Background/Purpose: In the general population, low vitamin D has been associated with adverse pregnancy outcomes including preterm birth, pre-eclampsia and small for gestational age. In the general pregnancy population, replacement of vitamin D has been proven to reduce adverse pregnancy outcomes. We examined whether low vitamin D was also associated with adverse pregnancy outcomes in a large lupus pregnancy cohort.

Methods: A total of 268 patients (431 pregnancies) had blood levels of 25 hydroxy vitamin D (25(OH) vitamin D) measured as part of cohort follow-up. Pregnancies were followed with outcomes characterized as miscarriage or preterm birth < 37 weeks. A GEE model was used to estimate odds ratios (OR) and significance.

Results: There were 365 (84.7%) live births, 51 (11.8%) miscarriages, and 15 (3.5%) terminations. 34.7% of patients were African-American, 54.9% were Caucasian, and 10.4% were of other ethnicities. Compared to the reference vitamin D group of 40-50 ng/mL, patients with a first vitamin D below 30 ng/mL during cohort follow up had significantly higher odds of miscarriage (Table 1), but a U-shaped curve was found, with higher risk at high 25(OH) vitamin D levels, as well. The result did not change after adjustment for lupus anticoagulant. Similarly, patients with first vitamin D below 20 ng/mL had significantly higher odds of preterm birth. There were 180 pregnancies (122 patients) in which 25(OH) vitamin D had been measured in the first or second trimester. In those, there remained a significant association of preterm birth with 25(OH) vitamin D levels < 20 ng/mL (Table 2). The OR for miscarriage (2.79), although high, did not reach statistical significance in this smaller sample.

Conclusion: We found a U-shaped relationship, with miscarriage and preterm birth more common at both LOW and at HIGH levels of 25(OH) vitamin D (with the reference group at 40-50 ng/mL). The association at low vitamin D levels mirrors what has been found in non-SLE pregnancies. The increase at high levels, though, cannot be explained, and has not been identified in the general pregnancy population. Although calcium supplements and prenatal vitamins are commonly prescribed in all pregnancies, particular monitoring of 25(OH) vitamin D levels (and replacement in those who are low) is not routine in SLE pregnancy management. Our data show, though, that there is a potential “therapeutic window”, such that over-replacement must be avoided.

ACR 2019-Low Vitamin D associated with Miscarriage Preterm Birth SLE-Table1

ACR 2019-Low Vitamin D associated with Miscarriage Preterm Birth SLE-Table2

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/low-vitamin-d-is-associated-with-miscarriage-and-preterm-birth-in-sle-with-a-u-shaped-relationship/