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Association of Bacterial Vaginosis and
Vitamin D Deficiency in Pregnancy:
What’s the Big
eal?
Anna Maya Powell, MD
Reproductive Infectious Disease Fellow
March 23, 2016
Disclosure
• I have no financial disclosures
• Study was funded by the W. K. Kellogg Foundation and by the South
Carolina Clinical & Translational Research (SCTR) Institute, with an academic
home at the Medical University of South Carolina, NIH/NCAT Grant number
UL1 TR000062.
• Vitamin D study drug and placebo provided by Church & Dwight.
Objective
• To investigate the association between bacterial
vaginosis and vitamin D deficiency in a prospective,
randomized cohort of pregnant patients
Introduction
What’s the Big
eal?
Vitamin D
• Pro-hormone
•
•
•
Important regulator of host immune response
Vitamin D influences innate and adaptive immune function of the female genital tract
[Aranow 2011]
Deficiency associated with increased susceptibility to gestational hypertension, preeclampsia, diabetes, and preterm delivery
• 78% of non-pregnant women
Vitamin D Deficiency in Pregnancy
• Deficiency in pregnant women is defined as a circulating 25(OH)D
level <40 ng/mL (100 nmol/L)
• Estimated to affect:
•
•
83% of pregnant women in 1st trimester
47% of pregnant women in 3rd trimester [Ginde 2009, Ginde 2010]
• Potentially avoidable large public health problem with low-cost
solution that may positively influence pregnancy outcomes
Bacterial Vaginosis (BV)
• Affects almost 30% of reproductive age women in US
• Dysbiosis caused by anaerobic overgrowth and loss of lactobacilli
• In pregnancy, has been associated with increased risk of preterm birth [Qin 2016,
Bodnar 2015], postpartum endometritis [Jacobsson 2002] and sexually transmitted
infections [Cherpes 2003, Weisenfeld 2003, Balkus 2014]
• Insufficient evidence that screening and treatment of asymptomatic BV reduces
incidence of preterm birth [McDonald 2007, Brocklehorst 2013]
• Prevention may be key
Vitamin D and Bacterial Vaginosis
• Maternal black race is a strong predictor for BV [Bodnar 2009, Davis
2010]
• Vitamin D deficiency (VDD) and BV are more common among in
black females
• Vitamin D deficiency appears to be an independent risk factor for
BV in first trimester pregnancy [Bodnar 2009]
High Dose Supplementation of Vitamin D to
non-pregnant women
• Turner et al randomized 118 symptomatic women with BV to BV treatment
plus 9 doses of 50,000 IU of cholecalciferol (vitamin D3) over 24 weeks
versus BV treatment plus placebo.
• Women in treatment group had significant increases in serum 25(OH)D
• BV recurrence was not reduced by vitamin D supplementation and time to
recurrence was 1 week shorter in treatment group.
Turner AN, Carr Reese P, Fields KS et al. A blinded, randomized controlled trial of high-dose vitamin D supplementation
to reduce recurrence of BV. Am J Obstet Gynecol 2014;211:479.e1-13.
Study Design
Kellogg Study
• Randomized controlled trial of vitamin D supplementation to a cohort of
healthy pregnant women (18-45 years) at MUSC
• 2012-2015: 257 women randomized to 400 IU versus 4400 IU vitamin D
formulation starting at 8-12 weeks gestation
• Pregnancy co-morbidities assessed included bacterial vaginosis
Vaginal self-swabs
• At visits 1, 4, and 7, subjects performed 3 vaginal
swabs
• 1st swab collected for gram stain
• 2nd swab collected for nucleic acid amplification test
• 3rd swab collected for evaluation of vaginal cytokines
Materials and Methods
Nugent Score Assignment1
Score
Morphotype
Lactobacillus
0
>30
1
5-30
2
1-4
3
<1
4
0
Gram variable rods
(Gardnerella,
Bacteroides)
Curved gram
negative bacilli
(Mobiluncus)
0
<1
1-4
5-30
>30
0
1-4
>5
http://www.uaz.edu.mx/histo/pathology/ed/ch_9b/c9b_clue.htm/
0-3
1Nugent
https://embryology.med.unsw.edu.au/embryology/index.php/File:Bacteria_-_gramstained_vaginal_smear_01.jpg
4-6
≥7
et al, 1991.
