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. Pregnancy-induced hypertension, noted as a diagnosis within medical records, occurred in 12%, 4% and 3% of pregnancies at 3100 m, 2410 m and 1600 m, respectively. Proteinuria greater than 1+ was noted in 28% and 9% of pregnancies at 3100 m and 1600 m, respectively. Blood pressure was generally higher in all pregnant women at high altitude based on medical records review. Further, in a small group of prospectively studied women with pregnancy-induced hypertension (PIH, hypertension without proteinuria or other organ system involvement), arterial oxygen saturation (which is largely determined by maternal arterial PO2) was inversely correlated with blood pressure. Thus women with the lowest saturations had the highest mean arterial pressures (Moore et al., 1982). Support for the idea that lowered maternal arterial oxygen pressure is associated with an increased risk of pre-eclampsia can also be found in the disease literature: women with a variety of congenital heart diseases associated with poor cardiac output or impaired lung transfer of oxygen to blood also have a markedly increased risk for pre-eclampsia (Shime et al., 1987). The Colorado group continued to pursue (in animal studies) the relationship between pregnancy, hypoxia and hypertension (Harrison and Moore, 1990; Harrison et al., 1986), uterine artery structure and growth (Rockwell et al., 2000), vascular reactivity (Harrison and Moore, 1989; Keyes et al., 1998; Mateev et al., 2003; Sillau et al., 2002; White et al., 1998, 2000) and the incidence and physiological correlates of preeclampsia in retrospective and prospective human studies (Jensen and Moore, 1997; Palmer et al., 1999; Zamudio et al., 1995a, b, c). Using a variety of research designs, including cohort studies, birth-certificate analyses and prospective longitudinal physiological analyses, the data have consistently shown anywhere from a two- to a fourfold elevation in the incidence of pre-eclampsia at high altitude using both strict criteria (primiparas with documented proteinuria and hypertension that resolved following delivery) and less strict, but clinically relevant criteria (e.g. hypertension plus evidence of other organ system involvement, such as neurological symptoms, abnormal liver function tests or platelet consumption). While strictly anecdotal, it is our impression that neurological symptoms are more common at high altitude, although the numbers of residents at > 2700 m and the limitations of epidemiological databases such as birth certificates preclude formal testing of this relationship. However, the general finding that pre-eclampsia is increased at high altitude has been replicated in Saudi Arabia, in women long resident at 3000 m, and in Bolivia, in women residing at 3600 m. In these larger-scale epidemiological analyses, there is a near twofold elevation in the incidence of pre-eclampsia at high altitude, independent of other risk factors, in both Saudi Arabia and Bolivia (Keyes et al., 2003; Mahfouz et al., 1994).
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