Congenital anomalies affect around 2% of new born babies. Many of these anomalies are suspected before birth following an ultrasound examination, or diagnosed as a result of an invasive prenatal diagnostic test such as chorion villous sampling (CVS) or amniocentesis. Such testing may be carried out because of a high risk screening test result, a family history of anomalies or an abnormal ultrasound scan.
Many European countries now offer screening in the first trimester of pregnancy. This includes a 12 week scan to measure the nuchal translucency which, combined with pregnancy specific blood test results, will provide a risk for trisomies 21, 18 and 13 (Down, Edwards and Patau syndrome). Those receiving a high risk may then opt for an invasive test to check the baby’s chromosomes.
Some major anomalies may be detected at the 12 week scan but most cannot be seen at this gestation. Further screening is therefore provided in the second trimester with an anomaly scan routinely offered, in most centres, between 18 and 22 weeks to check the baby carefully for significant problems. If one or more anomalies are seen, an amniocentesis may be offered to look for an underlying chromosome abnormality.
The number and types of anomalies suspected before birth will depend on what tests are available, the experience of the operator and the accuracy of the particular test. All of these factors are continually changing and vary between centres and countries.
EUROCAT Registries collect information on whether an anomaly was suspected prenatally, the gestation at first suspicion, the type of test that led to that suspicion and the outcome of the pregnancy. Monitoring detection rates for different anomalies, the types of tests used and the outcome of affected pregnancies is an important part of the work carried out by EUROCAT.
Scientific advancements have led to the development of new techniques for examining chromosomes. For many years the only method was karyotype analysis. This is still offered in the majority of European centres but many are now incorporating the new approaches.
QF-PCR (Quantitative fluorescent polymerase chain reaction ). This is used as a rapid test to detect common aneuploidies - trisomies 21, 18 and 13, 45,X, triploidy and often 47,XXX, 47,XXY and 47,XYY. Many centres use it as the first test and proceed to full karyotype or aCGH if no abnormality is detected. Some centres use it as their only test following high risk Down screening. Results are usually available within 3 days.
aCGH (array comparative genomic hybridisation) .This molecular technique can detect genomic deletions or duplications with far greater sensitivity (>100 times) than karyotyping. It is routinely used in many countries, in the postnatal setting, and is being introduced, cautiously, for prenatal use. Whilst of real value in detecting small pathogenic abnormalities, its high sensitivity has meant that it may also detect variants of uncertain significance that can be hard to interpret.
NIPT (non-invasive prenatal testing). Until recently, analysing fetal chromosomes has necessitated an invasive test – CVS, amniocentesis or fetal blood sampling - to retrieve fetal cells. These techniques carry a small risk of miscarriage. NIPT allows the extraction of fetal DNA from maternal blood within the first trimester. Current technology allows the examination of this DNA for the common aneuploidies to a high level of accuracy, however, an invasive test is still needed for confirmation. The development of greater accuracy and reliability is expected to remove that requirement in the future.
MRI (magnetic resonance imaging) can safely be used during pregnancy to look more carefully at fetal tissues. It is primarily used to look in more detail at the fetal brain, where an abnormality has been suggested by ultrasound scan, but can be used in other circumstances.
Definition of some prenatal terms
Prenatal Diagnosis is defined as a diagnosis suspected/made in a live fetus at any gestation.
Prenatal Screening involves one or more non-invasive tests for identifying fetuses who may be at higher risk of eg. Down Syndrome. Those women whose pregnancies have been identified to be at a higher risk may opt for a diagnostic test such as a CVS or amniocentesis.
Gestational Age at Discovery is the gestational age at which the fetus was first suspected to be malformed (excluding soft-markers) and indicates the time of the examination rather than the time when the result is known (see Guide 1.4).
For definitions of terms used in prenatal screening and diagnosis the following link may be helpful.