Genetics of Preterm Birth


The control of normal birth timing in mammals and the fundamental signals that initiate preterm birth in humans are critical areas of scientific investigation. Preterm birth is the leading cause of infant mortality throughout the world, and the single greatest challenge in women's and children's health today. Despite the recognised importance of this area of investigation, relatively limited advances have been made. In part, this limited success in revealing mechanisms results from divergence in the endocrine physiology of pregnancy between species. To have an effect on these biological and medical gaps in knowledge, new genetic studies in humans and comparative genomic investigations across species have been undertaken. In this article, the authors summarise the current status of genetic and genomic approaches to elucidate the control of birth timing.

Key Concepts:

  • Genetic factors, primarily in the maternal genome, contribute to preterm birth risk.

  • The physiology of human pregnancy differs from other species except for other higher primates.

  • Humans have unique constraints for birth timing related to foetal size and/or metabolism.

  • Candidate gene association studies have not been generally informative.

  • New data emerging from non‐biased genome‐wide approaches have suggested new pathways for birth timing and preterm birth risk.

Keywords: pregnancy; genomics; evolution; comparative biology; progesterone

Figure 1.

Detecting genetic associations with preterm birth may require stratification for other factors. (a) The maternal genotype at the locus A has no detectable effect on the mean gestation length. (b) Only after stratifying the population according to a second factor (shown by different colours), such as environment, race, or the paternal genotype, is the effect of the allele substitution on the length of gestation visible.

Figure 2.

Genes involved in control of birth timing may have been selected for their involvement in other traits. Locus A affects two traits that are both under strong selection; however, the genotype that increases immunity most (aA) may not be the same as the one enhancing pregnancy outcomes (aa). Across populations, the relative importance of the two traits differs. Moreover, other loci contributing to these traits evolve to accommodate the adverse effects in the local population.

Figure 3.

Comparison of human and mouse pregnancies. Fundamental differences in the anatomy and physiology between these species include uterine shape, number of embryos, and the site of generation of progesterone (P4) in late gestation. Reprinted with permission from Ratajczak et al. (). © The Company of Biologist Limited.



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Further Reading

Bezold KY, Karjalainen MK, Hallman M, Teramo K and Muglia LJ (2013) The genomics of preterm birth: from animal models to human studies. Genome Medicine 5: 34.

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Lengyel, Candice, Muglia, Louis J, and Pavličev, Mihaela(Sep 2014) Genetics of Preterm Birth. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0025448]