Paediatrics

Question 0

How many babies each year are screened using neonatal blood spot testing? Is this relatively large or small for a screening program in the UK?
Define screening?

Answer 0

It is one of the largest screening programs in the UK today, with about 800,000 babies screened every year.
Screening can be defined as “A process of identifying apparently healthy individuals who may be at increased risk of a disease or condition. They can then be offered information, further tests, and treatment to reduce their risk and/or any complications arising from that disease or condition.” - The UK National Screening Committee.

Question 1

When a newborn comes into this world within the first week they are given a screening test;what is it called, and what does it look for?
Where is the blood sample taken from?

Answer 1

Neonatal blood spot testing as part of the UK Newborn Screening Program.
Offered in the first week of life. The sample is taken from the heel.
Screens for:
1) Phenylketonuria.
2) Congenital hypothyroidism.
3) Sickle-cell disease.
4) Cystic fibrosis.
5) Medium chain acetyl-CoA dehydrogenase deficiency.

Question 2

If a screening test exists is it automatically worthwhile?

Answer 2

No! If a screening program is to have value, there has to be a benefit in intervening early, before symptoms develop, compared with intervening when they have already developed. I.e., this early intervention has to produce a better outcome.
A screening program might be a complete waste also if there is no effective treatment - because why bother to screen for it of you can’t do anything about it?

Question 3

In child health, what is the PCHR?

Answer 3

The Personal Child Health Record - lots of info recorded here, including if parents have declined neonatal blood spot testing.

Question 4

Is neonatal blood spot testing discussed with prospective patients before birth? If so, by whom and when?

Answer 4

Midwives discuss neonatal blood spot testing at several times during routine antenatal care, and again 24 hours before the test is taken.
All women in England are given a copy of “screening tests for you and your baby”. Similar arrangements are in place elsewhere in the UK.

Question 5

Is neonatal blood spot testing compulsory?

Answer 5

No.
It is strongly advised, but informed choice is important.
Is the test is declined, then that decision must be explored, md the reason documented in the PCHR.

Question 6

If a parent declines to have their baby have the blood spot test, who should be informed?

Answer 6

The GP, the health visitor, and the laboratory.

Question 7

In most cases, how long does the result of the blood spot test take to come back?

Answer 7

Usually 6-8 weeks. It is almost always normal. The results should be recorded in the PCHR.

Question 8

What happens if the neonatal blood spot test comes back as positive for one of the five things screened for?

Answer 8

Parents are contacted earlier(usually by the health visitor), and told if the test suggests that the baby is fetched by one of the conditions.
In this situation, the newborn’ screening laboratory arranges an appointment with the relevant specialist team for clinical assessment and diagnostic testing, as well as informing the GP of the positive result

Question 9

What might the role of the GP in the neonatal blood spot testing include? (3)

Answer 9

1) Discussions about neonatal blood spot screening with parents prior to testing.
2) Explanation of the results and their implications.
3) Ongoing primary care management of children identified through this screening test as having one of the conditions screened for.

Question 10

What is phenylketonuria?

Answer 10

A rare autosomal recessive condition affecting one in 10,000 babies born in the UK.
The carrier frequency is one in 50.
Affected individuals cannot metabolise phenylalanine, am amino acid found in many foods.
As a result, phenylalanine accumulates in the blood and tissues, and these high phenylalanine levels affect brain development, leading to learning disabilities and seizures.

Question 11

What enzyme is affected in phenylketomuria?

Answer 11

Phenylalanine hydroxylase; this means phenylalanine is not broken down to tyrosine.

Question 12

How do babies with phenylketomuria present clinically?

Answer 12

They are fine at birth.
But If the condition is left untreated, they start to show signs of mental retardation at around 6 to 12 months, and have a permanent learning disability by 2 years. Other possible features include light pigmentation, blue eyes, fair hair, eczema, and mousy odour.
A small proportion of the babies that test positive have a milder form called hyperphenylalanineanaemia, which results in milder learning disability.
The test may also result in picking up other conditions in which the phenylalanine level is raised e.g., galactosaemia.

Question 13

If a child is born with phenylketonuria, what should be offered to the parents?

Answer 13

Genetic counselling - there is a 1:4 chance that any future babies will have the same condition, as both parents will be carriers.
Prenatal diagnostic testing is not usually carried out, as the condition is not life threatening.
New siblings of children with PKU require testing for PKU within 48 hours of birth, in addition to the neonatal blood spot testing, which is still carried out.

Question 14

If a child with phenyketonurea is left untreated, what will their average IQ be? What chance of having seizures?

Answer 14

If left untreated, they will have an IQ of around 50, and about 25% will develop seizures.

Question 15

How is phenyketonurea treated?

Answer 15

A low phenylalanine diet should be instituted before the end of the first month, and continued throughout life. This will ameliorate the worst effects of the condition.

Question 16

How many babies in the UK are affected with congenital hypothyroidism? How is it divided, and which is more common and has subtypes? (3).

Answer 16

This affects 1 in 4000 babies in the uk.
The problem may be primary (caused by a defective thyroid gland) or secondary (caused by with he hypothalmic-pituitary axis).
Primary is more common, and may be caused by:
1) congenital absence of the thyroid gland.
2) an ectopic thyroid gland, where the gland has not developed normally and is incorrectly sited.
3) problems with thyroid hormone production (dyshormonogenesis).

