Globally, Preterm Birth (PTB) is the single largest cause of neonatal deaths. A birth that takes place before the mother has been pregnant for at least 37 weeks construes a preterm birth. In India, among the total 27 million babies born annually, 3.6 million babies are born preterm, and over 300,000 of these preterm babies die each year because of associated complications. India, with its highest number of PTBs and the highest number of preterm deaths worldwide, contributes 25% of the overall global preterm related deaths. Despite substantial efforts to introduce new therapies for prevention, it continues to contribute significantly to neonatal and infant mortality. The effects of PTB extend beyond the early infancy with substantial long-term consequences in late childhood and adult life.
A major reason for our inability to significantly reduce the burden of preterm birth is that the causes of preterm birth are not fully understood. Without a clear understanding of the causes, it is hardly possible to predict and therapeutically prevent preterm birth. Preterm birth is likely caused by a combination of physical, environmental and biological factors. Biological factors appear to be the predominant causes that predispose a woman to deliver babies preterm. Some of these biological evidences have been derived from studies on mouse and other mammals, because it is extremely difficult to collect scientific information on the natural history of pregnancy in the human.
To collect scientific information on pregnancy that may lead to a preterm birth, a woman has to be identified early in pregnancy, followed up through the duration of pregnancy during which clinical and life-style information must be collected. Biological changes taking place during this period must also be assayed by collecting blood and other biological materials from the pregnant woman. These are very difficult human biomedical studies. Further, because differences in biological responses and life-style factors are enormous from one pregnant woman to another, information needs to be collected on a large set of women for deriving robust conclusions.
After a series of national and international consultations, Department of Biotechnology (DBT), Ministry of Science and Technology, Government of India has launched a major national programme to identify the correlates, causes and predictive biomarkers of preterm birth. The overall long term goals of the PTB programme are to:
The scientific success of this programme is bound to have a major ripple-effect on discovery of preventive therapies. It will contribute significantly towards reduction in infant and maternal mortality rates.
Under its Grand Challenge Programme, the Department of Biotechnology, Ministry of Science and Technology, Govt. of India, has initiated a large multi–institutional and multi–phase research programme on PTB. The first-phase of the programme has formally been launched in December 2013 with a total financial outlay of Rs. 48.85 crore.
The PTB programme is establishing a hospital-based cohort of pregnant women starting from the first trimester, each of whom will be followed up until delivery. The cohort is being established in a district hospital in Gurgaon, Haryana.
Because of the multifactorial nature of preterm birth, scientific expertise from multiple domains of clinical, biological and statistical sciences are required to identify the correlates, causes and predictive biomarkers of preterm birth. Therefore, cross-disciplinary platform is being used to bridge expertise from disparate fields, such as, pediatrics, gynecology, infectious disease biology, epidemiology, microbiology, immunology, cellular & molecular biology, genetics, statistics and computational & systems biology.
1. Translational Health Science and Technology Institute (THSTI), Gurgaon: An autonomous Institute of Department of Biotechnology, Ministry of Science and Technology, Govt. of India
· Pediatric Biology Centre at THSTI is the main coordinator of the program.
· Centre for Human Microbial Ecology at THSTI is responsible for the microbiome analyses.
2. Gurgaon General Hospital, district hospital of Gurgaon in Haryana, is the main study site.
3. Safdarjung Hospital, New Delhi, will be responsible for the subjects referred from Gurgaon General Hospital during the study; Gurgaon General Hospital has a formal arrangement for referrals to Safdarjung Hospital.
4. National Institute of Biomedical Genomics, Kalyani, West Bengal, an autonomous institute of DBT, Ministry of Science and Technology, Govt. of India is responsible for genomic and epigenomic assays.
5. Regional Centre for Biotechnology, a category-II institution under the auspices of UNESCO, established by DBT, Ministry of Science and Technology, Govt. of India is responsible for proteomic analysis.
6. Clinical Development Services Agency, an extramural unit of THSTI is responsible for external monitoring and data management of the study.
7. Maulana Azad Medical College and All India Institute of Medical Sciences are providing scientific inputs and technical guidance.
In addition to these institutions, the National Rural Health Mission, Tata Consultancy Services, Department of Health Research and the Indian Council of Medical Research are also actively involved.
The data and biospecimens being collected in this study are of paramount value, not only for the present time but also for a long period into the future. Therefore, it is critical to collect and store data and biospecimens under globally-accepted quality assurance protocols. These protocols have been established with guidance from the World Health Organisation. Data storage and sharing will be under the guidelines being established by the Global Alliance for Genomics & Health (GA4GH), of which DBT is a partner.
A dedicated research team comprised of research physicians, nurses, attendants, field workers and field supervisors are stationed at Gurgaon General Hospital to facilitate relevant data collection. There is a separate project management team comprised of specialized groups looking after quality assurance, site and the data management. A separate room has been identified for taking informed consent from participants interested in participating in the study.
The Programme is being monitored by a Steering Committee represented by eminent national and international experts in important domain areas who are responsible for strategic guidance. A Programme Management Committee has been formed to address matters related to scientific, technical and financial aspects on regular basis and report to the Steering Committee.
Responsibilities of Collaborating Institutions
Details of NIBMG’s Work Plan
In the PTB Program, NIBMG will undertake genomic and epigenomic analyses and also statistical analyses of all data generated by the participating organizations. Since PTB is a complex and highly heterogeneous phenotype that is caused by a number of interacting genetic and environmental factors, investigating a single axis in isolation is unlikely to provide a complete understanding of the biological and physiological basis of PTB. A multifaceted approach – involving genomics, epigenomics and proteomics – holds a stronger promise for providing a deeper understanding of PTB.
• Can the maternal genotype predict PTB?
• What are the epigenomic associations with PTB? Do epigenomic changes take place over the period of pregnancy? If so, can epigenomic changes in the second or third trimester predict PTB?
An agnostic approach will be used for genomic assays and a genome-wide association study (GWAS) will be done. The epigenomic study will also be carried out at the whole genome level using the Infinium Human Methylation 450 BeadChip (Illumina). The overall plan for genomic and an epigenomic analyses to be undertaken by NIBMG is given below.
