Surviving birth at high altitude

Abstract

This Symposium Review examines challenges to surviving birth and infancy at high altitudes. Chronic exposure to the environmental hypoxia of high altitudes increases the incidence of maternal vascular disorders of pregnancy characterized by placental insufficiency, restricted fetal growth and preterm delivery, and impairs pulmonary vascular health during infancy. While each condition independently contributes to excess morbidity and mortality in early life, evidence indicates vascular disorders of pregnancy and infantile pulmonary vascular dysfunction are intertwined. By integrating our recent scientific and clinical observations in Bolivia with existing literature, we propose potential avenues to reduce the infant mortality burden at high altitudes and reduce pulmonary vascular disease in highland neonates, and emphasize the need for further research to address unresolved questions.

Keywords: hypoxia; postnatal adaptation; preeclampsia; pulmonary hypertension; sudden infant death.

Figure 1.

Neonatal and childhood (under-five) mortality rates across time at high, moderate, and low altitudes in Bolivia. Neonatal deaths per 1,000 births, shown on the left-hand axis, are represented by solid lines and circles. Under-five mortality rates per 1000 births, shown on the right axis, are represented by dashed lines and open circles. Four regions of different altitudes are shown: Potosí (4050 m, black), La Paz (3850 m, red), Chuquisaca (2054 m, dark green), and Santa Cruz (400 m, light green). Data were derived from publicly available Demographic and Health Surveys (DHS) for 1998, 2003, and 2008 and analyzed by the WHO Collaborating Center for Health Equity Monitoring (WHO, 2022). Created with BioRender.com.

Figure 2.

Illustration of one proposed link between preeclampsia and pulmonary hypertension (PH) risk. Maternal and fetal angiogenic imbalance due to the excess production and release of the antiangiogenic factor sFlt1 (soluble fms-like tyrosine kinase 1; depicted as blue circulating receptors) by the preeclamptic placenta have been implicated in impaired pulmonary vascular development and, in turn, a greater risk of neonatal PH or pulmonary vascular dysfunction. sFlt1 impairs angiogenesis by reducing the bioavailability of VEGF (vascular endothelial growth factor) required for fetal pulmonary vascular development (Compernolle et al., 2002; Staff et al., 2005; Wang et al., 2010; Powe et al., 2011; Heath-Freudenthal et al., 2022). Created with BioRender.com.

Figure 3.

The relative relationship between fetal pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) across gestation, birth, and abnormalities observed in persistent pulmonary hypertension of the newborn. Created with BioRender.com.