storing newborn blood spots: modern controversies

Storing Newborn Blood Spots: Modern Controversies Linda Kharaboyan, Denise Avard, and Bartha Maria Knoppers

hough in existence for over thirty-five years, due to the increasing panoply of possible tests. T Newborn screening programs are drawing

public attention. Many jurisdictions have mandatory newborn screening programs for treatable disorders. Disorders are detected through tests on blood spots drawn from a newborn's heel soon after birth and verified through a diagnostic test with follow-up. Unbeknownst to most parents, these blood spot cards are also stored thereafter. Indeed, while dried blood spots (DBSs) are primarily used for screening for health problems, experience demonstrates that they can be made useful in various contexts unrelated to screening.

Newborn dried blood spots have taken on a new life as a result of developments in genetics and the increasing ability of bioinformatics to link DNA information with clinical data. Additionally, storage and secondary uses have been documented to occur without parental consent. In the absence of uniform guidelines, there is an urgent need to develop policies that address the issue of dried blood spot storage, secondary use and the ensuing ethical, legal, and social dilemmas.

Internationally, regionally, and nationally, govern- mental, professional, and consumer organizations have contributed to the debate on the storage and retention

of newborn screening residual blood samples. Despite all these efforts, a consensus of opinion on any one issue has yet to be reached. We will compare current guidelines and policy documents that apply to banking DBSs and assess the similarities and differences as concerns consent to storage, length of storage, and access to stored samples. Our comparison examines countries from different regions of the world and offers different socio-political contexts for examining the rationale for storage and issues of confidentiality and consent. As novel uses of newborn spots emerge,' and as researchers and public officials contemplate mechanisms for the retention of DBSs by newborn screening laboratories2, it is crucial to outline current purposes and lengths of storage and adequate consent requirements for the secondary uses of archived bloodspots in research or otherwise.

Banking Residual DBSs: Purpose and Length? Purpose of Storing Since the late 1960s, newborn screening to detect congenital metabolic disorders has been standard paedi- atric procedure in newborn care in most industrial- ized countries. Early detection of pre-symptomatic disorders such as Phenylketonuria (PKU) and Congenital hypothyroidism (CH) has prevented chil-

~ ~ ~~

Linda Kharaboyan is a lawyer and holds an LL.B.fiom the Univemity ofMontreal (Quebec, Canada). She & a research asso- ciate in the Genetics and Society Project at the Centre de recherche en droit public at the University of Montreal and special- izes in bioethical and legal issues related to genetic screening and testing of minors. Denise Avard, holds a Bachelor's degree in Nursing and a Master's degree in Sociolomfiom the University of Ottawa (Ontario, Canada), as well as a Doctorate in So& Epidemiologyfiom the University $Cambridge, England. Currently, she &Research DiTeCtOTfOT the Genetics and S o k Q Project at the University of Montreal. Bartha Maria Knoppers is a Professor at law at the University of Montreal (Quebec, Canada). She obtained her Law degrees f i o m McGill University (Montreal, Quebec, Canada) and University of Cambridge (England), and her Doctoratefiom the Sorbonne University in Paris (France). She currently holds the Canada Research Chair in Law and Medicine and chairs the International Ethics Committee of the Human Genome Organization (HUGO).

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dren from suffering intellectual impairment, developmental delays, and even premature death.3 Screening of such disorders requires that a small blood specimen be taken from the heel of a baby. Blood samples, or dried blood spots (DBSs), are collected onto absorbent paper called Guthrie cards (named after James Guthrie, an American microbiologist who invented the screening test for PKU); and are retained for future reference for varying periods of time.4

Although the primary purpose of collecting blood samples from newborns is early detection and treatment of infants, stored DBSs are used in other contexts:

A) Conhatory diagnosis: Residual blood samples are essential for diagnostic purposes and to reassure those who may be falsely diagnosed by the screening program, including those having false- positive or false-negative results. In some cases they may also be used to enable follow-up contact with an infant's family to initiate an effective inter- vention for children diagnosed with a ~ondition.~ B) Quality assurance and public health needs: Residual DBSs are used to validate and develop testing methods. In epidemiological studies, they are used to provide information about prevalence of certain diseases and to assist in health surveillance.6 C) Research use: DNA information extracted from the blood spot is attractive to researchers to help understand different diseases and developmental disorders and in the study of gene-environment interactions. D) Clinical testing: DBSs are also being used for clinical testing for post-mortem identification of a genetic condition that may have contributed to a child's death. E) Non-medical use: Finally, DBSs have been con- sidered helpful in identifying kidnapped children7 or bodies of deceased persons (see the Netherlands example discussed below) and in certain cases have been subpoenaed by the courts to reveal paternity (see the New Zealand case discussed below) or to identify criminals.8

These various applications of DBSs will generally determine how long samples need to be retained for and whether they will be stored in an anonymous or identifiable manner.

