Genethics Essay Competition 2006

Newborn Screening Tests: Would you consent?

By Fiona Firth

The principle objectives of newborn metabolic screening programmes are to detect metabolic or genetic conditions which allow the child to appear healthy at birth, but with time grow more dangerous and can result in permanent disability or even death.  If these conditions are detected at birth, it may be possible to start treatment immediately and prevent or reduce the presentation of the disease.

In New Zealand, the programme tests for the seven conditions (see Table 1).  A family history of these diseases is not necessarily a reliable predictor of these conditions appearing in a newborn. Many of the tested diseases are autosomal recessive i.e. the infant has inherited two copies (one from each parent) of a defective recessive gene. The condition cystic fibrosis for example is inherited when both parents carry a faulty gene, the salt-transport gene.  Even if both parents carry the recessive defective gene there is still only a 25% chance their offspring inherits the disease because of the protection from the dominant gene (Table 2).  In New Zealand, only 12-15% of children who inherit cystic fibrosis know of another family member affected by the disease.

In the 1960s, Dr Robert Guthrie invented a test for the disease phenylketonuria by checking for the presence of an enzyme, phenylalanine, in a baby’s blood sample dried on a card. These discoveries started metabolic screening.  After phenylketonuria, other significant diseases where an amino acid could be analysed from blood on the Guthrie card were included. The conditions to be screened also had to be treatable and the test used must be specific to the disease and sensitive, so it could correctly identify abnormalities. Those diseases that could be tested for but where no appropriate intervention was possible were left out of the programme.  The tests included are metabolite tests i.e. they assess the amount of certain organic substances in the blood, which allows an inference as to whether or not a metabolic condition is present.   This is different from DNA testing where genetic techniques distinguish between individuals in a species using DNA samples and analyse the genes.

Starship Hospital in Auckland has recently installed a Tandem Mass Spectrometer, which screens for the seven disorders that are currently tested (Table 1) as well as for several more disorders routinely assessed in Australia and in some states in the USA.  It uses the same dried blood filter paper specimens that are currently collected from newborns but can screen more efficiently for specific metabolites and is able to detect broader categories of metabolic disorders – amino acid disorders, several urea cycle disorders, organic acid disorders and fatty acid oxidation disorders (Table 3). It is predicted to save the lives of at least five newborns a year and allow many others a better quality of life.

Informed consent is obtaining the agreement of a patient or, if the patient is not able to give informed consent, of those authorised to represent the interests of the patient. The person must have an understanding of all facts and implications of the action for which they are consenting for it to be informed consent.  In this case of newborn metabolic screening, because the newborn is unable to give permission, a parent must give consent or refusal on their babies behalf.  In New Zealand ensuring all parents really understand all the consequences of their decision is extremely difficult, but the decision made, by law, must be informed.  Parents in New Zealand give consent for the test but another consideration is informed consent for the prolonged storage of the Guthrie cards, which contain the baby’s DNA. As part of the consent process consideration should be given to the future use of the DNA by other bodies e.g. police or scientific researchers.  In some parts of the world e.g. parts of the USA and Canada, presumed consent for newborn screening tests is acceptable i.e. consent for these tests is given as part of overall consent for the medical and surgical procedures associated with the delivery of the baby. 

If I were Nurse Alison I would try to talk to Jude about her decision to refuse the screening for her baby.  I would explain that it is her right to refuse consent, but the tests are a positive ‘preventive’ measure, not a negative invasive action.  Loving the baby would not stop one of these diseases. With phenylketonuria giving the baby the special diet can prevent the brain damage i.e. I would stress all the positive aspects for her and explain it was in her and her family’s interest to have these tests.  I would draw her the punnett square (Table 2) to show her that just because no-one in her or her partner’s family have any of the seven diseases currently screened for it does not mean that they are not carrying the recessive gene.  I hope this would persuade Jude that she was acting in the baby’s best interest by consenting to the tests and that she would understand the brief pain her baby will feel with the heel prick is minor compared with all the knocks and scratches a baby/toddler gets in their daily life.  Perhaps Jude was concerned about the possibility of a positive result and the consequences, not just on this baby but on her other children and future children.  I could show her figures explaining the low prevalence of these diseases and again stress the ‘preventive’ aspects.  For society as a whole it is better to know the true prevalence of diseases. Early treatment, where possible, reduces the individual’s suffering and allows their full development to potentially help their community.  As well it reduces the financial cost to society of expensive hospital, physiotherapy and nursing care.

