Variations in executive function in toddlers after exposure to pre-pregnancy overweight and obesity and the mediating role of inflammation in a longitudinal pregnancy cohort study

Abstract

Objective: This study aimed to determine the association between pre-pregnancy overweight and obesity status in pregnant women and executive function (EF) development in toddlers and establish whether inflammatory biomarkers mediate this association.

Methods: This prospective cohort included 1,126 mother-infant pairs. Pre-pregnancy body mass index (ppBMI) was obtained from medical records, and the participants categorized into normal weight, overweight and obese groups according to standard ppBMI classifications. Toddlers' EF scores were assessed using the Behaviour Rating Inventory of Executive Functioning Preschool Version (BRIEF-P), with higher scores reflecting worse EF. Linear regression models were used to compared EF scores between toddlers of normal weight mothers and those of overweight and obese mothers. The mediating effects of mid-pregnancy inflammatory biomarkers were analyzed using the SPSS PROCESS plug-in.

Results: Compared with pre-pregnancy normal weight, pre-pregnancy overweight and obesity was associated with EF related behavioral dysfunction in the domains of inhibition (β = 3.20, 95 % confidence interval [CI]: 0.92, 5.48), shifting (β = 3.12, 95 % CI: 0.88, 5.36), emotional control (β = 3.44, 95 % CI: 1.18, 5.71), working memory (β = 4.17, 95 % CI: 1.87, 6.47) and planning/organization (β = 3.19, 95 % CI: 0.93, 5.45) in toddlers. Analysis of the association between high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6) levels in mid-pregnancy and EF in toddlers demonstrated that only hs-CRP was positively associated with EF (Global Executive Composite score, β = 0.28, 95 % CI: 0.07, 0.49). Mediation analysis revealed that maternal hs-CRP levels in mid-pregnancy mediated 17.4 % of the association between ppBMI and EF in toddlers, with an indirect effect of 0.75 (95 % CI: 0.31, 1.24) and a direct effect of 3.56 (95 % CI: 2.55, 4.58).

Conclusions: Pregnant women with pre-pregnancy overweight and obesity were more likely to have toddlers with worse EF, and mid-pregnancy maternal hs-CRP levels partially mediated this association. Future studies should explore whether improving the pro-inflammatory metabolic milieu in pregnancies complicated by excess weight could reduce the likelihood of increased EF related behavioral dysfunction.

Keywords: Cohort study; Executive function; Inflammation biomarkers; Overweight and obesity; Pre-pregnancy BMI; Toddler.