Normal Intrauterine Development of the Fetus of a Woman Receiving Extraordinarily High Doses of 1,25-Dihydroxyvitamin D3*

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Abstract
The course of pregnancy in a 28 yr old patient with hereditary insensitivity to 1,25-dihydroxyvitamin D (1,25-(OH)2D) was monitored. During pregnancy, she received 1,25-(OH)2D3 in doses of 17-36 .mu.g/day (usual dose for hypocalcemia, 0.25-1.0 .mu.g/day). 25-Hydroxyvitamin D3 (25OHD3), 25OHD2, 1,25-(OH)2D3 and 1,25-(OH)2D2 were separately measured to assess contributions to total 1,25-(OH)2D from endogenous biosynthesis (1.alpha.-hydroxylation of 250OHD2 or 25OHD3) vs. contributions from exogenously administred 1,25-(OH)2D3. Serum concentrations of 1,25-(OH)2D were extraordinarily high throughout gestation. The evaluations of total 1,25-(OH)2D in maternal plasma reflected large amounts from 1.alpha.-hydroxylation of 25OHD and oral intake of 1,25-(OH)2D3. At parturition, the Ca concentration was 9.6 mg/dl in maternal serum and 10.2 mg/dl in cord serum. The concentration of total 1,25-(OH)2D in cord serum was high (470 pg/ml; normal mean for placental venous serum, 19 pg/ml); most derived from transplacental passage of maternal 1,25-(OH)2D3 and not from fetoplacental biosynthesis. The child manifested mild hypercalcemia in the 1st 2 days of life, indicating that the 1,25-(OH)2D3 measured in cord serum was active in vivo. The child showed no somatic features of the syndrome of elfin facies and supravalvular aortic stenosis. Apparently, an extraordinarily high concentration of 1,25-(OH)2D in maternal serum throughout gestation was not apparently toxic to the fetoplacental unit, though the maternal metabolite entered the fetal circulation.
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