Association of preconception serum 25-hydroxyvitamin D concentrations with livebirth and pregnancy loss: a prospective cohort study
Lancet Diabetes and Endocrinology May 30, 2018 DOI:https://doi.org/10.1016/S2213-8587(18)30153-0
Sunni L Mumford mumfords at mail.nih.gov, PhD, Rebecca A Garbose, MD, Keewan Kim, PhDKerri Kissell, MDDaniel L Kuhr, MDUkpebo R Omosigho, MDNeil J Perkins, PhDNoya Galai, PhDRobert M Silver, MDLindsey A Sjaarda, PhDTorie C Plowden, MDEnrique F Schisterman, PhD
Conception and Vitamin D
- Birth rates doubled with male Vitamin D intervention – RCT Nov 2017
- The earlier the better- preconception vitamin D - June 2018
- Many fertility disorders associated with low vitamin D, still unsure how much is needed – Dec 2016
Fertility and Sperm category contains the following summary
Overview Women and Vitamin D
Overview Pregnancy and vitamin D Fertility and Vitamin D – several articles
Ensure a healthy pregnancy and baby - take Vitamin D before conception
Search VitaminDWiki for IVF OR "IN VITRO FERTILIZATION" 308 items as of April 2018
Search VitaminDWiki fore Testosterone 472 items as of Oct 2017
Search VitaminDWiki for "Assisted reproduction" 89 items as of Oct 2017
Search VitaminDWiki for "erectile dysfunction" 120 items as of July 2018
Conception and vitamin D snapshot as of 2012
Healthy pregnancies need lots of vitamin D has the following summary
|0. Chance of not conceiving||3.4 times||Observe|
|1. Miscarriage||2.5 times||Observe|
|2. Pre-eclampsia||3.6 times||Randomized Controlled Trial|
|3. Gestational Diabetes||3 times||Randomized Controlled Trial|
|4. Good 2nd trimester sleep quality||3.5 times||Observe|
|5. Premature birth||2 times||Randomized Controlled Trial|
|6. C-section - unplanned||1.6 times||Observe|
|Stillbirth - OMEGA-3||4 times||RCT - Omega-3|
|7. Depression AFTER pregnancy||1.4 times||Randomized Controlled Trial|
|8. Small for Gestational Age||1.6 times||meta-analysis|
|9. Infant height, weight, head size |
within normal limits
|Randomized Controlled Trial|
|10. Childhood Wheezing||1.3 times||Randomized Controlled Trial|
|11. Additional child is Autistic||4 times||Intervention|
|12.Young adult Multiple Sclerosis||1.9 times||Observe|
|13. Preeclampsia in young adult||3.5 times||Randomized Controlled Trial|
|14. Good motor skills @ age 3||1.4 times||Observe|
|15. Childhood Mite allergy||5 times||Randomized Controlled Trial|
|16. Childhood Respiratory Tract visits||2.5 times||Randomized Controlled Trial|
PDF is available free at Sci-Hub 10.1016/S2213-8587(18)30153-0
Vitamin D deficiency during pregnancy is associated with adverse pregnancy outcomes, although the association between preconception vitamin D concentrations and livebirth is unknown. We aimed to assess the association between preconception vitamin D and pregnancy outcomes among women with proven fecundity.
We did a secondary analysis of a prospective cohort from the block-randomised, double-blind, placebo-controlled EAGeR trial. Women aged 18–40 years with one to two previous pregnancy losses were recruited from June 15, 2007, to July 15, 2011, at four clinical sites in the USA and followed up for up to six menstrual cycles while attempting pregnancy and throughout pregnancy if they conceived. Serum 25-hydroxyvitamin D was measured at baseline (preconception) and 8 weeks of gestation. Outcomes of interest included clinical pregnancy, time to pregnancy, pregnancy loss, and livebirths. Risk ratios (RRs) and 95% CIs for livebirths, pregnancy, and pregnancy loss were estimated with weighted log-binomial regression. To assess time to pregnancy, we used discrete time Cox proportional hazards models to calculate fecundability odds ratios (FORs) with 95% CIs. EAGeR is registered with ClinicalTrials.gov, number NCT00467363.
