Presentation on theme: "Recommendations for Testing for Fetal Abnormalities"— Presentation transcript:
1 Recommendations for Testing for Fetal Abnormalities Lee P. Shulman MDNorthwestern Memorial Hospital Distinguished Physician and Professor and ChiefDivision of Reproductive GeneticsDepartment of Obstetrics and GynecologyFeinberg School of Medicine, Northwestern UniversityWe are very happy to be here to roll-out of MSS program. A big focus of this year’s meeting has been first trimester and integrated screening. We have partnered with Jefferson Hospital for many years. Jefferson Hospital has always been on the cutting edge in maternal fetal medicine just like Genzyme has.
2 ObjectivesDescribe the major ethical issues surrounding genetic testing for fetal abnormalities.Discuss how health care providers can improve the genetics literacy of their patients to enhance their understanding of the benefits, risks, and limitations of genetic screening and testing for fetal abnormalities.Identify when and how to refer patients seeking genetic testing for fetal abnormalities.
3 Screening is the testing of apparently well persons to identify those who might be at increased risk of having a disease.
4 Diagnosis is the testing of an individual to determine whether or not he a a particular disease or condition.
5 Increased Risk for Detectable Fetal Abnormalities Advanced maternal age (> 35 years-old at estimated date of deliveryFamily history of detectable Mendelian disorderParental chromosome rearrangement or aneuploidyExposure to specific chemical or radiation agentsCertain ultrasound findingsPositive maternal or genetic screening outcomes
6 Role of Genetic Counseling: Prior to Testing Detailed review of family & medical historyComprehensive pedigree analysisGenetic risk assessment & interpretationGenetic testing options, including risks, benefits & limitationsProvide educational materialsFacilitate patient informed consent
12 Efficacy and Safety: CVS and Amniocentesis Similar efficacyConfined placental mosaicism with CVSCytogenetic success over 99%Similar safetyMore losses after CVS because it is performed at an earlier gestational ageIncreased risk of loss with both procedures is approximately 0.5% over baseline
13 Screening Practices Second trimester 15.0 – 20.9 weeks AFP (NTD), hCG, uE3, inhibin ANTD, Down syndrome, trisomy 18First trimester10.3 – 13.8 weekshCG, PAPP-A, Nuchal translucencyDown syndrome, trisomy 18Integrated ScreeningCombines first and second trimester in a sequential, unified fashionCannot separate the two componentsMost effective approach to Down syndrome, trisomy 18 detectionAllows for NTD detection
18 Second Trimester Screening – Fetal Chromosome Abnormalities AFPb – hCGuE360% detection rate for Down syndrome, trisomy 18Inhibin ADetection rate may increase to 80%
19 The highlights of first trimester screening Provides an early answerRequires access to sonographers trained in NT measurementRequires access to CVSDoes not provide a risk assessment for ONTDAs I mentioned earlier, we believe in offering you a menu of high-quality options because we know that there is not one test to address all patients.Since each option has different components, each has different advantages and disadvantages.For example 1st screen is the only option that reports in the first trimester--
21 Nuchal translucency (NT) A critical component What is it?Measurement of the fluid that collects behind the fetus’ neckMeasured by ultrasound between 10 and 14 weeks’ gestationSize of fetus is 45 to 84 mmWhy is it important?Indication of fetal distress/abnormalitiesTrisomy 21, Trisomy 18, heart defectsMore fluid indicates a greater the risk of an abnormality10% of fetuses with NT of 3mm have major abnormalities90% of fetuses with NT of 6mm have major abnormalitiesNicolaides et al The week scan 1999
22 Best first trimester markers: NT and PAPP-A I know that one of your concerns is knowing the effect of using total hCG instead of free-B hCG. The strenght of any first trimester screening test come from the NT measurement. This is the best marker for DS. Based on SURUSS data,Wald et al, J Med Screen 2003
23 Sensitivity to detect one case Screening for Trisomy 21Procedures neededSensitivity to detect one case30% (Age) 10060% (BC)80% (NT)90% (NT+BC) 35
24 Ultrasound as a Screening Tool Improved ability to detect an increasing number of fetal anomaliesAble to reliably detect fetal anomalies in the first trimester3-D/4-DIncreased ability to provide meaningful information to women and couples
25 Limitations of Ultrasound as a Screening Tool Highly SubjectiveOperator experienceMachineTrainingQuality AssuranceDifficult to Assess Ability to Provide Accurate DiagnosisFalse PositiveFalse Negative
30 Ethnicity and Genetic Disease Ethnic/Racial Group Disorder Screening TestAcadian Tay-Sachs DNA molecular analysisserum hexosaminidase-AAfrican-Americans sickle cell disease presence of sickle cellhemoglobin (sickledex);confirmatory hemoglobinelectrophoresisAshkenazi Jews Tay-Sachs DNA molecular analysisCanavan DNA molecular analysisFamilial dysautonomia DNA molecular analysisMediterranean people b-thalassemia mean corpuscular volume(MCV) less than 80% from CBC;Southeast Asian and a-thalassemia mean corpuscular volumeChinese ethnic (MCV) less than 80% from CBC;groups DNA analysisAll ethnic groups cystic fibrosis DNA molecular analysis- should be offered to Caucasians and Ashkenazi Jews, made available to all other groups
32 CYSTIC FIBROSIS GENE Located on 7q 250,000 bp (250kb) 27 exons cDNA 6,100 bpCystic fibrosis transmembrane regulator; 1,480 amino acids
33 Population Carrier Screening by Ethnic Group BackgroundPublishedCarrier RiskRange ofTest Detection*Caucasian1/25 - 1/2978-90%AshkenaziJewish95-97%Hispanic1/4658-85%AfricanAmerican1/6560-80%Asian*varies by laboratory1/9033-38%
34 OFFEREDPhysician or other health care worker initiates the counseling about CF screeningMay be supplemented by written materials, videotape, CD, or other modalitiesSimilar to second trimester Maternal Serum Screening
35 RECOMMENDATIONS FOR MAKING CF SCREENING AVAILABLE Low Risk GroupsAfrican-AmericansHispanicsAsian-AmericansNo known admixture withhigher risk groups
36 MAKE AVAILABLEWritten material should be provided to lower risk racial or ethnic group(s)Risk for having a child with CFSensitivity of CF screeningWhen requested, additional information or counseling should be providedIf desired, CF screening should be provided
37 CONCLUSIONS 3 generation family history Counseling when appropriate Disorders, ethnicity, raceCounseling when appropriateCurrent StandardsSickle cell disease, - and -thalassemia, Jewish genetic disorders including Tay Sachs, Canavan, familial dysautonomia and CF