Expectant moms with low vitamin D levels at risk of miscarriage

Pregnant women with vitamin D deficiency run the risk of losing their foetuses in the womb, according to a meta-analysis.

Out of the 10 studies included (four trials n=666; six observational studies n=6,997), four found that women with blood vitamin D levels <50 nmol/L (deficient) had about twofold greater odds of miscarrying than those with >75 nmol/L (replete; odds ratio [OR], 1.94, 95 percent confidence interval [CI], 1.25–3.02; n=3,674; I², 18 percent). [Fertil Steril 2022;doi:10.1016/j.fertnstert.2022.04.017]

This risk increase persisted when women with insufficient vitamin D levels (50–75 nmol/L) were included (OR, 1.60, 95 percent CI, 1.11–2.30; six studies; n=6,338; I², 35 percent).

“Our study adds to previous meta-analysis data, focusing specifically on early pregnancy vitamin D assessment and miscarriage. Although a nonsignificant summary risk ratio (RR) for spontaneous abortion (1.04, 95 percent CI, 0.95–1.13) was previously identified, this likely reflects the sample size with only three eligible studies,” according to the investigators. [PLoS One 2017;12e0173605]

Placental dysregulation

Vitamin D’s role in pregnancy and miscarriage is supported by the presence of key vitamin D metabolic enzymes and the vitamin D receptor in the endometrium and first trimester placentae, the investigators pointed out. [Reprod Biol Endocrinol 2020;18:24; Am J Pathol 2002;161:105-114]

Previous studies provide evidence that the human placenta is a key tissue for the accumulation of both 25(OH)D and active 1,25-dihydroxyvitamin D (1,25(OH)2D), having the potential to influence trophoblast invasion, placental spiral artery remodeling, and immune cell function—processes that are impaired in human miscarriage. [Placenta 2015;36:403-409; J Endocrinol 2018;236:R93-R103; Front Cell Dev Biol 2020;8:601043]

“It is, therefore, possible that a low serum 25(OH)D level contributes to miscarriage pathophysiology via a concomitant decrease in placental 1,25(OH)2D and resultant placental dysregulation,” the investigators said.

They noted that, to date, there is still no concrete evidence that addresses whether preconception vitamin D status differentially affects the first and second trimester loss outcomes individually for women with recurrent miscarriage and spontaneous loss.

Intervention studies needed

“So, far, vitamin D was only known for its role to prevent late pregnancy complications. This review supports a new perspective on vitamin D in early pregnancy and could help inform women regarding the benefits of early supplementation and treatment compliance,” they added.

The investigators, however, acknowledged that the overall study quality was “low” or “very low” according to the Grading of Recommendations, Assessment, Development and Evaluations approach.

“Our review found insufficient evidence to accurately assess whether vitamin D treatment reduces the risk of spontaneous miscarriage or recurrent miscarriage. The trials identified, although inclusive of women with recurrent miscarriage, were confounded by a small sample size, varying interventional regimes, and high risk of bias,” the investigators said.

They called for well-designed, prospective trials to evaluate the potential benefit of preconception and the first trimester vitamin D treatment for women who are vitamin D deficient.