Prenatal Genetic Screening

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Genetics and Primary CareWhat’s New in Prenatal Genetic Screening


Genetics in Medicine: the 21st CenturyThe Human Genome Project has brought inherited health factors to the forefront Genetic risk assessment, screening and testing is becoming part of primary medical care Clinical genetics and primary care need to work together to offer appropriate services


We Are Working TogetherRisk assessment for common genetic conditions likely to be performed in the primary care/prenatal setting Screening and testing for genetic conditions increasingly performed in primary care/prenatal care Patients with rare or more complex genetic conditions, risks, or family histories likely continue to be served by genetics specialists


OutlinePreconception/prenatal genetic risk assessment and screening Family/personal history questionnaire Ethnicity-based screening Maternal serum screening and ultrasound How, When, Where to refer patients Resource Information


Family History QuestionnaireScreens for reproductive genetic risks Appropriate for patients considering pregnancy or already pregnant Contains referral guidelines for genetic services


Assessment AreasMaternal age Family medical history (both sides) Current pregnancy/pre-pregnancy history Ethnic background (both sides)


Maternal Age Maternal age 35 or older at time of delivery: increased risk for chromosome abnormalities Options for prenatal testing/screening: CVS Amniocentesis Multiple marker screening 1st or 2nd trimester, or combined Ultrasound


Family Medical HistoryFor a family history of a diagnosed genetic condition or birth defect and a patient who is currently pregnant, referral to a Prenatal Diagnosis Clinic is appropriate. Examples: Nephew with Duchenne Muscular Dystrophy Brother with Fragile X syndrome Previous child with spina bifida, etc.


Family Medical HistoryFor a non-specific, but concerning history, referral to a Medical Genetics Clinic (e.g. OHSU) is appropriate. Examples: Close family member with mental retardation, etiology unknown Multiple family members with ‘kidney disease’ Previous child with seizure disorder and developmental delay


Pregnancy HistoryDuring pregnancy, any reported exposures or maternal conditions would be reasonable to refer to a genetics service – especially those known to be teratogens E.g. accutane, seizure medications, lithium, coumadin, “street drugs”, high fevers, viral infections, maternal diabetes, etc. Preconception counseling should always include a discussion of folic acid Thought to decrease the risk of neural tube defects by 50-70% 0.4 mg is recommend for all women 4.0 mg is recommended for women at increased risk


Ethnicity-Based Genetic Carrier ScreeningPurpose: To detect couples at risk for prenatally diagnosable genetic diseases Tests offered based on ethnic background Should be offered to patients: Seeking preconception counseling, OR Seeking infertility care, OR During the first or early second trimester of pregnancy


PopulationConditionCarrier FrequencyCarrier Frequencies based on Ethnic Origin


Principles of Carrier ScreeningCounseling before screening should include: Purpose, voluntary nature of screening Range of symptoms and severity of each disease Risk of carrier status and affected offspring Meaning of positive and negative results Factors to consider in decision-making Further testing would be necessary for prenatal diagnosis


Informed Consent Utilize patient resources materials Patient brochures about CF and other ethnicity-based genetic screening available from multiple sources Carrier screening videos can be shown in office settings Document informed consent discussion and patient decision


Important PointsCarrier screening is optional Patient education/informed decision-making is crucial Testing can be done sequentially or concurrently If >12 weeks gestation, discuss concurrent testing Insurance coverage for carrier screening??? Varies by insurer (not covered by OHP and some other major insurers) Genetic counseling is available to carriers and strongly advised for carrier/carrier couples


Caucasian Patients: ACOG guidelines, Oct. 2001 Offer cystic fibrosis carrier screening to: Individuals with a family history of CF Reproductive partners of carriers/persons with CF Couples where one or both partners are Caucasian & are planning a pregnancy or seeking prenatal care “Make CF screening available” to couples in other racial or ethnic groups at lower risk


CF Carrier Screening1/25 to 1/29 carrier rate in general Caucasian population and Ashkenazi Jewish population Carrier screening by DNA mutation analysis ACOG suggests panel of 25 most common mutations Some labs do additional mutations but at higher cost Mutations differ in severity – contact genetics to discuss particular carrier results


Carrier Rates: Cystic Fibrosis


Asian PatientsStandard to review MCV If <80, screen for thalassemia w/quantitative hemoglobin electrophoresis Alpha-thalassemia carrier rates up to 1/20 Beta-thalassemia carrier rates 1/30 to 1/50 Cystic fibrosis carrier rate 1/90 or less Detection rate is very low (~ 30%) Not standard to do CF screening Make available upon patient request


Hispanic/Latino PatientsNo standard protocol for carrier testing Cystic Fibrosis: carrier rate 1/46 Beta-thalassemia: carrier rate 1/30 to 1/50 Sickle cell or other hemoglobin trait: Carrier rate 1/30 (Caribbean) to 1/200 Could review MCV as a general screen


African-American PatientsStandard to offer Sickle Cell screening Sickle cell carrier rate is 1/10 to 1/12 Use Hb electrophoresis (NOT sickle dex) Standard to review MCV Beta-thalassemia carrier rate about 1/75 If MCV low, offer thalassemia screen w/quantitative Hb electrophoresis CF carrier rate 1/65 no standards re: offering CF carrier screening


Ashkenazi Jewish PatientsStandard of care to offer carrier screening for: Tay-Sachs disease Cystic Fibrosis Canavan disease Familial Dysautonomia All autosomal recessive conditions Carrier testing for other disorders also available (high anxiety/family history?)


Maternal Serum Screening Tests maternal serum markers to detect increased risk of fetal trisomy 21, trisomy 18 and/or neural tube defects 2nd trimester maternal serum screening 1st trimester maternal serum screening (with or without nuchal translucency measurement) Integrated maternal serum screening Other variations combining 1st and 2nd trimester screening results


Maternal Serum ScreeningPatient education points: ‘This is only a screening test’ ‘The test is optional’ ‘A negative result does not guarantee a healthy baby’ ‘A positive result does not mean that the baby has a problem, BUT further testing (ultrasound & CVS or amniocentesis) would be offered’ Offered to all patients regardless of age – ‘there is a small risk in every pregnancy for these conditions’


2nd Trimester Serum Screening Timing: 15 to 20 weeks gestation Choices: Triple screen Quad screen Cost ~$200 Insurance coverage varies Triple covered by most, Quad by some


Triple ScreenAnalytes used (with maternal age): Alpha-fetoprotein (AFP) Unconjugated estriol (uE3) Beta-Human Chorionic Gonadotropin (b-HCG) Detection rates/screen-positive rates vary by lab Detection rates with a 5% screen-positive rate Down syndrome: 60-70% Trisomy 18: 60% NTD: 75-80%

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Last Updated: 8th March 2018

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