Genetic risk factors of preterm births in India

Preterm birth, before 37 weeks of gestation, is the leading cause of neonatal mortality. It is also associated with delayed development during early childhood, increased risk of adult onset of diseases and thereby imposes enormous burden on public health. India with the largest number of preterm births is the biggest contributor to the world’s prematurity burden. With the ultimate objective to acquire deep fundamental knowledge about preterm birth and to use this knowledge to find efficient and sustainable solutions to reduce the morbidity and mortality associated with preterm birth, an inter-institutional and interdisciplinary programme (Garbh-Ini ) was established by the Department of Biotechnology in 2014.

As part of the Garbh-Ini programme, DBT undertook to investigate the genomic and epigenomic underpinnings of preterm birth through a genome-wide association study (GWAS) on spontaneous preterm birth on 6,211 women from India. This is the first study in India as well as South East Asia.

In the findings of this GWAS study which is published in The Lancet Regional Health Southeast Asia, 19 single nucleotide polymorphisms (SNPs) associated with preterm birth in the study population were identified, out of which five SNPS were found to confer increased risk of early preterm birth (birth before 33 weeks). Additionally, four significantly associated trans-ethnic SNPs were identified which showed association both in Indian women as well as in the women belonging to the European ancestral population. Interestingly, these SNPs are well known to regulate important biological processes such as inflammation, apoptosis, cervical ripening, telomere maintenance, selenocysteine biosynthesis, myometrial contraction, and innate immunity.

This study on Indian population reveals important information by identifying both trans-ethnic and population-specific maternal genomic variants, that might affect different biological processes and molecular mechanisms culminating in spontaneous preterm birth. The SNPs showing trans-ethnic association requires further investigation in other populations which will help to understand its global clinical relevance.
From public health perspective, the genomic markers either alone or in combination with other clinical or biological variables could be evaluated for their predictive abilities, and their potential in early triaging of women at high risk of spontaneous preterm birthso that they can be subjected to appropriate antenatal medical care.