Association between serum vitamin D level during pregnancy and recurrent spontaneous abortion: A systematic review and meta‐analysis

Abstract

Problem Previous studies had shown that there might be an association between serum vitamin D concentrations and the occurrence of recurrent spontaneous abortion (RSA). However, the conclusions remained controversial. The objective of this study was to systematically review the evidence for an epidemiological association between vitamin D and RSA. Method of study The literature search was performed in the following databases: PubMed, Web of Science, Embase and Chinese databases. The I2 statistic was used to evaluate heterogeneity. Effect sizes were calculated using fixed or random effects models, including standardized mean difference (SMD), odds ratios (OR) and their 95% confidence intervals (95% CI). Then, we performed subgroup analysis, sensitivity analysis and publication bias analysis. Results Fourteen studies from five countries were included. Based on the results, patients with RSA had lower vitamin D levels than controls (SMD = ‐1.48, 95% CI: ‐2.01, ‐.94, P < .001), and pregnant women with vitamin D deficiency (VDD) had a higher risk of developing RSA (OR = 4.02, 95% CI: 2.23, 7.25, P < .001). There was remarkable heterogeneity between studies (I2SMD = 97.3%, P < .001; I2OR = 82.2%, P < .001). The results of the subgroup analysis suggested that heterogeneity may be caused by the assay method, age and region. Sensitivity analysis showed the analysis results were robust. Conclusion Patients with RSA had lower serum vitamin D levels than normal pregnant women, and pregnant women with VDD might be at higher risk for RSA.

No evidence of a causal relationship between miscarriage and 25-hydroxyvitamin D: a Mendelian randomization study

“…For instance, Tamblyn et al (2022) conducted a systematic review and meta-analysis and found that vitamin D deficiency and insufficiency were associated with miscarriage. Similarly, Chen et al (2022) found that patients with recurrent miscarriage had significantly lower serum 25OHD concentrations than normal pregnant women, and vitamin D deficiency during pregnancy might be a high risk factor for recurrent miscarriage. However, some studies did not find this association ( Subramanian et al , 2022 ).…”

“…Previous studies have shown that women with recurrent miscarriage have a reduction in 25OHD levels and decreased expression of 1-α-hydroxylase and vitamin D receptors at the maternal–fetal interface ( Wang et al , 2016 ; Yan et al , 2016 ; Li et al , 2017 ). Multiple recent meta-analyses have also shown that pregnant women with vitamin D insufficiency/deficiency have a significantly higher risk of miscarriage and recurrent miscarriage ( Chen et al , 2022 ; Tamblyn et al , 2022 ). However, there is a lack of high-quality evidence from randomized controlled studies.…”

Effects of vitamin D in pregnancy on maternal and offspring health-related outcomes: An umbrella review of systematic review and meta-analyses

“…Following deduplication, 673 meta-analyses remained, which underwent title and abstract screening with 123 meta-analyses selected for full-text screening. Finally, 16 meta-analyses met the inclusion criteria for this umbrella review [15][16][17][18][22][23][24][25][26][27][28][29][30][31][32][33][34].…”

Calcifediol in the management of vitamin D deficiency-related skeletal and extraskeletal diseases: overview and clinical cases

“… 64 In a meta-analysis of 14 studies, women experiencing recurrent miscarriages had significantly lower serum vitamin D concentrations compared with those who completed a normal pregnancy. 65 Despite these findings, it remains unclear whether vitamin D supplementation improves fertility or decreases the risk of adverse pregnancy outcomes such as pre-eclampsia, low birth weight and neonatal mortality. 60 …”