Prenatal Diagnosis General Caveats about Prenatal Diagnosis Preconception/Carrier Testing Genotype vs. Phenotype Prenatal Diagnosis Techniques

Prenatal Diagnosis General Caveats about Prenatal Diagnosis Preconception/Carrier Testing Genotype vs. Phenotype Prenatal Diagnosis Techniques

Prenatal Diagnosis General Caveats about Prenatal Diagnosis Preconception/Carrier Testing Genotype vs. Phenotype Prenatal Diagnosis Techniques

O’Kelley, Kaley, Host has reference to this Academic Journal, PHwiki organized this Journal Prenatal Diagnosis Objectives Read/learn OBJECTIVES on web page in addition to assigned text (pages 297-307 in Gelehrter et al.) Underst in addition to indications as long as in addition to utility of prenatal diagnostic tests Know applications, risks, benefits, timing, in addition to limitations of prenatal diagnostic techniques discussed in lecture in addition to readings Underst in addition to basic elements in addition to issues surrounding prenatal diagnosis in addition to counseling The goal of prenatal diagnosis is not to generate perfect babies. “The are no perfect human specimens – we are all genetically flawed in some way.” – F.Collins The goal of prenatal diagnosis is to help parents learn what they need to know about the health of their unborn child to help them make in as long as med decisions as long as themselves in addition to their family within the context of their own value system.

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Prenatal Diagnosis Using a wide variety of screening in addition to diagnostic tests to assess health of a fetus to: Manage the pregnancy Determine potential outcomes Plan as long as complications at birth Decide whether to continue the pregnancy Discover conditions that may impact future pregnancies General Caveats about Prenatal Diagnosis All couples have ~3% risk of having a child with congenital problems requiring intervention No 100% guarantees – even if prenatal tests are ‘normal’ All couples bring unique ethnocultural, moral, in addition to /or religious perspectives to the process Use of non-judgmental, non-directive genetic counseling is important in helping families make the best choice as long as them The decision to terminate or continue a pregnancy based on prenatal diagnostic findings is never an easy decision Goals of Prenatal Diagnosis in addition to Counseling Assess pregnancy Determine specific risks to fetus Evaluate prenatal diagnostic options Diagnosis fetus when desired in addition to possible Educate family about diagnosis, likely outcomes, potential in addition to management options Discuss risks, benefits, in addition to uncertainties Explore family concerns Provide risk assessment as long as other family members Provide psychosocial support in addition to follow-up

Who benefits from prenatal diagnosis Older women (> 35) at increased risk of chromosome disorders Individuals in populations at increased risk of a genetic disease: Tay-Sachs: Ashkenazi Jews, French Canadians Sickle cell anemia: Africans, Mediterraneans, Arabs, Turks, Indo-Pakistanis Thalassemias: Mediterraneans, Arabs, Turks, Indo-Pakistanis, Southern in addition to Southeast Asians Cystic Fibrosis: Caucasians Fragile X syndrome: All women () Family history of a genetic disease/chromosome disorder Maternal disease associated with increased risk of birth defects (diabetes, phenylketonuria) Known teratogen exposure during pregnancy Abnormal screening tests or ultrasounds Women who are concerned/worried What genetic tests are AVAILABLE What genetic tests should be OFFERED What genetic tests should be RECOMMENDED Preconception/Carrier Testing Couples/individuals in “high risk” populations considering pregnancy should be offered voluntary, in as long as med testing prior to pregnancy Appropriate education in addition to counseling about risks in addition to benefits of tests in addition to various reproductive options should be available prior to in addition to after testing

Cystic Fibrosis Autosomal recessive Progressive pulmonary disease Exocrine pancreatic dysfunction Infertility CFTR gene identified in 1989 over 800 mutations reported 1 in 25 Caucasians of Northern European ancestry are carriers of a CFTR mutation “All Caucasians should be offered preconception or prenatal CFTR mutation carrier screening” ACOG 10/2001 Genotype vs. Phenotype Severe CF – Mild CF – Male infertility