http://thunderhouse4-yuri.blogspot.com/2010/11/bacterial-vaginosis.html
257 patients randomized for trial
Excluded from BV analysis:
N=10 with SAB
N=3 with IUFD
Figure 1. Study Flow
245 patients analyzed for BV
study
Statistical Analysis
• Continuous variables are reported as mean values with standard
deviation and were analyzed using Student’s t-test and Wilcoxon
rank-sum tests
• Categorical variables were analyzed by Chi-square and Fisher’s
exact tests
• SAS 9.4 (Cary, NC) was used for statistical software
Definitions
• BMI categories:
• >40
• 30-40
• 20-30
• <20
• Vitamin D categories (ng/mL):
• <20
• <40
• >40
Results
Table 1. Maternal characteristics with and
without BV at baseline
Table 2. Study participants with and without
BV development
Factors associated with VD deficiency
• Among study participants, Caucasian women were significantly
more likely to have vitamin D level >40 throughout pregnancy
(p<0.0001)
• Vitamin D category (<40 ng/mL) significantly decreased over time
and differed by treatment group
• Younger women were more likely to have VD <20 ng/mL (p
<0.0005)
Distribution of Baseline Vitamin D (ng/mL) by
BV classification at visit 1
Distribution of Age by Vitamin D category
VDcat 1=
<20 ng/mL
VDcat 2=
<40 ng/mL
VDcat3=
>40 ng/mL
Mixed regression model
AA race had an odds ratio of 3.1 ( 95% CI 1.9-5.02) of bacterial vaginosis incidence
BMI >40 approached significance with BV (p=0.094)
Summary of Results
• African American women were more likely to have BV at pregnancy baseline
• Women with BV at start were more likely to have a lower mean vitamin D
level
• In univariate analysis, no significant differences in BMI; BMI >40 approached
significance in logistic modeling and may represent confounder
• No significant differences in pregnancy outcomes among women who
started with or developed BV in pregnancy
• No significant decrease in BV incidence in higher vitamin D
supplementation group
Discussion
Does vitamin D treatment prevent BV?
• While there may be an association between race
and BV prevalence, vitamin D supplementation
does not appear to prevent BV development in
pregnancy
Acknowledgments
Thank you!
• Dr Carol Wagner
• Judy Shary
• Dr Lisa Steed
References
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Nugent PR, Krohn MA, and Hillier SL. 1991. Reliability of diagnosing bacterial vaginosis is improved by a standardized method of Gram stain interpretation. J. Clin.
Microbiol. 29:297-301.
Jacobsson B, Pernevi P, Chidekel L, Jörgen Platz-Christensen J. Bacterial vaginosis in early pregnancy may predispose for preterm birth and postpartum endometritis.
Acta Obstet Gynecol Scand. 2002 Nov;81(11):1006-10.
Cherpes TL, Meyn LA, Krohn MA et al. Association between acquisition of herpes simplex virus type 2 in women and bacterial vaginosis. Clin Inf Dis 2003;37(3)319
Wiesenfeld, HL, Hillier SL, Krohn MA, Landers DV, Sweet RL. Bacterial vaginosis is a strong predictor of Neisseria gonorrheae and Chlamydia trachomatis infection.
Clin Inf Dis 2003;36(5):663.
Balkus JE, Richardson BA, Rabe LK, Taha TE, Mgodi N, Kasaro MP, Ramjee G, Hoffman IF, Abdool Karim SS. Bacterial vaginosis and the risk of trichomonas vaginalis
acquisition among HIV-1-negative women. Sex Transm Dis. 2014;41 (2)123.
Bodnar L, Krohn MA, Simhan HN. Maternal Vitamin D deficiency is associated with bacterial vaginosis in the first trimester of pregnancy. J Nutr. 2009 Jun;139(6):115761.
Hensel KJ, Randis TM, Gelber SE, Ratner AJ. Pregnancy-specific association of vitamin D deficiency and bacterial vaginosis. Am J Obstet Gynecol 2001;204:41.e1-9.
Brocklehurst P, Gordon A, Heatley E, Milan SJ. Antibiotics for treating bacterial vaginosis in pregnancy. Cochrane Database of Systematic Reviews 2013, Issue 1.
Qin LL, Lu FG, Yang SH, Xu HL, Luo BA. Does Maternal Vitamin D deficiency Increase the Risk of Preterm Birth: A Meta-Analysis of Observational Studies. Nutrients
2016 May 20;8(5.)
Bodnar LM, Platt RW, Simhan HN. Early-pregnancy vitamin D deficiency and risk of preterm birth subtypes. Obstet Gynecol 2015 Feb;125(2):439-47.