Congenital Heart Disease and High Altitude: Is Chronic Hypoxia a Common Factor in Intellectual Impairment?

I am very glad to come across an article by Dr. West on chronic hypoxia and its implications for permanent residents at high altitude (West, 2017). I have a few comments to make regarding the article.

The first is the discussion on the neuropsychological evaluation of permanent residents at high altitude. The studies that examine the relationship between hypoxia at high altitude and reduced performance accuracy and the underlying mechanism(s) seem to be sparse. Although the available data suggest that high altitude is associated with intellectual impairment, there could be significant variation in life style, diet, and quality of schooling, such that these factors could confound the outcome variables in neuropsychological testing. It is interesting to note that children born with congenital heart diseases (CHDs) have intellectual disability affecting different domains of neurodevelopment. Since many children with severe CHDs undergo surgical repair, which involve cardiopulmonary bypass, different anesthetic agents, and prolonged lengths of stay in an intensive care unit, the effect of hypoxia alone in these kids is difficult to ascertain.

Multiple animal studies demonstrate that prolonged anesthetic exposure at a young and developing brain is associated with neurological injury (Jevtovic-Todorovic et al., 2003; Brambrink et al., 2010). Similarly, retrospective studies in humans also suggest that aesthetic exposure results in adverse neurobehavioral outcomes in young children (Wilder et al., 2009; Flick et al., 2011). Children with CHD require sedation and general anesthesia on many occasions for diagnostic echocardiograms, computed tomography scanning, magnetic resonance imaging (MRI), cardiac catheterization, and for corrective and palliative surgeries, all of which may increase the risk for neurological injury. But, hypoxia has been associated with disruption of oligodendrocyte lineage, which is important for myelination, and this adverse effect could happen in a fetus with CHD especially in later stages of gestation, which are critical for brain maturation. Moreover, recent MRI studies on these fetuses or in postnatal life before any surgery have shown white matter injury and decreased total brain volume, which could be because of hypoxia (Morton et al., 2017). Similarly, knowledge on whether the residents of high altitude also have white matter injury, decreased brain volume, or other micro- and macrostructural brain abnormalities could provide insight into the intellectual impairment in this population. There is a possibility that hypoxia could be a common factor responsible for intellectual impairment in children with CHD and high-altitude residents, and whether they might have similar cerebral lesions on high-quality MRI would be useful to know.

The next interesting topic Dr. West discusses is the proposal of oxygenating rooms and buildings at high altitude. Although this sounds like a smart idea, I am very curious to know whether there have been any studies to support that these are indeed effective? In addition, the adverse effects of higher concentration of oxygen would be equally important to study before it could be used in human extensively. A major practical issue with oxygenating homes would be the economic burden, particularly to the developing countries. Again, being a pediatric cardiologist, I am trying to compare some of the new therapies that have recently been started in some fetal centers in the United States to give higher concentrations of oxygen to mothers of fetuses with severe CHD to relieve hypoxia in the fetus and subsequently prevent adverse hypoxic effects of hypoxia in utero (Kohl, 2010; Zeng, 2016). This new idea and practice have been met with controversy, given the adverse effect we could encounter of too much oxygen in fetuses including premature closure of the ductus arteriosus and retinopathy, which would be critical for survival in fetal life and early growth.