Length of Storage Our assessment of international statements and guidelines addressing newborn screening revealed that there is no general agreement on the length of retention of DBSs.g(see table) A review of some coun- try specific responses on this issue as well as testi- monies from public health laboratory directors indi-

cate that length of retention of DBSs varies in accor- dance with the purpose of retention. When stored only to ensure proper medical follow-up for screened newborns, the samples are not kept for long periods. For example, in Canada, the province of Quebec con- firmed that samples, which are used for confirmatory and quality control purposes, are kept for up to a year and are then destroyed.10 However, it appears that when DBSs are made available for future research, for screening program audit or to provide new medical information for the benefit of the family, samples may be stored for longer periods and sometimes even indefinitely. In France, where samples cannot be used for purposes other than those for which they have been collected, sample cards are destroyed soon after completion of testing.I1 It has nonetheless been suggested that cards be kept for retrospective diagnosis of genetic diseases resulting in the sudden deaths of infants.I2

The National Pathology Accreditation Advisory Council in Australia recommends that DBS cards be stored until the child reaches the age of twenty-fiveI3 instead of for a duration of fifty years as was previously recommended.'4 The Royal College of Pathologists in the U.K., for its part, suggests storage for twenty years or longer if no deterioration has occurred, specifylng that such cards may be useful sources of DNA for retrospective analysis and research.'5

In Denmark, blood samples from all neonates are stored indefinitely at the National Serum Institute.I6 Storing samples indefinitely and in identifiable form has allowed the Institute to rapidly respond to daily enquiries from hospitals, doctors, and midwives about analytical replies to PKU samples in view of a child's developmental problems. The samples have also per- mitted the pursuit of ongoing quality control and the improvement of analytical methods. In fact, such improvements have led to a fall in the number of false-positives from approximately 1% in 1985 to 0.04% in 1996.l7

Generally, although there is variability on the actual length of retention, it has been suggested that decisions concerning duration be made on the basis of the stability of the analytes of interest, the potential uses of DBS samples, and finally, the technical issues concerning proper storage and ease of retrieval.18

Informed Consent Most guidelines ultimately concur that length of storage should be communicated to the person authoriz- ing sample retention. (see table) Well informed parents are best placed to consider their child's health and should be aware that they or their child might or might not be contacted or affected by future studies or

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Storage of Newborn Blood Spots: International Comparison

Australia Canada Denmark France N e w Zealand UK USA

Length of time DBSs ore

stored

Until the child reaches 25'

Between I -30yrs2

Indefinitely) Destroyed soon after completion of testing4

Varies from 2 months to indefinitely5

20 years o r longer6

N o specific regulation

~ _ _ _ _ _

Varies state to state

2 weeks t o indefinitely7

N o specific regula- tions, however recommendations have been made to obtaii consent before stor

ingi5 and with regards t o what

information should be conveyed at the time of collectioni6

"Informed refusal 01 dissent" has been applied to sample

card collection rather than a

requirement for informed consente

HGSA recommends obtaining informed

consent9

Yes I O Yesi I It seems like no consent is neededi2

"Informed refusal 01 dissent" has been applied to sample

card collection rather than a

requirement for informed consent."

HGSA recommend! obtaining informed

consenti'

Must consent be sought for

storage?

N o mention Yes, unless they are

anonymized

Only depart- mental staff members

iuthorized by the Director ,f the Statens erum Institute lave access to he regi~ter.2~

N o specific regulation, but consent has ben recommended.19

For development oi new tests, consent

should not be required if samples are anonymized. If coded samples are required or if samples are to be used for research, ethical

review board approval is required."

If samples are not

anonymized, !thical review oard approval is required2'

In general, yes.

If testing is conducted on anonymous samples, then con-

sent is not required.

Ethical review is required if coded

samples are to be used."

Parent must be recontacted if

coded samples are to be used.22

Must consent be sought for future use?

N o mention N o mention N o mention N o mention The child

The child's parents

rhere is a memoran. dum of understand- ing between NSW Police and NSW

Health that samples would only be

sought by police t o identify remair1s.2~

The child

The child's parents

Nho can have occess?

