Infants at Altitude
abstract & Commentary
Synopsis: When presented with concentrations of oxygen similar to what would be found at high altitude, a small proportion of infants develop prolonged hypoxemia. The relationships between sudden infantile death and pulmonary hypertension due to altitude, however, have not been fully elucidated.
Source: Parkins KJ, et al. Effect of exposure to 15% oxygen on breathing patterns and oxygen saturation in infants: Interventional study. BMJ 1998;316:887-894.
Stimulated by two reports of sudden infant death following intercontinental flights, Parkins and colleagues became interested in the effects of airway hypoxia on respiratory control. Thirty-four seemingly healthy infants (mean age, 3 months), some of whom (13 of 34) were siblings of a sudden infant death victim were exposed to 15% oxygen. Respiratory patterns and oxygenation were noted during overnight recordings with the child in room air and in a reduced oxygen environment. Oxygen saturation was variable (85-100%) but had a lower mean (93%) in 15% oxygen (vs 98% in room air). Initial room air oxygen saturation, however, did not predict the extent of the subsequent fall in oxygen saturation. The amount of time spent with a regular breathing pattern was reduced with exposure to 15% oxygen, and episodes of "periodic apnea" were increased. (None of these pauses was greater than 20 seconds in duration, so they did not constitute true "apnea.") No baseline variables were identified that could predict which infants would develop prolonged oxygen desaturation. Parkins et al conclude that "airline travel and holidays at high altitude may result in hypoxemia in a small proportion of infants."
Comment by Philip R. Fischer, MD, DTM&H
It has been 14 months since Southall’s group published their paper, but it continues to stimulate discussion. Initially, it was accompanied by one editorial suggesting infants were safe in commercial aircraft1 and another questioning the wisdom of taking infants higher than 2000 meters.2 The BMJ pursued the issues in published correspondence, and both travel medicine practitioners and wilderness medicine participants have continued to discuss children at altitude through newsletters and electronic groups. Meanwhile, the lay literature includes reasonable but scientifically unsupported recommendations to avoid air travel under certain ages. What do the data actually say about infants at altitude?
Adaptation to Altitude
The paper by Parkins et al clearly showed that some, but not all, children drop their oxygen saturation during short-term exposure to hypoxic environments. Similarly, children living at high altitude have lower oxygen saturations than children dwelling at low altitude. At 4018 meters elevation, preschool-aged children had mean oxygen saturations of 87%; the fact that saturations were not as low in older children suggested that some adaptation was taking place.3 Acutely, it is not clear that the adaptive responses, such as the changed breathing pattern noted by Southall’s group, have clinical significance. Over time, however, children permanently exposed to high-altitude hypoxia show enhanced oxygen uptake associated with increases in ventilation, lung compliance, and pulmonary diffusion. Chest volumes and hemoglobin concentrations are also increased. In addition, the decreased partial pressure of oxygen in the lungs is associated with elevated pulmonary artery pressures.4 Thus, children living at altitude adapt during infancy to compensate for the hypoxia to which they are exposed. The risks of pulmonary hypertension, however, might negate some of the beneficial adaptations.
Pulmonary Hypertension at Altitude
There is evidence that chronic, altitude-associated pulmonary hypertension can be devastating for children. An autopsy study of 15 infants in Lhasa, Tibet (3600 meters above sea level), showed extreme medial hypertrophy of muscular pulmonary arteries and muscularization of pulmonary arterioles along with massive hypertrophy and dilation of the right ventricle.5 Interestingly, 14 of the 15 were of Han rather than indigenous Tibetan origin, and 13 of the 15 had been born at low altitude and then moved to Lhasa (mean duration of residence at altitude was two months among those who had immigrated). The pathologic findings suggested that the etiology was pulmonary vascular disease rather than parenchymal disease or primary cardiac disease. Affected individuals were not polycythemic (as are adults with "chronic mountain sickness"). Sui and colleagues claimed that such death is "not uncommon" in Tibet, but they didn’t actually present any population or historic data to support frequency or causality conclusions.
In the 1960s, 32 "healthy" children aged 1-14 years were subjected to right heart catheterization in Peru (approximately 4500 meters elevation).6 Pulmonary hypertension was common but became less significant with advancing age. In Colorado, 11 children became severely symptomatic with two deaths due to pulmonary hypertension.7 With treatment and relocation to lower altitude, the nine survivors were reported to be "enjoying a normal life."
What can we conclude from all this? Clearly, significant pulmonary hypertension has been reported in children born in and/or living at high altitude. It is reasonable to think that the low oxygen content at these altitudes was a significant etiologic factor. What is not clear is whether this maladaptation to high altitude is common, predictable, or a risk for travelers.
Might genetics play a role in predisposing some infants to pulmonary hypertension at altitude? It has been noted that Tibetans had higher arterial oxygen saturation at birth and during the first four months of life than Han newborns in the same setting.8 It was suggested that genetic factors might be protective for the Tibetan children. Indeed, genetic analysis has recently suggested that an allele dominant for higher oxygen saturation might be present in some Tibetans and might be providing them with a selective advantage in their high-altitude hypoxic environment.9 Interestingly, genetic factors even seem to affect the presentation of high-altitude pulmonary edema.10
Sudden Infant Death
The impetus for the study by Parkins et al was two anecdotal reports of "crib death" shortly after intercontinental travel (with a night-length duration of exposure to air pressure and oxygen content similar to that of approximately 2000 meters).11 Might altitude be related to sudden infant death (SID)?
