Abstract

Many premature infants develop hypocalcemia during the first 24 hours of life. Of these, twenty percent may have subsequent skeletal demineralization (osteopenia, rickets, long bone fractures). The underlying mechanisms are unknown but may involve abnormal vitamin D metabolism. The present proposal is designed to help clarify the role of the hormonal form of vitamin D, namely, 1,25 dihydroxyvitamin D (1,25(OH)2D) in the mineral economy of the fetus during intrauterine life. The following specific questions will be addressed: 1) What are the relative contributions of the fetal kidney and the placenta to fetal circulating 1,25(OH)2D concentrations during intrauterine life? 2) Are normal fetal circulating 1,25(OH)2D concentrations necessary for normal intrauterine mineral metabolism? 3) Are the placenta and fetal bone responsive target organs for the action of 1,25(OH)2D during fetal life? In phase I of our study, singleton sheep fetuses will be instrumented at 110 days of gestation (term 145) to determine the 1,25(OH)2D synthetic capacity of the fetal-placental unit. This will be done by measurement of the fetal Production and Metabolic Clearance Rates of 1,25(OH)2D and by measurement of the in vivo placental synthesis rate using an in vivo placental perfusion technique. Normal gestationally related changes in serum minerals and calcium regulating hormones will also be assessed longitudinally from 110 days to 138 days of gestation when normal placental mineral transfer and fetal mineral utilization rates will be determined. In phase II of our study, we will use bilaterally nephrectomized fetuses to determine the impact of loss of fetal renal 1,25(OH)2D synthetic capacity on fetal serum 1,25(OH)2D and mineral concentrations, placental mineral transfer and fetal mineral utilization rates. Based on our previous studies, fetal nephrectomy will result in fetal hypocalcemia, hyperphosphatemia and reduced fetal serum 1,25(OH)2D concentrations. We hypothesize that these changes result from reduced 1,25(OH)2D-mediated placental mineral transfer and disruption of normal bone mineralization and will be largely corrected by treatment with exogenous 1,25(OH)2D therapy. These combined studies will provide valuable insight into the functional role of 1,25(OH)2D during fetal life, as it relates to the etiology of hypocalcemia and bone demineralization in prematurity.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
1R01AR036487-01
Application #
3157620
Study Section
Human Embryology and Development Subcommittee 2 (HED)
Project Start
1986-01-01
Project End
1988-12-31
Budget Start
1986-01-01
Budget End
1986-12-31
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
University of Cincinnati
Department
Type
Schools of Medicine
DUNS #
City
Cincinnati
State
OH
Country
United States
Zip Code
45221