Jennifer A Tamblyn1, Nicole S P Pilarski2, Alexandra D Markland3, Ella J Marson3, Adam Devall4, Martin Hewison5, Rachel K Morris6, Arri Coomarasamy7. 1. Tommy's National Centre for Miscarriage Research, Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom; CARE Fertility Leeds, Leeds Teaching Hospital Trust, Seacroft Hospital, Leeds, England; Birmingham Women's and Children's Foundation Hospital Trust, Edgbaston, Birmingham, United Kingdom. Electronic address: j.tamblyn@bham.ac.uk. 2. Birmingham Women's and Children's Foundation Hospital Trust, Edgbaston, Birmingham, United Kingdom; Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom. 3. College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom. 4. Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom; Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, United Kingdom. 5. Tommy's National Centre for Miscarriage Research, Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom. 6. Birmingham Women's and Children's Foundation Hospital Trust, Edgbaston, Birmingham, United Kingdom; Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom; Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, United Kingdom. 7. Tommy's National Centre for Miscarriage Research, Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom; Birmingham Women's and Children's Foundation Hospital Trust, Edgbaston, Birmingham, United Kingdom.
Abstract
OBJECTIVE: To investigate whether a significant association between vitamin D status and the risk of miscarriage or recurrent miscarriage (RM) exists. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Women with miscarriage and RM. INTERVENTION(S): We searched the Ovid MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature, and Cochrane Central Register of Controlled Trials from database inception to May 2021. Randomized and observational studies investigating the association between maternal vitamin D status and miscarriage and/or vitamin D treatment and miscarriage were included. MAIN OUTCOME MEASURE(S): The primary outcome was miscarriage or RM, with vitamin D status used as the predictor of risk. Whether vitamin D treatment reduces the risk of miscarriage and RM was also assessed. RESULT(S): Of 902 studies identified, 10 (n = 7,663 women) were included: 4 randomized controlled trials (n = 666 women) and 6 observational studies (n = 6,997 women). Women diagnosed with vitamin D deficiency (<50 nmol/L) had an increased risk of miscarriage compared with women who were vitamin D replete (>75 nmol/L) (odds ratio, 1.94; 95% confidence interval, 1.25-3.02; 4 studies; n = 3,674; I2 = 18%). Combined analysis, including women who were vitamin D insufficient (50-75 nmol/L) and deficient (<50 nmol/L) compared with women who were replete (>75 nmol/L), found an association with miscarriage (odds ratio, 1.60; 95% confidence interval, 1.11-2.30; 6 studies; n = 6,338; I2 = 35%). Although 4 randomized controlled trials assessed the effect of vitamin D treatment on miscarriage, study heterogeneity, data quality, and reporting bias precluded direct comparison and meta-analysis. The overall study quality was "low" or "very low" using the Grading of Recommendations, Assessment, Development and Evaluations approach. CONCLUSION(S): Vitamin D deficiency and insufficiency are associated with miscarriage. Whether preconception treatment of vitamin D deficiency protects against pregnancy loss in women at risk of miscarriage remains unknown. REGISTRATION NUMBER: CRD42021259899.
OBJECTIVE: To investigate whether a significant association between vitamin D status and the risk of miscarriage or recurrent miscarriage (RM) exists. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Women with miscarriage and RM. INTERVENTION(S): We searched the Ovid MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature, and Cochrane Central Register of Controlled Trials from database inception to May 2021. Randomized and observational studies investigating the association between maternal vitamin D status and miscarriage and/or vitamin D treatment and miscarriage were included. MAIN OUTCOME MEASURE(S): The primary outcome was miscarriage or RM, with vitamin D status used as the predictor of risk. Whether vitamin D treatment reduces the risk of miscarriage and RM was also assessed. RESULT(S): Of 902 studies identified, 10 (n = 7,663 women) were included: 4 randomized controlled trials (n = 666 women) and 6 observational studies (n = 6,997 women). Women diagnosed with vitamin D deficiency (<50 nmol/L) had an increased risk of miscarriage compared with women who were vitamin D replete (>75 nmol/L) (odds ratio, 1.94; 95% confidence interval, 1.25-3.02; 4 studies; n = 3,674; I2 = 18%). Combined analysis, including women who were vitamin D insufficient (50-75 nmol/L) and deficient (<50 nmol/L) compared with women who were replete (>75 nmol/L), found an association with miscarriage (odds ratio, 1.60; 95% confidence interval, 1.11-2.30; 6 studies; n = 6,338; I2 = 35%). Although 4 randomized controlled trials assessed the effect of vitamin D treatment on miscarriage, study heterogeneity, data quality, and reporting bias precluded direct comparison and meta-analysis. The overall study quality was "low" or "very low" using the Grading of Recommendations, Assessment, Development and Evaluations approach. CONCLUSION(S): Vitamin D deficiency and insufficiency are associated with miscarriage. Whether preconception treatment of vitamin D deficiency protects against pregnancy loss in women at risk of miscarriage remains unknown. REGISTRATION NUMBER: CRD42021259899.