I .Australia - National Pathology Advisory Council, Retention of laboratory Records and Diagnostic Material 2002).

2. Personal Communication with provincial bublic Health Laboratory directors (October 2002).

3. Danish Medical Research Council, Heohh Science Informotion 6anks - Biobanks, Report, (January 1996). available at <htt ://www.forsk.dk/eng/ssvf/publ/biobanker-ukb.

4. J.F. t-! attei, "Ethical and Le I Issues Associated With the Conservation of Blood Samples," in .P.$arriaux and J.L. Dhondt, eds., New Horizons in Neonatal Screening (!Amsterdam: Elsevier Sciences, 1994): 4 1-45.

5. Human Genetics Society of Australasia HGSA , Policy Statement on the Retention, Storage and Use ofSample Lards A m Newborn Screening Programs. Australia 1999).

6. United Kingdom -idorking Party of the Royal Colle e of Pathologists and the Institute of Biomedical Science,Fhe Retention and Stora e of Pathological Records and Archives, Report of the Workingf'arty of Biomedical Science, 2nd edition (1999).

7.W.H. Hannon. L.O. Henderson, C. . Bell, "Newborn Screenin Quality Assurance" in M.J. Khou W Burke and E. .Thornson, eds., Eenetics and Public Health in the 2% Century (New Cork Oxford University Press, 2000): 243-260.

8. L. Skene, "Access to and Ownership of Blood Sam les for Genetic Tests: Guthrie Spots," journal of Law and Medicine !( 1997): 137- 139.

9. Human Genetics Society of Australasia HGSA , Policy Statement on the Retention, Storage and Use of Somple Lards A m Newborn Screening Programs. Australia, (I 999).

10. Ontario Law Reform Commission, Report on GeneticTestin Toronto: Ontario Law Reform Commission Ontario, I 995

I I. 8. Norgaard-Pederson. "Use of Stored Samples from the Danish PKU Register" in B.M. Knoppers, ed., Human DNA: law and Policy, International and Corn arative Perspectives (Amsterdam: Kluwer Law International, I 997): 83-3 I I.

12. National Consultative Ethics Committee, Opinion and Recommendations on "Genetics and Medicine :from rediaion to prevention", Report no. 46. France (October 30, 1998.

13. L. Skene, "Access to and Ownership of Blood Samples for Genetic

Tests: Guthrie S ots," journal o law and Medicine 5 (I 997): 137- 139. 14. National ConsuLtive Ethics &mmittee, Opinion and

Recommendations on "Genetics and Medicine: From Prediction to Prevention," Report no. 46, France (October 30. I995

IS.American Academy of Pediatrics AAP), "Serving the Jamily from

the Future," Pediatrics I06 no. 2, su pl. (2000): 359-422 I6.The American Colle e of Medical Zenetics (ACMG , IlStatement on

Storage of Use of d n e t i c Materials" (I 995 available at: <http://www.faseb.org/genetics/acmg/pol- I 7!htm; (last visited September I, 2004

17. National Health & kledical Research Council, National Statement on Ethical Conduct in Research Involving Humans. (Canberra: National Health and Medical Research Council, 1999)

18. B. Norgaard-Pederson, "Use of Stored Samples from the Danish PKU Register" in B.M. Knoppers. ed.. Human DNA: Low ond Policy, lnternotionol and Corn omve Perspeaive?; (Amsterdam: Kluwer Law International, 1997): 83-3 I I.

19. National Consultative Ethics Committee, Opinion and Recommendations on "Genetics and Medicine :From Prediction to Prevention," Report no. 46. France October 30, 1995).

20. Human Genetrcs Society of Austdasia HGSA Policy Statement on the Retention, Storage and Use of Sample t r d s &m Newborn Screening Pro rams. Australia, ( 1999).

2 I. UK, Human kenetics Commission, Inside Informotion: 6alancing lnteresu in the Use ofPersonal Genetic Data (May 2002 .

22.The New York State Task Force on Life and the Law, dnetic Testing and Screening in the A e of Genomic Medicine, Report 2000). available at <http://www.~ealth.state.n~us/nysdoh/tas~ce~screenin~.h~

23. B.Wilcken,V.Wiley, "Newborn Screening in New South Wales: storage of samples" at: <http://www.chw.edu.aulprof/services/ newborn/factsheets/stoia e.htm > (last September ,2004

24. B. Norgaard-Pederson, d e of Stored Samples from the kanish PKU Register" in B.M. Knoppers, ed., Human DNA: law and Policy, International and Corn amve Perspm'ves (Amsterdam: Kluwer Law International, I 997): 83-3 I I .

