Introduction

Most well-described risk factors for pre-eclampsia are constitutional maternal attributes, such as primiparity, obesity, ethnicity, chronic hypertension, renal disease, etc. (Eskenazi et al., 1991; Saftlas et al., 1990; Sibai et al., 1995; Stone et al., 1994), or behavioral attributes such as contraceptive practices or smoking (or the lack thereof) (Klonoff-Cohen et al., 1989, 1993; Sibai et al., 1995). Residence at high altitude (>2700 m) is the only external environmental factor that, to date, has been consistently linked with an increased incidence of pre-eclampsia (Keyes et al., 2003; Mahfouz et al., 1994; Moore et al., 1982; Palmer et al., 1999). Far from being a problem limited to only isolated human populations, more than 40 million people reside at elevations >2700 m, with their numbers increasing rapidly (Moore et al., 1998). The primary effect of high altitude is lowered arterial oxygen tension (PO2). Thus, of the several competing hypotheses concerning the etiology of pre-eclampsia, the data from high altitude support that hypoxia (presumably of the fetoplacental unit) is an underlying cause or at the very least contributes to the development of the syndrome. The high-altitude data additionally support altered immunological function, impaired placentation (shallow invasion) and ischemia or ischemia/reperfusion injury as possible etiological factors. This review considers the impact of lowered maternal arterial PO2 on pregnancy physiology and the development of pre-eclampsia.

High altitude and hypertension during pregnancy

The first published report indicating that residence at high altitude may be associated with an increased risk for pre-eclampsia was by Colorado researchers in 1982.