Complement Activation and Perinatal Outcomes in African American Women Open Access

Dunn, Alexis Brennae (2017)

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Background: Complement activation during pregnancy is essential for processes related to maternal-fetal immune tolerance and the immune response to infection. However, recent studies in predominantly white populations have shown that elevated levels of complement factors C3a and Bb during early pregnancy are associated with an increased risk for preterm birth (PTB). Bacteria are potent activators of complement, however the relationship between the microbiome and complement activation has not been explored in a pregnant population at high risk for PTB.

Purpose: This study explored the relationship between the vaginal microbiome, markers of complement activation, PTB associated clinical measures, and behavioral risk factors linked to infection and PTB.

Sample and Design: A prospective longitudinal study of 144 pregnant AA women enrolled in a larger study investigating biobehavioral determinants of the microbiome and the risk of PTB in AA women (1R01NR014800) were followed in this dissertation study. Women completed sociodemographic questionnaires and provided information about health behaviors and infection history. Blood and vaginal microbiome samples were collected between 8-14 weeks for evaluation of the vaginal microbiome and C3a/Bb levels. Medical record abstraction was completed to obtain data on clinical variables of interest (twenty-week cervical length and gestational age at delivery). Correlational and linear regression analysis were conducted to explore relationships between the select variables.

Results: The vaginal microbiome composition clustered into five distinct community state types (CSTs): (1) CST 1 Lactobacillus; (2) CST 2 Prevotella/Bacteroides; (3) CST 3 Snethia/Gardnerella; (4) CST 4 Lactobacillus iners; (5) CST 5 Shuttleworthia. Linear regression analyses concluded that neither the vaginal microbiome CSTs nor reproductive tract infection were associated with early pregnancy C3a or Bb levels. Similarly, neither C3a or Bb were significant predictors of the 18-20 week cervical length measurement or the gestational age at delivery. Age was significantly associated with increased C3a levels and a longer gestational age at delivery.

Conclusions: The vaginal microbiome CSTs and reproductive tract infection are not associated with C3a/Bb levels. Additionally, C3a/Bb levels are not associated with the clinical outcomes of interest. More studies are needed to identify factors that are associated with early pregnancy complement system activation in AA women.

Table of Contents

Chapter 1 - Introduction of Study


Table 1 Biological and Questionnaire Data Collection Instruments

12-14 Figure 1: Study Outline 21

Figure 2: Complement Activation Pathway to Preterm Birth


Chapter 2: The Microbiome and Complement Activation: A Mechanistic Model for Preterm Birth


Figure 2.1- Microbiome and Complement Dysregulation Pathway to

Preterm Birth 71

Figure 2.2- Dysregulation of Maternal Complement Activation During



Chapter 3: Complement Activation and the Vaginal Microbiome in African American Women During Early Pregnancy


Table 1 Sample Characteristics


Table 2 Complement/Microbiome Measures and Clinical Outcomes


Table 3 Associations Between Independent Variables, Covariates, and Dependent Variables


Table 4: Linear Regression Models: Community State Type with Complement


Table 5: Linear Regression Models: Reproductive Tract Infection and Complement


Figure 1: Heat Map of the Vaginal Microbiome Community State Types


Figure 2: Community State Types and Complement Levels


Chapter 4: Complement Activation and Pregnancy Outcomes: An analysis of C3a, Cervical length, and Length of Gestation


Table 1 Sample Characteristics


Table 2 Complement/Microbiome Measures and Clinical Outcomes


Table 3 Associations Between Independent Variables, Covariates, and Dependent Variables


Table 4: Complement Concentrations and Select Health Behaviors


Table 5: Linear Regression Models: Complement and Cervical Length


Table 6: Linear Regression Models: Complement and Gestational Age at Delivery


Chapter 5: Integrative Summary and Analysis


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