The effects of high altitudes on child growth and development

This study compares the growth characteristics of populations of Tibetan origin living in Nepal to high altitude populations of Peru and Ethiopia. Measurements were made on two groups of children, a sample of Sherpas living in the Everest region of northeast Nepal at elevations in excess of 3500 m, and a sample of Tibetan children living in Kathmandu at an altitude of 1000 m. Although the Tibetan children showed some growth advancement over the highland sample of Sherpas, the differences were less than might have been expected on the basis of work carried out in Peru, where long established high altitude populations live at similar elevations to those of Himalayan populations. In particular, some growth trends seen in Andean populations, such as the increased diameter of the chest wall, are not seen in populations of Tibetan origin. It is suggested that genetic influences may exert a stronger effect on the growth of high altitude populations than hitherto believed.Presented the Seventh International Biometeorological Congress, 17–23 August 1975, College Park, Maryland, USA.     

The disadvantaged child: A product of the culture of poverty,his education,and his life chances

Abstract

This study concerns the fertility of Sherpa and Tibetan women living at altitudes over 3,400 meters in Nepal. The average completed fertility (4.77 live births) and estimated crude birth rate (31 to 33 per 1,000) are low relative to low altitude peasant populations as well as to high altitude Andean peasants. Environmental phenomena (hypoxia, iodine deficiency) may be associated with retarded menarchial age and high infant mortality; but the major factors causing the low fertility appear to be cultural rather than environmental. Traditional ceremonial requirements delay the age at marriage until the mid or late twenties. Religious practices promote male and female celibacy. Migrant females and women married to migrant males report reduced fertility, probably because of poor nutrition and health care. Nonmigrant women living in villages that participate extensively in the cash economy have greater access to the growing market economy, health care, and education and report higher numbers of live births and fewer child deaths.     

Genetic polymorphisms in isolated Sherpa populations of Nepal

Data are reported on the incidence of variants in the ABO blood group system, four red cell enzyme polymorphisms, and the PTU taster/non-taster polymorphism in 155 Sherpas and Tamangs living in two villages in the isolated Rolwaling valley in east Nepal. The incidence of phenotype AB was unexpectedly high in one village, as has been reproted insome other high-altitude populations: possible causes are discussed. Each of the other polymorphisms has a different pattern of distribution between the populations studied; the Sherpas' allele distribution in the phosphoglucomutase (PGM) system seems to be distinct from the surrounding populations'. ABO gene frequencies suggest affinities between Sherpas in the study villages and old- and new-clan Sherpa populations, respectively, in Solu and Khumbu.     

Lack of prominent compensatory polycythemia in traditional native Andeans living at 4,200 meters

Red blood cell count (RBC), hemoglobin concentration ([Hb]) and hematocrit (Hct) were measured in 303 male Quechua children and adults, aged 6 to 57 years, living a lifestyle as traditional pastoralists and horticulturalists at a mean altitude of 4,200 m in the Southern Peruvian Andes. Values for RBC, [Hb], and Hct increased with age from middle childhood to young adulthood. However, among adults there was no significant association between age and any of these three parameters. Overall, there was approximately a 10-12% increase in the RBC, [Hb], and Hct above sea-level norms for all age groups. Mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) showed a slight but significant increase with age in children and adolescents, but the mean corpuscular hemoglobin concentration (MCHC) did not. We conclude that the study of highland Quechua Indians, living a traditional lifestyle as pastoralists and horticulturalists, does not support the long-held belief that altitude hypoxia provokes a dramatic compensatory polycythemia in healthy Andeans.     

Ventilation and hypoxic ventilatory response of Tibetan and Aymara high altitude natives

