Prepregnancy obesity and risk of placental inflammation at term: a selection bias analysis

Placental histopathology is a resource for investigating obesity-associated pregnancy conditions. However, studies oversample adverse pregnancies, biasing findings. We examine the association between prepregnancy obesity (risk factor for inflammation) and histologic placental inflammation (correlated with impaired infant neurodevelopment) and how selection bias may influence the association.

Singleton term deliveries between 2008 and 2012 from the Magee Obstetric Maternal and Infant database were analyzed. Prepregnancy body mass index (BMI) was categorized as underweight, lean (referent), overweight, and obese. Outcomes were diagnoses of acute (acute chorioamnionitis and fetal inflammation) and chronic placental inflammation (chronic villitis). Risk ratios for associations between BMI and placental inflammation were estimated using selection bias approaches: complete case, exclusion of pregnancy complications, multiple imputation, and inverse probability weighting. E-values approximated how susceptible estimates were to residual selection bias.

Across methods, obesity was associated with an 8-15% lower risk of acute chorioamnionitis, a 7%-14% lower risk of acute fetal inflammation, and a 12%-30% higher risk of chronic villitis relative to lean women. E-values indicated modest residual selection bias could explain away associations, though few measured indications of placental evaluations met this threshold.

Obesity may contribute to placental inflammation, and we highlight robust methods to analyze clinical data susceptible to selection bias.