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Who Performs the Screening Tests? 
The South Australian Neonatal Screening Centre is located within the Department of Chemical Pathology at the Women’s and Children’s Hospital 72 King William St, Adelaide, a leading Paediatric teaching hospital.
The role of the South Australian Neonatal Screening Centre is to identify and diagnose infants who are at risk of developing one of the screened disorders. This enables early medical intervention to prevent or significantly reduce the morbidity and mortality associated with the screened disorder.
The South Australian Neonatal Screening Centre was established in 1966 with the screening for Phenylketonuria, (PKU). The PKU test was developed by Dr. Robert Guthrie in the early 1960’s. Since these early beginnings the numbers of patients screened by the centre and the disorders tested for has grown, so that infants are now screened for over 30 different inherited disorders. To date, over 750,000 infants have been screened in South Australia with the detection of over 250 affected infants.
The South Australian Neonatal Screening Centre is at the fore front of research into newborn screening in the world and provides state of the art screening services for a number of states in Australia as well as several centres overseas.
Where are the tests sent?
The tests are sent to the South Australian Neonatal Screening Centre at the Women's and Children's Hospital in Adelaide, South Australia.
The South Australian Neonatal Screening Centre has been identified as a ‘Centre of Excellence’ in which a state of the art laboratory delivers a world class analytical and clinical service using the latest technology.
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How are the tests analysed?
The South Australian Neonatal Screening Centre analyses some 30,000 blood-spot samples every year. Tests are performed using a range of different testing methodologies and equipment incorporating the latest technological advances. The most recent equipment acquisition to the laboratory has been the introduction of Tandem Mass Spectrometry (MSMS). The introduction of MS-MS technology to the laboratory in 1999 allowed newborn infants to be tested for more than 30 inherited health problems known as ‘Inborn Errors of Metabolism’ (IEM). These IEM are due to defects associated with amino acid and fatty acid utilisation. The SA Neonatal Screening Centre is one of only 15 centres worldwide using tandem mass spectrometry for neonatal screening in 2001.
In the laboratory, 3 mm blood spot discs are punched from the blood collection cards and prepared for testing. These spots are used in a panel of screening tests to identify infants at risk for Congenital Hypothyroidism, Galactosaemia, Cystic Fibrosis, disorders of Amino Acid Metabolism, Fatty Acid Oxidation Defects and Organic Acidurias. Collectively, these health problems occur in one out of every 800 newborn infants.
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Which disorders are tested for?
Conditions that are tested for by the SA Neonatal Screening centre include:
Congenital Hypothyroidism
Congenital Hypothyroidism arises when the thyroid gland fails to develop normally and the baby is not able to make enough of the hormone thyroxine. This can be due to a number of causes including agenesis or an ectopic thyroid gland, and genetic disorders of thyroid hormonogenesis. Early detection and treatment of children with this disorder prevents the development of serious health problems such as growth retardation, and delays in mental development. Treatment with thyroxine at a dosage to produce concentrations in the upper quarter of the normal range enables the child to grow and develop normally.
Cystic Fibrosis
Cystic Fibrosis (CF) is an inherited problem affecting the mucus producing glands and sweat glands of the body. It is a disease that mainly affects the lung and pancreas. In December 1989 the SA Neonatal Screening Centre pioneered a two-tier biochemical and DNA technique for detecting newborn infants with Cystic Fibrosis. The first tier measures immunoreactive trypsin (IRT) in the blood spots and identifies a group of at increased risk infants with an IRT in the top 1 percent of the population. For the second tier, samples in the top 1% of the IRT population are tested for direct DNA mutational analysis to look for the most common CF mutations. This screening strategy identifies 96% of all infants with CF in our screening population. For those newborn infants who have a history of CF or clinical signs of the disease, direct DNA analysis is always performed regardless of the level of IRT.
