(21) Altitude and Risk of Pre-Eclampsia: Insights from a large-scale epidemiological study in Ecuador

Emma Mitchell-Sparke1,2; Bart Theeuwes3; Imogen Grant1; Dino A. Giussani4,5,6,7; Catherine Aiken1,5,6,7 

1Department of Obstetrics and Gynaecology, The Rosie Hospital and NIHR Cambridge Biomedical Research Centre, The University of Cambridge, Cambridge, UK

2Tufts University School of Medicine, Boston, MA, US

3Cambridge Stem Cell Institute, The University of Cambridge, Cambridge, UK

4Department of Physiology, Development, and Neuroscience, The University of Cambridge, Cambridge, UK

5Institute of Metabolic Science, Addenbrooke's Hospital, The University of Cambridge, Cambridge, UK

6Loke Centre for Trophoblast Research, The University of Cambridge, Cambridge, UK

7Cambridge Reproduction Strategic Research Initiative, The University of Cambridge, Cambridge, UK

Abstract Text:

Pre-eclampsia affects 2-8% of pregnancies globally and is a leading cause of maternal morbidity and mortality, particularly in low- and middle-income countries where healthcare resources are often limited. The condition arises from defective trophoblast invasion into maternal spiral arteries, leading to placental perfusion issues and widespread maternal endothelial dysfunction. While known risk factors include nulliparity, chronic hypertension, extremes of maternal age, obesity, and low socioeconomic status, there remains speculation about high altitude as a risk factor. This study aimed to evaluate the association between altitude, treated as a continuous variable, and the risk of pre-eclampsia in Ecuador, while accounting for socio-demographic influences. An epidemiological study design was employed, utilizing publicly available maternal health records from Ecuador's National Institute of Statistics and Census (INEC) for the years 2021–2023. Adjusted generalized additive models (GAMs) with cubic splines were applied to explore potential non-linear relationships between altitude and pre-eclampsia risk. Altitudes corresponding to the maternal residences of each patient in the dataset were assigned using advanced geospatial techniques and verified against known geographical patterns. Statistical analyses, including generalized additive models (GAMs), were employed to explore linear and non-linear relationships between altitude and pre-eclampsia risk. Models were fitted with restricted maximum likelihood (REML) and adjusted for maternal age, ethnicity, funding model, type of care, and residential area to control for the effects of possible confounding variables. The analysis found no significant increase in pre-eclampsia risk with increasing altitude in adjusted non-linear models. However, pre-eclampsia risk was significantly higher among women at the extremes of maternal age (p< 0.001) and those receiving publicly funded care (p< 0.001), suggesting the likely influence of socioeconomic disparities. Ethnicity was also a determinant of pre-eclampsia risk, though no interaction between ethnicity and altitude was observed. The absence of a clear impact of altitude on the risk of pre-eclampsia in this study may reflect context-dependent risk factors unique to Ecuador’s demographic, genetic, and environmental landscape. As such, further research using population-wide data from regions with significant altitude variation is vital to enhance understanding of pre-eclampsia risk and refine clinical resource allocation strategies in under-resourced, high-risk areas.



Funding: CEA is supported by the NIHR Cambridge Biomedical Research Centre (146281). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.