Making the case for expanding newborn screening in Malaysia

NBS typically involves a newborn getting their heel pricked for a blood sample to be screened for certain inherited and congenital diseases. — TNS

The objective of newborn screening (NBS) is the identification of serious and/or rare conditions that can affect a newborn’s future health and survival.

Many of these conditions – e.g. inborn errors of metabolism, endocrine diseases, haemoglobinopathies, spinal muscular atrophy, congenital heart disease and hearing loss – may not have clinically-detectable features at birth, thus hampering early detection that is vital for effective treatment and better outcomes.

NBS is a public health programme that helps to reduce the medical costs associated with serious and rare diseases by screening the entire population.

The rationale for NBS is based on the economic principle that screening all newborns and managing cases before they become symptomatic is more cost-effective than treating symptomatic individuals.

The economic benefits of NBS have been established in many countries.

What it involves

NBS is performed in the first 24 to 48 hours of life, and involves:

• Taking a few drops of blood from the baby’s heel and sending it to the laboratory, i.e. a heel prick test or newborn blood spot screening
• A hearing screen to ascertain how the baby responds to sound, and
• Pulse oximetry that measures blood oxygen levels to detect critical congenital heart disease.

The blood spot screening of many countries, particularly developed ones, covers:

• Metabolic conditions, e.g. phenylketonuria, maple syrup urine disease
• Hormonal conditions, e.g. congenital hypothyroidism, congenital adrenal hyperplasia
• Haematological (blood) conditions, e.g. haemoglobinopathy, thalassaemia, sickle cell disease
• Rare conditions, e.g. spinal muscular atrophy (SMA).

Screening the genes

The human body is made up of cells, each of which contains genetic information in a code called DNA (deoxyribonucleic acid), which makes everyone unique.

DNA works like a computer programme that instructs each cell in the body on what to do and how to do it.

The genome is a complete set of these instructions.

Science has now developed sufficiently to make it possible for this DNA information to be read to help the understanding of disease.

Sometimes, DNA changes can be inherited and passed down to family members.

These changes can mean that a person has a greater risk of developing certain conditions.

The use of newborn genomic screening (NGS) is a significant advancement in neonatal health assessment, foreshadowing a new era of early disease detection and prevention.

Until recently, population-based detection of treatable newborn disorders has been limited to metabolic and endocrine diseases, except for SMA.

This limitation has been due to technical constraints, because traditional screening methods rely on detecting excess metabolites.

On the other hand, NGS offers the possibility of substantially expanding NBS to include a wider range of treatable genetic conditions that would otherwise be undetected.

NGS has varied in different countries, with some implementing it at the population level and others in specific settings.

The initial findings of NGS reflect its feasibility and the potential to revolutionise neonatal care.

However, there are also challenges in implementation.

The diagnosis of many genetic conditions have been facilitated by technological advances in recent years.

In addition, some genetic conditions that have previously been untreatable have, in recent years, become treatable.

An example is SMA.

Spinal muscular atrophy

SMA is a genetic condition involving the failure of nerves in the spinal cord to transmit messages from the brain to muscles.

The muscles then become damaged and weak, and eventually, waste away (i.e. atrophy).

SMA affects all body muscles.

Muscles in the shoulders, hips and back are often the most severely affected, as well as muscles for feeding and swallowing, and those involved in breathing and coughing, resulting in increased likelihood of pneumonia and other lung problems.

However, SMA does not affect the intellect and senses.

There are different types of SMA. Most are caused by an altered gene.

The parents do not usually have SMA themselves.

In most cases, SMA can only be passed on to the child if both parents carry the altered gene.

In this situation, there is a one in four (25%) chance their child will have SMA; one in four (25%) chance their child will not carry the altered gene or have SMA; and two in four (50%) chance their child will carry the altered gene, but will not have SMA.

The likelihood of a child inheriting SMA can be different for some rarer SMA types as these may not be passed on at all.

In Malaysia, almost all babies with SMA Type 1 die in infancy, and those with less severe Type 2 or 3 will grow up handicapped.

This should not happen as SMA is treatable, even curable, with low-cost generic risdiplam and gene therapy.

SMA screening is available free in the public sector, as it is sponsored.

Challenges in NBS

While traditional NBS programmes focus on early childhood intervention, there is growing recognition that early detection of later-onset disorders can also offer substantial benefits.

There are challenges in NGS.

A major one is the variable penetrance, expressivity and pleiotropy of genetic variants, i.e. the highly different ways genes can express themselves.

It also raises serious privacy concerns, including risks of genetic discrimination, unauthorised access and unintended discoveries of familial relationships.

Misuse of data by insurers, employers or law enforcement could harm individuals and erode public trust.

Long-term data storage offers potential clinical benefits, but also increases the risk of misuse; hence, robust data protection policies are critical.

Parental distress, which is often due to misinterpretation of results, particularly false positives or ambiguous findings, can lead to misperceptions of their children.

NBS in Asean

NBS in the Malaysian public health sector currently involves glucose 6-phosphate dehydrogenase (G6PD) and thyroxine.

A G6PD-deficient individual can develop haemolytic anaemia, in which the red blood cells are destroyed earlier than the usual 90 days.

In most situations, G6PD deficiency does not cause problems, but problems can arise from exposure to certain medicines or foods.

Thus, knowing one has this condition is useful for patients and healthcare providers.

Thyroxine estimations diagnose congenital hypothyroidism, which is the most common cause of intellectual disability if left untreated.

NBS started in Thailand with the screening of two conditions, i.e. congenital hypothyroidism and phenylketonuria.

The programme has since been extended to 24 inborn errors of metabolism.

NBS started in the Philippines with the screening of five conditions, with one more added eight years later.

Since then, the programme has been extended to 29 conditions.

Singapore started with G6PD screening and added congenital hypothyroidism and inborn errors of metabolism later.

Their current metabolic screen covers more than 25 conditions.

Expanding our NBS programme

At the individual level, NGS has demonstrated significant benefits.

Policymakers have to grapple with managing individual risks across populations while maintaining equity, cost effectiveness and clarity in public health messages.

In short, NGS moves from a standardised, population-wide approach to a hybrid model, incorporating personalised genomics with broad public health goals.

This has implications for resource allocation, long-term follow-up infrastructure and ethical governance.

The fact is that with technological advances, more tests are available at affordable prices and many previously-untreatable conditions are treatable, saving long-term healthcare costs.

The question is what tests would be cost-beneficial at the population level.

Are the current number of NBS tests in Malaysia acceptable, especially when our neighbours have seen the light and expanded their numbers of NBS tests?

The answer is obvious.

Dr Milton Lum is a past president of the Federation of Private Medical Practitioners Associations and the Malaysian Medical Association. For more information, email [e-mail]. The views expressed do not represent that of organisations that the writer is associated with. The information provided is for educational and communication purposes only, and it should not be construed as personal medical advice. Information published in this article is not intended to replace, supplant or augment a consultation with a health professional regarding the reader’s own medical care. The Star disclaims all responsibility for any losses, damage to property or personal injury suffered directly or indirectly from reliance on such information.