Current Prenatal Screening Strategies for Down Syndrome In India

UNIVERSAL PRENATAL SCRRENING FOR DOWN SYNDROME: A WAY FORWARD IN INDIA

 In the modern world most couples planning to welcome newborns in their families releasing their dreams of parenthood must have come across the word ‘Down syndrome’ especially during their first three months of the pregnancy. DS was first reported in the literature since 1866, when Langdon John Down, a British physician practicing in London treated unique group of children with unique physical and mental characteristics and intellectually challenged children under his care. Later almost about a century later after the phenotypic description of DS, LeJeune in 1959 first time reported the cause and identified the occurrence due to an extra copy of chromosome 21 from patients with DS. By this time science had already enlightened us that all humans carry 23 pairs of thread-like structures called chromosomes tightly packed inside the nucleus of the cell and inheriting one each from our parents. These chromosomes also consist of genes or the genetic codes in the form DNA segments that are responsible for every human body function through formation of specific proteins responsible and distinctive unique features including hair, eye, skin, colours, height etc.  DS is the commonest chromosomal disorder that can cause mild to moderate intellectual disability in babies born with an extra copy of chromosome 21 arising due to some random errors during the early cell cycle division in the reproductive cells (eggs or sperms). It is the most prevalent autosomes chromosome abnormality in live-born babies, occurring in approximately 1 in 800 births worldwide. Unfortunately, population-based data on the birth prevalence of Down syndrome are critically lacking in the Indian medical literature.

In the past 25 years, there has been significant progress in the field of prenatal screening for chromosome abnormalities, especially in the detection of Down syndrome (trisomy 21). The most used approach is to perform screening tests at a single point in time during pregnancy. During the first trimester a combined first trimester screening (FTS) is currently the most common prenatal screening method that involves measuring an ultrasound marker, nuchal translucency (NT) along with analysing the levels of two hormones in the pregnant women, β-human chorionic gonadotropin (hCG) and pregnancy-associated plasma protein (PAPP-A) also known as the double marker test. If a pregnant woman receives a “High Risk” score or positive result in one in screening test, now she is typically required to undergo further invasive prenatal diagnostic procedure for taking out amniotic fluid or placental tissue for further confirmation of DS baby followed by more sensitive genetic investigations such as karyotype. Although maternal serum screening is generally considered safe method for screening DS, but it has some disadvantages. One drawback is that it has lower sensitivity and false positive results for detection of DS. Therefore, these results are obtained, it is necessary to follow up with further invasive testing procedures to confirm DS by getting access to facilities and doctors available at specialized centres in the big cities.

In recent years, non-invasive prenatal screening methods, also known as Cell-Free Fetal DNA Screening (NIPS/NIPT), have become increasingly popular worldwide, including in India. These new generation DNA sequencing-based investigation had shown tremendous potential in detection of DS with higher sensitivity, and high success rate in detecting major chromosome abnormalities including DS. This groundbreaking technique was first developed in 1997 by Dennis Lo and his team. They made a remarkable discovery that the blood of pregnant women contains cell-free DNA (cfDNA). It turns out that a significant amount of this cfDNA in the mother’s blood comes from the placenta and contains genetic material from the developing foetus. This makes it a suitable source for non-invasive prenatal testing. Further research into sequencing the maternal and fetal cell-free DNA has revealed the tremendous potential of this method as a universal prenatal screening method for detection of DS in women during course of pregnancy. In last one-decade women from the affordable class had access to expensive NIPS, or NIPT an extremely sensitive blood test, with an accuracy of over 99% in detecting trisomy 21 (Down Syndrome) in the developing foetus. Currently these technologies are expensive and beyond the reach of majority of women in India but offers a new ray of hope to detect DS and other common chromosome abnormalities observed during the pregnancy. NIPS is considered one of the safest and most convenient prenatal screening methods as it only requires a simple blood draw from the pregnant woman. This makes it a highly reliable screening test and potential candidate to be included in universal prenatal screening program that could also alleviate the anxiety of many pregnant women concerned about the possibility of having a baby with Down syndrome.  

After required number of days of conventional cytogenetics culture of 10-month baby blood sample in controlled laboratory conditions, we got to observe results with an extra copy of chromosome 21 in all the metaphase of cell cycle under the light microscope thus confirming the diagnosis of DS.  One of the most reliable investigations for confirming the presence of chromosomal abnormalities in a developing foetus is chromosome analysis, which is often known as karyotype. Even after many decades of DS discovery this untreatable disorder, it is still unheard or unidentified in many parts of the country including many small towns and cities due to lack of social awareness about the genetic disorders. As a result, this rare genetic disorder remains undiagnosed during pregnancy and babies are still born in absence of timely interventions to reduce the genetic burden. The early diagnosis of DS prenatally before the birth of child is challenging due to small number of trained and experienced doctors and lack of implementation of universal prenatal screening by different state government for early detection of DS. The implementation of highly sensitive prenatal screening methods can screen women at high risk of having a DS and now had to undergo invasive procedures by collecting tissue samples from the placenta or amniotic fluid from the pregnant woman. This approach can further reduce the risk of miscarriage or fetal loss related to the procedures performed only by experienced and trained doctors at the super speciality centres. But still these children born with Down syndrome still have a ray of hope to live happily and contribute to society, if intervened early by speech therapy, physiotherapy and occupational therapy and provided with proper medical attention for different health issues observed in DS and thus can have a better long-term outcome as compared to other genetic causes of intellectual disability. Also with the right patient support groups https://downsyndrome.in/ many affected children can also affectively managed with right treatment protocols as per professional recommendations and can live happy and productive lives (https://iapindia.org/pdf/care-of-child-with-down-syndrome.pdf).