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The newborn screening test found no abnormalities. So everything is fine with my baby?
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Examinations without abnormal findings may be falsely reassuring if we don’t know what we are testing and excluding.
There is a risk of around 3% in all pregnancies of having a child with congenital anomalies. Not all these malformations are of genetic aetiology. Some result, for example, from exposure to teratogenic agents – agents that can cause damage to the embryo, as they have the ability to interfere with embryonic development processes. Examples include some drugs (such as sodium valproate and warfarin), maternal diseases (such as uncontrolled diabetes mellitus or lupus), alcohol consumption or infections (such as syphilis and cytomegalovirus). The national programme for monitoring low-risk pregnancy includes a series of analytical screening tests, such as blood glucose to exclude diabetes mellitus, or VDRL to exclude syphilis.
Genetic diseases
Genetic diseases result from alterations in our genetic code and around 7000 are known.
They can result from alteration in the number of chromosomes or alteration of just one letter in a single gene. They can be inherited from one or both parents or be de novo (a sporadic error, not present in the parents’ DNA). With systemic repercussions or affecting only one organ (deafness, for example). With ultrasound alterations, clues only at birth, manifesting later in childhood or even in adulthood.
The newborn screening test
Early diagnosis of some diseases with early onset in childhood is possible through a set of tests performed on a blood sample, collected by heel prick in the baby – the newborn screening test. The sample is collected in the first days of a child’s life (ideally between the 3rd and 6th days of life). These are free tests with no mandatory character, but fortunately coverage is over 99%.
The decision on which diseases to study is supported by the severity of the disease – with risk of life or disruption of intellectual development – by the availability of a sensitive and specific test, available and effective treatment with clear advantage to the child.
The National Newborn Screening Programme in Portugal
In Portugal, the National Newborn Screening Programme (PNRN), previously the National Early Diagnosis Programme (PNDP), began in 1979. Currently, Portugal is among the countries in the world that test the most diseases: 29, including metabolic diseases, congenital hypothyroidism, Cystic Fibrosis, Sickle Cell Disease, Spinal Muscular Atrophy and the pilot study for Severe Combined Immunodeficiency. But they are 29 and not 7000 and based mostly on the measurement of metabolites related to the disease in question (that is, they diagnose pre-clinical disease and do not take advantage of the potential of genetic tests).
A newborn screening test without alterations reduces the risk of these 29 diseases and no others.
The evolution of genetic testing
Genetic studies, studies of errors in our DNA (our instructions) have evolved greatly over the last ten years: not only do they allow the study of hundreds to thousands of diseases at the same time, but they also have the potential to diagnose diseases even before their clinical manifestation.
So, if most of the diseases tested are genetic, why don’t we apply this technology more widely to newborn screening? Why don’t we study hypercholesterolaemia, cardiac arrhythmias with risk of sudden death or dozens of other syndromes associated with preventable symptoms? What are the main obstacles to its immediate application?
The main challenges
First, applicability! Whether or not there are measures to offer and whether diagnosis is in the child’s interest.
Secondly, come the technical limitations and indeterminate results: not all genetic alterations associated with disease are detectable by current tests and we don’t understand everything we find. There are results uncertain in their meaning, there are diseases with variable expression (different symptoms in different individuals), with incomplete penetrance (not all individuals with the genetic alteration will have manifestations of the disease). This uncertainty is not compatible with the objective of a screening test.
Thirdly, there is the question of price, accessibility and universality of tests. There are costs associated with the technique, the necessary infrastructure, training of human resources, necessary research.
Lastly, there are ethical questions. Should diseases with later development in childhood, or even in adulthood, be studied? How is individual choice protected when dealing with children?
Genomic newborn screening: the future
There are pilot studies being developed in several countries around the world – so-called genomic newborn screening (gNBS in the English acronym). Several important aspects are being taken into account: criteria for selection of diseases to test according to their prevalence in different populations, age and clinical presentation of diseases, proven and available treatments and other measures, selection of data to report, advantages for society and above all for the individual, respecting their individuality.
Evolution in Genetics has reduced uncertainty in results, test costs, and increased therapeutic solutions. Furthermore, the importance of early diagnosis for optimising patient monitoring cannot be ignored, from hospital choice to tests to be performed, possible dietary changes, surgeries (to be performed or avoided), preventions, to the choice and therapeutic success. Delay in diagnosis has costs, economic and, more importantly, human.
Today, with limits, responsibility and ethics, it is possible to do it right at birth through genomic newborn screening (who knows, one day it will still be during pregnancy through non-invasive genomic tests).
Portugal cannot be left behind in this boat. There are costs that are investments with returns. Betting on genetics in healthcare measures is one of them.
About the author
Dr. Marta Zegre de Amorim is a medical specialist in Genetics with almost 20 years of clinical experience and research in medical genetics, oncogenetics and rare diseases. She is currently an Assistant in Medical Genetics at Hospital Lusíadas Lisboa, where she also assumes coordination responsibilities. At Quilaban, she performs the Medical Affairs function, with regular involvement in training activities, congresses and scientific initiatives related to genetic sequencing, epigenetics and precision medicine.
Throughout her career, she has participated in national and international research projects, developed collaborative work in reference centres such as Addenbrooke’s Hospital (Cambridge) and SickKids (Toronto), and has dozens of scientific publications in clinical genetics, hereditary syndromes and oncogenetics.
