An Examination of Inter-pregnancy Intervals as a Risk Factor for Stillbirth Open Access

Gupta, Priya Mehta (2015)

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Context: It is estimated that 1 in 160 pregnancies in the United States annually end in stillbirth (SB, fetal death ≥ 20 weeks gestation). The causal risk factors of SB are unknown, however, short and long inter-pregnancy intervals (IPI) have commonly been reported as risk factors for other adverse perinatal outcomes.

Objective: This analysis seeks to examine the association between IPI and SB risk among an ethnically, racially, and geographically diverse population.

Methods: The Stillbirth Collaborative Research Network (SCRN) study was a multi-site, population-based case-control study from March 2006 to September 2008 with surveillance for all stillbirths at 59 tertiary care hospitals over 5 catchment areas ensuring access to at least 90% of deliveries. This analysis was restricted to singleton pregnancies among multiparous or multigravid women. Exclusion criteria included pregnancy terminations, incarcerated women, or those who were unable to provide informed consent. Weighted logistic regression models were used to depict the association of short and long intervals on stillbirth risk. Weighted backward elimination for interaction and weighted all-possible subsets approach to confounding were conducted at a 5% significance level. All models were created using SAS 9.3.

Results: Compared with IPI between 18-23 months, short intervals (<6 months) and long intervals (60-100 months) were associated with increased risk of stillbirth (Odds Ratio [OR]: 1.6; 95% Confidence Interval [CI]: 0.8, 3.2) and (OR: 2.4; 95%CI: 1.3, 4.7) respectively, controlling for age, race, education, insurance, BMI, smoking status, alcohol consumption, marital status, use of assisted reproductive technologies, and prior pregnancy outcome. Final models controlled for all ten covariates of interest and were selected based on HL statistics and AUC. True confounders differed between short and long intervals. For the combined analysis, the relationship between IPI and SB risk was confounded by age, BMI, education and prior pregnancy outcome; when restricted to short intervals, confounders in this study included age, insurance, and prior pregnancy outcome. The relationship between long intervals and SB was not confounded by any of the suspected covariates.

Conclusions: Short and long IPI contributed to an increased risk of SB controlling for selected covariates. However, only long intervals were associated with a statistically significant increase in SB risk.

Table of Contents

List of Tables 1

List of Figures 2

Terms and Definitions 3

Introduction 5

Chapter 1: The Stillbirth Collaborative Network 8

Known Risk Factors of Stillbirth 9

Chapter 2: Review of the Literature regarding Inter-pregnancy intervals 17

Inter-pregnancy Intervals and Stillbirth Risk 18

Inter-pregnancy Intervals and Adverse Birth Outcomes 20

Chapter 3: Hypothesized Mechanisms by which Inter-pregnancy intervals may contribute to adverse birth outcomes 31

Chapter 4: Methods 36

Study Design 36

Study Population 36

Sampling Controls 37

Analysis Weights 37

Exclusions 38

Data Description 39

Statistical Analysis 41

Chapter 5: Results 44

Descriptive Statistics 44

Logistic Models for Inter-pregnancy Intervals 45

Logistic Models for Short Inter-pregnancy Intervals 47

Logistic Models for Long Inter-pregnancy Intervals 48

Chapter 6: Discussion 50

Chapter 7: Strengths and Weaknesses 54

Chapter 8: Future Public Health Implications 57

References 60

Tables 69

Figures 79

Appendix 81

Institutional Review Board (IRB) Protocol 82

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