1191 women had available data on preconception 25-hydroxyvitamin D concentrations. 555 (47%) women were classified as having sufficient concentrations (≥75 nmol/L) and 636 (53%) as having insufficient concentrations (<75 nmol/L).
Women with sufficient preconception 25-hydroxyvitamin D were more likely to
- achieve clinical pregnancy (adjusted RR 1.10 [1·01–1·20])
- and livebirth (1.15 [95% CI 1·02–1·29])
than were women with insufficient concentrations. Among women who achieved pregnancy, sufficient preconception 25-hydroxyvitamin D, but not that at 8 weeks of gestation, was associated with reduced risk of pregnancy loss (preconception RR per 25 nmol/L 0·88 [95% CI 0·77–0·99]; 8 weeks of gestation 0·98 [0·95–1·01]). No association was observed with fecundability in women with sufficient versus those with insufficient preconception 25-hydroxyvitamin D concentrations (adjusted FOR 1·13 [95% CI 0·95–1·34]).
Sufficient preconception 25-hydroxyvitamin D (≥75 nmol/L) was associated with increased likelihood of pregnancy and livebirth. Increased vitamin D concentrations before conception, but not in early pregnancy, were associated with reduced pregnancy loss.
- Lerchbaum E, Obermayer-Pietsch B. Vitamin D and fertility: a systematic review. Eur J Endocrinol 2012; 166: 765-78.
- Halloran BP, Deluca HF. Effect of Vitamin-D deficiency on fertility and reproductive capacity in the female rat. J Nutr 1980; 110: 1573-80.
- Ozkan S, Jindal S, Greenseid K, et al. Replete vitamin D stores predict reproductive success following in vitro fertilization. Fertil Steril 2010; 94: 1314-19.
- Farzadi L, Khayatzadeh Bidgoli H, Ghojazadeh M, et al. Correlation between follicular fluid 25-OH vitamin D and assisted reproductive outcomes. Iran J Reprod Med 2015; 13: 361-66.
- Hewison M. Vitamin D and immune function: autocrine, paracrine or endocrine? ScandJ Clin Lab Invest Supplementum 2012; 243: 92-102.
- Lagishetty V, Liu NQ, Hewison M. Vitamin D metabolism and innate immunity. Mol Cell Endocrinol 2011; 347: 97-105.
- Fung JL, Hartman TJ, Schleicher RL, Goldman MB. Association of vitamin D intake and serum levels with fertility: results from the Lifestyle and Fertility Study. Fertil Steril 2017; 108: 302-11.
- Moller UK, Streym S, Heickendorff L, Mosekilde L, Rejnmark L. Effects of 25OHD concentrations on chances of pregnancy and pregnancy outcomes: a cohort study in healthy Danish women. Euro J Clin Nutr 2012; 66: 862-68.  Download the PDF from VitaminDWiki
- Schisterman EF, Silver RM, Lesher LL, et al. Preconception low-dose aspirin and pregnancy outcomes: results from the EAGeR randomised trial. Lancet 2014; 384: 29-36.
- Schisterman EF, Silver RM, Perkins NJ, et al. A randomised trial to evaluate the effects of low-dose aspirin in gestation and reproduction: design and baseline characteristics. Paediatr Perinat Epidemiol 2013; 27: 598-609.
- Sjaarda LA, Radin RG, Silver RM, et al. Preconception low-dose aspirin restores diminished pregnancy and live birth rates in women with low-grade inflammation: a secondary analysis of a randomized trial. J Clin Endocrinol Metab 2017; 102: 1495-504.
- Freeman J, Wilson K, Spears R, Shalhoub V, Sibley P. Performance evaluation of four 25-hydroxyvitamin D assays to measure 25-hydroxyvitamin D2. Clin Biochem 2015; 48: 1097-104.