In the United States, the incidence of SIDS was noted to correlate directly with altitude of residence.12 Two other factors, however, must be considered before becoming alarmed by this report. First, studies of SIDS are plagued by diagnostic variability in different reports and studies. Not all sudden infant deaths are truly idiopathic and due to SIDS. This is clearly noted by Southall’s group. One of their subjects studied as a sibling of two SIDS victims later died; it was eventually learned that all three children in that family were actually victims of infanticide. Second, the association of altitude with SIDS should be re-evaluated again now that sleep position and passive smoke exposure have been clearly linked to SIDS and interventions focused on these factors are drastically reducing the incidence of SIDS in the United States. If altitude is an important factor in the etiology of SIDS, it is likely not the most important factor. Caution is needed before restricting all infants from exposure to commercial aircraft or to high altitudes.
Acute Mountain Sickness
What of acute mountain sickness in children? In 1993, it was reported that 28% of children aged 9-14 years developed signs of acute mountain sickness when vacationing at 2835 meters elevation.13 Interestingly, however, 21% of similar children vacationing at sea level developed similar symptoms, and it wasn’t clear how much of the "mountain sickness" was due to elevation as opposed to other factors such as travel, anxiety, and disruption of daily routine. More recently, younger, preverbal children were studied.14 Twenty-two percent of children aged 3-36 months were symptomatic for acute mountain sickness, a frequency similar to that reported in adults. There is also some evidence that the inflammation of a viral upper respiratory tract infection might predispose some children to high-altitude pulmonary edema.15 Studies on the efficacy of acetazolamide in preventing mountain sickness in children have not been reported.
A Personal Plea
In the wake of World War II, it was considered "unethical" to do research in children. Now, the dearth of data on which to base good pediatric care has prompted a swing in what is considered "ethical." The National Institutes of Health are now encouraging that most research projects include children. Clearly, the effects of high-altitude exposure are different in children than in adults. More investigation is needed to help advise parents and to care for children who might be born in or travel to high-altitude areas.
The first commentary I wrote for Travel Medicine Advisor Update was in 1995 and dealt with earache in children traveling by air. I noted that there were no data on which to base a decision about the prophylactic use of pseudoephedrine in traveling children and suggested that research was needed. That commentary prompted a project that was published in May in Archives of Pediatrics and Adolescent Medicine. Perhaps this commentary will prompt someone else to further investigate the acute, subacute, and chronic problems of altitude exposure in children. Such work is sorely needed.
In the Meantime
While awaiting more definitive data, we can summarize the current understanding about children at altitude. First, children do undergo physiologic adaptations trying to respond to low-oxygen, high-altitude environments. Second, pulmonary hypertension is not an unusual part of a child’s adaptation at altitude and can present as life-threatening right heart failure. Sudden infant death has not been causally linked to airplane travel or high-altitude travel. Third, occasionally children develop so much pulmonary hypertension at altitude that their survival is placed in jeopardy. Fourth, there are some genetic factors linked to a child’s adaptation to altitude, but it is not currently possible to predict which children risk adverse health effects at altitude. Fifth, acute mountain sickness occurs in children as in adults, but preventive therapy has not been tested.
So, should infants be prohibited from traveling in commercial aircraft or from visiting high-altitude locations? There are no clear data to support such a prohibition. Nonetheless, infants traveling at high altitude, like all other children, should be taken promptly to competent medical care if they act sick and have tachypnea.
References
1. Milner AD. BMJ 1998;316:873-874.
2. Pollard AJ, et al. BMJ 1998;316:874-875.
3. Gamponia MJ, et al. Arch Dis Child 1998;78:461-465.
4. De Meer K, et al. Eur J Pediatr 1995;154:263-272.
5. Sui GJ, et al. J Pathol 1988;155:161-170.
6. Sime F, et al. Am J Cardiol 1963;11:142-149.
7. Khoury GH, Hawes CR. J Pediatr 1963;62:177-185.
8. Niermeyer S, et al. N Engl J Med 1995;333:1248-1252.
9. Beall CM, et al. Hum Biol 1997;69:597-604.
10. Hanaoka M, et al. Circulation 1998;97:1124-1128.
11. Cottrell JJ. Chest 1988;92:81-84.
12. Getts AG, Hill HF. Dev Med Child Neurol 1982;24: 61-68.
13. Thies MK, et al. AJDC 1993;147:143-145.
14. Yaron M, et al. Arch Pediatr Adolesc Med 1998; 152:683-687.
15. Durmowicz AG, et al. J Pediatr 1997;130:838-840.
Infants spending time at high altitude:
a. risk sudden myocardial infarction and death.
b. might have low oxygen saturations while sleeping.
c. usually develop severe pulmonary hypertension.
d. only rarely show signs of acute mountain sickness.
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