Vitamin D deficiency is associated with a prothrombotic state (tHCY) rather than inflammation in patients with recurrent spontaneous abortion: a retrospective cohort study

Previous studies have suggested that vitamin D deficiency is common in patients with recurrent spontaneous abortion (RSA) and may be associated with immune-inflammatory imbalance and a prothrombotic state. In light of this, this study aims to investigate the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels and inflammatory response as well as prothrombotic state in RSA patients.

A retrospective cohort study was conducted on 220 RSA patients who visited our reproductive medicine center between January 2022 and August 2023. Clinical data were analyzed, and serum levels of 25(OH)D, inflammatory markers (IL-6, TNF-α, IL-10, hsCRP), prothrombotic state indicators [total homocysteine (tHCY), D-dimer], glucolipid metabolism parameters, thyroid function, immune cell subsets and ovarian reserve function were assessed. According to 25(OH)D levels, these RSA patients were stratified into a severe deficiency group (<10 ng/mL, n=14), a deficiency group (10 to <20 ng/mL, n=140), an insufficiency group (20 to <30 ng/mL, n=53), and a sufficiency group (≥30 ng/mL, n=13). The abovementioned indicators were compared among the groups. Mann-Whitney U test was used for comparisons between 2 groups. For comparisons among more than 2 groups, Kruskal-Wallis H test was performed followed by Dunn’s post hoc test. Spearman and partial correlation analyses were applied to evaluate associations between 25(OH)D and related indicators.

Vitamin D deficiency or insufficiency was observed in 94.09% of the cohort. Compared with the patients with 25(OH)D ≥20 ng/mL, those with levels <20 ng/mL had significantly higher tHCY levels [8.35 (7.23 to 9.60) μmol/L vs 7.60 (6.35 to 8.95) μmol/L, P=0.007]. No statistical differences were observed in the intergroup comparisons in glucolipid metabolism, thyroid function, inflammatory markers, immune cell subsets or ovarian reserve function. Spearman correlation analysis showed that serum 25(OH)D levels were negatively correlated with tHCY (r=-0.222, P<0.01), and this association remained significant after adjusting for age and body mass index (r=-0.188, P=0.019). In the patients with 25(OH)D <30 ng/mL, a weak negative correlation was observed between 25(OH)D and IL-6 (r=-0.159, P<0.05), but this difference was not statistically significant after adjustment.

Vitamin D deficiency is quite common in RSA patients. Lower 25(OH)D levels are associated with an altered prothrombotic profile, particularly elevated tHCY, whereas their association with inflammatory markers appears limited. These findings suggest that vitamin D status may be involved in the regulation of thrombotic risk associated with RSA.