The Role of Genetics in Preterm Birth

Abstract

Preterm birth (PTB), defined as the birth of a child before 37 completed weeks gestation, affects approximately 11% of live births and is the leading cause of death in children under 5 years. PTB is a complex disease with multiple risk factors including genetic variation. Much research has aimed to establish the biological mechanisms underlying PTB often through identification of genetic markers for PTB risk. The objective of this review is to present a comprehensive and updated summary of the published data relating to the field of PTB genetics. A literature search in PubMed was conducted and English studies related to PTB genetics were included. Genetic studies have identified genes within inflammatory, immunological, tissue remodeling, endocrine, metabolic, and vascular pathways that may be involved in PTB. However, a substantial proportion of published data have been largely inconclusive and multiple studies had limited power to detect associations. On the contrary, a few large hypothesis-free approaches have identified and replicated multiple novel variants associated with PTB in different cohorts. Overall, attempts to predict PTB using single “-omics” datasets including genomic, transcriptomic, and epigenomic biomarkers have been mostly unsuccessful and have failed to translate to the clinical setting. Integration of data from multiple “-omics” datasets has yielded the most promising results.

Leptin and Leptin Receptor Polymorphisms in Infants and Their Parents: Correlation with Preterm Birth

“…PTBs occur at less than 37 weeks' gestational age, accounting for 75% of perinatal mortality. Up to now, the preterm birth rate has risen dramatically in most industrialized countries; it is estimated to be around 12-13% in the USA and 5-9% in Europe [13,16]. Despite its high incidence, the exact pathogenesis of preterm delivery is still not known.…”

“…Recent estimates report that PTB affects approximately 11% of all livebirths, or approximately 15 million PTB per year [12]. Twin studies have also suggested that genetics account for 17-36% of PTB risk [13]. In attempting to understand the heritability of PTB, both maternal and fetal genetics have been assessed.…”

“…In attempting to understand the heritability of PTB, both maternal and fetal genetics have been assessed. It has been suggested that maternal genetics are responsible for 22.8% of the variations in gestational age in spontaneous births, with fetal genetics responsible for 12.7% of the variation [13]. Concerning metabolic and biosynthetic pathway-related polymorphisms, sustaining metabolic homeostasis is vital for embryonic development and survival.…”