- Fraser WD, Milan AM. Vitamin D assays: past and present debates, difficulties, and developments. Calcif Tissue Int 2013; 92: 118-27
- Mumford SL, Silver RM, Sjaarda LA, et al. Expanded findings from a randomized controlled trial of preconception low-dose aspirin and pregnancy loss. Hum Reprod 2016; 31: 657-65.
- Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011; 96: 1911-30.
- van Buuren S. Multiple imputation of discrete and continuous data by fully conditional specification. Stat Methods Med Res 2007;
- 16: 219^-2.
- Rudick B, Ingles S, Chung K, Stanczyk F, Paulson R, Bendikson K. Characterizing the influence of vitamin D levels on IVF outcomes. Hum Reprod 2012; 27: 3321-27
- Pacis MM, Fortin CN, Zarek SM, Mumford SL, Segars JH. Vitamin D and assisted reproduction: should vitamin D be routinely screened and repleted prior to ART? A systematic review. J Assist Reprod Genet 2015; 32: 323-35.
- Andersen LB, Jorgensen JS, Jensen TK, et al. Vitamin D insufficiency is associated with increased risk of first trimester miscarriage in the Odense Child Cohort. Am J Clin Nutr 2015; 102: 633-38.
- Ota K, Dambaeva S, Han AR, Beaman K, Gilman-Sachs A, Kwak-Kim J. Vitamin D deficiency may be a risk factor for recurrent pregnancy losses by increasing cellular immunity and autoimmunity. Hum Reprod 2014; 29: 208-19.
- Mirzakhani H, Litonjua AA, McElrath TF, et al. Early pregnancy vitamin D status and risk of preeclampsia. J Clin Invest 2017; 126: 4702-15.
- Hollis BW, Johnson D, Hulsey TC, Ebeling M, Wagner CL. Vitamin D supplementation during pregnancy: double-blind, randomized clinical trial of safety and effectiveness. J Bone Miner Res 2011; 26: 2341-57.
- Wise LA, Wesselink AK, Mikkelsen EM, et al. Dairy intake and fecundability in 2 preconception cohort studies. Am J Clin Nutr 2017; 105: 100-10.
- Somigliana E, Paffoni A, Lattuada D, et al. Serum levels of 25-hydroxyvitamin D and time to natural pregnancy. Gynecol Obstet Invest 2016; 81: 468-71.
- Du H, Daftary GS, Lalwani SI, Taylor HS. Direct regulation of HOXA10 by 1,25-(OH)2D3 in human myelomonocytic cells and human endometrial stromal cells. Mol Endocrinol 2005; 19: 2222-33.
- Jiang X, O’Reilly PF, Aschard H, et al. Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels. Nat Commun 2018; 9: 260.
- Wilcox AJ, Weinberg CR, O’Connor JF, et al. Incidence of early loss of pregnancy. N Engl J Med 1988; 319: 189-94.
- Zinaman MJ, Clegg ED, Brown CC, O’Connor J, Selevan SG. Estimates of human fertility and pregnancy loss. Fertil Steril 1996; 65: 503-09.
- Blomberg Jensen M, Lawaetz JG, Petersen JH, Juul A, Jorgensen N. Effects of vitamin D supplementation on semen quality, reproductive hormones and live birth rate: a randomized clinical trial. J Clin Endocrinol Metab 2018; 103: 870-81.
- Andrews KW, Palachuvattil J, Gusev PA, Dang P, Savarala S, Han F for the Dietary Supplement Ingredient Database Team. USDA Dietary Supplement Ingredient Database Release 3.0 (DSID-3), non-prescription prenatal multivitamin/mineral (MVM) dietary supplement study research summary. US Department of Agriculture. March, 2015. https://dietarysupplementdatabase.usda.nih.gov/dsid_database/Prenatal_MVM_%20res%20summary%207-31-17final.pdf (accessed May 1, 2018).
|359 visitors, last modified 05 Sep, 2018, URL: