The Effect of Pre-Pregnancy Obesity on Stillbirth: Mediation by Systemic and Placental Inflammatory Markers Public

Abstract

BACKGROUND: Maternal obesity is a known risk factor for stillbirth, and both obesity and pregnancy are known to induce chronic, low-grade inflammation in the body. Obesity in pregnancy has been associated with a systemic increase in plasma proinflammatory cytokines which then accumulate in the placenta and cause a proinflammatory intrauterine environment. Placental inflammatory conditions such as chorioamnionitis have been shown to be more common in stillbirths compared to live births. Therefore, it is plausible that markers of both systemic and placental inflammation might mediate the relationship between pre-pregnancy obesity and stillbirth.

METHODS: Using data from the Stillbirth Collaborative Research Network, univariate and multivariate logistic regression was used to evaluate the relationship between pre-pregnancy obesity and stillbirth. The relationship between obesity and inflammation as well as inflammation and stillbirth were also evaluated. Systemic mediators of interest included maternal serum C-reactive protein, ferritin, and white blood cell count. Placental markers of inflammation included histologic chorioamnionitis of the chorionic plate and placental free membranes. Mediation analyses were preformed using Valeri and VanderWeele’s SAS macro for mediation. 

RESULTS: In crude and adjusted models, obesity was significantly associated with stillbirth (ORcrude = 1.67, 95% CI: 1.28, 2.18, ORadjusted = 1.68, 95% CI: 1.27, 2.22). With the exception of maternal elevated serum C-reactive protein, strong associations were found between maternal inflammatory markers and stillbirth with ORs ranging from 2.53 (95% CI: 1.98, 3.25) to 4.02 (95% CI: 2.99, 5.42). Little to no association was found between maternal obesity and inflammatory markers. Similarly, adjusted ORs for the effect of obesity that operates through systemic and placental inflammatory markers (indirect effects) were weak, ranging from 0.97 to 1.08.

CONCLUSION: Markers of both systemic or placental inflammation do not appear to mediate the relationship between pre-pregnancy obesity and stillbirth. However, stillbirth does appear to be associated with inflammatory markers. More research is required to further explore the role of inflammation as an intermediate. 

Table of Contents

INTRODUCTION 1

METHODS 4

Study Design and Data Source 4

Case and Control Ascertainment 4

Data Collection 5

Study Population and Missing Data 6

Data Weights 7

Obesity 8

Mediators 8

Confounders 9

Analytic Plan 9

RESULTS 11

DISCUSSION 14

Principal Findings 14

Limitations 16

CONCLUSION 18

TABLES AND FIGURES 19

REFERENCES 25

About this Master's Thesis

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School	Rollins School of Public Health
Department	Epidemiology
Subfield / Discipline	Epidemiology - MPH & MSPH
Degree	M.P.H.
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Obstetrics and Gynecology
Mot-clé	placental inflammation maternal obesity stillbirth systemic inflammation inflammation pre-pregnancy obesity
Committee Chair / Thesis Advisor	Drews-Botsch, Carolyn, Emory University

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