There was a recent news article that was widely shared in the social network apps regarding a Bangalore couple that accused the doctor and the hospital for missing out on the prenatal diagnosis of Down syndrome. This is a fall out of lack of clear understanding about the condition, the testing strategy, the pros and cons of the screening tests.
Down syndrome is the common chromosomal abnormalities that can result in live birth. It is characterized by the presence of an extra copy of the 21st chromosome. This extra copy comes due to an error during the production of the gametes, the ova or less commonly sperm. Presence of an extra copy of the 21st chromosome leads to a characteristic phenotype including a striking facial appearance, decrease in intelligence quotient, increased risk of congenital heart defects, gastrointestinal defects, childhood leukemias, early Alzheimer’s.
Prenatally, the only way to confirm or firmly refute the presence of an extra copy of the chromosome is by performing a karyotype (KT) of the fetus. The cells required to perform this KT test can be obtained from the placenta (chorionic villus sampling), amniotic fluid (amniocentesis), or the fetal blood (fetal blood sampling). In practice, the actual site of sampling is dependent on the gestational age at which the procedure is done.
However, all of these procedures are “invasive” procedure and are associated with a slight risk of procedure-related miscarriage. Moreover, KT is by itself an expensive and labour intensive test requiring expertise. Therefore, it is not practical to offer fetal KT (invasive testing) for all pregnant women to detect a condition that occurs at a rate of about 1 in 962.
In developed countries, there are screening strategies that indirectly identify women who are at higher than average risk of carrying a Down syndrome fetus. Initially this was based solely on maternal age such that women over 35 years were offered invasive testing. With more research, several other tests were developed: the Triple screening test, the quadruple screening test, the combined screening test, the integrated test, and the non-invasive cell free fetal DNA based test. Of these, the triple screening test is considered obsolete, the cell-free fetal DNA based testing is yet to be validated for large scale application, and the integrated test has the disadvantage of multiple visits for a single result. Currently, the standard of care is the combined screening test at 11 – 14 weeks that involves measurement of the fetal crown rump length and fetal nuchal translucency by ultrasound and measurement of the placental products : free-β hCG and Pregnancy Associated Plasma Protein – A. In those women who miss the time window, a quadruple screening is offered.
In India, there is lack of understanding of some of the basic issues involved in Down Syndrome screening: firstly, opting for screening is purely a personal choice to be made by the parents after understanding about the condition, the testing strategy and its consequence. Secondly, every practitioner, hospital or institution should have a “screening program” and know this is different from the “screening test”.
The screening program should have as its components
- a policy of spreading awareness of the condition and testing among its clients,
- space and time for the clients to discuss and clarify their doubts,
- written information leaflets that specify the detection rate, false positive rate, screen positive cut off for their program
- a program director who will audit the entire program on a regular basis, accredited operators and labs that are evaluated on an ongoing basis
The most important component is the pretest and post test counseling: parents should be made to understand that the screening test only detects about 90% (for the combined test) or 80% (the quadruple test) of all Down syndrome fetuses. Hence even when the screening test returns a low-risk result, there is a small possibility of the baby being born with Down syndrome. They should also understand that the vast majority of the fetuses who are identified as high risk would actually turn out to be normal after performing KT. For example, in the largest published study from India(Manikandan et al., 2017), the actual number of Down syndrome was about 1 for every 25 screen positive case,which is on par with data from other countries.This data comes from Mediscan systems, a tertiary level fetal medicine centre based in Chennai and a premier institute for training in fetal medicine in India. The team of authors involved in this work include Fellows in Fetal medicine, Consultants in Fetal medicine and Clinical Genetics, and Genetic counsellors. Understanding this concept is important since no decision on pregnancy termination should ever be made based on the screening test result.
In the review article “Down Syndrome Screening in India: Are we there yet?” we discuss the rationale behind screening for Down syndrome, the need for understanding the concepts of the screening tests, the Indian scenario and the responsibility of the clinicians and hospitals while implementing the screening program. We hope that this article would help the clinicians to get a much better insight into the concepts of screening for Down syndrome and avoid situations such as the one I highlighted at the beginning.
Manikandan, K., Rangaraj, A., Ganesan, P., Reddy, V., Suresh, S., Jagadeesh, S.M., Suresh, I., Seshadri, S., 2017. The First Trimester Combined Screening Test in the Indian Population: Insights from a Cohort of 27,647 Pregnancies. J. Fetal Med. https://doi.org/10.1007/s40556-017-0127-1
Dr. K Manikandan
The author is MD (OBGYN, JIPMER), DNB (OBGYN), MRCOG and is Fellow in Fetal Medicine, Mediscan Systems. He is a member Editorial Board Gynecologist at Specialty Medical Dialogues.