Human Evolution, Genomics, and Birth Timing: New Approaches for Investigating Preterm Birth

Abstract

Preterm birth and its complications remain one of the most challenging problems in neonatology. Although preventative strategies to reduce preterm birth have been a long-standing goal, limited progress has been achieved in reducing its incidence. In part, the barriers to designing better interventions to prevent preterm birth have reflected our incomplete understanding of human pregnancy maintenance and termination because events differ in humans compared with most other species. In this review, we highlight new insights into understanding progesterone signaling during pregnancy that may allow humans to enter labor without overt, systemic progesterone withdrawal, which indicates a lack of progesterone action despite abundant circulating levels at parturition. Hypotheses regarding how increased human brain size in the context of pelvic or metabolic constraints have shaped the time for birth are discussed, and how this information can facilitate population genetic studies are provided. With increasing access to genomic information from humans, nonhuman primates, and other mammals, as well as growing numbers of well-phenotyped cohorts related to pregnancy outcomes, new opportunities related to the discovery of prematurity prevention options are now available.