Screening in Pregnancy and Infancy

Types of screening

Screening means testing people who have no symptoms in order to find out who is at higher risk of a condition. It is offered to a whole group (a population), not just to people who are known to be ill.

In the Leaving Certificate course, you should be able to describe three kinds:

• Antenatal screening is carried out during pregnancy. Examples: ultrasound scans and blood tests. A condition it can detect (as a risk): Down syndrome. Tests on the baby's cells (CVS, amniocentesis) are also done in pregnancy, but they are diagnostic tests, not screening.

• Genetic screening looks for a gene or chromosome change. Examples: carrier testing of parents, a karyotype, or testing for a known family condition. A condition it can detect: cystic fibrosis (carrier testing).

• Postnatal screening is carried out after birth. Example: the newborn blood spot test (heel prick) for PKU and other conditions, and the newborn hearing test. A condition it can detect: PKU.

PKU: an inherited metabolic disorder

Phenylketonuria (PKU) is caused by a faulty gene for the enzyme phenylalanine hydroxylase. This enzyme normally converts the amino acid phenylalanine (found in protein) into tyrosine.

PKU is autosomal recessive. The gene is on a non-sex chromosome, and a person only has PKU if they inherit two copies of the recessive allele. People with one copy are carriers: they are healthy but can pass the allele on.

Without the enzyme, phenylalanine cannot be broken down. It builds up in the blood and its by-products (phenylketones) appear in the urine. High phenylalanine damages the developing brain.

Newborn screening and treating PKU

In Ireland, the newborn bloodspot screening programme (the "heel prick" or Guthrie test in older books) is offered to every baby, usually between day 3 and day 5. A few drops of blood from the heel are dried on a card and tested in a laboratory for PKU and several other rare conditions.

Why early detection matters. A baby with PKU looks completely healthy at birth. Damage builds up over weeks and months as phenylalanine accumulates. If PKU is found in the first days, treatment starts before any harm is done.

Treatment is a diet low in phenylalanine:

• Foods rich in protein must be restricted, because protein contains phenylalanine. Examples: meat, fish, eggs, milk, cheese, nuts and soya.

• Special low-protein foods and a phenylalanine-free formula supply the other amino acids that are needed. A small, carefully controlled amount of phenylalanine is still allowed, because it is an essential amino acid that the body cannot make.

• Blood phenylalanine is checked regularly.

The diet keeps phenylalanine low enough that it does not damage the brain. It does not cure PKU; it must be kept up, and is especially important for children while the brain is developing.

PKU and pregnancy. A woman with PKU who eats freely will have high phenylalanine in her blood. Phenylalanine crosses the placenta and can damage the foetus's developing brain and heart, even if the baby does not have PKU. So she must return to the strict diet before conception and throughout pregnancy, so that levels are low during the earliest stages of development.

Antenatal tests: scans and prenatal diagnosis

Antenatal tests fall into two groups. Screening tests estimate risk. Diagnostic tests give a firm answer but are invasive.

In amniocentesis, a thin needle passes through the mother's abdomen and removes a small sample of amniotic fluid, guided by ultrasound. In CVS, cells are taken from the chorionic villi, part of the developing placenta. Both give cells that can be grown and analysed.

Reading screening results

No test is perfect. Two measures matter:

• Detection rate (sensitivity): the percentage of affected cases that the test finds.

• False-positive rate: the percentage of unaffected cases that the test wrongly flags as positive.

The surprise is that most positive results are false positives, because the condition is rare and there are so many unaffected pregnancies. That is why a positive screening result is never the end of the story. It means "higher risk", and the woman is offered a diagnostic test to confirm or rule out the condition.

Down syndrome, karyotypes and ethics

Down syndrome is caused by trisomy 21: three copies of chromosome 21 instead of two, giving 47 chromosomes in each body cell.

Non-disjunction. In meiosis, chromosomes (or chromatids) normally separate so that each gamete gets one of each. If the two copies of chromosome 21 fail to separate (in meiosis I, or the chromatids in meiosis II), one gamete gets two copies of chromosome 21 and another gets none. If the gamete with two copies is fertilised by a normal gamete (one copy), the zygote has three.

The risk of non-disjunction rises with the age of the mother.

Karyotype. Foetal cells from amniocentesis or CVS are grown, stopped during metaphase, stained and photographed. The chromosomes are arranged in pairs by size and banding pattern. In Down syndrome, the karyotype shows three chromosomes in position 21 (47 in total).

Ethical issues

You may be asked to discuss ethics. Give both sides, for example:

• Informed choice and autonomy: parents have the right to information and to decide, but results can lead to very difficult decisions, including whether to continue the pregnancy.

• Risk of the test: invasive tests carry a small risk of miscarriage, which must be weighed against the information gained.

• Attitudes to disability: screening may suggest that lives with a disability are less valuable, or may reduce support for people with Down syndrome and their families.

• Anxiety and false positives: a high-risk result causes stress, and may turn out to be wrong.

• Privacy and equality: genetic information must be kept confidential, and access to testing should be fair.

Why untreated PKU damages the brain, and is screening worthwhile?

Metabolism. Without phenylalanine hydroxylase, phenylalanine is not converted to tyrosine. Phenylalanine rises in the blood and tissues. Some is converted to phenylketones instead. Tyrosine becomes short, and it is needed to make neurotransmitters such as dopamine and the pigment melanin (so untreated children can be fair-skinned).

Brain development. High phenylalanine crosses the blood–brain barrier. It interferes with the uptake of other amino acids needed to make proteins, with myelin formation and with synapse development in the first years of life, when the brain grows rapidly. The result is intellectual disability, seizures and behavioural problems. The damage is largely irreversible, which is why treatment must start early.

Evaluating population-wide screening for PKU.

PKU is a good example of a condition suited to screening: it is serious, has a simple reliable test, and an effective treatment exists if it is found early.

Vuelve al principio: the heel-prick test protects children because PKU is detectable at birth, before any symptoms, and a low-phenylalanine diet started early prevents brain damage. We test every baby because the condition cannot be seen and the benefit for the few affected children is very large.

Summary