Infants who emerge from the screening process with an elevated IRT and two copies of CF mutations are diagnosed as having CF. Babies with only one identified CF mutation may have another, rarer CF mutation, or, more likely, they may simply be one of the 1 in 25 South Australians who are CF carriers. These infants will need to be recalled for a sweat test to exclude the diagnosis for CF. In this group, infants with a positive sweat test will have CF while those with a negative sweat test will simply be a carrier of a CF mutation. Advances in antibiotic therapy and pancreatic enzyme replacement have greatly improved the quality and lengthened the life span of individuals affected by CF.
Amino Acid Metabolism Disorders
Inherited problems, which affect the breakdown of proteins into amino acids, are grouped under the heading ‘Amino Acid Metabolism Disorders’. Phenylketonuria is the most common disorder in this group. Other examples of disorders in this group include Maple Syrup Urine Disease and Homocystinuria.
Almost all patients with PKU have an inherited deficiency of the enzyme phenylalanine hydroxylase (PAH), which breaks down the amino acid phenylalanine to tyrosine. If left untreated, phenylalanine accumulates in plasma and tissues to toxic levels, causing irreversible intellectual disability. Because phenylalanine is an essential amino acid derived entirely from the diet, treatment by restriction of phenylalanine intake, combined with a phenylalanine - free amino acid supplement, makes it possible to lower plasma phenylalanine concentrations, and prevent damage to the brain.
Galactosemia
Galactosemia is an inherited disorder where infants are unable to metabolise galactose. The treatment for this disorder consists of a diet that excludes foods that are the major sources of galactose such as milk and other foods where lactose is added during manufacture such as some breads, margarine and cakes. Children with Galactosemia need to maintain this diet for life. Untreated, galactose builds up in the body causing a number of different harmful effects such as cataracts, and liver damage, which if left untreated can be fatal.
Fatty Acid Oxidation Defects
Infants born with a fatty acid oxidation defect cannot use their stored fat to provide energy during times of stress or sickness. In times of stress or illness the body uses up all of its blood sugar for energy, resulting in low blood sugar levels which can be fatal if not treated. Medium-chain Acyl-Coenzyme A dehydrogenase (MCAD) deficiency is one example of a fatty acid oxidation defect. MCAD is part of a chain of enzymes that act together in the body to turn fat into energy. Treatment for children with MCAD deficiency involves ensuring that the child eats often so that the body does not get to a stage where it needs to break down fat for energy. There is a range of different disorders in this group that vary in their severity and treatment, depending on the particular enzyme that is missing. For more information on MCAD see "Jackson’s Story".
Organic Acidurias
Organic Acidurias is the name given to a group of disorders in which the body lacks an enzyme leaving it unable to break down amino acids. This inability to completely breakdown amino acids results in the build up of toxic chemicals wthin the cell which if left untreated, can lead to convulsions and coma.
Treatment for these disorders requires close dietary management to reduce the build up of the toxic chemicals while allowing normal growth and development.
Lysosomal Storage Disorders Pilot Project
 Since 1998, a pilot project has been in operation at the South Australian Neonatal Screening Centre that aims to detect another group of inherited disorders called ‘Lysosomal Storage Disorders’. The Lysosomal Storage Disorders (LSD’s) are a group of genetic disorders that affect 1 in 7,700 infants born in Australia. Infants with a LSD will develop bone and soft tissue abnormalities which will affect their growth and development and may lead to severe intellectual disability in some LSD types. The basis for these disorders is problems with the lysosomal compartments within the cell. Lysosomes act as the cell’s recycling system, breaking down complex materials for recycling within the cell. Infants born with a LSD appear normal at birth, but progressively develop problems as these materials build up within the cell over time. The results of the Lysosomal Storage Disorder Pilot Project will be used to determine the effectiveness of the test in identifying neonates at risk of having a LSD.
How will I be contacted with results?
The laboratory runs screening tests each working day. Once specimens are received by the laboratory, tests are run either on the same day, or the next working day.
After testing has been completed, the referring hospital or health professional will be contacted by the SA Neonatal Screening Centre via mail or telephone depending on the outcome of the tests.
