The Gestational Vaginal Microbiome and Spontaneous Preterm Birth among Nulliparous African American Women

Abstract

Introduction Early markers to identify pregnant women at high risk for spontaneous preterm birth (SPTB) have not been established and preventive options are limited. Recent attention has focused on examining the importance of characterizing the vaginal microbiome to predict SPTB.

Results We examined the diversity and structure of the vaginal microbiome in nulliparous African American women during early pregnancy and compared 13 women who delivered preterm and 27 women who delivered at term. Samples were taken at one of two points in gestation, before 16 weeks or between 20 and 24 weeks. Among women who delivered preterm, we found lower bacterial diversity with lower abundance of Coriobacteriaceae, Sneathia, Prevotella, and Aerococcus compared with women delivering at term (linear discriminant analysis score > 3.0). The Shannon diversity index was not significantly different between the groups (p-value = 0.239). Phylogenetic diversity and Chao1 suggested a lower diversity in the vaginal microbiota of women who delivered preterm compared with term, but these findings were not significantly different (p = 0.077 and p = 0.066, respectively).

Conclusion These data suggest that the vaginal microbiome of women delivering preterm had lower diversity than women delivering after 37 weeks, although these findings need to be explored in a larger sample of nulliparous African American women.

Keywords

vaginal microbiome - spontaneous preterm birth - diversity - Coriobacteriaceae - Sneathia - Prevotella - Aerococcus