I agree with much of Lynnne’s point of view.  If she has been researching on the internet, like I did, she may have come across the site AboutNewbornScreening.com where there were quotes like this “I can accept that he had a disease.  I can accept that he died from it.  What I can’t accept is that there is a test out there that could have detected it and I could still have my son with me - Ms RS, whose 3 month old son died from MCAD, a detectable metabolic disorder”.  MCAD is treatable, and with this and other treatable conditions it is in the baby’s and parents best interest to have information from as many tests as possible.  If a disease is untreatable it is difficult to decide whether you would want to know about it or not and this is where I do not completely agree with Lynne.  From society’s point of view it is not cost effective to screen for a wide range of tests where there are no effective interventions.  Governments have to decide if they want to put scarce health resources into expanding the screening programme or some other area.  Lynne may be rich and be willing to pay for the additional tests privately but this is not really fair across all society.  Another potential problem is that some tests have false positive results i.e. the screening test is positive but further tests show no evidence of the disease.  This causes a lot of unnecessary anxiety.  So perhaps not all possible tests should be included.

In my opinion it is good to include screening tests for conditions that do not show up until adulthood.  I think the child should be told about the problem.  Knowledge gives power and the child and whole family can prepare for the onset of the disease.  This could involve, depending on the disease, special diets to slow the onset of the condition, strengthening exercises, choice of an appropriate career.  The disadvantages of knowing you are going to get a disease are that it could be depressing and you might not want to get married and have a family because you might pass it on to future children.

Most countries that have newborn screening programmes confine the tests to diseases that are treatable i.e. there is a direct benefit from early diagnosis, the benefit is balanced against the cost of the test and treatment, the test is reliable and there is a system in place to deal with babies found to have the disease.  From a public health view it is hard to argue against this, but if it were my baby I think I would want to know.  If the test found a disease where a treatment was available, but was very expensive and not funded by the government I would try and get the money myself somehow, like get a house mortgage.  This is not practical from a public health standpoint however.

In summary, I think the New Zealand system for newborn screening is working well and should be expanded to include additional tests that can be detected with a tandem mass spectrometer.  Careful consideration has to be given to consent issues particularly regarding length of storage of the Guthrie cards and what can be done with the stored material.
 

