Invited Commentary: The Causal Association Between Obesity and Stillbirth—Strengths and Limitations of the Consecutive-Pregnancies Approach

Abstract

There has been a resurgence in analyses of consecutive pregnancies (or similarly, sibling designs) in perinatal and pediatric epidemiology. These approaches have attractive qualities for estimating associations with complex multifactorial exposures like obesity. In an article appearing in this issue of the Journal, Yu et al. (Am J Epidemiol. 2019;188(7):1328–1336) apply a consecutive-pregnancies approach to characterize the risk of stillbirth among women who develop obesity between pregnancies (“incident obesity”). Working within a causal framework and using parametric and nonparametric estimation techniques, the authors find an increase in stillbirth risk associated with incident obesity. Risk differences varied between 0.4 per 1,000 births (95% confidence interval (CI): 0.1, 0.7) and 6.9 per 1,000 births (95% CI: 3.7, 10.0), and risk ratios ranged from 1.12 (95% CI: 1.02, 1.23) to 2.99 (95% CI: 2.19, 4.08). The strengths of this approach include starting from a clearly defined causal estimand and exploring the sensitivity of parameter estimates to model selection. In this commentary, we put these findings in the broader context of research on obesity and birth outcomes and highlight concerns regarding the generalizability of results derived from within-family designs. We conclude that while causal inference is an important goal, in some instances focusing on formulation of a causal question drives results away from broad applicability.

Interpregnancy weight change: associations with severe maternal morbidity and neonatal outcomes

“…We note that incident obesity due to interpregnancy weight gain may reflect a shorter duration of exposure to mechanisms like inflammation or metabolic dysfunction than that experienced by individuals with established, long-term obesity. (31) Mechanisms for associations between low BMI and SMM are unclear. In a prior mediation analysis, we reported that the association between prepregnancy obesity and SMM was explained by accounting for comorbidities and cesarean delivery, but these mediators did not affect the association between low BMI and SMM, suggesting different pathways.…”

Studies of recurrent outcomes in perinatal epidemiology: To describe, explain or predict?

“…In doing so, they broach an issue that is omnipresent in perinatal epidemiology: recurrent pregnancy outcomes. Whether across a woman's pregnancies or across generations, information on a past pregnancy outcome is often helpful for understanding the present 2 . But how, specifically, should this information be used?…”

“…Whether across a woman's pregnancies or across generations, information on a past pregnancy outcome is often helpful for understanding the present. 2 But how, specifically, should this information be used? There is relatively little guidance on the unique considerations of formulating research questions related to recurrent outcomes.…”

The Authors Respond to “Issues With the Consecutive-Pregnancies Approach”

“…We thank Drs. Snowden and Leonard (1) for elaborating on the generalizability of our results on the relationship between incident obesity and stillbirth (2). To quantify the association between incident obesity and stillbirth, we restricted our analyses to women who were not obese at the time of their first pregnancy.…”