Prenatal Diagnosis Techniques Maternal Serum Screening Tests Triple screen (alpha-fetoprotein, beta-HCG, in addition to estriol) as long as neural tube defects in addition to chromosome trisomies Visualization of the fetus Ultrasound – 2D in addition to 3D Other (very special circumstances -X-ray, fetoscopy) Genetic in addition to biochemical studies of fetal cells Amniocentesis Chorionic villus sampling Fetal blood sample (percutaneous umbilical sample) Circulating fetal cells in maternal blood Maternal serum alpha-fetoprotein (MSAFP) Levels increase with gestational age in amniotic fluid in addition to cross placenta into maternal bloodstream With neural tube (anencephaly, spina bifida) in addition to body wall defects (gastroschisis, omphalocele) AFP is HIGH Using MSAFP along with detailed ultrasound study is sensitive to detect open body wall in addition to neural tube defects MSAFP is LOWER in trisomies but using MSAFP alone to pick up trisomies is not sensitive or specific MSAFP most sensitive between 16-18 weeks To interpret must know gestational age, twin status, maternal health status(diabetes), in addition to race – falsely high in addition to falsely low values are often due to poor gestational dating Maternal serum beta-human chorionic gonadotropin (MSb-hCG) Produced early by trophoblasts during pregnancy Elevated by first missed period in addition to used as a pregnancy test Elevated hCG in the mid-late 2nd trimester in trisomies Most sensitive when used in correlation with MSAFP level eg. MSAFP low AND MSb-hCG high suggests increased risk of a trisomy VERY elevated hCG in the mid-late 2nd trimester along with an absence of a fetus suggests trophoblast disease (molar pregnancy)

level gestational age HCG AFP Maternal Serum Estriol Derived from adrenal gl in addition to hormone which is further metabolized by the placenta Tends to be lower in trisomies in addition to in neural tube defects associated with adrenal hypoplasia MSAFP vs “Triple Screen” Increased MSAFP alone is pretty sensitive as long as open body wall defects ( eg. >95% as long as anencephaly, 80% as long as spina bifida) Decreased MSAFP alone is NOT very sensitive as long as trisomies (only 25%) “Triple screen” increases sensitivity (eg. to about 60% as long as Down syndrome) Use of more biomarkers further increases sensitivity, but no panel 100% sensitive or specific

Disorder AFP hGC hCG/AFP ratio Trisomy 21 Trisomy 18 Anencephaly Spina Bifida Twins Fetal death N N N N

Ultrasonography Non-invasive – no known risks to mother or fetus 2-D, 3-D high resolution in addition to fetal echocardiograms Assess fetal proportions, sex, position, growth; placenta, amniotic fluid Accurately estimate fetal age At 6 weeks can see developing embryo Between 16-20 weeks gestation is optimal time to screen as long as congenital anomalies as long as prenatal diagnosis False positive in addition to false negative findings – conditions with subtle findings may be missed, (eg. trisomy 21)

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Gastroschisis Some conditions detected by ultrasound Neural tube defects Body wall defects Major organ abnormalities Oligo- or polyhydramnios Major limb abnormalities Growth disturbances

Genetic Amniocentesis Invasive technique to obtain fetal cells Study chromosomes, DNA, or biochemical profile of fetus Approach via mother’s abdomen under ultrasound guidance Enough fluid after 14 weeks of gestation to per as long as m safely Most often pre as long as med between 15 in addition to 20 weeks gestation Risks: fetal loss – < 0.5% higher than normally expected trauma in addition to infection, risk of club foot reported when done < 13 weeks Later in pregnancy (eg. third trimester), amniotic fluid can be taken to assess fetal lung maturity prior to a premature delivery Chorionic Villus Sampling Invasive technique to obtain fetal cells Study chromosomes, DNA, or biochemical profile of fetus Most often approached through the vagina but may be approached through the abdomen of mother Most often per as long as med between 10-13 weeks gestation, but as early as 9 weeks in addition to any time after 13 weeks More genetic material from cells to study right away Risks: fetal loss rate slightly higher than amnio - about 1% Very slight risk of increased limb abnormalities if done < 10 weeks risk of infection Management After Loss of a Fetus due to Miscarriage in addition to Termination Conduct clinical evaluation/autopsy to confirm diagnosis Offer parents an opportunity to see fetus if miscarriage , still birth or late termination due to genetic problems Name, photograph,obtain hair, memorialize, bury Provide referrals to social work/psychological services in addition to support groups as appropriate Arrange follow-up genetic counseling Most importantly be aware, available, in addition to sensitive to needs - all people will deal loss in different ways MEDICINE AND PUBLIC HEALTH ETHICAL, LEGAL, SOCIAL ISSUES GENETICS / SCIENCE / TECHNOLOGY Primum non nocere “I will apply treatment as long as the benefit of the sick according to my ability in addition to judgment; I will keep them from harm in addition to injustice” 3rd paragraph Physician’s Hippocratic Oath

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