Vitamin D Levels Can Influence Risk of Miscarriage, Premature Delivery in Women with Lupus

New data from a Johns Hopkins-led team is underlining the urgent need for greater understanding of the impact of systemic lupus erythematosus (SLE), as well as specific drivers of risk, for adverse pregnancy outcomes.

Results of the study, which examined the role of 25-hydroxy vitamin D insufficiency and BMI on adverse pregnancy outcomes in SLE, describe the presence of a U-shaped curve association between vitamin D level and adverse pregnancy outcomes, with the lowest prevalence of adverse pregnancy outcomes observed among those with a maternal serum 25-hydroxy vitamin D level of 40-59 ng/dL.

There are few topics in medicine to have been examined as thoroughly for potential utility as vitamin D. According to a 2018 study, more than 25,000 research articles had been published examining associations of vitamin D with health and disease from 1900-2014. In a 2021 study, vitamin D supplementation was associated with improved disease activity and fatigue in vitamin D deficient/insufficient SLE patients.

Still, as evidence by current study from the Johns Hopkins School of Medicine, there remains a significant amount of interest in examining the role of serum vitamin D levels on outcomes in various conditions.

The current study, which was presented by at the Congress of Clinical Rheumatology (CCR) East 2023 annual meeting, was led Michelle Petri, MD, MPH, professor of Medicine and director of the Lupus Center, with the intent of estimating associations between 25-hydroxy vitamin D levels and BMI with adverse pregnancy outcomes in SLE. With this in mind, investigators designed their study as an analysis of data from the Hopkins Lupus Cohort, which is a 2000-patient cohort of SLE patients with follow-up every 3 months.

Limiting their study to patients with pregnancies with serum vitamin D levels available during pregnancy, investigators identified 270 pregnancies for inclusion in their statistical analysis. Of note, patients were also required to have outcomes data related to pregnancy, including due date, birth date, gestational age, and complications of pregnancy.

When examining mean serum 25-hydroxy vitamin D levels during pregnancy, 12 had a level below 20 ng/dL, 45 had a level from 20-29 ng/dL, 78 had a level from 30-39 ng/dL, 87 had a level from 40-49 ng/dL,28 had a level of 50-59 ng/dL, and 20 had a level of 60 ng/dL or greater. When examining BMI categories, 23 had a BMI of less than 20 kg/m2, 97 had a BMI of 20-25 kg/m2, 53 had a BMI of 25-30 kg/m2, 23 had a BMI of 30-35 kg/m2, and 17 had a BMI exceeding 35 kg/m2.

Upon analysis, investigators found a U-shape curve associations between maternal serum 25-hydropxy vitamin D level and the combined adverse pregnancy outcomes in SLE (P=.0061). Further analysis suggested the same trend was present when miscarriage and premature deliveries were examined separately but this P value failed to reach statistical significance, which investigators attribute to smaller numbers. The percentage of pregnancies with either miscarriage or premature delivery based on mean serum 25-hydroxy vitamin D during pregnancy are listed below:

• <20 ng/dl: 100% (n=12)
• 20-29 ng/dL: 51% (n=23)
• 30-39 ng/dL: 44% (n=34)
• 40-49 ng/dL: 25% (n=22)
• 50-59 ng/dL: 29% (n=8)
• 60+ ng/dL: 53% (n=11)

Investigators pointed out the presence of lupus anticoagulant or anticardiolipin was not a confounding factor in analyses examining associations of mean serum 25-hydroxy vitamin D levels and outcomes. When examining the effect of BMI, results indicated a BMI of less than 25 kg/m2 was independently associated with lower frequency of miscarriage but not with premature delivery or birth weight, irrespective of 25-hydroxy vitamin D levels.¹

“Over half of the miscarriages and most preterm births in SLE are not from obstetric antiphospholipid syndrome. Additional targets and interventions are needed. We recommend monitoring 25-hydroxy vitamin D levels before and during SLE pregnancies,” wrote investigators.¹

References:

1. Madanchi N, Fava A, Goldman DW, Jacobson R, Magder LS, Petri M. Association Between Vitamin D, Body Mass Index, and Adverse Pregnancy Outcomes in Systemic Lupus Erythematosus. Paper presented at: Paper presented at: Congress of Clinical Rheumatology (CCR) East 2023 Annual Meeting. Destin, FL. May 4 – 7, 2023.
2. Brüggmann D, Alafi A, Jaque J, et al. World-wide research architecture of vitamin D research: density-equalizing mapping studies and socio-economic analysis [published correction appears in Nutr J. 2018 Feb 20;17 (1):25]. Nutr J. 2018;17(1):3. Published 2018 Jan 6. doi:10.1186/s12937-018-0313-6
3. Magro R, Saliba C, Camilleri L, Scerri C, Borg AA. Vitamin D supplementation in systemic lupus erythematosus: relationship to disease activity, fatigue and the interferon signature gene expression. BMC Rheumatol. 2021;5(1):53. Published 2021 Dec 3. doi:10.1186/s41927-021-00223-1
4. Hopkins Lupus Cohort. National Institutes of Health. https://reporter.nih.gov/search/-nZiyVgiZkimm9M-CLQ0hw/project-details/10000765. Accessed May 6, 2023.