 This is an example of the report form sent to the hospital or health professional when the screening test for a particular infant has shown that the baby’s screening test is "all clear".
The hospital or health professional has the ultimate responsibility to ensure that the results for each baby are received, checked against the birth records and recorded in the infant’s’ medical records.
It is essential that all birthing centres and hospitals cross check that all infants have been screened and accounted for. In the event that no report has been received, the neonatal screening laboratory must be notified.
What does a negative screening result mean?
A 'negative’ screening test result indicates that the test results in that sample are all within the normal range.
If a screening test produces a negative result, the hospital or referring doctor should receive the results from the South Australian Neonatal Screening Centre within 7 – 10 days of the laboratory receiving the sample.
What does a ‘re-sample’ result mean?
A ‘re-sample’ is a result which indicates that a sample will need to be recollected from a particular infant. There are a number of reasons why a sample may need to be re collected including:
1. Sample problems
 2. Inappropriate sample collection time
(i.e. sample not taken at 48 hours of age)
3. Borderline and equivocal test results
1. Sample Problems
Problems with the way in which the sample was collected, dried or handled may result in the laboratory requesting a repeat collection to be performed. Some of these problems include:
- Insufficient blood volume
- Contamination of the sample by an interfering agent
- Separation of the sample into red blood cells and serum
- Inappropriate drying conditions resulting in an unusable sample
- Incomplete blood saturation
- Layering of fresh blood on top of already dried blood
2. Correct Timing of Sample Collection
It is important that the sample is taken from the infant at a least 48 hours of age. Any variance in the timing may create a need for the sample to be recollected
3. Borderline and Equivocal Test Results
Some results may be on the boundaries of what is considered the normal range for a particular compound. In these cases the laboratory will ask for a repeat blood spot test to be done in order to confirm the test result.
In the majority of cases, those infants who are recalled for a second sample return a normal result once the sample has been re tested. The doctors and midwives caring for the very small number of infants who record a positive result for one of the disorders tested for in the Neonatal Screening test panel are notified of these results immediately by telephone.
What does a ‘positive result’ mean?
A positive result indicates that the child is at risk of having that particular disorder.
These screening results are always provisional.
Confirmation of the diagnosis of the disorder requires further testing. This may be a blood test, urine test or both. It is also essential to confirm that the screening test results actually belong to the infant whose name appears on the screening card.
All positive results are telephoned to the treating doctor or midwife and are faxed, wherever possible, on the same day.
Confirmatory Testing of Positive Screening Results
The South Australian Neonatal Screening Centre in association with the National Referral and Metabolic Laboratory at the Women’s and Children’s Hospital can provide a full range of confirmatory tests for any positive screening results. This may be a blood test, urine test or both. It is also essential to confirm that the screening test results actually belong to the infant whose name appears on the screening card. The laboratory will discuss suitable samples for confirmatory testing with the referring doctor when a positive screening result is found.
For more information on the range of other metabolic, enzyme or molecular tests undertaken within the Department of Chemical Pathology at the Women’s and Children’s Hospital see the links below:
- For a general list or search of all the tests offered by the Department of Chemical Pathology
Available Tests and Screens (to come)
- For general information on the enzyme and molecular analysis
National Referral Laboratory
- For general information on metabolic tests
Metabolics and Therapeutics
What screening tests should I do on a premature or sick infant?
Premature or sick infants pose a challenge to any screening Centre. Often these infants may be on intravenous fluids and antibiotics and may not have had sufficient protein and lactose to show up abnormalities. To overcome these problems, many hospitals have implemented the collection of several blood spot specimens over the period of hospitalisation. The frequency and timing of these collections will vary and it is important to check with your institution’s protocol before undertaking sample collection, however as a minimum, a sample should always be collected at 48 hours after birth and again before discharge.
We have found re-sampling at around 30 days of age to be very helpful in extremely low birth rate infants.
If you have any queries about when to collect specimens on sick or premature infants, please contact the laboratory for advice.
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