Vitamin D and the Supravalvar Aortic Stenosis Syndrome

Abstract

Pregnant rabbits were given high doses of vitamin D to determine whether the vitamin crossed the placenta and to explore the relationship between maternal hypervitaminosis D and congenital supravalvar aortic stenosis. The blood levels of antirachitic substance in the mothers given vitamin D and their offspring were 7 and 9 times greater than in the control mothers and offspring, respectively, indicating that transplacental passage occurred. Serum calcium levels in the offspring whose mothers received vitamin D were significantly higher when compared to control values. A total of 14 abnormalities of the aorta were noted in the 34 offspring whose mothers received vitamin D. Aortic lesions that appeared similar anatomically to supravalvar aortic stenosis in man were noted in six rabbits. Also, one rabbit showed a supravalvar fibrous band and another had an abnormality of the proximal portion of the aorta observed only on microscopic examination. Six additional offspring at age 3 months showed generalized vitamin D vasculotoxicity, without supravalvar narrowing of the aorta, of an advanced type commonly seen in the adult animal given massive doses of the vitamin. Thirty-five control offspring and nine rabbits born to mothers on vitamin D-deficient diets showed no abnormalities of the aorta. The results suggest that an in utero derangement in vitamin D metabolism on the part of mother or fetus, or of both may be responsible for supravalvar aortic stenosis, especially when the latter is associated with infantile hypercalcemia. The questions raised by the experimental findings are emphasized.