Highest, lowest vitamin D levels predict adverse pregnancy outcomes in lupus
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Key takeaways:
- Risks for miscarriage, preterm delivery and small for gestational age were greatest at the highest and lowest levels of vitamin D.
- The lowest risks were seen in the range of 40 ng/mL to 59 ng/mL.
Among pregnant women with systemic lupus erythematosus, those who demonstrate either high or low levels of serum vitamin D are more likely to experience miscarriage, preterm delivery and other adverse outcomes, according to data.
The researchers, who published their findings in Arthritis Care & Research, recommended monitoring maternal 25(OH) vitamin D levels during pregnancy, with a target range of 40 ng/mL to 59 ng/mL.
“Adverse pregnancy outcomes, including preterm birth, pre-eclampsia and miscarriages, are frequent in systemic lupus erythematosus,” Michelle Petri, MD, MPH, of Johns Hopkins University, told Healio. “Vitamin D really isn’t a vitamin — it is a sterol hormone with importance in pregnancy.”
To examine how vitamin D levels impact pregnancies among women with SLE, Petri and colleagues conducted a study of patient data from the Hopkins Lupus Cohort. The analysis included 260 pregnancies with 25(OH) vitamin D levels assessed using chemiluminescence immunoassay at each cohort visit. Vitamin D levels were compared with the incidence of miscarriage, premature delivery and small for gestational age, as well as a composite outcome of all three.
Patients in the cohort were seen every 6 weeks during pregnancy. Pregnant women were prescribed prenatal multivitamins containing around 400 international units of vitamin D. In cases of low vitamin D, weekly or daily supplements were given to achieve a serum concentration of 40 ng/mL or higher, which a previous Hopkins Lupus Cohort analysis found to improve proteinuria and disease activity.
According to the researchers, the results revealed a “U-shaped” relationship between maternal 25(OH) vitamin D and miscarriage, preterm delivery and small for gestational age. Overall, risks were highest at concentrations below 20 ng/mL and above 60 ng/mL, while they were lowest between 40 ng/mL and 59 ng/mL.
Meanwhile, the strongest link was between premature delivery and vitamin D levels in the second trimester, as nine of 10 pregnancies with low vitamin D at that point resulted in a preterm delivery. Miscarriage or preterm delivery also resulted from all 11 pregnancies from mothers with mean 25(OH) vitamin D below 20 ng/mL.
“I never expected to find a ‘U-shaped’ curve,” Petri said. “We dread this in medicine. It means there is a ‘sweet spot’ — levels of 40 ng/mL to 59 ng/mL — and we must serially monitor during pregnancy to maintain patients in the best range.”
In their study, the researchers wrote that they were “not able to explain the U-shaped curve.”
“We hypothesize that at higher levels, vitamin D can recruit different immunologic networks leading to the increased risk of adverse pregnancy outcomes or a negative impact on calcium-related placental pathways,” Petri and colleagues wrote. “A similar ‘U-shaped curve’ has been observed for vitamin D and cardiovascular events in chronic kidney disease.”
The researchers concluded that while the results do not “prove causation,” they “strongly suggest” greater risks at higher and lower levels of 25(OH) vitamin D.
“Based on our findings, we recommend monitoring of maternal serum 25(OH) vitamin D levels throughout SLE pregnancies and supplementing patients with vitamin D insufficiency or deficiency, aiming for 25(OH) vitamin D range of 40ng/mL59 ng/mL,” they wrote. “Over-supplementation should be avoided.”
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