Birth to the Medical Home. New 6 orn Screenin :A Blueprint for


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policies. Most guidelines agree with the process described in the following paragraphs.

Although length and purpose of storage might not represent major concerns for new parents, ideally, written information about sample collection, storage and future uses must be given to all parents as part of the newborn screening program.19 It is advisable that this information be relayed to parents by health professionals, such as gynaecologists, obstetricians or nurses, during prenatal visits, to ensure that parents have fully understood the information that has been provided and to give them the opportunity to ask questions.

Information pamphlets should describe the reasons for storage, specifylng whether DBSs will be used for diagnostic testing and treatment, for control and doc- umentation of previously performed analyses should suspicion of diseases arise later in life, quality assurance of screening programs, for the development of new and better assays, in epidemiological studies, for specific disease testing if unexpected events occur during the newborn’s first year of life or after, or for research projects.20

In addition, information should be given on methods of storage (anonymized, coded, or identifiable). Parents should be told about the security measures that have been implemented to protect the confidentiality of medical and genetic information found on the dried blood spot cards. In Denmark, for instance, after the screening tests are completed, the filter paper is stored in a freezer with the sample serial number, whilst the information on the data sample and the child’s personal identification information, such as name, date of birth, weight, and mother’s civil registry number are stored separately in a locked fill- ing cabinet. The sets of information and the samples are stored in two different buildings to ensure maximum security and patient confidentiality.21

Furthermore, parents should receive information regarding those who will have access to the stored DBSs and whether permission will be sought from them or from an Ethical review board should any third parties wish to have access to the samples for research use. (see table)

Whether held for a short period or an undefined length of time, stored genetic data must be held con- fidential at all times. Storage methods shall define what degree of confidentiality is afforded to newborn screening samples.

Protecting the ConJidentiality of Stored Samples Dried blood spots can be stored unidentified (anonymized), linked, or with identifiers. The use of the blood spot for research purposes raises questions

regarding the need to protect privacy and confidentiality, and whether newborn screening programs should be contacting parents for their consent. In the case of linked or identified specimens, the American Academy of Pediatrics has indicated that parents should be informed of the specimen retention policy and asked for consent to storage of residual blood spots.22

The manner in which DBSs and their genetic information are stored is important above all when deter- mining whether or not consent is required for secondary uses of samples. In general, it is recommended that archived dried blood samples be made available for research only if identifiers have been removed.23 The anonymization of data has been thought to set aside the need to seek explicit consent. Indeed, if DBSs are not identifiable then they are not “personal” and data-subjects consequently stand only a very low risk of being harmed.24 Nevertheless, whereas consent is waived when archived samples are anonymized, to anonymize DBSs without seeking consent at the time of collection for anticipated, anonymized research, is viewed by some as questionable and could undermine public trust in research.25

When investigators require access to linked or coded samples, seeking renewed consent from the parents (or from the subject, if the latter has reached the legal age to consent) is the general principle. In exceptional circumstances and when specific criteria are satisfied, ethical review boards have been given authority to waive consent requirements. Such is generally the case when research is of minimal risk, when it will not adversely affect the subject’s rights and wel- fare, when it is impracticable to obtain consent and whenever appropriate, subjects will be provided with pertinent information after participation.26 Subject to ethical review board approval and provided that parental consent has been obtained, the use of identified or coded samples has also been deemed acceptable if researchers are able to demonstrate that DBSs are the best samples around and that similar data would not be available from adults.27 In contrast, some have suggested that existing medical records and stored samples containing identifying information be made available for research without explicit individual consent or ethical review board approval if the study does not require that that donors be re-contacted or identified.28

Given that the vast majority of newborn dried blood samples are collected and then stored for diagnostic or therapeutic purposes, the mere purpose of collecting DBSs automatically entails inclusion of identifying information, such as the patient’s name, hospital identification number, etc.29 If blood spots are stored

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with identifiers, the infant can be identified and such data would still bear a threat to privacy. To ensure privacy of the genetic data found on dried blood spots, it would be ideal to anonymize the samples before storing them, once confirmatory diagnosis has been completed. If all identifiers from the residual samples were removed, there would be no danger of linking a blood spot to the actual donor: thus eradicating any possible disclosure of information to third parties. Although from the donor's privacy standpoint, anonymization would seem the best solution, this can only occur after the period of time suitable for valida- tion of positive cases because the laboratory needs access to the identifier if the newborn is screened positive.

