Association Between 25-hydroxyvitamin D Levels and Adverse Pregnancy Outcomes in Systemic Lupus Erythematosus

We evaluated the association of 25-hydroxyvitamin D (25(OH)D) levels with adverse pregnancy outcomes in systemic lupus erythematosus (SLE).

The Hopkins Lupus Cohort includes visits of pregnant patients, including assessment of 25(OH)D levels at each visit. We examined the relationship between 25(OH)D levels and adverse pregnancy outcomes (miscarriage, preterm delivery, and small for gestational age). We also used a time-to-event analysis to assess whether time-varying of 25(OH)D levels were associated with time to miscarriage or preterm delivery.

In subgroups of patients defined by the average of 25(OH)D levels, we observed significantly different risks of miscarriage (P = 0.0045), preterm delivery (P = 0.0007), and the composite measure of all three adverse pregnancy outcomes (P = 0.011). The highest risks were observed among those with the lowest or highest levels of vitamin D. Nine of 10 pregnant patients with low vitamin D levels during the second trimester resulted in having a premature delivery. The time-to-event model confirmed the same U-shaped association after adjustment for SLE disease activity; however, the increased risk among those with highest levels of vitamin D was not statistically significant. Body mass index did not appear to be a confounding factor.

Our study is not able to prove causation, but the results strongly suggest an association of 25(OH)D at both lower and higher levels with adverse pregnancy outcomes. We recommend the monitoring of maternal serum 25(OH)D levels during SLE pregnancies, aiming for the ideal range of 40 to 59 ng/mL.