Low vitamin D in pregnancy linked to potentially harmful vaginal bacteria in black women

May 29, 2019

Vitamin D, sometimes known as the sunshine vitamin, has long been known to be important for a healthy pregnancy. Pregnant mothers take vitamin D supplements to ensure their own health and that of their unborn child.

But how does vitamin D affect the bacteria residing in the vagina, known as the vaginal microbiome, during pregnancy?

That depends on the mother's race, according to a recent study by researchers at the Medical University of South Carolina (MUSC) and Virginia Commonwealth University (VCU).

Their findings, published online in March in the Journal of Perinatology, are being featured as part of a collection of manuscripts from the integrative Human Microbiome Project (iHMP/HMP2) published today in the Nature family of journals.

The natural microbiome is made up of "friendly bacteria" that help prevent infection by harmful microbes. Disruptions of that natural microbiome can leave women vulnerable to infection.

The research team showed that the makeup of bacteria in the vaginal microbiome differed between black women with lower vitamin D and white women with higher vitamin D.

In the MUSC trial of 387 healthy pregnant women of diverse ethnicity, black women with lower levels of vitamin D during pregnancy had more Megasphaera - a type of bacteria linked to bacterial vaginosis, which is a common dysbiosis or disorder in the vaginal canal. In contrast, white women with higher levels of vitamin D had more lactobacilli, a type of bacteria that promotes vaginal health. The study did not find any bacteria significantly associated with vitamin D status in Hispanic women. The Kellogg Foundation and the National Institutes of Health (NIH) funded the trial.

Bacterial vaginosis, which is the disruption of a healthy vaginal microbiome, can increase the risk for infertility, spontaneous abortion, and preterm birth.

Black women are twice as likely to be diagnosed with bacterial vaginosis. According to the Centers for Disease Control and Prevention, they are more than twice as likely to give birth early preterm - less than 33 weeks into pregnancy - than white women. Black women are also more likely to be deficient in vitamin D.

"If you have a rich, darker pigment, you need more sunlight exposure to penetrate through the melanin in your skin to activate the conversion of 7-dehydrocholesterol to vitamin D," explains Carol Wagner, M.D., a neonatologist at MUSC Children's Health who led the study.

Wagner teamed up with Kimberly Jefferson, Ph.D., a bacteriologist at VCU, to investigate a possible link between racial disparities in vitamin D deficiency, bacterial vaginosis, and pregnancy outcomes.

A team of investigators at VCU, which includes Jefferson, Gregory Buck, Ph.D., and Jerome Strauss, M.D., Ph.D., lead the NIH Human Microbiome Project-funded study "Multi-Omic Microbiome Study: Pregnancy Initiative (MOMS-PI)." The study is focused on the role of the vaginal microbiome in pregnancy.

"An association between vitamin D deficiency and bacterial vaginosis has been observed in the past," says Jefferson.

"We wanted to know whether certain bacterial taxa could be implicated and whether these taxa were associated with preterm birth."

Women enrolled in the MUSC trial were followed from their first trimester until delivery. One group of women took 400 international units (IU) of vitamin D per day, which is the average dose found in prenatal vitamins. The other group took 4400 IU per day. Wagner and her colleagues have previously shown that to be a safe and effective dose for achieving vitamin D sufficiency in pregnant women, regardless of race.

The researchers evaluated vitamin D status monthly by measuring levels of a vitamin D metabolite. The South Carolina Clinical & Translational Research (SCTR) Institute's Research Nexus provided laboratory support. Vaginal swabs were taken at each visit, and samples were sent to VCU for analysis.

On average, women taking the 4400 IU supplement per day achieved greater than 40 ng/mL of the metabolite by the end of the study, which is a healthy range for pregnant women. These women had vaginal microbiomes with higher levels of healthy lactobacillus bacteria compared to women with <30 ng>

One bacterial species linked to bacterial vaginosis, G. vaginalis, decreased significantly over the course of the study for women in both groups.

"Certain, potentially harmful bacteria become reduced in abundance as pregnancy progresses," says Jefferson.

"This may be a defense mechanism that has evolved to protect the growing fetus during pregnancy."