In short, DBSs necessarily are identifiable at the time of screening. During the period of confirmatory diagnostic testing, coding would serve to protect privacy. Subsequent anonymization should follow if storage unrelated to confirmatory testing is foreseen.

Secondary Uses of Archived Samples Identifiable samples have been deemed indispensable not only for quality control, forensic needs, and autop- sy requests, but also for research.30 Rapid and exten- sive developments in genetic research have triggered unprecedented demands for genetic specimens from a broad array of society. The specimens most widely available are those of newborn screening pr0grams.3~ As thousands of dried blood spots from whole popula- tions are stored every year, it is easy to understand why these samples represent such an immense value for researchers and others. DNA is a stable, unbiased sample given that it includes all newborns. Secondary uses of samples raise consent and privacy issues. Because Guthrie cards potentially include genetic information about individuals, it is important that privacy not be invaded without valid reason. Stored identifiable, blood spots can threaten individual privacy by revealing health information about an individual or about his or her family members. When in the hands of insurers, employers, or other third parties, these samples might also prove to be harmful leading to misinformation, discrimination, or stigma- tizati~n.~Z The following three case studies will illus- trate situations where the storage and further use of residual DBSs for non-medical reasons have raised ethical dilemmas. These are just a few examples that help demonstrate some of the privacy, confidentiality, consent, and public awareness concerns regarding the storage and secondary use of DBSs.

Stored Residual Dried Blood Spots for Identzjkation Emerging controversies are frequently due to the am- biguity as to who owns samples and who may have

access to Guthrie cards and to any linked information. Often, individuals having provided these specimens may have had no knowledge that they would be used for any purpose other than testing relevant to their immediate medical care or the care of their newborn babies. Between 1995 and 2000, the National Insti- tute for Public Health and the Environment (RIVM) of The Netherlands (on recommendation of the Newborn Screening Steering Committee) began to store Guthrie cards from all newborns. Initially, DBS cards were coded and stored for five years, but in view of the growing interest of long-term epidemiological studies, in 1998 the maximum storage duration was changed to indefinite. Over that period, several groups of investigators applied for and were given access to these Guthrie cards. As consent for storage and further use had not been obtained from parents prior to storage, parental consent was sought before release when researchers wished to link demographic data to the cards.

Nevertheless, parents, government officials, and the population as a whole had never been informed that newborn screening cards were being stored. In May of 2000, this information became publicly known after the explosion of a fireworks factory in the town of EnschedC, where twenty-one people instantly died and an entire residential area was destroyed. As identification of the bodies had become almost totally impossible, journalists suggested that the dried blood spot collection be used to identify the human remains.33 Public outrage about stored samples occurred when the existence of such a collection became known; more so in light of the 1995 Code for Good Conduct which established that human tissue samples including blood samples could not be used for other purposes without the owner's explicit consent, unless they were made completely anonymous.

To remedy the fact that parents had not been given the opportunity to consent to other uses, the Minister of Health offered parents of children born between 1995-2000 the choice of requesting the destruction of their child's Guthrie card. In addition, the Newborn Screening Steering Committee decided that the maximum length of storage would again be for five years and that parents would receive explicit information to allow for appropriate informed consent for storage.34

Stored DBS for Paternity Testing Others might also have an interest in DBSs for secondary uses, either for paternity testing and forensic or law enforcement purposes.

Guthrie Test samples have been banked in New Zealand for more than thirty years. In 1999, in an action for paternity, a man asked the High Court to have his child's blood sample released for DNA analy-

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Potential predicaments regarding the secondary uses of DBSs might seem far-fetched today, but they are certainly not unfounded. Modern

controversies will emerge each time an identifiable blood sample from a newborn screening test is stored and used for a purpose other

than that for which it wits originally intended.

sis after the baby's death. The mother claimed that releasing the sample would be unlawful since it would be used for a purpose other than the original intent. Furthermore, she stated that she had not been informed that a blood sample for Guthrie Test analysis had been taken from her child and that she had never consented for this sample to be obtained, to be stored indefinitely, or to be used by the National Testing Centre.

