Maternal obesity and childhood asthma risk: Exploring mediating pathways

Abstract

BackgroundGrowing evidence for the effect of maternal obesity on childhood asthma motivates investigation of mediating pathways.ObjectiveTo investigate if childhood body mass index (BMI), gestational weight gain (GWG) and preterm birth mediate the association of maternal obesity on childhood asthma risk.MethodsWe used electronic medical records from mother–child pairs enrolled in Kaiser Permanente Northern California integrated healthcare system. Children were followed from their birth (2005–2014) until at least age 4 (n = 95,723), age 6 (n = 59,230) or age 8 (n = 25,261). Childhood asthma diagnosis at each age was determined using ICD‐9/10 codes and medication dispensings. Prepregnancy BMI (underweight [<18.5], normal [18.5–24.9], overweight [25–29.9], obese [≥30] kg/m2) were defined using height and weight measurements close to the last menstrual period date. Child's BMI (Centers for Disease Control and Prevention BMI‐for‐age percentiles: underweight [<5th], normal [5th–85th], overweight [85th–95th], obese [>95th]) were obtained using anthropometric measurements taken the year preceding each follow‐up age. GWG (delivery weight‐prepregnancy weight) was categorised based on Institutes of Medicine recommendations (inadequate, adequate, excessive). Implementing first causal inference test (CIT) then causal mediator models (to decompose the natural direct and indirect effects), we examined the potential mediating effect of childhood BMI, GWG, and preterm birth on the association between prepregnancy BMI (continuous and categorical) and childhood asthma.ResultsOverall, risk of childhood asthma increased as prepregnancy BMI increased (age 4 risk ratio: 1.07, 95% confidence interval: 1.04, 1.09, per 5 kg/m2 increase in BMI; similar for age 6 and 8). CIT identified childhood BMI and preterm birth, but not GWG as potential mediators. Causal mediation models confirmed childhood BMI, but not preterm birth, as having a partial mediating effect. Results were similar for age 6 and 8, and when continuous mediators (instead of binary) were assessed.ConclusionsChildhood overweight/obesity has a modest mediating effect on the association between prepregnancy BMI and childhood asthma.

Multiple mediators, causal assumptions and potential caveats

“…In this issue of Pediatric and Perinatal Epidemiology, Rosenquist and colleagues 2 apply causal mediation analysis to explore mediating pathways between maternal obesity and childhood asthma, which has a well-established connection. 3 They hypothesise that this association may be explained by three possible mediators for which they had available data: (i) gestational weight gain; (ii) preterm birth and (iii) childhood body mass index (BMI).…”

“…For example, in Figure 1B, we provide an example DAG where we have replaced C4 with preterm birth. In their article, Rosenquist et al 2 addressed this by conducting a sensitivity analysis using an approach based on inverse probability weighting to measure the joint-mediated effect via both preterm birth and childhood BMI. This approach examines the combined indirect effect through both mediators simultaneously and is a good first step in understanding the combined causal indirect pathway.…”