Project Details
Description
Altitude is defined as the vertical distance between a point on earth and sea level.
(1) It is estimated that more than 140 million people permanently live at altitudes greater than 2,500 meters above sea level (masl).
(2) Arterial oxygen pressure (PaO2) is inversely related to altitude. At levels of 2600 meters above sea level, PaO2 is around 60 mmHg.
With an increase in altitude to 3650 meters above sea level, PaO2 decreases to 54 mmHg and reaches 43 mmHg at extreme altitudes such as in La Rinconada, Peru at 5100 meters above sea level (2,3) The study of the altitude and the populations that live in these conditions, has allowed us to understand the physiological phenomena, the impact of this exposure on the morbidity and mortality of the population, as well as different mechanisms related to adaptation to hypoxia. It has been described that permanent residence at altitude is related to ventilatory, cardiovascular, reproductive and even cognitive changes.
(4,5)The reproductive implications of exposure to altitude include changes such as later menarche and earlier menopause. (2) Comparative studies have shown that there are pregnancy-specific adaptations to altitude situations.
An increase in ventilation and tidal volume has been found.
This is probably explained by hormonal sensitization by progesterone and estrogen in the bulbar respiratory center and carotid body.
(4,6) McAuliffe et al evaluated blood gases at sea level and at 4300 meters above sea level during pregnancy and in non-pregnant women. They found significant differences in Po2, PCo2, HCO3, base excess and SaO2 between the arterial gases of non-pregnant women living at altitude and sea level.
Regarding pregnant women, minute ventilation was higher at altitude related to an increase in respiratory rate.
Likewise, changes were reflected with higher levels of Ph and PO2, lower Hb, arterial content of O2, HCO3 and base excess in relation to altitude.
(6) It has been observed that at higher altitudes there is a decrease in FEV1, probably related to interstitial edema and the consequent increase in airway resistance.
(4,7) The capacity to increase cardiac output during pregnancy at altitude may be limited by failure in the mechanisms to decrease peripheral vascular resistance.
This is related to changes in molecular concentrations in favor of the relative concentration of endothelin-1 compared to nitric oxide metabolites, with vasoconstrictor and vasodilator activity respectively (8).
These molecular changes of pregnancy share signaling pathways with placental development.
Higher levels of vasoconstrictor and inflammatory substances have been associated with a higher risk of preeclampsia.
Bashir et al found higher serum concentrations of vasoactive and inflammatory substances such as ET-1, TXA2 and TNFa with a decrease in vasodilator metabolites derived from Nox in women pregnant at altitude (2700 masl) and with preeclampsia compared to women at 500 masl and without preeclampsia. (8).
The usual hemodilutional effect of pregnancy may be less evident at higher altitudes due to the erythropoietic stimulation of chronic hypoxia, increasing blood viscosity and decreasing blood flow.
(4). The most relevant observed repercussions of altitude on pregnancy are preeclampsia and reduced fetal growth.
Zamudio et al reviewed the different studies that have made observations on the decrease in uterine blood flow, circulating inflammatory and vasoconstrictor factors of placental origin, placental oxidative stress and greater vascular reactivity with sympathetic α-adrenergic activation as intermediate factors between altitude and the risk of preeclampsia.
(9). The development of preeclampsia is related to a failure of trophoblastic invasion and remodeling of the spiral arteries that lead to decreased placental blood flow.
Placental morphological differences have been observed at altitude compared to sea level, such as the reduction of villous tertiary branches and the remodeling of spiral arteries, which causes less uteroplacental flow (9).
Aksoy et al evaluated women living at medium altitude (1890 meters above sea level) and at sea level (31 meters above sea level) with Doppler ultrasound.
They observed higher Pulsatility Indices (PI) and Resistance Indices (RI) of the uterine arteries at sea level compared to medium altitude (p<0.05).
(10). Krampl et al observed lower IR and IP of the uterine artery at 4300 meters above sea level
(eleven). However, it has been postulated that changes in vascular resistance do not necessarily reflect volumetric changes (9).
Other authors such as Brown et al did not find differences in the PI of the uterine artery comparing altitude at 400 meters above sea level vs. 4100-4300 meters above sea level, however they did observe an increase in uterine blood flow with altitude, associated with higher rates of fetal hypoxia indicating a possible compensatory mechanism against growth restriction (12).
Other mechanisms such as the cytokine cascade and molecules such as sFlt1, VEGF, IL6, IL8, TNFa, sympathoadrenal overactivation and the decrease in placental antioxidant enzymes are postulated as mechanisms that intervene in women with susceptible phenotypes, facilitating the development of preeclampsia in altitude, but not as a single causal pathway.
(9) A risk effect has been observed between altitude level, Hb levels and the risk of preeclampsia.
For every 1000 meters of increase in altitude, Hb concentration increases by 1.52 g/dL.
