Dr Rajanikanth Vangala

Empowering a mother is enabling a brighter future for the country. A major goal of clinicians is to bring down maternal mortality and premature births and do prenatal defect detection. This goal can be achieved by prenatal screening for birth defects, which, until recently, required invasive methods like collecting amniotic fluid, which contains foetal cells — mostly of epithelial origin — or chorionic villus samples, which have mesodermal connective tissue and trophoblastic cells of the placenta. These invasive techniques do carry a greater risk, including that of foetal loss. However, the increasing knowledge about circulating cell-free fetal DNA (ccffDNA) and its presence in the mother’s blood has led to the development of non-invasive prenatal screening or testing (NIPS or NIPT). Every human being carries cell-free DNA. However, pregnant women carry around 10-15% ccffDNA, depending on several factors such as the inverse association with an increase in maternal weight. These ccffDNA fractions from each chromosome can help in identifying specific genetic aspects or defects in the foetus. For example, statistically significant higher levels of DNA fragments from chromosome 21 correlate with trisomy 21 (Down syndrome). The small amounts of DNA fragments are further analyzed in bioinformatics by comparing them with reference human genome to identify anomalies. Cost-effective, targeted sequencing has been developed now, for example, for chromosomes 13, 18, 21, X and Y.

Adhering to guidelines

NIPS was introduced in India in 2012 and is now spreading quickly in all major cities. There are approximately 26 million births every year in India and NIPS could truly help improve health systems. However, it is imperative that medical specialists and obstetricians be aware of the relevant recommendations and guidelines so that the test can be used properly. Based on the guidelines of American College of Medical Genetics and Genomics (ACMG), NIPS has been limited to screening assessments and is not used for diagnostics. This suggests that there may be potential residual risk of disease, albeit very low, even if the test comes back normal. However, this is true in case of any other biochemical or ultrasound study. This aspect must be explained to the patient clearly. Would-be parents and family in India may expect these tests to be 100% accurate, like in the case of invasive tests such as amniocentesis and chorionic villi tests. The recommendations and guidelines must be adhered to in explaining the scientific rationale of such tests, and probably, a simplified meta-analysis of relevant studies could be presented to the patient.

One of the most important factors in a healthy pregnancy is the age of mother at the time of giving birth. In India, the proportion of women who are greater than 35 years of age at the time of delivery is increasing to 2-5%. The second important factor to be considered is the high rate of consanguineous marriages in the country, leading to increased incidences of birth defects. Even as chromosomal aneuploidies are increasing, there are very few centres that offer quality services for premarital or prenatal genetic screening / testing and counselling. While NIPS may soon become popular in cities in India, the penetration of rural areas will be a huge hurdle as even basic medical services are yet to be made ubiquitous there. One of the important mechanisms that can help in reaching out are referrals to non-governmental clinics and centres. Furthermore, many rural and peri-urban patients refuse screor proenings cedures due to socio-cultural and religious reasons related to the sanctity of pregnancy. There is an urgent need for bringing awareness among all sections of the society about the value of science when adopted in correct ways. This also means that companies and the government must invest outside sequencing technologies and personnel training.

Translating scientific knowledge

Improving the molecular or genetic quotient will determine the future progress of humanity. Both commercial and not-for-profit organizations must come forward with unique models of translating scientific knowledge to the layman. We all know that science is the basis of the modern medical practices and progress that can truly reduce the disease burden. The majority of scientists work in their laboratories and publish in scientific journals which are not suitable for general public consumption. However, scientists always want to translate their knowledge for public benefit. Presently there are no platforms for this purpose, which opens up great opportunities. It is the right time for clinicians and scientists to join hands in grabbing these opportunities and creating platforms to translate molecular and clinical knowledge outcomes to the public. This can truly help devise an ethical way of bringing change in the society and in transmitting the true value of technological development. The ethical discussion also brings up the question of pricing and affordability. Even if prices are reduced, NIPS will still be a financial burden among less-advantaged populations. They may, in spite of having knowledge of genetics. give religious or other reasons for not availing the services. A novel mechanism of subsidy for economically weaker sections may see a surge in the usage of the technology and give better value addition to scientific discoveries. Giving birth to a baby with genetic abnormalities is often seen as a huge burden by families in the absence of a support system for the parents and the children. This can become a major cause of concern when there are an increased number of women seeking abortions, and in places where such abortions are illegal, they end up receiving unsafe abortions. These aspects need to be understood thoroughly before taking NIPS services ahead in the future.

The majority of NIPS offered in low- and middle-income countries, including India and China, are based on European or US accreditations. The genetic screening does not generally come under local regulatory oversight. The legal provisions in India, which tend to focus on abortion and reproductive technologies, must also consider the value of giving proper prenatal detection of foetal aneuploidy. This gives time to families to be prepared for the birth, and have all the required resources to deal with the complications, including the social, moral and psychological consequences. The legal provisions on abortions can vary, including the regulation on foetal sex determination imposed in India to prevent sex selection. As India prohibits sex selection, screening companies, medical practitioners and genetic counsellors must be careful to follow the applicable norms. Ultimately, the success of any genetic screening will depend on the inclusiveness of clinicians, scientists, professionals of other fields, the public, patients, insurance providers and local governments.

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