• References

• 1 Hodek J-M, von der Schulenburg J-M, Mittendorf T. Measuring economic consequences of preterm birth - methodological recommendations for the evaluation of personal burden on children and their caregivers. Health Econ Rev 2011; 1 (1) 6
• 2 Martin JA, Hamilton BE, Osterman MJK, Curtin SC, Matthews TJ. Births: final data for 2012. Natl Vital Stat Rep 2013; 62 (9) 1-68
• 3 Matthews TJ, MacDorman MF. Infant mortality statistics from the 2010 period linked birth/infant death data set. Natl Vital Stat Rep 2013; 62 (8) 1-26
• 4 Howson CP, Kinney MV, McDougall L, Lawn JE ; Born Too Soon Preterm Birth Action Group. Born too soon: preterm birth matters. Reprod Health 2013; 10 (Suppl. 01) S1
• 5 Drassinower D, Običan SG, Siddiq Z, Heller D, Gyamfi-Bannerman C, Friedman AM. Does the clinical presentation of a prior preterm birth predict risk in a subsequent pregnancy?. Am J Obstet Gynecol 2015; 213 (5) 686.e1-686.e7
• 6 Bafghi AST, Bahrami E, Sekhavat L. Comparative study of vaginal versus intramuscular progesterone in the prevention of preterm delivery: a randomized clinical trial. Electron Physician 2015; 7 (6) 1301-1309
• 7 Romero R, Hassan SS, Gajer P , et al. The vaginal microbiota of pregnant women who subsequently have spontaneous preterm labor and delivery and those with a normal delivery at term. Microbiome 2014; 2 (1) 18
• 8 DiGiulio DB, Callahan BJ, McMurdie PJ , et al. Temporal and spatial variation of the human microbiota during pregnancy. Proc Natl Acad Sci U S A 2015; 112 (35) 11060-11065
• 9 Menard JP, Mazouni C, Salem-Cherif I , et al. High vaginal concentrations of Atopobium vaginae and Gardnerella vaginalis in women undergoing preterm labor. Obstet Gynecol 2010; 115 (1) 134-140
• 10 Nelson DB, Hanlon A, Hassan S , et al. Preterm labor and bacterial vaginosis-associated bacteria among urban women. J Perinat Med 2009; 37 (2) 130-134
• 11 DiGiulio DB, Romero R, Kusanovic JP , et al. Prevalence and diversity of microbes in the amniotic fluid, the fetal inflammatory response, and pregnancy outcome in women with preterm pre-labor rupture of membranes. Am J Reprod Immunol 2010; 64 (1) 38-57
• 12 Wilks M, Wiggins R, Whiley A , et al. Identification and H(2)O(2) production of vaginal lactobacilli from pregnant women at high risk of preterm birth and relation with outcome. J Clin Microbiol 2004; 42 (2) 713-717
• 13 Subramaniam A, Kumar R, Cliver SP , et al. Vaginal microbiota in pregnancy: evaluation based on vaginal flora, birth outcome, and race. Am J Perinatol 2015;
• 14 Hyman RW, Fukushima M, Jiang H , et al. Diversity of the vaginal microbiome correlates with preterm birth. Reprod Sci 2014; 21 (1) 32-40
• 15 Royce RA, Jackson TP, Thorp Jr JM , et al. Race/ethnicity, vaginal flora patterns, and pH during pregnancy. Sex Transm Dis 1999; 26 (2) 96-102
• 16 Nelson DB, Bellamy S, Gray TS, Nachamkin I. Self-collected versus provider-collected vaginal swabs for the diagnosis of bacterial vaginosis: an assessment of validity and reliability. J Clin Epidemiol 2003; 56 (9) 862-866
• 17 Menard J-P, Fenollar F, Raoult D, Boubli L, Bretelle F. Self-collected vaginal swabs for the quantitative real-time polymerase chain reaction assay of Atopobium vaginae and Gardnerella vaginalis and the diagnosis of bacterial vaginosis. Eur J Clin Microbiol Infect Dis 2012; 31 (4) 513-518
• 18 Nugent RP, Krohn MA, Hillier SL. Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain interpretation. J Clin Microbiol 1991; 29 (2) 297-301
• 19 Caporaso JG, Lauber CL, Walters WA , et al. Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms. ISME J 2012; 6 (8) 1621-1624
• 20 Caporaso JG, Kuczynski J, Stombaugh J , et al. QIIME allows analysis of high-throughput community sequencing data. Nat Methods 2010; 7 (5) 335-336
• 21 Lozupone C, Hamady M, Knight R. UniFrac—an online tool for comparing microbial community diversity in a phylogenetic context. BMC Bioinformatics 2006; 7: 371
• 22 Clarke KR. Non-parametric multivariate analyses of changes in community structure. Austral Ecol 1993; 18 (1) 117-143
• 23 Anderson MJ. A new method for non-parametric multivariate analysis of variance. Austral Ecol 2001; 26 (1) 32-46
• 24 Segata N, Izard J, Waldron L , et al. Metagenomic biomarker discovery and explanation. Genome Biol 2011; 12 (6) R60
• 25 Ravel J, Gajer P, Abdo Z , et al. Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci U S A 2011; 108 (Suppl. 01) 4680-4687
• 26 Nelson DB, Hanlon A, Nachamkin I , et al. Early pregnancy changes in bacterial vaginosis-associated bacteria and preterm delivery. Paediatr Perinat Epidemiol 2014; 28 (2) 88-96
• 27 Verstraelen H, Verhelst R, Claeys G, De Backer E, Temmerman M, Vaneechoutte M. Longitudinal analysis of the vaginal microflora in pregnancy suggests that L. crispatus promotes the stability of the normal vaginal microflora and that L. gasseri and/or L. iners are more conducive to the occurrence of abnormal vaginal microflora. BMC Microbiol 2009; 9: 116
• 28 Nelson DB, Hanlon AL, Wu G, Liu C, Fredricks DN. First trimester levels of BV-associated bacteria and risk of miscarriage among women early in pregnancy. Matern Child Health J 2015; 19 (12) 2682-2687
• 29 Forney LJ, Gajer P, Williams CJ , et al. Comparison of self-collected and physician-collected vaginal swabs for microbiome analysis. J Clin Microbiol 2010; 48 (5) 1741-1748
• 30 Ma J, Coarfa C, Qin X , et al. mtDNA haplogroup and single nucleotide polymorphisms structure human microbiome communities. BMC Genomics 2014; 15: 257
• 31 Fettweis JM, Brooks JP, Serrano MG , et al. Vaginal Microbiome Consortium, Jefferson KK, Buck GA. Differences in vaginal microbiome in African American women versus women of European ancestry. Microbiology 2014; 160 (Pt 10): 2272-2282