Current Definition of Vitamin D Status Misclassifies Maladapted Children of First Generation African Immigrants to the Northern US

Abstract

Skin pigmentation, vitamin D inactivation and genetic variation of vitamin D binding protein (DBP) are all essential mechanisms for adaptive vitamin D metabolism in African children living near the equator. The widely used measurement of total serum 25-hydroxyvitamin D (25OHD) test ignores their inherent differences and maladaptive vitamin D metabolism, and potentially misclassifies their vitamin D status in northern parts of the United States. The goal of this multi-center international cross-sectional observational study was to better define vitamin D status in Somali immigrants living in the northern US. Well children aged 6 months to 7 years from Minnesota (US-born of Somali descent, n=55) and in Uganda (n=95) were enrolled. 25OHD and other vitamin D metabolites (24,25(OH)2D) were measured by immune-affinity extraction and liquid chromatography-tandem mass spectrometry. Parathyroid hormone (PTH) and hypocalcemia status were used as indicators of insufficiency. DBP haplotypes were determined. Ninety-one percent of the Minnesota Somali participants had 25OHD levels <30 ng/mL (vs 48% in Ugandans). Compared to the Ugandan group, and despite better nutritional status (milk intake), MN Somali children had lower 25OHD (23.7 ng/mL vs 30.1; p<0.0001) and calcium levels (9.1 mg/dL vs 9.5; p<0.0001), and higher PTH levels (47 pg/mL vs 36; p<0.0001). Somalis had a significantly higher frequency (57% vs 14% in Ugandans; p<0.001) of calcium in the lower level of normal even at 25OHD levels > 20 (American Academy of Pediatrics (AAP) cutoff for sufficiency). This was not significantly different from the Somali group with 25OHD < 20 (p<0.3). The high affinity allele Gc1f was the predominant DBP variant in both Somalis and Ugandans, yet MN Somalis had a higher percentage of low serum calcium status. The Somali group had significantly higher levels of vitamin D inactivation (higher 24,25(OH)2D) despite having lower 25OHD levels, raising a concern of maladaptive vitamin D metabolism and inherent susceptibility to vitamin D deficiency independent of limited cutaneous vitamin D synthesis as a result of darker skin tone. These results suggest that 25OHD levels 20-30 ng/mL (above the AAP cutoff for sufficiency (>20 ng/mL)) are common in children of Somali descent in northern US, and are clinically significant. Also, while African children living near the equator possess adaptive mechanisms for acquisition and utilization of vitamin D, those same mechanisms could render them susceptible to insufficiency when migrating to high latitude regions such as the northern US.