Although newborn screening in New Zealand is not mandated by law and explicit consent to screening is not required, section 7 of the Code of Health and Disability Services Consumers' Rights 1996 states the right to make an informed choice and give informed consent before health services are provided (7(1)), with regard to storage ("(10)) and return or disposal of bodily substances obtained in the course of health care procedures (7(9)). Despite the fact that the mother had never been informed nor had she been asked to consent to blood withdrawal for newborn screening, Auckland High Court in H v. Q5 ordered the Auckland Healthcare Services to produce to the Court the newborn screening dried blood spot sample card and that DNA analysis of the blood sample be undertaken.36

The court decision also revealed other situations where the National Testing Centre (NTC) of New Zealand could release PKU samples:

1) Where there is a mistake made in the testing of the sample and a case of one of the screened conditions is missed. In this situation the original sample would be sent to another new born screening laboratory for checking on different equipment. This is a crosscheck on the sample and also useful from quality assurance perspective. This release of the sample would be initiated by the Director of the NTC.

2 ) The circumstances of family disease, for example, cystic fibrosis. If there is to be a pre-natal diagnosis, then there may be a request for genetic testing from the previous child. In the case of cot death where there is a suspicion of some type of metabolic disease, and it may not be possible to obtain another sample. These are almost always samples required where the child is dead and there is no other suitable sample, where they are looking

for genes or molecules. The requests are made from the Specialist with specific or implied consent from the family. 3) Requests from the Police, usually for dead people, and ID of human remains. This is usually with parental consent, take the example of the 'Sounds Murders'. There have been exceptions where the parents were implicated in the child's disappear- ance, and there was no consent, the Police obtained the sample by search warrant. 4) When parents request the return of the sample. The NTC publishes pamphlets to inform parents about Guthrie testing. The pamphlets which are distributed by the Lead Maternity Carer to parents have a paragraph on the back page notifying them that they can request the return of the sample. The paragraph informing parents that they may request the samples was added to the revised pam- phlet June 1997. The NTC will return the blood samples to parents. The parents are given advice on how to keep the samples in a safe place as they may be required in future for screening purposes. 5 ) Court Order, which is a new situation for the NTC.37

Even if a Court order can lawfully rule to allow for the release of a Guthrie card, as it did in H v. G and in the Watson murder trial also in New Zealand, where Guthrie Cards were released and used to identify spots of blood found at an alleged crime scene,3* health care professionals have an obligation to inform parents that DBSs may be used in different circumstances. A key feature is to make sure that parents have been given adequate information regarding who might have access to stored DBSs and what subsequent uses can be foreseen.

In addition, when children become capable of mak- ing their own medical decisions, it would be desirable and appropriate that they themselves be asked to consent for continuing storage and use.39 Although children constitute a vulnerable category and deserve special protection, it is not acceptable that they be bound to the permission given by their parents many years back, especially if their privacy is directly involved and they are deemed mentally capable or legally competent to decide at the time when the samples are to be reused.

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Stored DBSs for Anonymized Health Research Although dried blood samples may be extremely helpful from a public health surveillance standpoint and despite the fact that anonymized samples are least likely to breach privacy or violate individual rights, ethical issues may surface when utilizing anonymized or linked data without adequate informed consent or at a minimum, without notification.

One of the dilemmas of anonymized testing for transmissible diseases such as HIV, is that if dried blood samples are anonymized, there is no way to identify and re-contact a patient if he or she has tested positive. As an example, studies designed to meas- ure the prevalence of HIV among childbearing women in the state of New York were heavily criti- cized since anonymized DBS samples were used without consent and because HIV infected babies were being denied treatment seeing as their samples had been an~nymized.~~ Parents were therefore deprived of the knowledge of their infant's state of health and were unable to take precautionary measures to pre- vent future transmissions or provide adequate care for their child before manifestation of the virus.41 Yet, inevitably, introducing informed consent requirements could lead to bias selection since at risk parents would chose not to participate for fear of possible repercussions for employment or insurance. Moreover, the scientific value of the comprehensive nature of the database would be reduced.

By means of case presentations on the utilisation of newborn blood spots and the review of policy statements, we wish to demonstrate the need to be prospective and to foster informed discussion on ethical, social and legal questions. This being said, the use of anonymized samples is to be endorsed if patients have been notified that their child's blood spot will be anonymized and used in future research studies and that they have not objected. To ensure that informed choices are made, parents must also be notified that if tested samples are to be anonymized, there is no way of identifylng their child as being at risk for other diseases and thus no possibility of conveying such information to them. Finally, notification or anonymization should not induce us to believe that research can be conducted without some level of ethical review.

Conclusion Primarily performed by public health laboratories, newborn screening is in fact one of the largest genetic testing and screening programs of many nations. In light of the growing use of DBSs and their potential secondary applications, proactive solutions should be envisaged to ensure proper protection of choice, con-

sent, and the privacy and confidentiality of genetic information.

