Effect of a Nonoptimal Cervicovaginal Microbiota and Psychosocial Stress on Recurrent Spontaneous Preterm BirthFunding This study was funded by NIH R01NR014784 (M.A.E.) and K23 ES022242 (H.H.B.). Funding sources had no role in study design, in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.
Objective While select cervicovaginal microbiota and psychosocial factors have been associated with spontaneous preterm birth, their effect on the risk of recurrence remains unclear. It is also unknown whether psychosocial factors amplify underlying biologic risk. This study sought to determine the effect of nonoptimal cervicovaginal microbiota and perceived stress on the risk of recurrent spontaneous preterm birth.
Study Design This was a secondary analysis of a prospective pregnancy cohort, Motherhood and Microbiome. The Cohen's Perceived Stress Scale (PSS-14) was administered and cervical swabs were obtained between 16 and 20 weeks of gestation. PSS-14 scores ≥30 reflected high perceived stress. We analyzed cervicovaginal microbiota using 16S rRNA sequencing and classified microbial communities into community state types (CSTs). CST IV is a nonoptimal cervicovaginal microbial community characterized by anaerobes and a lack of Lactobacillus. The final cohort included a predominantly non-Hispanic Black population of women with prior spontaneous preterm birth who had recurrent spontaneous preterm birth or term birth and had stress measurements (n = 181). A subanalysis was performed in the subset of these women with cervicovaginal microbiota data (n = 74). Multivariable logistic regression modeled adjusted associations between CST IV and recurrent spontaneous preterm birth, high stress and recurrent spontaneous preterm birth, as well as high stress and CST IV.
Results Among the 181 women with prior spontaneous preterm birth, 45 (24.9%) had high perceived stress. We did not detect a significant association between high stress and recurrent spontaneous preterm birth (adjusted odds ratio [aOR] 1.67, 95% confidence interval [CI]: 0.73–3.85). Among the 74 women with prior spontaneous preterm birth and cervicovaginal microbiota analyzed, 29 (39.2%) had CST IV; this proportion differed significantly among women with recurrent spontaneous preterm birth (51.4%) compared with women with term birth (28.2%) (p = 0.04). In models adjusted for race and marital status, the association between CST IV and recurrent spontaneous preterm birth persisted (aOR 3.58, 95% CI: 1.25–10.24). There was no significant interaction between stress and CST IV on the odds of spontaneous preterm birth (p = 0.328). When both stress and CST IV were introduced into the model, their associations with recurrent spontaneous preterm birth were slightly stronger than when they were in the model alone. The aOR for stress with recurrent spontaneous preterm birth was 2.02 (95% CI: 0.61–6.71) and for CST IV the aOR was 3.83 (95% CI: 1.30–11.33). Compared to women with neither of the two exposures, women with both high stress and CST IV had the highest odds of recurrent spontaneous preterm birth (aOR = 6.01, 95% CI: 1.002–36.03).
Conclusion Among a predominantly non-Hispanic Black cohort of women with a prior spontaneous preterm birth, a nonoptimal cervicovaginal microbiota is associated with increased odds of recurrent spontaneous preterm birth. Adjustment for perceived stress may amplify associations between CST IV and recurrent spontaneous preterm birth. Identification of modifiable social or behavioral factors may unveil novel nonpharmacologic interventions to decrease recurrent spontaneous preterm birth among women with underlying biologic risk.
CST IV, a nonoptimal microbiota, is associated with increased odds of recurrent spontaneous preterm birth.
Adjustment for perceived stress amplified associations between CST IV and recurrent spontaneous preterm birth.
Identification of modifiable psychosocial factors may unveil novel nonpharmacologic interventions to decrease recurrent preterm birth.
