Latest advances in perinatal genomic medicine

The field of genomics is evolving exponentially in various medical areas, this advance is especially relevant in the area of perinatal medicine. The perinatal period covers the period from gestation to the birth of the baby. During this stage there are different types of screening and diagnostic tests based on genomics that are key to know the health of the fetus or newborn. In this article we explain the evolution of perinatal genomic medicine and the latest clinical advances.

Evolution of Genomics in Prenatal Medicine

?Non-invasive prenatal testing

The major milestone in the evolution of prenatal screening occurred with the discovery and characterization of free fetal DNA in maternal blood, which led to the development of non-invasive prenatal tests that are now part of every obstetrician's routine clinical practice.

?Today, although there are a variety of testing methodologies, most tests offer high performance for common trisomies and sex chromosome aneuploidies, the most obvious difference being the inclusion of additional tests such as microdeletions, autosomal chromosome aneuploidies or partial aneuploidies.

?Although such alterations may be of interest from a clinical point of view, the limitations of the technology used may significantly affect the positive predictive value. For this reason, when choosing a test and testing options, consideration should be given to whether the overall performance of the test is affected by the incorporation of additional conditions.

?The continuous advancement of this type of testing has led to a new clinical application of noninvasive maternal blood testing: the detection of possible chromosomal alterations in cases of miscarriage. About 70% of miscarriages are caused by aneuploidy. Until now, to determine whether there is a chromosomal alteration after a case of involuntary fetal loss, it was necessary to study the abortive remains. The problem is that the overall success rate is quite low, around 53%, mainly due to culture failures or maternal cell contamination. The clinical use of non-invasive prenatal testing for the presence of chromosomal abnormalities not only facilitates sample collection, but has dramatically increased the success rate of this type of testing.

?Diagnostic tests during pregnancy

?Studies of deletions and duplications are usually performed using microarray technology, and if no alteration is detected it is advisable to proceed to the molecular study of genetic variants that may be related to the signs observed. The problem that arises in these cases is that it is necessary to perform additional gene sequencing, and since this is an additional technology, obtaining a result can take a long time.

?Genetic diagnosis in the presence of ultrasonographic alterations has also evolved considerably in the last decade. When ultrasound findings are detected during pregnancy that raise suspicion of a genetic anomaly, it is necessary to take a fetal DNA sample by amniocentesis or chorionic villus sampling in order to determine whether the fetus has any genetic alteration. In these cases, in the first line, we proceed to the study of deletions and duplications with a resolution adapted to prenatal diagnosis, that is to say, making sure that the partial aneuploidies detected are pathogenic or probably pathogenic.

?In recent years, sequencing technology has advanced ostensibly and today it is possible to study deletions and duplications on the sequencing product, which enables subsequent molecular study without the need for additional technology. That is to say, by using a single technology it is possible to study both deletions/duplications and molecular alterations, undoubtedly another milestone in prenatal diagnosis.

?Evolution of genomics in neonatal care

?Neonatal screening originated in the 1950s and 1960s when Dr. Robert Guthrie developed a blood test for phenylketonuria shortly after birth. In the 1990s, MSMS tandem mass spectrometry is introduced that allows detection of a large number of inherited metabolic disorders in a single assay. Since then, newborn screening has become one of the most effective public health programs covering all newborns. Logically, screening is limited to a set of pathologies for cost-effectiveness reasons.

?With the advance of sequencing technology and projects such as BabySeq, genetic studies in newborns have begun to become a reality. Last year the UK NHS launched its Newborn Genomes Programme project in which the DNA of 100,000 newborns will be sequenced with the aim of finding new ways to improve the health of newborns.

?There are already genetic tests for neonatal screening that make it possible to broaden the spectrum of diseases evaluated beyond biochemical tests, which makes it possible to adapt the medical or nutritional care of children, in some cases preventing the development of the pathology and in others reducing the impact on their health.

?We have reviewed the progress and milestones of perinatal genomics in recent years, with the enormous progress of exome and genome sequencing, the use of genetic testing is being incorporated with force little by little in clinical practice both preventive and diagnostic, always at the service of patient and specialist.

At Veritas, we prioritize the health of our patients by offering screening and genetic diagnosis services. We have specialists in various medical areas who can provide guidance on the most appropriate genetic test for each clinical case. We have a wide portfolio of genetic tests based on whole exome and genome sequencing that provide key information to the specialist, with specific tests oriented to perinatal care:

• myPrenatal: Non Invasive Prenatal Test
• myNewborn: Genetic screening test for actionable childhood-onset diseases