Week 6.2 Prenatal Genetic Testing and Disability Ethics

Conceptual Underpinnings: Prenatal Genetic Testing

• Definition: Prenatal genetic testing involves obtaining genetic information about a developing fetus during an established pregnancy.

• Distinction from Pre-implantation Testing: Prenatal testing is distinct from pre-implantation genetic testing (PGT), which involves screening embryos during the IVF (In-Vitro Fertilization) process before a pregnancy is established.

• The Intersection of Science and Ethics: The course objective is to understand how biological mechanisms intersect with social and ethical analyses.

Evolution of Prenatal Medicalization

• Historical Development: The medicalization of pregnancy evolved through three technological waves that provided increasingly deeper "windows" into fetal development.

• Ultrasounds and Sonography (1960s): The first wave, involving visual imaging to gain insights into development.

• Maternal Blood Tests (1980s): Tests used to infer health status or genetic risks based on protein or hormone levels in the pregnant person's blood.

• Sampling Fetal DNA (1970s/80s): The direct sampling of fetal genetic material to determine traits or chromosomal status.

Screening vs. Diagnostic Testing Methodologies

• Screening Tests:

  • Purpose: To determine the "odds," "chances," or "risk" of a fetus having a specific genetic trait.

  • Nature: Less invasive (imaging or maternal blood draws) and more affordable.

  • Limitations: Less accurate; prone to false negatives (result says no finding when the trait is present) and false positives (result says trait is present when it is not).

  • Clinical Use: Often used as a "first line" of testing to identify if further investigation is needed.

• Diagnostic Tests:

  • Purpose: To provide a definitive and accurate diagnosis.

  • Nature: Involves direct sampling of fetal DNA; more invasive and typically more expensive.

  • Reliability: High accuracy with fewer false results, though no test is $100\%$ accurate.

Aneuploidy and Chromosomal Variations

• Aneuploidy: A condition where there are more or fewer chromosomes than the standard expected count in a karyotype.

• Trisomy 21 (Down Syndrome): A specific type of aneuploidy involving $3$ copies of chromosome $21$ instead of the standard $2$.

• Trisomy 13 and 18: Other common chromosomal variations screened for during prenatal testing.

• Sex Chromosome Aneuploidy: Variations in the number of X or Y chromosomes, often associated with intersex traits.

Advanced Diagnostic Techniques: Amniocentesis and CVS

• Amniocentesis:

  • Timing: Performed between $15$ and $20$ weeks of gestation.

  • Procedure: A needle is used to sample amniotic fluid, which contains fetal skin cells and DNA excreted by the fetus.

  • Risk: Carries a small associated risk of miscarriage.

• Chorionic Villus Sampling (CVS):

  • Timing: Performed between $10$ and $13$ weeks (about $5$ to $7$ weeks earlier than amniocentesis).

  • Procedure: Samples the chorionic villi—cells that form the placenta.

  • Fetal Origin of the Placenta: The placenta develops from the fertilized egg, meaning its DNA is identical to the fetus's DNA, not the pregnant person's DNA.

  • Risk: Also carries a risk of miscarriage due to its invasive nature.

NIPT (Non-Invasive Prenatal Testing) and Cell-Free DNA

• NIPT/NIPS/Cell-Free DNA Testing: A newer technology (validated around $2011$) that blurs the line between screening and diagnosis.

• Mechanism: Fragments of fetal DNA (cell-free DNA or cfDNA) float in the maternal bloodstream. These fragments can be isolated from the pregnant person's blood for genetic analysis.

• Advantages: It is non-invasive and can be performed as early as $9$ weeks gestation.

• Evolution of Recommendations: Originally recommended only for pregnant persons over age $35$ (due to higher statistical odds of aneuploidy). The American College of Obstetricians and Gynecologists (ACOG) now recommends offering NIPT to all pregnant persons regardless of age, though it should still be limited to screening for aneuploidy.

• Future Concerns: There is potential for NIPT to expand into testing for single-gene (monogenic) traits or non-medical traits, raising significant ethical concerns regarding accuracy and parental pressure.

Ethical Dilemmas and the Future of Prenatal Testing

• Individual Choice vs. Social Pressure: While reproduction is personal, choices are influenced by doctors, community values, religious beliefs, and political regulations.

• Justice and Access: Questions arise regarding whether testing will only be available to the wealthy (technological gatekeeping) or if "care deserts" (geographic areas lacking reproductive health resources) will limit options for others.

• Selective Termination: Trisomy $21$ is a flashpoint for controversy. In some countries, like Iceland, nearly $100\%$ of pregnancies with a positive Down Syndrome diagnosis are terminated. Analysts question if this constitutes a form of modern eugenics by selecting against entire categories of human experience.

• Regulation: Current legal landscapes, such as abortion bans or the Alabama Supreme Court ruling declaring IVF embryos as people, significantly impact the availability and ethics of prenatal testing.

