Adequate Vitamin D Levels Prior to Conception Improve Birth Odds

Pam Harrison

June 11, 2018

Women with a history of pregnancy loss but who are not infertile are more likely to become pregnant and deliver a live infant if their preconception levels of vitamin D are sufficient, new research indicates.  

Vitamin D levels prior to conception also influenced the risk of pregnancy loss, the same analysis shows. 

"We are excited about the findings because vitamin D is easy to measure, and it's safe and relatively inexpensive to take supplementation, so it's an exciting field of research," author Robert M. Silver, MD, professor and chairman of obstetrics and gynecology, University of Utah, Salt Lake City, told Medscape Medical News

Silver cautioned, however, that "the association we observed does not yet prove that [vitamin D] supplementation will change outcomes," so more research is needed. 

The study was published online May 30 in the Lancet Diabetes & Endocrinology, by Sunni L. Mumford, PhD, of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, and colleagues.

Good Preconception Vitamin D Levels Tied to More Live Births

Although previous research in non-IVF populations has suggested a beneficial role of vitamin D, these studies typically recruited women in early pregnancy, and thus had limited ability to record and assess early pregnancy losses. Moreover, these studies did not take into account the importance of preconception health, say Mumford and colleagues.

So they carried out a secondary analysis of the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial.

EAGeR was originally designed to evaluate the effect of low-dose aspirin on reproductive outcomes in women with one to two previous pregnancy losses. Participants were recruited from June 15, 2007, to July 15, 2011, at four US clinical sites and followed for up to six menstrual cycles while attempting pregnancy and, if they conceived, throughout pregnancy.

Blood samples were collected both prior to randomization and at 8 weeks of gestation, and 25-hydroxyvitamin D (25[OH]D) levels were measured. 

A total of 1191 women had evaluable preconception 25[OH]D levels, and of these, 47% had adequate concentrations, defined as 75 nmol/L or more. The remaining 53% had insufficient levels of less than 75 nmol/L.

Interestingly, 91% of the cohort reported taking a multivitamin, and vitamin D levels were similar between multivitamin users and nonusers, the investigators point out.

They first observed that higher vitamin D concentrations prior to conception were associated with an increased likelihood of any pregnancy (as determined by human chorionic gonadotropin [hCG]). 

In an adjusted model, women with adequate preconception vitamin D concentrations were also more likely to achieve a clinical pregnancy, at a risk ratio (RR) of 1.10. 

Similarly, women with adequate preconception vitamin D concentrations were more likely to achieve a live birth, at an RR of 1.15, compared to women with insufficient vitamin D concentrations.

Although there was no significant difference in miscarriage rate between women with sufficient and insufficient preconception vitamin D levels, they "were lower in women with pregnancy losses than in those without," the study authors note, such that for each 25 nmol/L increase in 25[OH]D concentrations, the risk of pregnancy loss was lower, at an RR per 25 nmol/L of 0.88.

In contrast, early pregnancy concentrations of 25[OH]D were not associated with pregnancy loss after 8 weeks of gestation, the researchers say.

"Our data indicate...a potential beneficial role of preconception vitamin D status...a protective role for vitamin D in promoting pregnancy, which could have clinical implications for fertile couples attempting to conceive," they emphasize. 

Given that both 25[OH]D and calcitriol, its biologically active form, have immune-modulating functions, both forms of vitamin D might exert their favorable effects in pregnancy by ameliorating the maternal–fetal immunologic response, the researchers hypothesize, explaining that fetal survival depends on an immune-tolerant environment in the mother. 

Outcome Frequencies by Preconception Vitamin D Status

Outcome Insufficient preconception
25[OH]D level
(< 75 nmol/L)
Sufficient preconception
25[OH]D level
(
75 nmol/L)
P value
hCG-detected pregnancy, % 60 71 .0001
Clinical pregnancy, % 54 66 <.0001
Any pregnancy loss, % 15 16 NS
Live birth, % 44 54 .0009
hCG: human chorionic gonadotropin
NS: not significant

 

Silver suggests that the next step is to see whether women with low vitamin D levels have better pregnancy outcomes if they take vitamin D supplementation before becoming pregnant.

Currently, the American College of Obstetricians and Gynecologists does not recommend physicians routinely assess vitamin D levels in women wanting to conceive.

Further research is also needed to determine the optimal intake of vitamin D for healthy reproductive outcomes, Mumford and colleagues conclude.

The authors have reported no relevant financial relationships.

Lancet Diabetes Endocrinol. Published online May 30, 2018. Abstract

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