Though low levels of the vitamin D metabolite were associated with a genus of bacteria related to bacterial vaginosis in black women, the study did not provide evidence that vitamin D deficiency directly causes bacterial vaginosis.

This is perhaps because few women in this study were profoundly deficient in vitamin D. Since 2015, women at greatest risk of vitamin D deficiency have been identified during their prenatal visit at MUSC and prescribed supplements.

"We typically see the dramatic changes in the women who are most deficient and then you make them replete," says Wagner.

"We had far fewer women in this study who were profoundly vitamin D deficient, which is a good thing but can blunt the treatment effect."

Based on this study and her previous research, Wagner advocates for women, especially black women, to be mindful of their vitamin D status during pregnancy.

"Women who are thinking about getting pregnant or are early in their pregnancy, especially black women, need to think about vitamin D status and that vitamin D affects many systems in the body," explains Wagner.

"We really want women to be replete and ideally to have a level around 40 ng/mL, because it will not only affect their vaginal microbiome, but really more importantly their placental function and immune function."

Jefferson plans to continue exploring the relationships between vitamin D and the vaginal microbiome.

"We want to know how the body protects itself from potentially harmful infectious agents during pregnancy," says Jefferson.

"Our understanding of the relationship between the human host and the microbiome of the reproductive tract is in its infancy but, as we increase our knowledge in this area, we hope to reduce the ethnic disparity in preterm birth and empower women to achieve healthier pregnancies."
The content of the article summarized by this release is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

About MUSC and MUSC Health

Founded in 1824 in Charleston, MUSC is the oldest medical school in the South, as well as the state's only integrated, academic health sciences center with a unique charge to serve the state through education, research and patient care. Each year, MUSC educates and trains more than 3,000 students and 700 residents in six colleges: Dental Medicine, Graduate Studies, Health Professions, Medicine, Nursing and Pharmacy. The state's leader in obtaining biomedical research funds, in fiscal year 2018, MUSC set a new high, bringing in more than $276.5 million. For information on academic programs, visit http://musc.edu.

As the clinical health system of the Medical University of South Carolina, MUSC Health is dedicated to delivering the highest quality patient care available, while training generations of competent, compassionate health care providers to serve the people of South Carolina and beyond. Comprising some 1,600 beds, more than 100 outreach sites, the MUSC College of Medicine, the physicians' practice plan, and nearly 275 telehealth locations, MUSC Health owns and operates eight hospitals situated in Charleston, Chester, Florence, Lancaster and Marion counties. In 2018, for the fourth consecutive year, U.S. News & World Report named MUSC Health the number one hospital in South Carolina. To learn more about clinical patient services, visit http://muschealth.org.

MUSC and its affiliates have collective annual budgets of $3 billion. The more than 17,000 MUSC team members include world-class faculty, physicians, specialty providers and scientists who deliver groundbreaking education, research, technology and patient care.

About VCU and VCU Health

Virginia Commonwealth University is a major, urban public research university with national and international rankings in sponsored research. Located in downtown Richmond, VCU enrolls more than 31,000 students in 217 degree and certificate programs in the arts, sciences and humanities. Thirty-eight of the programs are unique in Virginia, many of them crossing the disciplines of VCU's 11 schools and three colleges. The VCU Health brand represents the VCU health sciences academic programs, the VCU Massey Cancer Center and the VCU Health System, which comprises VCU Medical Center (the only academic medical center and Level I trauma center in the region), Community Memorial Hospital, Children's Hospital of Richmond at VCU, MCV Physicians and Virginia Premier Health Plan. For more, please visit http://www.vcu.edu and vcuhealth.org.

About the South Carolina Clinical & Translational Research Institute

The South Carolina Clinical and Translational Research Institute (SCTR), a National Institutes of Health Clinical and Translational Science Awards hub, is the catalyst for changing the culture of biomedical research, facilitating sharing of resources and expertise, and streamlining research -related processes to bring about large-scale, change in the clinical and translational research efforts in South Carolina. Our vision is to improve health outcomes and quality of life for the population through discoveries translated into evidence-based practice. For more information, visit https://research.musc.edu/resources/sctr.

Medical University of South Carolina

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