Children with sickle cell and low vitamin D may face more pain crises
Review of 12 studies also found links to hospitalizations and organ damage
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Vitamin D deficiency in children and adolescents with sickle cell disease (SCD) was consistently associated with worse clinical and laboratory outcomes, including more frequent pain crises and hospitalizations, a review of published studies found.
The 12 studies evaluated also linked low vitamin D levels to complications affecting the bones, kidneys, and lungs, along with changes in blood tests related to anemia (low hemoglobin levels) and the breakdown of red blood cells, known as hemolysis.
How vitamin D may relate to sickle cell severity
These findings suggest that “monitoring vitamin D status can help clinicians identify patients at higher risk for severe disease manifestations and guide more comprehensive care strategies,” the researchers wrote.
The study, “A systematic review on clinical and laboratory effects of vitamin D deficiency in children with sickle cell disease,” was published in Nutrition and Health.
SCD is an inherited disease caused by genetic changes that lead to the production of abnormal hemoglobin, a protein that carries oxygen in red blood cells. When oxygen levels are low, the abnormal hemoglobin can clump together, causing the cells to become stiff and sickle-shaped. These cells die sooner than healthy red blood cells and can block blood vessels, leading to symptoms such as anemia and painful vaso-occlusive crises (VOCs).
Vitamin D is found in some foods and made by the body when skin is exposed to sunlight. It is best known for helping maintain healthy bones, but it also helps regulate the immune system and inflammation. This may be particularly important in SCD, because inflammation can contribute to blocked blood vessels.
Vitamin D deficiency is common among children with SCD and has previously been associated with several complications of the disease.
To better understand these links, researchers reviewed published studies examining how vitamin D levels were associated with complications and blood test results in children and adolescents with SCD. They included 12 studies in their final analysis.
Pain crises and hospitalizations among key findings
Four studies found an association between vitamin D deficiency and pain crises, also called VOCs. In one U.S. study, 74% of children who experienced pain crises had vitamin D deficiency. Lower vitamin D levels in the blood were also significantly associated with pain episodes.
Another U.S. study found that children with chronic pain had significantly lower blood vitamin D levels than those without chronic pain.
Four studies also found an association between vitamin D deficiency and more frequent hospitalizations. Some of these studies found that lower vitamin D levels were significantly associated with longer hospital stays and more emergency department visits for pain. One study also reported a significant association between vitamin D deficiency and recurrent infections.
Several studies also looked at whether vitamin D deficiency was associated with damage to organs commonly affected by SCD.
In one study, lower vitamin D levels were significantly associated with poorer lung function, measured by percent-predicted forced expiratory volume in one second (FEV1), which compares how much air a person can forcefully breathe out in one second with the amount expected for someone of similar age and size. The association was found using a statistical model that accounted for fewer factors. However, lung complications and other lung function measures were not significantly related to vitamin D status.
Another study found that vitamin D deficiency was associated with markers of structural kidney damage.
Two studies linked low vitamin D levels to weaker bones or more frequent fractures. However, another study found no significant association between vitamin D levels and bone mineral density, a measure of bone health.
Studies find changes in anemia and hemolysis markers
Several studies also examined blood test results. Some found that children with vitamin D deficiency had significantly lower hemoglobin levels and significantly higher levels of markers of red blood cell breakdown.
“Due to several limitations in the data presented across the studies, including small sample sizes and variability in outcome measures, a meta-analysis [which combines data from separate studies] was not feasible,” the team wrote. “The studies we reviewed employed different methodologies and outcome measures, making it difficult to aggregate the results in a meaningful way.”
The researchers also noted that the studies could not determine whether vitamin D deficiency contributed to more severe SCD or was a consequence of more severe disease.
The researchers emphasized the importance of these findings, writing, “Recognizing these associations highlights the need for careful clinical surveillance and targeted interventions to mitigate complications and improve quality of life in this vulnerable population.”
The researchers also discussed the possible influence of socioeconomic conditions. One study involving adults with SCD linked greater socioeconomic disadvantage to lower vitamin D levels. A separate study of children with SCD found that lower family income was associated with more emergency department visits for pain. Together, these findings suggest that socioeconomic conditions may help explain some of the associations between vitamin D deficiency and SCD severity.
Finally, the researchers concluded, “Supplementation could potentially mitigate these outcomes; however, current reviews are not yet robust enough to recommend this therapy.”