Potential predicaments regarding the secondary uses of DBSs might seem far-fetched today, but they are certainly not unfounded. Modern controversies will emerge each time an identifiable blood sample from a newborn screening test is stored and used for a purpose other than that for which it was originally intended. Considering the potential epidemiological and research value of dried blood spots for genetics, health service, and quality control, it is important to ensure that informed consent has been obtained prior to the reuse of the samples as the best possible way of protecting the child's interests while avoiding future access problems and promoting freedom of research.

While DBS banks might facilitate epidemiological analysis, improve health service planning, and better identification of individuals in need of preventive treatment or services, it is crucial that the health care potential of these banks not be darkened by questionable practices that have the potential to shatter public confidence in the value of newborn screening purposes per se. Introducing regulatory policies and security measures to regulate the length of sample retention and access to identifiable samples will help ensure that DBSs do not automatically end up as part of law enforcement or government DNA databases, or in the hands of other third parties including health insurance companies, employers, and academic institutions.

Transparency, supervision, strict rules for scientific study and informed consent requirements, are rules that a properly regulated biobank should live by. Gaining public confidence and participation is also critical. Following similar policies, public health agen- cies should:

Set out guidelines that define appropriate research

Develop model consent forms; Develop educational material to inform parents that residual blood spots will be safeguarded against unwarranted access and used only with their consent or anonymized and subject to ethical review.

use of stored DBSs;

As revealed by the policy review and through the three case studies, there is currently a lack of clear and con- sistent policies; thus, apprehension concerning the secondary uses of stored identified information is not without foundation. This however can be addressed through open dialogue between the public and the screening community. Ideally, if individuals understood the purposes and value of storage of newborn DBSs and if they were assured that health informa-


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tion and privacy would be protected against unjust discrimination by health insurance providers, employers, educational institutions, and others, then perhaps they would be less apprehensive of having to deal with presumed “Big Brothers” everywhere.

References 1. J.E. McEwen and P.R. Reilly, “Stored Guthrie Cards as DNA

‘Banks:”American Journal ofHuman Genetics 55 (1994): 196-200. 2. B.L. Therrell, W.H. Hannon, K.A. Pass, et al., “Guidelines for the

Retention, Storage, and Use of Residual Dried Blood Spot Samples after Newborn Screening Analysis: Statement of the Council of Regional Networks for Genetic Services,” Biochemical and Molecular Medicine 57 (1996): 116-24.

3. W.H. Hannon, L.O. Henderson, and C.J. Bell, “Newborn Screening Quality Assurance” in M.J. Khoury, W. Burke, and E.J. Thomson, eds., Genetics and Public Health in the 21st Century (New York: Oxford University Press, 2000): 243-60.

4. Human Genetics Society of Australasia (HGSA), Policy Statement on the Retention, Storage and Use of Sample Cards from Newborn Screening Programs, Australia, (1999).

5.American Academy of Pediatrics (AAP), “Serving the Family from Birth to the Medical Home. Newborn Screening: A Blueprint for the Future,” Pediah.ics 106, no. 2, suppl. (2000): 389-422.

6. See Therrell, supra note 2. 7. See AAP, supra note 5. 8. K. Elkin, “Guthrie Cards: Legal and Ethical Issues,”NewZealand

Bioethics Journal 1 (2000): 22-26. 9. See Therrell, supra note 2; See HGSA, supra note 4; Association

francaise pour le dkpistage et la prkvention des handicaps de l’en- fant (AFDPHE), “Les Prklivements de Sang sur Papier pour le Depistage Nkonatal. Recommandations pour leur Collecte, leur llaitement et leur Conservation,” Archives o!e Pidiatrie 2 (1995): 3-7.

10. Personal communication with Dr. Claude Laberge from the Centre Hospitalier de l’Universit6 Laval in November 2002.

11. See AFDPHE, supra note 9. 12. France - National Consultative Bioethics Committee (CCNE),

opinion and Recommendations on ‘’Gemties andMedicine: Fmm Prediction to Prevention,” Report, No. 46 (October 30,1995).

13. Australia - National Pathology Accreditation Advisory Council, Retention ofhborato y Rewrds and Diagnostic Material (2002).

14. Australia - National Pathology Accreditation Advisory Council, Retention ofLaboTatoy Recorh and Diagnostic Material (1998).

