Genetic testing and screening: newborn Screening and prenatal Testing/Screening

Genetic testing and screening:newborn Screening and prenatalTesting/Screening Sonia M. Suter, M.S., J.D. Assoc. Prof. of Law George Washington University

Overview of Talk • History of NBS • Issues Associated with NBS • Prenatal Testing and Screening (“PTS”) • Routinization of PTS and Its Implications

Newborn Screening • Most systematic form of genetic screening • Began with PKU in 1960s, broad expansion • Public health program • To identify diseases where early intervention can reduce/eliminate mortality, morbidity, disability • More than testing, whole system • Legislatively implemented • NBS legislation in every state • State-by-state variation

PKU screening • Phenylketonuria (PKU) • Autosomal recessive metabolic disorder • MR unless eliminate phenylalanine from diet • Initially, not legislated or through health dept. • Strong advocacy for mandatory legislation • Reluctance of individual physicians to test • Most states mandated screening, early 60s • 43 had formal statutes by 1973 • Health dept NBS units in 1960s and 70s

Beyond PKU • Broader range of screening tests • 1960s: galactosemia, maple syrup urine disease, homocystinuria • 1970s: congenital hypothyroidism • 1980s: sickle cell disease • Practice NBS varies from state to state • Great lack of uniformity diseases screened for • Usually tested for handful of conditions

NBS today • Technological advances • From one assay per condition • To tandem mass spectrometry: > 40 conditions • Move toward uniform panel of disorder • ACMG recommended panel of 29 core disorders • 25 secondary conditions detected incidentally • Consensus toward much broader testing • Every state does or will test for > 30 conditions • Some up to 57 (limited knowledge/treatment)

Issues in NbS • Screening criteria • Mandatory or elective? • Storage of samples • Inequities of system • Pressures toward ever expansive screening • Risks associated with expansion

1) Screening Criteria • Scientific considerations • Validity of test • Efficacy of available treatments • Political considerations • Relevance of cost: test, dollars saved, etc. • Advocacy groups • Ethical considerations • Communitarian v. individualistic perspective

Screening Criteria • Benefit to newborn (> 40 years) • Effective treatment or early intervention • Natural history of disease adequately understood • Benefit to family • Enhances reproductive decision making • Benefit to society • Learn about natural history of disease • Whether technology allows screening • Screen unless compelling reason not to • Cost/benefit analysis • Rare diseases: screening cost/detection large

2) Mandatory or elective? • Legal/ethical principle of consent • Treatment of children requires parental consent • But public health paradigm: • mandatory if condition poses threat to others • Governmental authority to mandate? • Police power: • Power to regulate for public welfare • Parens patriae: • Power to act as parent for those in need of protection

Norm Has been Mandatory • 48 states mandate NBS • All but 4 have opt out for religious reasons • Some allow opt out for any reason • Few parents actually opt out (or realize option) • 3 require informed parental consent

Rationale for Mandatory • Urgent need for early diagnosis • Benefit of treatment • Risks of testing/treatment minimal • Practical way to ensure kids tested • Few acceptable reasons to decline • More cost effective

Arguments Against Mandatory • Police power inapt • Doesn’t fit public health model • Threat to future children? • Parens patriae inapt • Limit on state’s ability to override parental choices • Not clear decisions always based on concern for child • State often doesn’t provide treatment • Goes against norm of parental consent • Comparable to other risks parents may take • Very few decline when consent required • Better follow up if parents informed

Consent v. informed consent? • Is informed consent an absolute? • Is informed consent too costly? • Compromise – limited disclosure? • That child has been screened for several diseases • Need to follow-up positive result immediately • Let parents know where they can get more info • If positive result, some information re: disease • Confirmed diagnosis, detailed information

3) Storage of Blood Spots • Retention time varies from state to state • Some indefinitely, some only months • Legal uses of samples varies • Need for adequate confidentiality protection • Potential research source • Valuable national repository of genetic material • Must consent be provided? If anonymized? • Mandatory nature complicates question

4) Inequities of NBS • State-by-state practices source of inequity • Variation in test panels across states • Services received by families varies • Costs of various elements of screening varies • Technical decisions about cut-off for positive

5) Pressures to expand NBS • Moving toward broader notion of benefit • Incidental identification of diseases • Technological imperative • Consistent with personalized medicine • Knowledge is power, is responsible • Strong pressure from parents/support groups

6) Risks of such expansion • Identify diseases with no benefit/ knowledge • Increased risk of false positives/negatives • Increased incidental findings • Even greater burden on infrastructure

a) Untreatable conditions • “Sick child” label • Stigmatization • Impact on parent-child relationship/ family • Treatment odyssey • Unnecessary use of dollars • Severity can vary, so why not wait until symptoms and diagnosis?

b) False Negatives/ Positives • False negatives • Risk at various levels of program • False reassurance: will physicians be less likely to make diagnosis than if no screening? • False positives • Anxiety, confusion, uncertainty • Mislabeling children as ill • Clinically insignificant positives, if don’t know natural history of disease