With Hb greater than 14.5 and altitude less than 2000 meters above sea level (OR: 1.73; 95% CI: 1.06-2.81); between 2000 and 3000 m altitude (OR: 1.95; 95% CI: 1.44-2.64); and more than 3000 m altitude (OR: 1.42; 95% CI: 1.17-1.73) for the development of preeclampsia, without behaving as a dose-response effect.
(2) In 1997 Jensen et al reported an analysis of birth records between 1989 and 1991 in Colorado counties (915-3350 masl). After including variables related to low birth weight such as maternal age, education, ethnicity, marital status, nulliparity, previous children small for gestational age, comorbidities and complications in the analysis models, they identified altitude as a risk factor. independent, non-collinear and additive risk for the risk of low birth weight (aOR 1.7 95%CI 1.2-2.3).
(13) A similar analysis on the Colorado population, enhanced with geolocation tools to pinpoint maternal altitude, was published by Bailey et al in 2019.
They included birth records between 2007 and 2016; Considering covariates of interest available in the records, they found that the mother's altitude (>2500 meters above sea level) had an aOR of 1.29 (95% CI 1.18-1.37) with low birth weight.
(14) Comparative studies between pregnant women living at sea level and at different altitude levels have shown a 3-fold increase in intrauterine growth restriction (IUGR), late fetal mortality and congenital malformations.
It has been reported that for every 1000 meters of increase in altitude, birth weight decreases by 102g-120g.(2,4,7) Other studies have proposed that although this relationship exists, its behavior is not linear.
The analysis of birth statistics of 74 counties based on data from the Division of Vital Statistics, National Center for Health Statistics made by Zahran et al observed that between 304.8-761.7 meters above sea level there was a decrease of 18.41 grams (95% CI –22.8 , –14.0) compared to children born at less than 304.8 meters above sea level. Between 762-1218.9 meters, newborns were on average 51.61 grams smaller (95% CI = –62.3, –41.0) and children born at more than 1219.2 meters were on average 80.84 grams (95% CI –95.3, –66.4) smaller than children born below 304.8 meters.
(15) Altitude as a geographical condition is an exposure that conditions low PaO2.
Pregnancy is a process that requires physiological maternal adaptation. When this develops in altitude conditions, it imposes greater physiological challenges and a greater risk of perinatal complications.
The study of birth weight and perinatal mortality related to exposure to altitude will help describe the role of low barometric pressures and hypoxia in births in the Colombian population.
(1) It is estimated that more than 140 million people permanently live at altitudes greater than 2,500 meters above sea level (masl).
(2) Arterial oxygen pressure (PaO2) is inversely related to altitude. At levels of 2600 meters above sea level, PaO2 is around 60 mmHg.
With an increase in altitude to 3650 meters above sea level, PaO2 decreases to 54 mmHg and reaches 43 mmHg at extreme altitudes such as in La Rinconada, Peru at 5100 meters above sea level (2,3) The study of the altitude and the populations that live in these conditions, has allowed us to understand the physiological phenomena, the impact of this exposure on the morbidity and mortality of the population, as well as different mechanisms related to adaptation to hypoxia. It has been described that permanent residence at altitude is related to ventilatory, cardiovascular, reproductive and even cognitive changes.
(4,5)The reproductive implications of exposure to altitude include changes such as later menarche and earlier menopause. (2) Comparative studies have shown that there are pregnancy-specific adaptations to altitude situations.
An increase in ventilation and tidal volume has been found.
This is probably explained by hormonal sensitization by progesterone and estrogen in the bulbar respiratory center and carotid body.
(4,6) McAuliffe et al evaluated blood gases at sea level and at 4300 meters above sea level during pregnancy and in non-pregnant women. They found significant differences in Po2, PCo2, HCO3, base excess and SaO2 between the arterial gases of non-pregnant women living at altitude and sea level.
Regarding pregnant women, minute ventilation was higher at altitude related to an increase in respiratory rate.
Likewise, changes were reflected with higher levels of Ph and PO2, lower Hb, arterial content of O2, HCO3 and base excess in relation to altitude.
(6) It has been observed that at higher altitudes there is a decrease in FEV1, probably related to interstitial edema and the consequent increase in airway resistance.
(4,7) The capacity to increase cardiac output during pregnancy at altitude may be limited by failure in the mechanisms to decrease peripheral vascular resistance.
This is related to changes in molecular concentrations in favor of the relative concentration of endothelin-1 compared to nitric oxide metabolites, with vasoconstrictor and vasodilator activity respectively (8).
These molecular changes of pregnancy share signaling pathways with placental development.
Higher levels of vasoconstrictor and inflammatory substances have been associated with a higher risk of preeclampsia.
Bashir et al found higher serum concentrations of vasoactive and inflammatory substances such as ET-1, TXA2 and TNFa with a decrease in vasodilator metabolites derived from Nox in women pregnant at altitude (2700 masl) and with preeclampsia compared to women at 500 masl and without preeclampsia. (8).