Newcomers acclimatizing to high altitude and adult male Tibetan high altitude natives have increased ventilation relative to sea level natives at sea level. However, Andean and Rocky Mountain high altitude natives have an intermediate level of ventilation lower than that of newcomers and Tibetan high altitude natives although generally higher than that of sea level natives at sea level. Because the reason for the relative hypoventilation of some high altitude native populations was unknown, a study was designed to describe ventilation from adolescence through old age in samples of Tibetan and Andean high altitude natives and to estimate the relative genetic and environmental influences. This paper compares resting ventilation and hypoxic ventilatory response (HVR) of 320 Tibetans 9–82 years of age and 542 Bolivian Aymara 13–94 years of age, native residents at 3,800–4,065 m. Tibetan resting ventilation was roughly 1.5 times higher and Tibetan HVR was roughly double that of Aymara. Greater duration of hypoxia (older age) was not an important source of variation in resting ventilation or HVR in either sample. That is, contrary to previous studies, neither sample acquired hypoventilation in the age ranges under study. Within populations, greater severity of hypoxia (lower percent of oxygen saturation of arterial hemoglobin) was associated with slightly higher resting ventilation among Tibetans and lower resting ventilation and HVR among Aymara women, although the associations accounted for just 2–7% of the variation. Between populations, the Tibetan sample was more hypoxic and had higher resting ventilation and HVR. Other systematic environmental contrasts did not appear to elevate Tibetan or depress Aymara ventilation. There was more intrapopulation genetic variation in these traits in the Tibetan than the Aymara sample. Thirty-five percent of the Tibetan, but none of the Aymara, resting ventilation variance was due to genetic differences among individuals. Thirty-one percent of the Tibetan HVR, but just 21% of the Aymara, HVR variance was due to genetic differences among individuals. Thus there is greater potential for evolutionary change in these traits in the Tibetans. Presently, there are two different ventilation phenotypes among high altitude natives as compared with sea level populations at sea level: lifelong sustained high resting ventilation and a moderate HVR among Tibetans in contrast with a slightly elevated resting ventilation and a low HVR among Aymara. Am J Phys Anthropol 104:427–447, 1997. © 1997 Wiley-Liss, Inc.     

Growth of Qinghai Tibetans living at three different high altitudes

This study compares the stature, weight, skinfolds, upper arm muscle area, and chest dimensions of Tibetan children, adolescents, and young adults who were born and raised, or who had lived from infancy, at 3,200 m, 3,800 m, and 4,300 m in Qinghai Province, People's Republic of China. While the individuals measured in Qinghai are among the tallest and heaviest Tibetans reported in the literature, they are nevertheless smaller and lighter than well-off children living at low altitude. The pattern of size variation among Tibetan males and females measured at the three high altitudes, along with evidence of a secular trend at 4,300 m, suggests that nutrition may significantly effect growth at high altitude. Only minor differences in thorax dimensions exist between Tibetan males and females measured at 3,200 m and 3,800 m. However, Tibetan males at 4,300 m possess slightly narrower and deeper chests (during and after adolescence) than males at 3,200 m and 3,800 m. Since individuals from 3,800 m and 4,300 m belong to the same local populations, this characteristic is unlikely to be genetically determined. However, it may be related to differences in the degree of hypoxia or to the influences of other environmental conditions.     

Growth differences between children of highland and coastal Ecuador

This study examines patterns of growth in height and weight among children (<60 months) of highland and coastal agricultural communities of Ecuador. Highland children are significantly shorter, but not significantly lighter than their coastal peers. Linear growth rates (cm/6 months) are comparable between the two samples. Growth rates for body weight (kg/6 m) are similar in highland and coastal boys, whereas highland girls display larger weight gains than their coastal counterparts. In both regions, linear growth is compromised to a much greater extent than growth in body weight, and growth faltering for both height and weight is most pronounced between birth and 24 months of age. The similarity in growth rates between the highland and coastal samples suggests that high altitude hypoxia plays a relatively small role in shaping growth during the first five years after birth. Rather, it appears that most of the disparity in height between the two samples can be attributed to differences established by 6 months of age. The pattern of growth retardation seen in both regions during the first 24 postnatal months is similar to that observed among impoverished populations throughout the world and is likely associated with the influence of nutritional and disease stressors. After 2 years of age, little or no “catch up” growth is seen in height, whereas improvements in weight gain are more pronounced, especially among highland girls. Ongoing research is investigating the nutritional and socio-economic correlates of growth within each region. © Wiley-Liss, Inc.     

Hypoxia Adaptations in the Grey Wolf (Canis lupus chanco) from Qinghai-Tibet Plateau