Legal aspects of False positives/negatives [out?] • False negatives: possible malpractice claim • But questions of governmental immunity • E.g., formulation testing standards • Must show lack of due care and • would have received treatment if diagnosed • False positives: legal remedy unlikely • Damages likely to be emotional distress • Law reluctant to recognize pure emotional distress

C) Incidental findings • E.g., MS/MS identifies core diseases and incidentally finds others (secondary group) • Or identify carrier child, unaffected • Should these be reported to families? • What considerations? • Treatment • Knowledge of natural history of disease • Sensitivity/specificity • Costs: stigmatization, treatment odyssey • Benefits: family planning

D) Enhances systemic burdens • Education HCPs and families • Technical issues associated with new tests • F/U to diagnosis to treatment each disease • Long-term treatment and management • An inadequate infrastructure -> risk of • Failure to detect • Failure to F/U or • Failure to treat

prenatal Testing/ Screening • Another area of with fairly long history • Not explicit health program like NBS • No system of legislation like NBS • Voluntary • But expansion and routinization of PTS

Prenatal Testing/Screening • Prenatal Testing • Amniocentesis: 16-18 weeks • CVS: 10-12 weeks • Ultrasound • Prenatal Screening • Trisomies • PAPP-A and US: 11-14 weeks • Triple or quadruple screen: (15-20 weeks) • Neural Tube defects • AFP (15-20 weeks) • Ultrasound

Issues of PTS • Must be voluntary • Consent must be informed • But increasingly routinized • Pressures toward testing • True choice is more limited • Informed consent may be inadequate, especially with prenatal screening • Implications of routinization with expansion of range of tests

Routinization of PTS • Societal norms • Pressures from medical profession • Legal pressures

Societal norms • Sense of moral obligation to screen/test • Good parents test – “doing what’s best” • Limited understanding of limits of tests • Limited understanding of limits of options • Belief medically required • Desire for control and reassurance • Sense of knowledge as power • May be some desire for “quality control,” especially if increase range of testing abilities

Medical Pressures • Value of knowledge • Preparation for delivery • Helps family prepare • Implied values simply in offering test • Personal biases in favor of knowledge?

Legal pressures • Best protection against wrongful birth suit to have tested and disclosed results • Creates incentive to pressure patients to screen/test • Fear of liability led to ACOG alert: • “Imperative” to advise every OB patient of MSAFP screening 1985 • In spite of uncertain value • Created new standard of care

Legal pressures • CA mandate to offer MSAFP screening • National goal to screen 90% pregnant women • Study of providers and patients found • Providers encouraged or pushed screening • Repeated offer when patients refused • Some told patient to take test • Limited discussion of meaning/purpose • Very general description of conditions screened for • Didn’t explain options/decisions if positive • Didn’t explain voluntary • Many patients didn’t understand it was voluntary

Legal Pressures • 2007 ACOG Recommendations: • Down syndrome screening should be offered to all women regardless of age < 20 weeks • Advised that all women should have option of diagnostic testing regardless of age • Neural tube screening mid-trimester for women who elect only first-trimester screening for DS • Recognizes decision to have amnio/CVS based on many factors • Affects standard of care, legally • Will these recommendations be incentive to push rather than merely offer tests?

Implications of Routinization • Limits choice • Anxiety • Weakens informed consent • Impact on disabled community • Limits broader social discussion about moral implications of new and future PTS

Weakens Informed Consent • Limited time to discuss options • Move from genetics centers to OB offices • Prenatal screening becomes one of multiple tests • Limited discussion about • Meaning of screening • Conditions screened for • Possibility of false positives • Whether screening accords with patients’ values • Possibility of termination (reluctance to discuss)

Limited Choice and Anxiety • Limits Choice • Patients don’t understand they have choice • Pressures from health care professionals may be difficult to resist • Anxiety with screening false positives even after normal amniocentesis • Didn’t understand screening v. testing • Believed positive results meant diagnosis • Convinced something must be wrong • Hadn’t considered need for further testing

Impact on Disabled Community • Routinization of PTS is potentially stigmatizing to the disabled community • Suggests social consensus about elimination of certain conditions through termination • Reduces complexity of the decisions • Presumptions about quality of life and meaning of disability • Focus on eliminating disabilities, draws attention away from disabling social barriers

Moral Implications • Medicalizes difficult personal, moral decisions about reproduction • Suggests neutrality of the information, and masks the moral dimensions of choices • As possibility increases to use PTS for traits, society must grapple with moral issues • If we treat as “neutral” knowledge more difficult

Final Points • Adhering to recommended principles of screening with NBS and prenatal screening? • Programs should be voluntary • Should have a federal agency to oversee and standardize screening programs • Evidence of substantial public benefit • Benefits outweigh costs • Means of evaluation of program established • Investigative pre-test • 1975 “Genetic Screening: Programs, Principles and Research • NBS may have been less successful • Prenatal isn’t treated under public health model

Genetic testing and screening: newborn Screening and prenatal Testing/Screening