The usual hemodilutional effect of pregnancy may be less evident at higher altitudes due to the erythropoietic stimulation of chronic hypoxia, increasing blood viscosity and decreasing blood flow.
(4). The most relevant observed repercussions of altitude on pregnancy are preeclampsia and reduced fetal growth.
Zamudio et al reviewed the different studies that have made observations on the decrease in uterine blood flow, circulating inflammatory and vasoconstrictor factors of placental origin, placental oxidative stress and greater vascular reactivity with sympathetic α-adrenergic activation as intermediate factors between altitude and the risk of preeclampsia.
(9). The development of preeclampsia is related to a failure of trophoblastic invasion and remodeling of the spiral arteries that lead to decreased placental blood flow.
Placental morphological differences have been observed at altitude compared to sea level, such as the reduction of villous tertiary branches and the remodeling of spiral arteries, which causes less uteroplacental flow (9).
Aksoy et al evaluated women living at medium altitude (1890 meters above sea level) and at sea level (31 meters above sea level) with Doppler ultrasound.
They observed higher Pulsatility Indices (PI) and Resistance Indices (RI) of the uterine arteries at sea level compared to medium altitude (p<0.05).
(10). Krampl et al observed lower IR and IP of the uterine artery at 4300 meters above sea level
(eleven). However, it has been postulated that changes in vascular resistance do not necessarily reflect volumetric changes (9).
Other authors such as Brown et al did not find differences in the PI of the uterine artery comparing altitude at 400 meters above sea level vs. 4100-4300 meters above sea level, however they did observe an increase in uterine blood flow with altitude, associated with higher rates of fetal hypoxia indicating a possible compensatory mechanism against growth restriction (12).
Other mechanisms such as the cytokine cascade and molecules such as sFlt1, VEGF, IL6, IL8, TNFa, sympathoadrenal overactivation and the decrease in placental antioxidant enzymes are postulated as mechanisms that intervene in women with susceptible phenotypes, facilitating the development of preeclampsia in altitude, but not as a single causal pathway.
(9) A risk effect has been observed between altitude level, Hb levels and the risk of preeclampsia.
For every 1000 meters of increase in altitude, Hb concentration increases by 1.52 g/dL.
With Hb greater than 14.5 and altitude less than 2000 meters above sea level (OR: 1.73; 95% CI: 1.06-2.81); between 2000 and 3000 m altitude (OR: 1.95; 95% CI: 1.44-2.64); and more than 3000 m altitude (OR: 1.42; 95% CI: 1.17-1.73) for the development of preeclampsia, without behaving as a dose-response effect.
(2) In 1997 Jensen et al reported an analysis of birth records between 1989 and 1991 in Colorado counties (915-3350 masl). After including variables related to low birth weight such as maternal age, education, ethnicity, marital status, nulliparity, previous children small for gestational age, comorbidities and complications in the analysis models, they identified altitude as a risk factor. independent, non-collinear and additive risk for the risk of low birth weight (aOR 1.7 95%CI 1.2-2.3).
(13) A similar analysis on the Colorado population, enhanced with geolocation tools to pinpoint maternal altitude, was published by Bailey et al in 2019.
They included birth records between 2007 and 2016; Considering covariates of interest available in the records, they found that the mother's altitude (>2500 meters above sea level) had an aOR of 1.29 (95% CI 1.18-1.37) with low birth weight.
(14) Comparative studies between pregnant women living at sea level and at different altitude levels have shown a 3-fold increase in intrauterine growth restriction (IUGR), late fetal mortality and congenital malformations.
It has been reported that for every 1000 meters of increase in altitude, birth weight decreases by 102g-120g.(2,4,7) Other studies have proposed that although this relationship exists, its behavior is not linear.
The analysis of birth statistics of 74 counties based on data from the Division of Vital Statistics, National Center for Health Statistics made by Zahran et al observed that between 304.8-761.7 meters above sea level there was a decrease of 18.41 grams (95% CI –22.8 , –14.0) compared to children born at less than 304.8 meters above sea level. Between 762-1218.9 meters, newborns were on average 51.61 grams smaller (95% CI = –62.3, –41.0) and children born at more than 1219.2 meters were on average 80.84 grams (95% CI –95.3, –66.4) smaller than children born below 304.8 meters.
(15) Altitude as a geographical condition is an exposure that conditions low PaO2.
Pregnancy is a process that requires physiological maternal adaptation. When this develops in altitude conditions, it imposes greater physiological challenges and a greater risk of perinatal complications.
The study of birth weight and perinatal mortality related to exposure to altitude will help describe the role of low barometric pressures and hypoxia in births in the Colombian population.
Keywords
Low birth weight, altitude, neonatal mortality.
| Status | Finished |
|---|---|
| Effective start/end date | 7/1/20 → 12/31/21 |
UN Sustainable Development Goals
In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This project contributes towards the following SDG(s):
Main Funding Source
- Installed Capacity (Academic Unit)
Location
- Bogotá D.C.
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