Disability Justice and Models of Disability

• Medical Model: Views disability as an individual biological problem or "misfortune" that needs to be cured or fixed.

• Social Model: Views disability as the product of an environment that fails to accommodate variation. The problem is the "stairs," not the person using the "wheelchair."

• Fetal Value: Dr. Rosemarie Garland-Thompson argues that disability is a culturally fabricated narrative rather than a inherent negative. Disability justice advocates challenge the "ableist assumption" that people with genetic conditions fundamentally suffer more than others.

Deaf Culture and Genetic Perspectives

• deaf (lowercase d): Refers to the audiological condition of hearing loss.

• Deaf (uppercase D): Refers to a cultural, linguistic, and community identity. Deaf culture considers itself a linguistic minority group (e.g., users of ASL or American Sign Language).

• Community Views: Research (e.g., from $1998$) shows that some individuals within the Deaf community view genetic testing for deafness as potentially devaluing to their culture. Some may even prefer to have children who share their Deaf identity and linguistic heritage.

Questions & Discussion

• Q: How invasive are Amniocentesis vs. CVS?

• A: Both carry miscarriage risks. CVS can be done via the cervix (trans-cervically) or the abdomen, whereas Amniocentesis is typically abdominal. The specific risk data between the two varies but both are considered invasive compared to NIPT.

Slide Notes:

What is Prenatal Testing?

• 3 Main Kinds of Tests

  • Ultrasound / Sonography - first used late 1960

  • Blood Tests from Pregnant Person - first developed in 1980s

  • Direct Sampling of Fetal DNA - first used in 1970s in US, now coupled with targeted genetic screening and testing

Q: The main difference between prenatal genetic screening tests and prenatal genetic

diagnostic tests is that:

A: Screening test results establish odds that the fetus carries a genetic trait, while

diagnostic test results say more definitively whether there is a genetic trait

Screening Tests:

• includes ultrasound/sonography, blood tests from pregnant woman, and NIPT

• Non-invasive (imaging, blood draw)

• More affordable

• Establish risk or odds of developing a disease/condition (requires diagnostic test to confirm)

• Less accurate (more false positives and false negatives)

Diagnostic Tests:

• Direct Sample of Fetal DNA

• Invasive (amnio or CVS, small risk of miscarriage)

• More expensive (e.g., genetic tests)

• Identifies/confirms a disease/condition

• More accurate (fewer false positive and false negatives)

Blood Screening Tests:

• Hormone and protein tests (not genetic tests) that indicate odds of:

  • Spina bifida

  • Several aneuploidies (e.g., trisomy 21) - additional or reduced numbers of specific chromosomes

Non-Invasive Prenatal Testing (NIPT)

• Blood from pregnant person → analyzes fetal DNA in bloodstream

• Clinical availability:

  • 2011: Trisomy 13, 18, and 21; age > 35

  • 2013: expanded to sex chromosome aneuploidies, microdeletions, microduplications

  • Now: some single gene conditions are available but not recommended

  • Discussion about other tests becoming available

  • ACOG currently recommends offering to all pregnant persons for aneuploidy detection

Ethical Questions About Prenatal Testing

• The field is (and has been) dealing with questions about the complexities of choice and hard questions about genetic testing, reproduction, and eugenics:

  • Is choice confined to the individual, or do families, communities, science, and society more broadly influence the choices that are available and expectations about which choices are “best”?

  • How do technology and medicine contribute to the complexities of choice?

  • How do broader views of disability shape the landscape of prenatal testing? How are disability justice advocates and communities pushing back?

  • How does the history of eugenics relate to contemporary genetic testing efforts in reproduction?

“deaf” reflects an audiological condition - multiple genetic contributors (but not always genetic)

“Deaf” reflects a cultural, linguistic, and community connection

Sign language community is a cultural and linguistic minority group

Culturally Deaf individuals hold more negative attitudes toward genetic research and genetic testing for deafness than non-culturally deaf or hearing individuals

Culturally Deaf individuals also have some interest in genetic information

Culturally Deaf individuals desire more involvement in the design and implementation of genetic research that directly affects them

Role of physicians in shaping decision-making:

• Inadequate information and reinforcement of stereotypes

• Disregarding of testimonials of people with DS and families

• Counseling to terminate

• Hyperfocus on medical aspects

• “...by discussing DS solely as a medical condition—and failing to recognize that it is also a lived social experience—physicians reinforce the medical model of disability and the notion that disability itself, not societal discrimination against people with disabilities, is the problem to be solved”

Eugenics claims derived from:

• Population-level rates of selective abortion after DS prenatal testing are high in many countries

• Questions about nature of choice in light of social expectations and lack of services for people with disabilities

• Authors distinguish between “historical eugenics” and “contemporary eugenics”

• Authors note that it is unhelpful to characterize all prenatal testing as eugenic, or to blame parent(s), doctors, etc