• 25(OH)D levels throughout pregnancy and following delivery
• bone mineral density of both mother and infant

The purpose of this study is to determine the effectiveness of vitamin D supplementation during pregnancy starting at the beginning of the second trimester. Mothers will be randomized to one of three vitamin D dosing groups: 400, 2,000 or 4,000 international units per day. It is hypothesized that the highest dosing regimen will result in a better vitamin D status of women regardless of their ethnicity or race.

The prevalence of hypovitaminosis D in reproductive aged African-American women occurs at a rate of > 40%. Two factors have contributed to this public health problem: an inadequate DRI for vitamin D and avoidance of sun exposure/use of sunscreen. This startling rate of hypovitaminosis D requires that the DRI for vitamin D in pregnancy be evaluated in a detailed manner. The Cochrane Library (2002) released a report stating that there is insufficient data to evaluate the effects of vitamin D supplementation during pregnancy. Recently, the safety of prolonged supplementation with up to 25x's DRI (10,000 IU/day) was demonstrated in nonpregnant adults. It is essential to determine what dose of vitamin D is required to eliminate hypovitaminosis D during pregnancy and provide the fetus/neonate with adequate vitamin D stores during development and growth, particularly in darkly pigmented individuals. The aim of this research proposal, then, is to determine the efficacy, effectiveness, and safety of maternal vitamin D supplementation (as a function of ethnicity and UV exposure) in the prevention of hypovitaminosis D in the pregnant mother and her fetus/neonate. We hypothesize that darkly pigmented mothers will require substantially higher oral supplementation with vitamin D to eliminate hypovitaminosis D as compared to their Caucasian counterparts. We propose a comprehensive clinical trial to test our hypothesis. Mothers at 12 weeks' gestation will be randomized to one of three vitamin D treatment groups:

1. Control, 400-,
2. 2,000-, or
3. 4,000 IU/day to be continued throughout pregnancy.

Calcium and vitamin D homeostasis and skeletal remodeling in the mother will be monitored closely throughout the pregnancy. Bone density of the mother will be measured at 12 weeks' gestation and one-month postpartum. Follow-up growth and skeletal integrity assessments of the infant will be performed at birth, 1, 6 and 12 months stratified by infant feeding regime. Through these proposed studies, the prevalence of hypovitaminosis D among mothers, their developing fetuses and neonates, and the utility of maternal therapeutic intervention with vitamin D for both mother and fetus/infant will be assessed.

• Drug: cholecalciferol (vitamin D3)
  randomized control trial of three vitamin D doses: 400, 2000 and 4000 IU/day
• Drug: cholecalciferol
  comparing vitamin D requirements of pregnant women and their fetuses from 12 weeks' gestation through pregnancy
  Other Name: vitamin D3

• Active Comparator: cholecalciferol-400 IU
  Control group receiving 400 IU/day plus 0 IU vitamin D3 as placebo/day
  Interventions:

  • Drug: cholecalciferol (vitamin D3)
  • Drug: cholecalciferol
• Experimental: cholecalciferol 2000 IU
  Experimental group receiving 2000 IU total vitamin D3/day.
  Interventions:

  • Drug: cholecalciferol (vitamin D3)
  • Drug: cholecalciferol
• Experimental: cholecalciferol 4000 IU
  Experimental group receiving 4000 IU/day cholecalciferol
  Interventions:

  • Drug: cholecalciferol (vitamin D3)
  • Drug: cholecalciferol

• Hollis BW, Johnson D, Hulsey TC, Ebeling M, Wagner CL. Vitamin D supplementation during pregnancy: double-blind, randomized clinical trial of safety and effectiveness. J Bone Miner Res. 2011 Oct;26(10):2341-57. doi: 10.1002/jbmr.463. Erratum in: J Bone Miner Res. 2011 Dec; 26(12):3001.
• Hollis BW, Wagner CL. Vitamin D requirements and supplementation during pregnancy. Curr Opin Endocrinol Diabetes Obes. 2011 Dec;18(6):371-5.
• Hollis BW. Circulating 25-hydroxyvitamin D levels indicative of vitamin D sufficiency: implications for establishing a new effective dietary intake recommendation for vitamin D. J Nutr. 2005 Feb;135(2):317-22. Review.
• Hollis BW, Wagner CL. Normal serum vitamin D levels. N Engl J Med. 2005 Feb 3;352(5):515-6; author reply 515-6. No abstract available.

Inclusion Criteria:

1. Women who are within the ages of 16-45 years
2. In good general health
3. Less than 12 weeks pregnant (based on last menstrual period)

Exclusion Criteria:

1. Mothers with preexisting type I or type II diabetes
2. Mothers with preexisting hypertension
3. Mothers with preexisting parathyroid disease or uncontrolled thyroid disease
4. Mothers with multiple fetuses (e.g., twins, triplets, etc.)