The Tibetan grey wolf (Canis lupus chanco) occupies habitats on the Qinghai-Tibet Plateau, a high altitude (>3000 m) environment where low oxygen tension exerts unique selection pressure on individuals to adapt to hypoxic conditions. To identify genes involved in hypoxia adaptation, we generated complete genome sequences of nine Chinese wolves from high and low altitude populations at an average coverage of 25× coverage. We found that, beginning about 55,000 years ago, the highland Tibetan grey wolf suffered a more substantial population decline than lowland wolves. Positively selected hypoxia-related genes in highland wolves are enriched in the HIF signaling pathway (P = 1.57E-6), ATP binding (P = 5.62E-5), and response to an oxygen-containing compound (P≤5.30E-4). Of these positively selected hypoxia-related genes, three genes (EPAS1, ANGPT1, and RYR2) had at least one specific fixed non-synonymous SNP in highland wolves based on the nine genome data. Our re-sequencing studies on a large panel of individuals showed a frequency difference greater than 58% between highland and lowland wolves for these specific fixed non-synonymous SNPs and a high degree of LD surrounding the three genes, which imply strong selection. Past studies have shown that EPAS1 and ANGPT1 are important in the response to hypoxic stress, and RYR2 is involved in heart function. These three genes also exhibited significant signals of natural selection in high altitude human populations, which suggest similar evolutionary constraints on natural selection in wolves and humans of the Qinghai-Tibet Plateau.     

Adaptation and mal-adaptation to ambient hypoxia; Andean, Ethiopian and Himalayan patterns

The study of the biology of evolution has been confined to laboratories and model organisms. However, controlled laboratory conditions are unlikely to model variations in environments that influence selection in wild populations. Thus, the study of "fitness" for survival and the genetics that influence this are best carried out in the field and in matching environments. Therefore, we studied highland populations in their native environments, to learn how they cope with ambient hypoxia. The Andeans, African highlanders and Himalayans have adapted differently to their hostile environment. Chronic mountain sickness (CMS), a loss of adaptation to altitude, is common in the Andes, occasionally found in the Himalayas; and absent from the East African altitude plateau. We compared molecular signatures (distinct patterns of gene expression) of hypoxia-related genes, in white blood cells (WBC) from Andeans with (n = 10), without CMS (n = 10) and sea-level controls from Lima (n = 20) with those obtained from CMS (n = 8) and controls (n = 5) Ladakhi subjects from the Tibetan altitude plateau. We further analyzed the expression of a subset of these genes in Ethiopian highlanders (n = 8). In all subjects, we performed the studies at their native altitude and after they were rendered normoxic. We identified a gene that predicted CMS in Andeans and Himalayans (PDP2). After achieving normoxia, WBC gene expression still distinguished Andean and Himalayan CMS subjects. Remarkably, analysis of the small subset of genes (n = 8) studied in all 3 highland populations showed normoxia induced gene expression changes in Andeans, but not in Ethiopians nor Himalayan controls. This is consistent with physiologic studies in which Ethiopians and Himalayans show a lack of responsiveness to hypoxia of the cerebral circulation and of the hypoxic ventilatory drive, and with the absence of CMS on the East African altitude plateau.     

Different hematologic responses to hypoxia in Sherpas and Quechua Indians

Previous studies of the erythropoietic response to hypoxia in high-altitude natives suggest that the hematocrit and hemoglobin values in Himalayan natives (Sherpas) are lower than expected for the altitude, perhaps because of a genetic adaptation. However, differences in sampling techniques and experimental methods make comparisons difficult. Our studies were carried out to compare the erythropoietic response with the same altitude in age-matched natives of the Himalayas and Andes by the same experimental techniques. Healthy male subjects were selected in Ollagüe, Chile (n = 29, 27.3 +/- 5.9 yr) and in Khunde, Nepal (n = 30, 24.7 +/- 3.8 yr). Both of these villages are located at 3,700 m above sea level. Hematologic measurements confirmed lower hematocrit values in Nepal (48.4 +/- 4.5%) than in Chile (52.2 +/- 4.6%) (P less than 0.003). When subjects were matched for hematocrit, erythropoietin concentrations in Chile were higher than in Nepal (P less than 0.01). Detailed measurements of blood O2 affinity in Nepal showed no differences in shape or position of the O2 equilibrium curve between Sherpas and Western sojourners. Our results indicate that although Quechua Indians have higher hematocrits than Sherpas living at the same altitude, nevertheless they may be functionally anemic.     

Dreams of a Final Sherpa

This exploration of a Himalayan Sherpa ritual engages contemporary cultural anthropology debates concerning ethnographic essentialism, positivism, and so-called postmodernist approaches. The author notes a parallelism between Buddhist Sherpa ritual processes that call upon patrons to engage in mimesis with idealized images of themselves and ethnographic representations that call for Sherpas to become that which is desired by foreign others. A positivist reading of Sherpas thus leads us toward both a necessary reflexivity about the effects of our writing upon them and the adoption of a strategic essentialism aware of its karmic consequences.     

