Pharmacology and toxicology
Several fat-soluble vitamins with a central role in calcium metabolism are referred to collectively as vitamin D. Vitamin D promotes the resorption of calcium and phosphate from the intestines. The daily requirement for vitamin D is 5pg calciferol (I(ig x 40 iu; 1 iu X 0.025 |<g). Vitamin D deficiency causes a disturbance in bone growth and development, which manifests itself as rickets in children and as osteomalacia in adults. Vitamin D2 (ergocalciferol) and vitamin D3 (colecalciferol), are found in milk, cod-liver oil, and butter. Colecalciferol and ergocalciferol are transformed into the active form of vitamin D under the influence of UV rays. In the fetus, the active form of vitamin D is related to the maternal concentration - i.e., it is normally about 70-90% of this concentration, but increases significantly to over 100% when the maternal vitamin D concentration is deficient (Pitkin 1975).
A longitudinal study up to the age of 9 years, covering 198 mother-child pairs, indicated that vitamin D deficiency in late pregnancy may lead to significantly reduced ossification of the whole skeleton, and in particular of the lower spine. A lower than normal calcium concentration in the cord blood may also predict poorer ossification (Javaid 2006).
Other derivatives of vitamin D are aljacalcidol and calcitriol.
Dihydrotachysterol is a vitamin D analog for Ihe treatment of hypoparathyroidism. There have been no studies on its use during pregnancy. However, dihydrotachysterol dosages are adjusted to maintain physiological conditions. Therefore, developmental toxicity is unlikely.
Pciricalcitol is a synthetic vitamin D derivative used for the prevention and treatment of secondary hyperparathyroidism and osteoporosis. There is no experience with treatment during pregnancy.
Recommendation. During pregnancy, very high doses of vitamin D are contraindicated because they can lead to hypercalcaemia in both the mother and the newborn. For healthy women, the need for vitamin D does not increase in pregnancy. When the diet is balanced, there is no need for supplementation. However, if there is a documented deficiency, supplementation, vitamin D may - or even must - be given until the maternal plasma concentrations are normal. This also applies to high doses for inherited dominant X-chromosomal vitamin D-resistant rickets needing treatment. In this case, it seems that a genetically healthy fetus is not damaged even with daily doses as high as 20000 IU. Where there is phosphate diabetes, interruption of the vitamin D therapy should be discussed if the maternal symptoms allow this. Generally speaking, with these diseases the calcium and phosphate concentrations in the blood of both mother and newborn should be measured regularly.
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