Spontaneous preterm birth (SPTB) affects more that 12 percent of all births among urban women and contributes to more than one-third of all infant deaths. Numerous adverse pregnancy outcomes have been prospectively linked to BV including SPTB. Despite the consistently strong epidemiologic link between BV and SPTB, many BV positive pregnant women deliver healthy, term infants and the current treatment options for BV are largely ineffective. Microbiologic variations exist among BV positive women and this variability may explain the limited effectiveness of metronidazole in curing BV and/or reducing SPTB risk.
The aims of this amended, competing continuation application are: 1) to evaluate whether Gardnerella vaginalis, Mobiluncus curtisii, Atopobium vaginae, Leptotrichia amnionii, and the Clostridiales bacteria designated Bacterial Vaginosis-Associated Bacterium (BVAB) 1,2 or 3 measured in the first trimester of pregnancy are important, independent predictors of SPTB, and 2) to evaluate whether consistently high levels of Gardnerella vaginalis, Mobiluncus curtisii, Atopobium vaginae, Leptotrichia amnionii, and Bacterial Vaginosis-Associated Bacteria (BVAB) 1,2 or 3, measured at two points during pregnancy, are an important, independent predictor of SPTB. Women attending their first prenatal care visit at Temple University with a pregnancy of 12 weeks gestation or less will be recruited. Baseline data collection will be standardized and include a structured in- person interview, buccal swab for genotyping of three inflammatory genes, and vaginal swabs to detect the presence and degree of BV based on Gram stain. In addition, the concentrations of selected vaginal bacteria will be measured using PCR assays targeting 16S rRNA genes from the BV-associated bacteria of interest. Repeat vaginal swabs will be collected between18-20 weeks gestation to examine the change in these bacteria and the role of consistently high levels of BV-associated bacteria and SPTB risk. In this case-cohort study, we will enroll and classify 2200 pregnant women over a three year period and randomly sample 20 percent of the underlying population to generate the subcohort. We will identify all SPTB cases occurring within and outside the subcohort and compare the results to the remaining subcohort. Given the public health impact of high rates of infant morbidity and mortality due to SPTB, these results may identify a group of women at high risk of SPTB based on early pregnancy BV profile characteristics. These results will also examine the biologic mechanisms and co-factors most responsible for the increased risk of SPTB among urban, BV positive women and the ineffectiveness of current BV treatment options.

Public Health Relevance

Spontaneous preterm birth (SPTB) affects more that 12 percent of all births and contributes to more than one-third of all infant deaths. Despite the consistently strong epidemiologic link between BV and SPTB, many BV positive pregnant women deliver healthy, term infants. The results from this study will add valuable information regarding the specific BV-associated bacteria most related to SPTB and may explain the current limited effectiveness of BV treatment in reducing the risk of SPTB.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD038856-09
Application #
8061641
Study Section
Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section (IRAP)
Program Officer
Reddy, Uma M
Project Start
2000-04-01
Project End
2013-03-31
Budget Start
2011-04-01
Budget End
2013-03-31
Support Year
9
Fiscal Year
2011
Total Cost
$453,924
Indirect Cost
Name
Temple University
Department
Public Health & Prev Medicine
Type
Schools of Allied Health Profes
DUNS #
057123192
City
Philadelphia
State
PA
Country
United States
Zip Code
19122
Nelson, Deborah B; Shin, Hakdong; Wu, Jingwei et al. (2016) The Gestational Vaginal Microbiome and Spontaneous Preterm Birth among Nulliparous African American Women. Am J Perinatol 33:887-93
Nelson, Deborah B; Hanlon, Alexandra L; Wu, Guojiao et al. (2015) First Trimester Levels of BV-Associated Bacteria and Risk of Miscarriage Among Women Early in Pregnancy. Matern Child Health J 19:2682-7
Seravalli, Laura; Patterson, Freda; Nelson, Deborah B (2014) Role of perceived stress in the occurrence of preterm labor and preterm birth among urban women. J Midwifery Womens Health 59:374-9
Nelson, Deborah B; Hanlon, Alexandra; Nachamkin, Irving et al. (2014) Early pregnancy changes in bacterial vaginosis-associated bacteria and preterm delivery. Paediatr Perinat Epidemiol 28:88-96
Herring, Sharon J; Nelson, Deborah B; Pien, Grace W et al. (2014) Objectively measured sleep duration and hyperglycemia in pregnancy. Sleep Med 15:51-5
Herring, Sharon J; Foster, Gary D; Pien, Grace W et al. (2013) Do pregnant women accurately report sleep time? A comparison between self-reported and objective measures of sleep duration in pregnancy among a sample of urban mothers. Sleep Breath 17:1323-7
Mitchell, Caroline; Gottsch, Michelle L; Liu, Congzhou et al. (2013) Associations between vaginal bacteria and levels of vaginal defensins in pregnant women. Am J Obstet Gynecol 208:132.e1-7
Nelson, Deborah B; Komaroff, Eugene; Nachamkin, Irving et al. (2013) Relationship of selected bacterial vaginosis-associated bacteria to Nugent score bacterial vaginosis among urban women early in pregnancy. Sex Transm Dis 40:721-3
Herring, Sharon J; Nelson, Deborah B; Davey, Adam et al. (2012) Determinants of excessive gestational weight gain in urban, low-income women. Womens Health Issues 22:e439-46
Nelson, Deborah B; Hanlon, Alexandra; Hassan, Sarmina et al. (2009) Preterm labor and bacterial vaginosis-associated bacteria among urban women. J Perinat Med 37:130-4

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