Pregnancy at high altitude: evolutionary and historical perspectives.

Pregnancy encompasses the portion of the life cycle subjected to among the strongest of evolutionary pressures owing to the nature of mammalian reproduction and the characteristics of the human species. The pioneering work of early investigators such as Joseph Barcroft, Donald Barron, Giacomo Meschia, James Metcalfe and others laid the groundwork for identifying constraints affecting each of the three major players in mammalian reproduction-fetus, placenta and mother-for meeting the increased oxygen and other nutrient demands required for fetal growth and maternal wellbeing. The papers comprising this special issue illustrate how each player responds under the conditions of the chronic hypoxia present at high altitude, as well as under other circumstances limiting oxygen supply. Recognizing the contributions of each player and the importance of their interactions can point the way towards actionable targets for developing new therapies for improving both immediate and later-in-life outcomes for both mother and child.This article is part of the discussion meeting issue 'Pregnancy at high altitude: the challenge of hypoxia'.