Question 17

When did neonatal blood spot testing for congenital hypothyroidism begin in the UK? What does it measure, and what does it show when things have gone wrong? If it is positive, what further tests does the baby require?

Answer 17

It was begun in1979!
It measures foetal TSH, which is elevated in congenital hypothyroidism.
If high, babies require full thyroid function testing, and possibly imaging to confirm the diagnosis.

Question 18

In utero, when does the foetal thyroid gland start producing hormones (usually)? Can maternal thyroxine compensate if levels are low?

Answer 18

The foetal thyroid gland usually starts working from about 20 weeks.
The maternal thyroxine cannot work on the baby, therefore babies are sometimes born symptomatic, with constipation, jaundice, poor feeding, and a protruding tongue. (Note however, that few cases are identified clinically - it is usually the result of the blood spot test).

Question 19

Is congenital hypothyroidism inherited?

Answer 19

90% of cases are sporadic. A few are inherited, usually the subtype that have problems with dyshormonogenesis. However, in the few cases that are inherited, parents should be offered genetic counselling.

Question 20

Are there any problems with congenital hypothyroid screening? (2)

Answer 20

1) some babies identified by the screening program have transitory hypothyroidism, with thyroid function normalising later in childhood. This is more common in preterm babies.
2) babies with secondary hypothyroidism will not be detected, as these babies have hypopituidism, and TSH is normal or low.

Question 21

With cystic fibrosis, how many people are affected, and how many people are carriers? What is the mode of inheritance?

Answer 21

It is an autosomal recessive condition, one of the most common affecting the Caucasian population.
1 in 2500 live births will have CF, and 1 in 25 people are carriers!

Question 22

What is the underlying genetic/molecular cause with CF?

What areas are affected?

Answer 22

CF is due to a gene mutation that gives rise to a faulty cell membrane calcium channel.
In the lung, this leads to the production of thick sticky mucous, which results in thick, sticky mucous and eventual loss of lung function.
In the gut this leads to impaired digestion of food.
Other problems encountered are frequently osteoporosis, diabetes, infertility, and liver disease.

Question 23

How does the newborn blood test for CF work in the UK?

Answer 23

It is offered in two stages.
First, the level of immunoreactive trypsynogen (IRT) is measured. This is abnormally raised in babies with CF. However, prematurity and faecal contamination can give falsely raised samples.
The level of IRT falls after birth, and becomes unreliable around week 8, thus samples must be taken before this time.
Samples with high IRT are subjected to the second stage of the test, a DNA test; initially, it looks for the 4 most common CfTR mutations with together account for 80% of CF in the UK. If this is negative, a second DNA test is carried out which looks for a wider range of mutations.

Question 24

Is a second blood spot test ever required for CF screening?

Answer 24

If the first test was ambiguous (I.e., the IRT was raised, but only one or no CFTR mutations were found on the DNA analysis), a repeat blood spot is taken between day 21 and 28.

Question 25

How many life births in the UK does medium chain acetyl co-A dehydrogenase deficiency (MCADD) affect? What is it?
When is it most dangerous?

Answer 25

It affects 1:10,000 live births in uk, ie., rare!
BUT is part of the neonatal blood spot testing so important to be aware of.
Children with this have probe
EMIS metabolising fat due to a deficiency in medium chain acetyl-CoA dehydrogenase. This enzyme is important to provide energy when fasting ; without it, toxic metabolises are formed, hypoglycaemia can result, encephalopathy and even death can occur.
(Especially at times of extreme fasting or exercise).

Question 26

When was testing for MCADD made part of blood spot testing on neonates?

Answer 26

Only since 2009! But now it is part of the test.

Question 27

If a baby has a positive blood spot test for MCADD, what happens next?

Answer 27

Further diagnostic testing is carried out involving blood and urine testing.

Question 28

What is the genetic inheritance pattern of MCADD? What impact would this have for future or existing siblings of an affected child? Why test existing siblings?

Answer 28

It is autosomal recessive.
Unscreened siblings should be offered screening.
Existing siblings may be tested because they may have the disease but thus far be asymptomatic, or they may be carriers.
Obviously, any future children born of the same union of parents has a 1:4 chance of having this condition.

Question 29

If a pregnant women or her partner knows that she either has or is a carrier of MCADD, what measures are put in place?

Answer 29

This should be identified in antenatal booking and the woman referred to a genetic counsellor or a paediatrician.
This is because earlier screening of the baby at 24-48 hours of life may be indicated.

Question 30

Is homocystinuria and tyrosinaemia currently tested for in the uk in neonatal blood spot testing?

Answer 30

Sneaky!

This is included in the test in Northern Ireland, but not in the rest of the uk.

Question 31

What are common causes of a chronic cough in children (less serious) (6)

Answer 31

1) Post nasal drip
2) Cough variant asthma
3) Reflux and aspiration
4) Post viral cough
5) Chronic sinusitis
6) Habit cough

Question 32

What are causes of rarer and more serious chronic cough in children? (4)

Answer 32

1) Cystic fibrosis.
2) Congenital anatomical abnormalities.
3) Immunodeficiency.
4) Interstitial Lung Disease.