The morphologic and biochemical effects of vitamin D in pregnant rabbits and their offspring were studied. Four groups of four pregnant does were given 100,000 IU, 10,000 IU, and 1,000 IU vitamin D2 or placebo im during pregnancy. Prestudy serum Ca, P, 25-hydroxy vitamin D (25-OHD), and cholesterol levels were not different between the control and vitamin D-supplemented does. At midgestation, the vitamin D-supplemented dose had significantly higher serum Ca levels than did controls (16.4 ± 0.6, mean ± SE, vs. 15.3 ± 0.4 mg/dl), higher serum P than control, (6.41 ± 0.06 vs. 4.50 ± 0.54 mg/dl), higher serum 25-OHD than controls (39 ± 6 vs. 21 ± 2 ng/ml), and higher serum cholesterol than controls (64.0 ± 17.2 vs. 27.5 ± 8.2 mg/dl, Wilcoxon rank, P < 0.05). At term, the vitamin D-supplemented does had significantly higher serum Ca than controls (15.2 ± 0.6 vs. 12.3 ± 0.10 mg/dl), higher serum P than controls (5.06 ± 0.48 vs. 2.96 ± 0.55 mg/dl), and higher serum 25-OHD levels than controls (50 ± 5 vs. 35 ± 5 ng/ml, Wilcoxon rank, P < 0.05). Two maternal does from the 100,000 D group that had serum 25-OHD levels greater than 100 ng/ml developed aortic medical calcifications. The 100,000 vitamin D does had a significantly higher number of abortions, 6 of 26 pregnancies, compared with control, 0 of 27 pregnancies (X2P < 0.01). In the newborns, only the 10,000 D group had higher serum ionized Ca, 6.21 ± 0.28 vs. 5.26 ± 0.06 mg/dl in controls (Wilcoxon rank, P < 0.001). There were no significant differences in newborn 25-OHD and cholesterol levels among the four groups. Newborn aortic root showed supravalvular lesions in 2 of 11 newborns in the 10,000 D group (X2P < 0.05) and 6 of 20 newborns in the 100,000 D group (X2P < 0.01) compared with no lesions in the controls (0 of 27). No supravalvular lesions were found in the 1,000 D group. Thus, high doses of vitamin D during pregnancy affect fetal death, maternal calcium and cholesterol homeostasis, neonatal calcium homeostasis, and cause calcific aortic lesions in the mother and an apparent dose-related development of supravalvular aortic lesions in the newborn.Speculation
Maternal vitamin D toxicity during pregnancy contributed to the development of supravalvular aortic lesions in the fetus which might lead to the infantile hypercalcemia syndrome. Vitamin D might have a direct toxic effect on maternal and fetal vascular areas of high turbulence flow.