Keywordscervicovaginal microbiota - microbiome - perceived maternal stress - spontaneous preterm birth - recurrent spontaneous preterm birth
Received: 20 July 2020
Accepted: 22 August 2020
08 October 2020 (online)
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- 1 Elovitz MA, Gajer P, Riis V. et al. Cervicovaginal microbiota and local immune response modulate the risk of spontaneous preterm delivery. Nat Commun 2019; 10 (01) 1305
- 2 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
- 3 Callahan BJ, DiGiulio DB, Goltsman DSA. et al. Replication and refinement of a vaginal microbial signature of preterm birth in two racially distinct cohorts of US women. Proc Natl Acad Sci U S A 2017; 114 (37) 9966-9971
- 4 Stout MJ, Zhou Y, Wylie KM, Tarr PI, Macones GA, Tuuli MG. Early pregnancy vaginal microbiome trends and preterm birth. Am J Obstet Gynecol 2017; 217 (03) 356.e1-356.e18
- 5 Brown RG, Chan D, Terzidou V. et al. Prospective observational study of vaginal microbiota pre- and post-rescue cervical cerclage. BJOG 2019; 126 (07) 916-925
- 6 Kindinger LM, MacIntyre DA, Lee YS. et al. Relationship between vaginal microbial dysbiosis, inflammation, and pregnancy outcomes in cervical cerclage. Sci Transl Med 2016; 8 (350) 350ra102
- 7 Kindinger LM, Bennett PR, Lee YS. et al. The interaction between vaginal microbiota, cervical length, and vaginal progesterone treatment for preterm birth risk. Microbiome 2017; 5 (01) 6
- 8 Fettweis JM, Serrano MG, Brooks JP. et al. The vaginal microbiome and preterm birth. Nat Med 2019; 25 (06) 1012-1021
- 9 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
- 10 Gajer P, Brotman RM, Bai G. et al. Temporal dynamics of the human vaginal microbiota. Sci Transl Med 2012; 4 (132) 132ra52
- 11 Borgdorff H, Verwijs MC, Wit FWNM. et al. The impact of hormonal contraception and pregnancy on sexually transmitted infections and on cervicovaginal microbiota in African sex workers. Sex Transm Dis 2015; 42 (03) 143-152
- 12 MacIntyre DA, Chandiramani M, Lee YS. et al. The vaginal microbiome during pregnancy and the postpartum period in a European population. Sci Rep 2015; 5: 8988
- 13 Vodstrcil LA, Twin J, Garland SM. et al. The influence of sexual activity on the vaginal microbiota and Gardnerella vaginalis clade diversity in young women. PLoS One 2017; 12 (02) e0171856
- 14 Ravel J, Brotman RM, Gajer P. et al. Daily temporal dynamics of vaginal microbiota before, during and after episodes of bacterial vaginosis. Microbiome 2013; 1 (01) 29
- 15 Brooks JP, Buck GA, Chen G. et al. Changes in vaginal community state types reflect major shifts in the microbiome. Microb Ecol Health Dis 2017; 28 (01) 1303265
- 16 McDonald SW, Kingston D, Bayrampour H, Dolan SM, Tough SC. Cumulative psychosocial stress, coping resources, and preterm birth. Arch Women Ment Health 2014; 17 (06) 559-568
- 17 Shapiro GD, Fraser WD, Frasch MG, Séguin JR. Psychosocial stress in pregnancy and preterm birth: associations and mechanisms. J Perinat Med 2013; 41 (06) 631-645
- 18 Loomans EM, van Dijk AE, Vrijkotte TGM. et al. Psychosocial stress during pregnancy is related to adverse birth outcomes: results from a large multi-ethnic community-based birth cohort. Eur J Public Health 2013; 23 (03) 485-491
- 19 Staneva A, Bogossian F, Pritchard M, Wittkowski A. The effects of maternal depression, anxiety, and perceived stress during pregnancy on preterm birth: a systematic review. Women Birth 2015; 28 (03) 179-193
- 20 Nkansah-Amankra S, Luchok KJ, Hussey JR, Watkins K, Liu X. Effects of maternal stress on low birth weight and preterm birth outcomes across neighborhoods of South Carolina, 2000-2003. Matern Child Health J 2010; 14 (02) 215-226
- 21 Seravalli L, Patterson F, Nelson DB. Role of perceived stress in the occurrence of preterm labor and preterm birth among urban women. J Midwifery Womens Health 2014; 59 (04) 374-379
