTS)Integrated Prenatal Screening (IPS)Serum Integrated Prenatal Screening (SIPS)1st blood sample11-14 weeks11-14 weeks11-14 weeksNuchal translucency ultrasound11-14 weeks11-14 weeksNONE2nd blood sampleNONE15-20 weeks15-20 weeksResults available

12-15 weeks16-21 weeks16-21 weeksDetection rate(accuracy)Of every 100 pregnancies with Down syndrome, about 80-85 will be detectedOf every 100 pregnancies with Down syndrome, about 85-90 will be detected Of every 100 pregnancies with Down syndrome, about 80-90 will be detectedFalse positive rate

About 3 to 9 out of 100 pregnancies (3-9%)About 2 to 4 out of 100 pregnancies (2-4%)About 2 to 7 out of 100 pregnancies (2-7%)

300/330 - appleby17Test/ProcedureFirst Trimester Screening (FTS)Integrated Prenatal Screening (IPS)Serum Integrated Prenatal Screening (SIPS)Diagnostic test if prenatal screening test is positiveCVS 11-13 weeksIf CVS is not available, you could have amniocentesis diagnostic testing as described in the next column Amniocentesis15-22 weeksAmniocentesis15-22 weeksDiagnostic test results available at: 13-15 weeks 17-24 weeks 17-24 weeksAbortion - if you decide to have this - could be performed at:13-23 weeksTiming will depend on local availability17-23 weeksTiming will depend on local availability17-23 weeksTiming will depend on local availabilityOR Continuation with pregnancyBirthBirthBirth

18Trisomy 21: Down syndrome(3 instead of 2 #21 chromosomes)People with Down syndrome have both physical and mental disabilities.medical problems include congenital heart defects which may lead to early mortalityrange of physical and mental abilities - there is no way to predict how serious any of the disabilities will begastrointestinal abnormalities such as obstructions of the esophagus or the duodenum are fairly commonmay require surgery shortly after birthhigher than average incidence of acute lymphocytic leukemia300/330 - applebyPregnancy Termination Rates for Down Syndrome Fetuses1999 research program report:53.2% of recorded Down syndrome fetuses were prenatally diagnosed and electively abortedWorldwide range of termination of DS fetuses in 1999: 26.7% in Alberta; 84% in Paris, FranceOver the 7 years of the study, prevalence of DS newborns decreasedIncreasing numbers of DS fetuses are aborted1999 data suggest up to 90% of Down Syndrome fetuses were abortedMore recent data identifies a reduction in numbers of abortions - 67% to 85%300/330 - appleby192009, UK

Three babies are being aborted every day due to Down's syndrome, according to a study which shows the number of terminations has more than trebled in the last 20 years.http://www.telegraph.co.uk/health/healthnews/6440705/Three-babies-aborted-every-day-due-to-Downs-syndrome.html The Problem With an Almost-Perfect Genetic World By AMY HARMONPublished: November 20, 2005Some bioethicists envision a dystopia where parents who choose to forgo genetic testing are shunned, or their children are denied insurance. Parents and people with disabilities fear they may simply be more lonely. And less money may be devoted to cures and education. STRENGTH IN NUMBERS Genetic testing may adversely affect children with Down syndrome. 20

300/330 - applebyContrasting ViewsLippman says that prenatal diagnosis is presented as:An aspect of public health designed to reduce the frequency of selected birth defects (p.233)She believes that women are pressured by society and physicians to undergo testing COERCIONWertz & Fletcher say that women are reproductively empowered by prenatal tests, and that the tests support their ability to have healthy children (p.233)

Do you think that prenatal diagnosis should be offered as an aspect of public health? Would you find prenatal testing empowering or coercive?

300/330 - appleby21Lippman says that society has malfunctioned because it cannot accommodate the disabled in its midstDoes society have an obligation to adjust to disabled individuals?Should society (or schools) accommodate people with disabilities?Does having a child with a disability cause suffering, or is suffering caused by societys discriminatory practices?300/330 - appleby22Adrienne Asch: Prenatal Diagnosis and Selective AbortionMy moral opposition to prenatal testing and selective abortion flows from the conviction that life with disability is worthwhile and the belief that a just society must appreciate and nurture the lives of all people, whatever the endowments they receive in the natural lottery.people with disabilities thrive in our societythey take from others, but also contribute to families, friends, the economythey are full members of the human and moral community23300/330 - appleby Sources:Prenatal diagnosis and selective abortion: A challenge to practice and policy. Adrienne Asch.

American Journal of Public Health.Washington: Nov 1999. Vol.89, Iss.11;pg.1649,9pgshttp://proquest.umi.com/pqdweb?index=53&did=46115887&SrchMode=1&sid=1&Fmt=3&VInst=PROD&VType=PQD&RQT=309&VName=PQD&TS=1130866878&clientId=18854 300/330 - appleby24Will increased use of prenatal diagnosis shift social resources away from people with disabilities?Yes, I believe it will because:

No, I dont believe it will because: 25

300/330 - applebyJudge Orders Doctor To Pay Parents Over Daughter's BirthBy Dave Reynolds, Inclusion Daily Express; January 31, 2003VANCOUVER, BRITISH COLUMBIA-A Supreme Court justice ruled this week that a physician must pay a divorced couple $325,000 for the "distress and expense" of giving birth to a child with Down syndrome.Justice Michael Catliff determined that Dr. Ken Kan was negligent when he did not order an amniocentesis test for Lui-Ling "Lydia" Zhang, of Vancouver, which likely would have found that her unborn daughter, Sherry, had Down syndrome. Zhang has said that she would have aborted her pregnancy had she known that before the baby was born in April 1997

Zhang has seen Sherry just eight times in the last five years.300/330 - appleby26GE3LS research stands forGenomics-relatedEthical,Environmental,Economic,Legal andSocial researchDr. Scherer heads a team of the countrys leading geneticists, developmental pediatricians and genome scientists taking part in a 10-nation project studying autism. With funding from Genome Canada, the team is working on isolating genes that may make someone susceptible to autism. Once those genes have been identified, physicians will be able to diagnose the condition much earlier and treat it more effectively.300/330 - appleby27

http://www.genomecanada.ca/en/ge3ls/

Dr. Steve Scherer of the Hospital for Sick Children and the University of TorontoWhat will happen if (or when) there is a prenatal test to detect the likelihood (or certainty) that an expected child will be autistic?300/330 - appleby28