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  • Mr Ken Emmanuel, Consultant Gynaecologist

Lack of association found between vitamin D and miscarriage risk

March 8, 2024

There is no association between 25-hydroxyvitamin D (25OHD) and miscarriage, according to a recent study published in Human Reproduction Online.


  1. Vitamin D deficiency, marked by concentrations below 10 ng/ml (as per the American Institute of Medicine) or 20 ng/ml (per the Endocrine Society), affects a significant portion of the global population, particularly pregnant women, potentially leading to adverse pregnancy outcomes.

  2. Researchers employed mendelian randomization analysis, utilizing single-nucleotide polymorphisms as instrumental variables, to investigate the association between serum 25OHD concentrations, vitamin D deficiency, and miscarriage risk.

  3. Data for the study was sourced from the UK Biobank, a large prospective cohort study, and genome-wide association studies data from the FinnGen consortium, ensuring a robust dataset for analysis.

  4. Despite widespread vitamin D deficiency, the study found minimal causal association between serum 25OHD concentrations, vitamin D deficiency, and miscarriage risk, suggesting that these factors may not significantly impact the likelihood of miscarriage.

  5. The study underscores the need for future research, specifically focusing on women of childbearing age and diverse ethnic groups, to further elucidate the relationship between vitamin D status and pregnancy outcomes.

Vitamin D is a vitamin synthesized through ultraviolet light or in small amounts in food. It is converted to 25OHD in the liver, then to 1,25OHD in the kidney for vital biological functions.

The nutritional status of vitamin D can be assessed through 25OHD, with concentrations below 10 ng/ml considered vitamin D deficiency by the American Institute of Medicine. The Endocrine Society has stricter criteria, considering concentrations below 20 ng/ml of vitamin D deficiency. Concentrations this low are reported in 30% to 80% of individuals worldwide.

Vitamin D deficiency risk is increased in pregnant women. Additionally, vitamin D regulates certain reproductive processes such as extrachorionic trophoblast invasion and spiral artery remodeling. Adverse outcomes of vitamin D deficiency in pregnancy include preeclampsia, gestational diabetes mellitus, low birth weight, preterm labour, and miscarriage.

Currently, data about vitamin D deficiency and miscarriage is lacking. To evaluate this association, investigators conducted a mendelian randomization (MR) study.

Single-nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs) if they were strongly associated with the exposure, not related to any cofounding factors, and not associated with the outcome except through the exposure. Serum 25OHD concentration and vitamin D deficiency were both considered exposures.

Data was obtained from the UK Biobank, a prospective cohort study including over 500,000 individuals aged 40 to 69 years from 2006 to 2010. Genome-wide association studies (GWAS) for serum 25OHD concentrations were collected from 417,580 individuals.

Concentrations of 25OHD were measured using a chemiluminescent immunoassay (Diasorin Liaison), with MR analysis results described based on the impact of a one-unit change in 25OHD levels. International Classification of Diseases (ICD) 8 to 10 codes were used to define vitamin D deficiency.

GWAS data about miscarriage was obtained from the FinnGen consortium R9 version and defined using ICD-10 O03, ICD-9 634, and ICD-8 643 codes. SNP independence was determined using PhenoScanner, ensuring IV was independent of cofounders.

There were 113 SNPs with genome-wide significance, 100 of which were used to evaluate the association between serum 25OHD concentration and the odds of miscarriage and 98 to evaluate the association with the number of miscarriages. For vitamin D and the odds and number of miscarriages, these numbers were 7 and 5, respectively.

Little casual association was found between a one-unit increase in serum 25OHD concentration and decreased miscarriage risk, with an odds ratio (OR) of 0.995. Similar outcomes were reported for the number of miscarriages.

A one-unit increase in vitamin D deficiency also had little casual association with miscarriage risk, with an OR of 0.993, as well as the number of miscarriages. These results remained consistent in subsequent analyses.

These results indicated 25OHD and vitamin D deficiency do not impact miscarriage. Investigators recommended future GWAS data specifically for women of childbearing age and other ethnic groups.


Zhang F, Huang J, Zhang G, et al. No evidence of a causal relationship between miscarriage and 25-hydroxyvitamin D: a Mendelian randomization study. Hum Reprod Open. 2024. doi:10.1093/hropen/hoae011

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