- 22 Ruiz RJ, Fullerton J, Brown CEL, Schoolfield J. Relationships of cortisol, perceived stress, genitourinary infections, and fetal fibronectin to gestational age at birth. Biol Res Nurs 2001; 3 (01) 39-48
- 23 Gennaro S, Shults J, Garry DJ. Stress and preterm labor and birth in Black women. J Obstet Gynecol Neonatal Nurs 2008; 37 (05) 538-545
- 24 Yonkers KA, Smith MV, Forray A. et al. Pregnant women with posttraumatic stress disorder and risk of preterm birth. JAMA Psychiatry 2014; 71 (08) 897-904
- 25 Dole N, Savitz DA, Hertz-Picciotto I, Siega-Riz AM, McMahon MJ, Buekens P. Maternal stress and preterm birth. Am J Epidemiol 2003; 157 (01) 14-24
- 26 Lobel M, Cannella DL, Graham JE, DeVincent C, Schneider J, Meyer BA. Pregnancy-specific stress, prenatal health behaviors, and birth outcomes. Health Psychol 2008; 27 (05) 604-615
- 27 Amabebe E, Anumba DOC. Psychosocial stress, cortisol levels, and maintenance of vaginal health. Front Endocrinol (Lausanne) 2018; 9: 568
- 28 Guendelman S, Kosa JL, Pearl M, Graham S, Kharrazi M. Exploring the relationship of second-trimester corticotropin releasing hormone, chronic stress and preterm delivery. J Matern Fetal Neonatal Med 2008; 21 (11) 788-795
- 29 Levine TA, Alderdice FA, Grunau RE, McAuliffe FM. Prenatal stress and hemodynamics in pregnancy: a systematic review. Arch Women Ment Health 2016; 19 (05) 721-739
- 30 Ruiz RJ, Gennaro S, O'Connor C. et al. CRH as a predictor of preterm birth in minority women. Biol Res Nurs 2016; 18 (03) 316-321
- 31 Shapiro GD, Séguin JR, Muckle G, Monnier P, Fraser WD. Previous pregnancy outcomes and subsequent pregnancy anxiety in a Quebec prospective cohort. J Psychosom Obstet Gynaecol 2017; 38 (02) 121-132
- 32 Laughon SK, Albert PS, Leishear K, Mendola P. The NICHD Consecutive Pregnancies Study: recurrent preterm delivery by subtype. Am J Obstet Gynecol 2014; 210 (02) 131.e1-131.e8
- 33 Meis PJ, Klebanoff M, Thom E. et al. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Engl J Med 2003; 348 (24) 2379-2385
- 34 Blackwell SC, Gyamfi-Bannerman C, Biggio JR. et al. 17-OHPC to prevent recurrent preterm birth in singleton gestations (PROLONG Study): a multicenter, international, randomized double-blind trial. Am J Perinatol 2019; 37 (02) 127-136
- 35 Cohen S, Kamarck T, Mermelstein R. A global measure of perceived stress. J Health Soc Behav 1983; 24 (04) 385-396
- 36 Silveira ML, Pekow PS, Dole N, Markenson G, Chasan-Taber L. Correlates of high perceived stress among pregnant Hispanic women in Western Massachusetts. Matern Child Health J 2013; 17 (06) 1138-1150
- 37 Faulkner JR, Minin VN. Locally adaptive smoothing with Markov random fields and shrinkage priors. Bayesian Anal 2018; 13 (01) 225-252
- 38 Grobman WA, Parker CB, Willinger M. et al. Eunice Kennedy Shriver National Institute of Child Health and Human Development Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b) Network*. Racial disparities in adverse pregnancy outcomes and psychosocial stress. Obstet Gynecol 2018; 131 (02) 328-335
- 39 Kramer MS, Lydon J, Goulet L. et al. Maternal stress/distress, hormonal pathways and spontaneous preterm birth. Paediatr Perinat Epidemiol 2013; 27 (03) 237-246
- 40 Ferguson KK, Rosen EM, Barrett ES. et al. Joint impact of phthalate exposure and stressful life events in pregnancy on preterm birth. Environ Int 2019; 133 (Pt B): 105254
- 41 Culhane JF, Rauh V, McCollum KF, Hogan VK, Agnew K, Wadhwa PD. Maternal stress is associated with bacterial vaginosis in human pregnancy. Matern Child Health J 2001; 5 (02) 127-134
- 42 Nansel TR, Riggs MA, Yu KF, Andrews WW, Schwebke JR, Klebanoff MA. The association of psychosocial stress and bacterial vaginosis in a longitudinal cohort. Am J Obstet Gynecol 2006; 194 (02) 381-386
- 43 Gur TL, Bailey MT. Effects of stress on commensal microbes and immune system activity. Adv Exp Med Biol 2016; 874: 289-300