Statistical analyses
We undertook causal mediation analyses to examine the effects of SGA on caesarean delivery with and without TOL. The analyses were performed for all subjects in toto , but we also performed separate analyses for women with and without one prior caesarean delivery. The results of these stratified analyses (eTables 3-8 in the Supplement) were similar to the overall analysis, so we have presented the overall analyses here.
The effects of exposure and mediator on caesarean delivery were estimated from a multiplicative scale (log-linear Poisson regression models with a log-link function and robust variance, with risk ratio [RR] as the effect measure) and an additive scale (log-linear Poisson regression models with an identity-link function and robust variance, with the risk difference [RD] as the effect measure). We undertook a causal mediation analysis based on a counterfactual framework (11, 20) to disentangle the total effect of the SGA-caesarean association that could be attributable to a pure mediation effect by gestational age, to an interaction effect (by gestational age), and no interaction or mediation effects (21, 22). This method decomposes the total effect of SGA on caesarean delivery (exposure-outcome association) in the presence of gestational age (mediator) with which the SGA (exposure) may interact. The resulting 4-way decomposition includes: (i) effect of SGA on mode of delivery in the absence of the mediator (i.e., at 39-40 weeks [reference]); (ii) interaction effect when the mediator is left to what it would be in the absence of the SGA exposure (i.e., among AGA births); (iii) mediated interaction; and (iv) pure effect mediated through gestational age. Stated differently, these 4 effects correspond to the portion of the SGA-caesarean delivery association that is neither due to mediation or interaction with gestational age (also referred to as the controlled direct effect [CDE]), just to interaction but not mediation (referred to as the reference-interaction [INTREF]), to both mediation and interaction (referred to as the mediation-interaction [INTMED]), and to just mediation but not interaction (referred to as the pure indirect effect [PIE]). The sum of these 4 decomposed effects amount to 100% on the RD scale.
To facilitate easier interpretation of causal effects, we focus on the proportion of the SGA-caesarean delivery association that is directly attributed to exposure to SGA (i.e., the CDE) and two other measures in the primary analysis: proportion of the SGA-caesarean delivery association that is mediated through gestational age and the proportion attributable to an interaction between SGA and gestational age (22). The full analysis of the 4-way decomposition is shown in eTables 3-8 in the supplement. 95% confidence intervals (CI) for all of causal estimates were derived from the bootstrap resampling method with 2000 replications.