Mediation analysis
Gestational age features on the causal pathway between chronic
hypertension and perinatal mortality as an mediator
(Supplemental Figure 2 ); therefore, any adjustment for preterm
delivery in the assessment of the perinatal mortality risk in relation
to chronic hypertension would lead to collider bias.(32) To resolve this
issue, we undertook a causal mediation analysis based on the
counterfactual framework(33, 34) to decompose the total effect (TE) of
chronic hypertension on perinatal mortality into the natural direct
effect (NDE; the effect of the exposure [chronic hypertension] on
the outcome [perinatal mortality] if the mediator [preterm
delivery <37 weeks] were set to what it would have been,
probably contrary to the fact, in the absence of the exposure) and the
natural indirect effect (NIE; the effect of the exposure on the outcome
when the exposure is present after setting the mediator to what it would
have been, probably contrary to the fact, with versus without the
exposure).(35, 36) We also estimated the controlled direct effect (CDE;
the effect of chronic hypertension on mortality that is not mediated
through preterm delivery). The TE, NDE, NIE and CDE were estimated on
multiplicative scale with RR and 95% CI as effect measure.
In addition, we estimated the proportion mediated (PM; the proportion of
the TE that is mediated through preterm delivery), and the proportion
eliminated (PE; the proportion of the chronic hypertension-perinatal
mortality association that might be eliminated by blocking the effect of
chronic hypertension on preterm delivery). The PE is the proportion of
perinatal deaths that could be prevented by designing interventions to
reduce preterm delivery associated with chronic hypertension. All 95%
CI estimates were based on 1000 bootstrap samples.