Table 1:  Conditions Currently Tested for in New Zealand

Condition	Caused by	Leads to	Treated by	Prevalence	Cases helped/year
Biotinidase Deficiency	Lack of an enzyme called biotinidase leading to a deficiency in biotin due to a faulty inherited gene from both carrier parents	Seizures, brain damage, eczema, hearing loss and eye problems. In severe cases can cause coma and death	Taking biotin (vitamin H)	1 in 50 000 newborns	Morbidity-mortality is prevented in one baby per year
Congenital Adrenal Hyperplasia	Lack of an enzyme in the adrenal gland	A deficiency in the hormones cortisol and aldosterone and too much androgen (a form of a male sex hormone) and can cause early or, in female children, incorrect development male characteristics. Can also cause vomiting, dehydration, electrolyte changes, cardiac arrhythmias and death.	Steroid medication to return hormone levels to normal. Female babies are usually operated on soon after birth	1 in 20 000 newborns	Morbidity and mortality is prevented in 2-4 babies per year
Cystic Fibrosis	Irregular secretions in parts of the body such as the lung and pancreas because the body creates thicker mucus than normal	Chest infections, unwanted salt loss, poor growth and shortened life – a life expectancy of 25 years	Daily airway clearance, med-icines, high energy diets. plenty of water, daily exercise	1 in 3 000 newborns	Morbidity is reduced in 14-16 newborns per year
Galactosaemia	Defect of an enzyme that prevents the conversion of galactose contained in milk to glucose	Jaundice, cataracts and life-threatening illnesses	A special diet including a replacement of foods containing milk	1 in 120 000 newborns	Morbidity & mortality red-uced in 1-3 newborns per year
Congenital Hypothyroidism	The thyroid gland being too small or absent	Brain damage, growth problems, respiratory and feeding problems, dry skin and rough hair	Taking a thyroid hormone daily in tablet form	1 in 4 500 newborns	Developmental delay prev-ented in 11-13 newborns per year
Maple Syrup Urine Disease	Missing enzyme resulting in loss of ability to metabolise amino acids leucine, isoleucine and valine so these amino acids build up in the body	An unusual increase in the acdity of body fluids such as the blood so the baby will vomit, become not interested in their food, have seizures, brain damage and may lapse into a coma causing death	Special diet  low in proteins, but contains the essential proteins that can only be gained from food	1 in 250 000 newborns	Mortality prevented in one baby every 4-5 years
Phenylketonuria	A missing enzyme in the liver resulting in a build-up of an amino acid called phenylalanine found in protein	Severe brain damage	Diet including special milk-shakes & protein in bread, pasta, chips, fruits and vegetables	1 in 15 000 newborns	Severe developmental delay prevented in 4-5 infants per year

 

Table 2:  Inheritance of Cystic Fibrosis

 

Parents with:	Healthy Salt-Transport Gene	Defective Cystic Fibrosis Gene
Healthy Salt-Transport Gene	Salt-transport: Salt- transport (normal, healthy child, 25% chance)	Salt-transport: Cystic fibrosis (carrier but not affected, 50% chance)
Defective Cystic Fibrosis Gene	Salt-transport: Cystic fibrosis (carrier but not affected, 50% chance)	Cystic fibrosis: Cystic fibrosis (sufferer of cystic fibrosis, 25% chance)

 

 

Table 3:  Some Conditions that can be Tested by Tandem Mass Spectrometry

 

Condition Group	Condition	Currently Tested
Endocrine Disorders	1° & 2° congenital hypothyroidism	yes
	thyroxine binding globulin deficiency	no
	congenital adrenal hyperplasia	yes
Haemoglobin Disorders	sickle cell anaemia	no
	haemoglobin SC disease	no
Genetic Disorders	biotinidase deficiency	yes
	cystic fibrosis	yes
Metabolic Disorders: Galactosaemias	classic galactosaemia	yes
	galactokinase deficiency	no
Metabolic Disorders: Fatty acid oxidation disorders	carnitine uptake deficiency CPT 1 deficiency MCAD deficiency M/SCHAD deficiency	no no no no
Metabolic Disorders: Organic acidaemias	glutaric acidaemia malonic acidaemia	no no
Metabolic Disorders: Amino acidaemias	homocystinuria maple syrup urine disease PKU tyrosinaemia	no yes yes no

Bibliography

Websites:
en.wikipedia.org/wiki/Informed_consent
http://www.lbl.gov/Education/ELSI/genetic-testing.html
kidshealth.org/parent/system/ medical/newborn_screening_tests.html
www.aboutnewbornscreening.com
www.acmg.net/resources/policies/ ACT/condition-analyte-links.htm
www.humgen.umontreal.ca/int/genedit.cfm?idsel=1247
www.mchb.hrsa.gov/screening/
www.ncsl.org/programs/health/screeningprivacy.htm
www.psychology.org.nz

 

Other references:
Lion Foundation helps Starship.  Press release 24.02.2006
In the Blood: New born Screening.  The Gamma Series of the Royal Society of New Zealand.  May 2006.
Retention of Guthrie cards: reassuring parents.  Medicine Today February, 2004
Your Newborn Baby’s Blood Test, National testing Centre, Auckland, May, 2004.