Louise B Andersen1, Jan S Jørgensen2, Tina K Jensen3, Christine Dalgård3, Torben Barington4, Jan Nielsen5, Signe S Beck-Nielsen6, Steffen Husby7, Bo Abrahamsen8, Ronald F Lamont9, Henrik T Christesen10. 1. Institute for Clinical Research and Hans Christian Andersen Children's Hospital. 2. Institute for Clinical Research and Department of Obstetrics and Gynecology. 3. Department of Environmental Medicine, Institute of Public Health, University of Southern Denmark, Odense, Denmark; 4. Odense Patient Data Explorative Network (OPEN), Department of Clinical Immunology, and. 5. Center for Clinical Epidemiology, Odense University Hospital, Odense, Denmark; 6. Institute for Clinical Research and Department of Pediatrics, Hospital of Southwest Denmark, Esbjerg, Denmark; 7. Institute for Clinical Research and Hans Christian Andersen Children's Hospital, Odense Child Cohort, Hans Christian Andersen Children's Hospital, Odense, Denmark; 8. Institute for Clinical Research and Odense Patient Data Explorative Network (OPEN), Department of Medicine, Holbæk Hospital, Holbæk, Denmark; and. 9. Institute for Clinical Research and Division of Surgery, University College London, Northwick Park Institute of Medical Research Campus, United Kingdom. 10. Institute for Clinical Research and Hans Christian Andersen Children's Hospital, henrik.christesen@rsyd.dk.
Abstract
BACKGROUND: Miscarriage is the most common negative outcome of pregnancy, and identification of modifiable risk factors is potentially of great importance for public health. Low vitamin D concentrations in pregnancy are widespread worldwide, and vitamin D deficiency is implicated in immune cell regulation at the feto-maternal interface and several diseases of pregnancy. OBJECTIVE: We investigated whether 25-hydroxyvitamin D serum concentration was a modifiable risk factor for early miscarriage. DESIGN: In a prospective cohort study of 1683 pregnant women donating serum before gestational week 22, we investigated the association between maternal serum concentrations of serum 25-hydroxyvitamin D [25(OH)D] and the risk of subsequent miscarriage (n = 58). RESULTS: The adjusted hazard of first-trimester miscarriage was lower with higher 25(OH)D concentrations (HR: 0.98; 95% CI: 0.96, 0.99). Concentrations of 25(OH)D <50 nmol/L were associated with a >2-fold increased adjusted HR for miscarriage (HR: 2.50; 95% CI: 1.10, 5.69). Concentrations of 25(OH)D were not associated with an increased risk of second-trimester miscarriage. CONCLUSIONS: We found an association between 25(OH)D and first-trimester miscarriages, suggesting vitamin D as a modifiable risk factor for miscarriage. To test this hypothesis, randomized controlled trials should investigate the possible effect of vitamin D supplementation to increase 25(OH)D concentrations in early pregnancy, or before conception, to decrease risk of miscarriage. This trial was registered at clinicaltrials.gov as NCT02434900.
BACKGROUND: Miscarriage is the most common negative outcome of pregnancy, and identification of modifiable risk factors is potentially of great importance for public health. Low vitamin D concentrations in pregnancy are widespread worldwide, and vitamin D deficiency is implicated in immune cell regulation at the feto-maternal interface and several diseases of pregnancy. OBJECTIVE: We investigated whether 25-hydroxyvitamin D serum concentration was a modifiable risk factor for early miscarriage. DESIGN: In a prospective cohort study of 1683 pregnant women donating serum before gestational week 22, we investigated the association between maternal serum concentrations of serum 25-hydroxyvitamin D [25(OH)D] and the risk of subsequent miscarriage (n = 58). RESULTS: The adjusted hazard of first-trimester miscarriage was lower with higher 25(OH)D concentrations (HR: 0.98; 95% CI: 0.96, 0.99). Concentrations of 25(OH)D <50 nmol/L were associated with a >2-fold increased adjusted HR for miscarriage (HR: 2.50; 95% CI: 1.10, 5.69). Concentrations of 25(OH)D were not associated with an increased risk of second-trimester miscarriage. CONCLUSIONS: We found an association between 25(OH)D and first-trimester miscarriages, suggesting vitamin D as a modifiable risk factor for miscarriage. To test this hypothesis, randomized controlled trials should investigate the possible effect of vitamin D supplementation to increase 25(OH)D concentrations in early pregnancy, or before conception, to decrease risk of miscarriage. This trial was registered at clinicaltrials.gov as NCT02434900.
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