Health characteristics and outcomes of two randomized vitamin D supplementation trials during pregnancy: A combined analysis

Combined analysis of two randomized pregnancy supplementation trials conducted in South Carolina. Pregnant women with singleton pregnancies were randomized in early pregnancy to vitamin D3 doses of 400 IU/day, 2000 IU/day, or 4000 IU/day and followed with monthly visits through delivery.

Vitamin D3 (cholecalciferol) was given orally as a daily regimen during pregnancy. In the active arms, women received 2000 IU/day or 4000 IU/day, with the dose delivered through a prenatal vitamin plus vitamin D tablet; supplementation began in early pregnancy and continued through delivery, with one trial including a 1-month run-in before randomization.

Higher-dose vitamin D3 improved maternal and neonatal vitamin D status, but did not show clear statistically significant reductions in pregnancy comorbidities. Final maternal 25(OH)D was higher with 2000 IU/day and 4000 IU/day than control (37.1 and 41.9 ng/mL vs 30.7 ng/mL), and cord blood 25(OH)D was also higher with 4000 IU/day (25.4 ng/mL vs 18.2 ng/mL). Vitamin D sufficiency increased with dose, including maternal 25(OH)D >=32 ng/mL in 68.7% of the 2000 IU group and 76.2% of the 4000 IU group. The authors concluded that higher-dose supplementation was associated with better vitamin D repletion, with a trend toward fewer comorbidities and a need for confirmatory studies.

Clinical outcome findings were not definitive, with no significant between-group differences for the comorbidity composites despite biomarker improvements. The analysis combined two trials and some reported sample counts differed across tables/flow diagrams, and adherence influenced observed effects. The study was not designed to provide strong power for rare maternal or neonatal clinical endpoints.