Ashlyn Oakes

Vitamin B deficiency could increase pregnant women’s risk of delivering preterm, a new meta-analysis finds.

The study, which was published on Feb. 1 in the American Journal of Epidemiology, assessed data from 18 independent studies in order to measure the effect of vitamin B12 on gestation period and birth weight.

First and corresponding author Tormod Rogne began the study in 2013 while researching at Yale under epidemiology professor Michael Bracken SPH ’70. Bracken taught him methods of systematic review and meta-analysis, Rogne said.

“We found that there was a more clear-cut association between B12 deficiency and shorter length of gestation, as opposed to vitamin B deficiency and risk of low birth weight,” he said.

Rogne said the team initially hypothesized that a lack of vitamin B12 could detrimentally affect growth in the womb, based on experimental studies highlighting B12’s importance in cellular growth and differentiation.

Ultimately, though, the researchers did not find a linear association between maternal levels of B12 and birth weight but instead saw a correlation between B12 deficiency and low birth weight. They also observed a linear association between maternal levels of the vitamin and length of gestation, which goes hand in hand with low birth weight.

“There are two major contributing factors to low birth weight: You have either preterm birth or fetal growth restriction,” Rogne said, adding that the team interpreted the observed increased risk of low birth weight as a result of a shorter period of gestation rather than restricted fetal growth.

According to the meta-analysis, few studies have looked at vitamin B12, and recent analyses have been inconclusive concerning the vitamin’s role in preterm and low-weight birth. Twenty-four researchers from the Yale School of Public Health and institutions in Norway and the Netherlands collaborated to obtain original data from the studies selected for the meta-analysis, as well as to address as many possible confounders as was pragmatic, Rogne said.

The 18 studies included in the analysis spanned 11 different countries of varying ethnicities and national incomes. In each study, pregnant women’s blood was routinely screened for concentration of vitamin B12 as they progressed throughout their pregnancies.

Rogne said that while the team cannot report any causal relationship, they can point to an association based on data from observational studies. However, assuming that B12 deficiency is actually causally related to risk of preterm birth, there is reason to conduct randomized control trials with vitamin B12 supplements, which is the “next logical step,” he added.

“If vitamin B12 were shown to be important for improving pregnancy outcomes, then supplementation would be especially important in some [developing] countries where natural [B12] levels are low,” said Bracken, a co-author of the study. “But first, large-scale trials are needed to document the efficacy and safety of B12. The published work provides the support for launching such trials.”

“Limitations of the study may include not adjusting for all possible confounders, like socioeconomic status and nutritional intake,” Rogne said.

Additionally, vitamin B12 deficiency may be a symptom of an underlying nutritional problem rather than being the cause of preterm birth, according to the meta-analysis.

Rogne said he hopes other researchers take note of the study and conduct further trials, but added that people should read the paper with “healthy skepticism.”

“Even though we found an association, there might be that, in proof, there is no association, but we have highlighted that this is a topic that needs further evaluation, and we hope that we have contributed so that others will conduct a large randomized control trial,” he said.

In 2015, preterm birth affected one out of every 10 babies born in the United States, and the preterm birth rate among African-American women was roughly 50 percent higher than that of white women, according to the Centers for Disease Control and Prevention.