A Novel Candidate Region for Genetic Adaptation to High Altitude in Andean Populations

Humans living at high altitude (≥2,500 meters above sea level) have acquired unique abilities to survive the associated extreme environmental conditions, including hypoxia, cold temperature, limited food availability and high levels of free radicals and oxidants. Long-term inhabitants of the most elevated regions of the world have undergone extensive physiological and/or genetic changes, particularly in the regulation of respiration and circulation, when compared to lowland populations. Genome scans have identified candidate genes involved in altitude adaption in the Tibetan Plateau and the Ethiopian highlands, in contrast to populations from the Andes, which have not been as intensively investigated. In the present study, we focused on three indigenous populations from Bolivia: two groups of Andean natives, Aymara and Quechua, and the low-altitude control group of Guarani from the Gran Chaco lowlands. Using pooled samples, we identified a number of SNPs exhibiting large allele frequency differences over 900,000 genotyped SNPs. A region in chromosome 10 (within the cytogenetic bands q22.3 and q23.1) was significantly differentiated between highland and lowland groups. We resequenced ~1.5 Mb surrounding the candidate region and identified strong signals of positive selection in the highland populations. A composite of multiple signals like test localized the signal to FAM213A and a related enhancer; the product of this gene acts as an antioxidant to lower oxidative stress and may help to maintain bone mass. The results suggest that positive selection on the enhancer might increase the expression of this antioxidant, and thereby prevent oxidative damage. In addition, the most significant signal in a relative extended haplotype homozygosity analysis was localized to the SFTPD gene, which encodes a surfactant pulmonary-associated protein involved in normal respiration and innate host defense. Our study thus identifies two novel candidate genes and associated pathways that may be involved in high-altitude adaptation in Andean populations.     

青海高原6－7岁小儿红细胞形态定量分析

应用计算机辅助形态测量系统,对我国青海高原贵南县（海拔３１００ｍ）、玛多县（海拔４３００ｍ）６－７岁小儿红细胞形态进行了定量分析。与北京市儿童（平原地区）相比,高原正常儿童细胞平均周长、面积、直径较平原对照组大,而红细胞平均厚度减小（Ｐ＜０．０１）。且红细胞平均周长、面积、直径与海拔高度呈正相关。红细胞平均厚度与海拔高度呈负相关（Ｐ＜０．０００１）。在高原低氧状态下,红细胞形态的这种改变使红细胞比表面代偿性增加,这将更利于红细胞与周围的气体交换。红细胞形态的这种适应性改变具有重要的生理学意义。     

Growth and nutritional status of Tibetan children at high altitude

Growth and development are clearly affected by high-altitude exposure to hypoxia, nutritional stress, cold or a combination of these factors. Very little research has been conducted on the growth and nutritional status of children living on the Tibetan Plateau. The present study evaluated the environmental impact on human growth by analyzing anthropometric characteristics of Tibetan children aged 8-14, born and raised above 4000 m altitude on the Himalayan massif in the prefecture of Shegar in Tibet Autonomous Region. Data on anthropometric traits, never measured in this population, were collected and the nutritional status was assessed. A reference data set is provided for this population. There was no evidence of wasting but stunting was detected (28.3%). Children permanently exposed to the high-altitude environment above 4000 m present a phenotypic form of adaptation and a moderate reduction in linear growth. However, it is also necessary to consider the effects of socioeconomic deprivation.     

青藏高原与安第斯高原地区儿童青少年的身高、体重和胸围的对比

通过青藏高原和安第斯山高原地区儿童青少年身高、体重和胸围的比对,探讨高原地区儿童青少年生长发育的规律和特点,找出儿童青少年生长发育的高原地区差异,进一步改善高原地区居民的健康状态,促进儿童青少年生长发育,为高原医学和高原人类学的发展提供理论基础。本文以青藏高原和安第斯山高原地区儿童青少年为研究对象。选择在西藏出生长大、经体检证明身体健康6-21岁藏族男女(父母3代藏族)共2813例有效样本(男,1417例;女,1396例),在知情同意情况下直接测量了身高、体重和胸围。印度、秘鲁、玻利维亚、智利等国家和地区儿童青少年生长发育资料从文献中获取。去除不完整的无法比较及年代过于久远的材料,排除小样本及数据不全和不符合要求的样本,严格控制质量。所有测量数据输入SPSS13.0统计软件包。对数据进行描述性统计分析、独立样本t检验、方差分析等统计学处理。结果显示:1)青藏高原儿童青少年男女身高高于安第斯山男女。2)青藏高原儿童青少年的体重与安第斯山儿童青少年相近。3)青藏高原儿童青少年的胸围明显小于安第斯山儿童青少年。高原地区与非高原地区儿童青少年生长发育相比有相似性又有特殊性(如发育水平低,胸径较大,生长发育指标普遍低于WHO(2007)和本国国内水平)。西藏藏族儿童青少年比安第斯山的发育好,两者具有不同的体质特征,这可能与生态环境、高原缺氧、遗传因素和社会经济文化等多种因素有关。     

