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Perinatal epidemiology often aims to evaluate exposures on infant outcomes.When the exposure affects the composition of people who give birth to liveinfants (e.g., by affecting fertility, behavior, or birth outcomes), this "livebirth process" mediates the exposure effect on infant outcomes. Causalestimands previously proposed for this setting include the total exposureeffect on composite birth and infant outcomes, controlled direct effects (e.g.,enforcing birth), and principal stratum direct effects. Using perinatal HIVtransmission in the SEARCH Study as a motivating example, we present twoalternative causal estimands: 1) conditional total effects; and 2) conditionalstochastic direct effects, formulated under a hypothetical intervention to drawmediator values from some distribution (possibly conditional on covariates).The proposed conditional total effect includes impacts of an intervention thatoperate by changing the types of people who have a live birth and the timing ofbirths. The proposed conditional stochastic direct effects isolate the effectof an exposure on infant outcomes excluding any impacts through this live birthprocess. In SEARCH, this approach quantifies the impact of a universal testingand treatment intervention on infant HIV-free survival absent any effect of theintervention on the live birth process, within a clearly defined targetpopulation of women of reproductive age with HIV at study baseline. Ourapproach has implications for the evaluation of intervention effects inperinatal epidemiology broadly, and whenever causal effects within a subgroupare of interest and exposure affects membership in the subgroup.

When exposure affects subgroup membership: Framing relevant causal questions in perinatal epidemiology and beyond