15.United Kingdom - Working Party of the Royal College of Pathologists and the Institute of Biomedical Science, The Retention and Storage of Pathobgical Records and Archives, Report of the Working Party of Biomedical Science, 2d. edition (1999).

16. B. Norgaard-Pederson, “Use of Stored Samples from the Danish PKU Register” in B.M. Knoppers, ed., Human DNA: Law and Policy, International and Comparative Perspectives (Amsterdam: Kluwer Law International, 1997): 303-11.

17. Danish Medical Research Council, Health Science Infirmation Banks - Biobanks, Report, (January 1996), available at <http://www.forsk.dk/eng/ssvf/publ/biobanker-uk/> .

18. See Therrell, supra note 2 19. See D. Avard, L. Kharaboyan, and B.M. Knoppers, “Using ‘Spots’

in Research: Moving Beyond Screening and lleatment” in

Association of Public Health Laboratories, 2002 Newborn Screening and Genetic Testing Symposium Proceedings (Phoenix, November 4-7 2002): 319-21.

20. See Norgaard-Pederson, supra note 16. 21. See Danish Medical Research Council, supra note 17. 22. See AAP, supra note 5. 23. L. B. Andrews, J.E. Fullarton, NA. Holtzman, et al., eds.,

Assessing Genetic Risks: Implications for Health and Social Policy (Washington, D.C.: National Academy Press, 1993): at 277; The New York State Task Force on Life and the Law, Genetic Testing and Screening in the Age of Genomic Medicine, Report (2000), available at <http://www.health.state.ny.us/ nysdoh/taskfce/screening.htm>; American Society of Human Genetics, “Statement on Informed Consent for Genetic Research,” American Journal of Human Genetics 59 (1996): 471-74; K. Tomoeda and I. Matsuda, “Biomedical Ethics and Mass Screening of the Newborn in Japan,” Eubios Journal of Asian and International Bioethics 8 (1998): 75-76.

24. The Nuffield ’hst , Learningj-om Experience: Privacy and the Secondary Use of Data, Report (2002); Royal College of Physicians Committee on Ethical Issues in Medicine, “Research Based on Archived Information and Samples,” Journal of the Royal College of Physicians of London 33 (1999): 264-66.

25. E. Clayton, K. Steinberg, M.J. Khoury, et al., “Informed Consent for Genetic Research on Stored Tissue Samples,” JAMA 274

26. National Bioethics Advisory Commission (NBAC), Research Involving Human Biological Materials: Ethical Issues and Policy Guidance, Report (1999).

(1995): 1786-92.

27. See New York State lbk Force, supra note 23. 28. N.J. Wald and M. Law, “The Threat to the Use of Records and

Stored Blood Samples in Medical Screening Research,” Journal ofMedica1 Screening 8 (2001): 58-59.

29. See NBAC, supra note 26. 30. See Therrell, supra note 2. 31. D. Mills, “Alternative Uses of Guthrie Spots from Newborn

Screening Programs. Increased Demand for DNA Specimens: Genetic Drift Newsletter 15 (1998), available at <http://www. mostgene.org/gd/gdvol15b.htm > (last visited October 3,2003).

32.G.J. Annas, “Privacy Rules for DNA Databanks. Protecting Coded ‘Future Diaries’,’’JAMA 270 (1993): 2346-2350.

33.Personal communication with Dr. Gerard Loeber from the RIVM in November 2002.

34. J.G. Loeber and B. Elvers, “(1l)legality of Long Term Storage of Newborn Filter Paper Cards,” Proceedings of the Newborn Screening and Genetics Symposium (Washington: Association of Public Health Laboratories, 2001).

35. H v G. [M/1868/98]. 1999. Upheld in H v G (2000) 18 FRNZ 572.

36. New Zealand - Health and Disability Commissioner, Auckland Healthare -Report on Opinion, Case 99HDC09011(2000).

37. See H v G, supra note 34. 38. See Elkin, supra note 8. 39. Id. 40. D. Abramson, “Passing the Test: New York’s Newborn HIV

Testing Policy, 1987-1997,” in MA. Stoto, DA. Almario, and M.C. McCormick, eds., Reducing the Odds - Preventing Perinatal Transmission of HIV in the United States (Washington: National Academy Press, 1999): 313-40.

41. D. Roy, “Anonymous HIV Seroprevalence Studies: Ethical Conditions,” in B.M. Knoppers and C.M. Laberge, eds., Genetic Screening. From Newborn to DNA Typing (Amsterdam: Elsevier Science Publishers, 1990): 95-110.

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