Nutritional status and mortality of highland children in Nepal: Impact of sociocultural factors

This study investigates the nutritional status of native children in the highlands of Nepal (1,700–3,000 m) and explores the relationship between child mortality and surviving children's nutritional status. A random sample of 145 households from 11 villages in the Koshi Hill Zone in east Nepal was surveyed, and the nutritional status of the 438 children <14 years of age living in these households was assessed by means of anthropometry. We found a severe growth retardation in the Nepalese children compared to lowland reference groups as well as to highland children from the Andes. Child mortality and altitude are not significantly different between higher (Brahman and Chetri) and lower (Baisya and Sudra) caste households. A lower caste status and higher altitude of the household is associated with a significantly better nutritional status in offspring. In multiple regression analyses, improved nutritional status in children is significantly associated with lower caste (P = 0.001), higher altitude (P = 0.009), and less crowding (P = 0.001) but not with sibling mortality (P = 0.11). We thus conclude that nutritional status of children in households in the highlands of Nepal is associated with the household's socioeconomic status and altitude but not with mortality among siblings. © 1996 Wiley-Liss, Inc.     

Differences in physical growth of Aymara and Quechua children living at high altitude in Peru

Physical growth of Amerindian children living in two Aymara and three Quechua peasant communities in the Andean highlands of southern Peru (altitude 3,810–3,840 m) was studied, taking into account differences in the microclimate, agronomic situation, and sociodemographic variables. Anthropometric measurements were taken in 395 children aged under 14 years of age in a sample of 151 families in these communities, who were surveyed for sociodemographic variables as well. Data on the land system were available for 77 families. In comparison with reference populations from the United States (NCHS) and The Netherlands, stature, weight, head circumference, and midupper arm circumference (but not weight for stature) in the sample children were reduced. Growth retardation increased after the age of 1 year. Stature and weight in the present sample were very similar compared with previously published data on growth of rural Aymara children living near Lake Titicaca in Bolivia. Head circumference, midupper arm circumference, and weight for stature were significantly larger in Aymara children compared with Quechua children. Land was significantly more fragmented in Aymara compared with Quechua families, but amount of land owned was not different. Perinatal and infant mortality was elevated in Aymara vs. Quechua communities. Most families in Aymara communities used protected drinking water. One Quechua community had a severe microclimate, grim economic outlook, and weak social cohesion. Children in this community showed significant reductions in weight and midupper arm circumference compared with their peers in the other communities. We conclude that (presumably nutritionally mediated) intervillage and Aymara-Quechua differences in childhood physical growth existed in this rural high-altitude population in Peru and were associated with microclimate and the village economy, sociodemographic factors, and differences in the land system. © 1993 Wiley-Liss, Inc.     

High Altitude Hypoxia, Culture, and Human Fecundity/Fertility: A Comparative Study

This paper presents new demographic findings for a high altitude Himalayan population residing in Ladakh, India, and reviews problematic issues regarding the hypothesized relationship between fertility/fecundity and altitude in the Himalayas in light of these findings. It concludes that the low completed fertility ratio reported for the Sherpas of Khumbu, Nepal, is not caused by hypoxia-induced low fecundity, but is the product of cultural factors affecting the exposure of females to the risk of intercourse, a critical confounding factor that has not received adequate consideration in previous studies. Contrary to earlier reports, the present study demonstrates that all high altitude Himalayan populations for which published data exist exhibit moderately high fertility and fecundity, and do not differ significantly in their fertility levels. Furthermore, it argues that the claims for a statistically significant difference in fertility between high, moderate, and low altitude Himalayan populations are groundless, and suggests that a parallel reevaluation of Andean findings is required. [fertility, fecundity, hypoxia, Himalayas, Andes]