Vitamin D Deficiency and Sudden Unexpected Death in Infancy and Childhood: A Cohort Study

Abstract

We sought to (1) determine if there is an increased prevalence of vitamin D deficiency (VDD) in cases of sudden death in infancy and childhood; (2) establish whether there is a link between VDD and infection; and (3) assess if the level of vitamin D can be related to abnormalities in the skeletal survey and rib histology in our cohort. The postmortem reports of cases in which vitamin D levels were measured in 2009 and 2010 were retrieved. When parental consent for audit had been granted, rib histology and skeletal surveys were reviewed. Plasma 25-hydroxyvitamin D levels were measured in 41 postmortem cases. Ten (24.5%) had adequate levels, 5 (12%) had suboptimal levels, 16 (39%) had moderate deficiency, and 10 (24.5%) had severe deficiency. We had only 4 cases with VDD and infection. There were 25 cases of unexplained death in our cohort, and 76% of these had inadequate vitamin D levels. The rib histology was abnormal in 69% of cases that had inadequate vitamin D levels, while the radiology was abnormal in 19% of cases. A significant proportion of infants and children who died suddenly and unexpectedly had inadequate levels of vitamin D. We were unable to confirm or exclude an association between VDD and infection due to the small number of cases with confirmed infection. Further multicenter studies are needed to confirm our findings and explore possible associations between VDD and other known risk factors for sudden unexplained death in infancy and childhood.

Letter to the editor

“…Third, we agree with the statement that the study from Cohen et al has shown that microscopic signs of rickets are not seen on radiography [5]. However, this paper did not address causality between low vitamin D levels, without the presence of radiological findings, and fracture risk.…”

Rickets or abuse? A histologic comparison of rickets and child abuse-related fractures

“…In addition, there is a focal periosteal cellular reaction with irregularly contoured neo-bone formation (arrow). In contrast to case #1, the bony trabeculae display their usual orderly appearance beyond the area of disruption childhood [18]. 25-hydroxyvitamin D (25-OHD) levels are considered to be the best marker for vitamin D status, and this compound is relatively stable in post-mortem serum samples [20]; therefore consideration should be given to performing this analysis in pediatric autopsy cases provided that a sufficient amount of blood is available.…”

“…The histology of vitamin D-deficiency rickets has been described in the pathology literature [15][16][17][18][19], and is characterized within long bones by widening of the growth plate accompanied by architectural disarray. This is a result of a failure of the chondrocytes within the zone of hypertrophy to undergo apoptosis, and leads to the accumulation of hypertrophic cartilage.…”

Misinterpretation of birth-related growth plate injuries as classic metaphyseal lesions

“…Indeed, the cases of CML's cited by Sieswerda-Hoogendoorn, included their own, all reported from significantly northern latitudes (mean-48.91N; range-41.91 to 53.31N) [1,3,[12][13][14]. Although no study purported to evaluate the presence of metabolic bone disease it was recently observed that rickets may be radiologically overlooked in over 90% of pathologically proven cases in infants presenting o1 year of age [15,16]. Thus, rickets cannot be dismissed as a potential contributing factor in cases of breechrelated "CMLs" merely based upon lack of the flagrant clinical or radiographic evidence seen in classical forms of disease in older infants and toddlers.…”