Detecting the Effects of Early-Life Exposures: Why Fecundity Matters

Abstract

Prenatal exposures have meaningful effects on health across the lifecourse. Innovations in causal inference have shed new light on these effects. Here, we motivate the importance of innovation in the characterization of fecundity, and prenatal selection in particular. We argue that such innovation is crucial for expanding knowledge of the fetal origins of later life health. Pregnancy loss is common, responsive to environmental factors, and closely related to maternal and fetal health outcomes. As a result, selection into live birth is driven by many of the same exposures that shape the health trajectories of survivors. Lifecourse effects that are inferred without accounting for these dynamics may be significantly distorted by survival bias. We use a set of Monte Carlo simulations with realistic parameters to examine the implications of prenatal survival bias. We find that even in conservatively specified scenarios, true fetal origin effects can be underestimated by 50% or more. In contrast, effects of exposures that reduce the probability of prenatal survival but improve the health of survivors will be overestimated. The absolute magnitude of survival bias can even exceed small effect sizes, resulting in inferences that beneficial exposures are harmful or vice-versa. We also find reason for concern that moderately sized true effects, underestimated due to failure to account for selective survival, are missing from scientific knowledge because they do not clear statistical significance filters. This bias has potential real-world costs; policy decisions about interventions to improve maternal and infant health will be affected by underestimated program impact.

African American Unemployment and the Disparity in Periviable Births

“…Consistent with this argument, unplanned births among underrepresented minorities and low socioeconomic groups also declined during the recession [56]. Other literature, however, suggests that some fraction of the decline may arise from selection in utero [57].…”

Environmental hazards, social inequality, and fetal loss: Implications of live-birth bias for estimation of disparities in birth outcomes

“…This issue has recently received increasing attention in the environmental and perinatal epidemiology and social sciences literature. 9 – 12 …”

GWAS on Birth Year Infant Mortality Rates Provides New Evidence of Recent Natural Selection

“…The approach builds on decades of demographic and epidemiologic research that considers how cohort traits are shaped by mortality exposure early in life 17-21 . These studies provide several types of indirect evidence of early-life cohort selection: the differential survival of robust subpopulations through inhospitable disease environments during gestation and infancy (e.g., female versus male survival 22,23 ); nonlinear associations between disease environments and phenotypic traits like birth weight or height 24 ; and phenotypic traits among descendants of people exposed to war and famine in early life 25,26 .…”