Promise and Pitfalls of the Sibling Comparison Design in Studies of Optimal Birth Spacing

Abstract

Numerous observational studies have shown that infants born after short interpregnancy intervals (the interval between birth and subsequent conception) are more likely to experience adverse perinatal outcomes than infants born following longer intervals. Yet, it remains controversial whether the link between short interpregnancy interval and adverse outcomes is causal, or confounded by factors such as low socio-economic position, inadequate access to healthcare, and unintended pregnancy. Sibling comparison studies, which use a woman as her own control by comparing exposure and outcome status of her different pregnancies (i.e., comparing sibling offspring), have gained popularity as a strategy to reduce confounding by these difficult-to-measure factors that are nevertheless relatively stable within women. A variant of the design, used by Regan et al. in this issue (Am J Epidemiol 2018;XX:XXX-XXX), is a maternally-matched design based on a single interpregnancy interval per woman. Using real and simulated data, we highlight underappreciated shortcomings of these designs that may limit the validity of study findings. In particular, we illustrate how the single-interval variant appears to derive estimates from comparisons between different mothers, not within mothers. Future studies of optimal birth spacing using sibling comparison designs should examine in detail the potential consequences of these methodological limitations.