Miscarriage 10 percent more likely for each 10 ng less vitamin D at preconception – May 2018

Association of preconception serum 25-hydroxyvitamin D concentrations with livebirth and pregnancy loss: a prospective cohort study

The Lancet – Diabetes and Endocrinology OI: https://doi.org/10.1016/S2213-8587(18)30153-0

Sunni L Mumford, PhD mumfords at mail.nih.gov, Rebecca A Garbose, MD, Keewan Kim, PhD, Kerri Kissell, MD, Daniel L Kuhr, MD, Ukpebo R Omosigho, MD, Neil J Perkins, PhD, Noya Galai, PhD, Robert M Silver, MD, Lindsey A Sjaarda, PhD, Torie C Plowden, MD, Enrique F Schisterman, PhD

PDF is available free at Sci-Hub   10.1016/S2213-8587(18)30153-0

Background
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.

Methods
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.

Findings
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]).

Interpretation
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.