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. 2025 Aug;132(9):1269-1277.
doi: 10.1111/1471-0528.18186. Epub 2025 Apr 29.

Associations of Metabolic Syndrome and Insulin Resistance With Attenuated Executive Function Post-Preeclampsia: A Nested Case-Control Study

Robert-Jan Alers  1   2 , Chahinda Ghossein-Doha  2   3 , Yentl Brandt  4   5 , M Eline Kooi  4   5 , Suzanne C Gerretsen  5 , Jacobus F A Jansen  5   6 , Walter H Backes  5   6 , Vincent van de Ven  7 , Petra P M Hurks  8 , Marc E A Spaanderman  1   2
Affiliations

Associations of Metabolic Syndrome and Insulin Resistance With Attenuated Executive Function Post-Preeclampsia: A Nested Case-Control Study

Robert-Jan Alers et al. BJOG. 2025 Aug.

Abstract

Objective: Preeclampsia contributes to maternal cognitive problems, particularly involving executive functions. These higher-order cognitive functions-including working memory, organisation of materials, and task focus-are essential for adaptive, purposeful, and goal-directed behaviour. Similar cognitive problems are observed in metabolic syndrome and insulin resistance. This study investigates whether these conditions are also associated with executive function after preeclampsia.

Design: Nested case-control study.

Setting: Maastricht University Medical Centre+, a tertiary care hospital.

Population: Women 0.5 to 30 years after preeclampsia.

Methods: The Behaviour Rating Inventory of Executive Function for Adults provided a measure of executive function performance. The National Cholesterol Education Program Adult Treatment Panel III defined metabolic syndrome. The Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) quantified insulin resistance. Participants were matched on age, postpartum time, and educational attainment. Associations of attenuated executive function with metabolic syndrome, its constituents, and insulin resistance were examined with conditional logistic regression.

Main outcome measures: Odds ratios and population attributable fractions for the associations of attenuated executive function with metabolic syndrome, its constituents, and insulin resistance.

Results: In 155 matched pairs, attenuated executive function was associated with metabolic syndrome (odds ratio 4.20 (95% confidence interval 1.58-11.14)), hyperglycaemia (2.96 (1.13-7.79)), and obesity (3.86 (2.00-7.47)). Attenuated executive function related to HOMA-IR (7.26 (3.75-14.07)), and was 13% (6%-20%) attributable to metabolic syndrome and 56% (49%-67%) to insulin resistance.

Conclusions: Metabolic syndrome and insulin resistance are associated with attenuated executive function after preeclampsia. Our findings provide leads for future studies focused on improving post-preeclamptic cognitive performance.

Keywords: cognition; cognitive impairment; executive function; insulin resistance; maternal health; metabolic syndrome; obstetrical complication; postpartum; preeclampsia.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Odds ratios and population attributable fractions of reporting Behaviour Rating Inventory of Executive Function for Adults (BRIEF‐A) determined clinically relevant attenuated executive function in relation to the presence of metabolic syndrome (Model A), presence of metabolic syndrome constituents (model B), presence of hyperglycaemia, obesity and Homeostatic Model Assessment of Insulin Resistance (HOMA‐IR) (model C), and HOMA‐IR (model D). Odds ratios are presented as odds ratio (95% confidence interval) and population attributable fractions (PAF) as PAF (95% confidence interval). Abbreviations: BIC, Bayesian information criterion; HDL, high‐density lipoprotein; HOMA‐IR, homeostatic model assessment of insulin resistance; PAF, population attributable fraction; VIF, variance inflation factor. *PAF was calculated for the 75th HOMA‐IR (≥ 2.0) percentile defining insulin resistance.
FIGURE 2
FIGURE 2
Fractions of Behaviour Rating Inventory of Executive Function for Adults (BRIEF‐A) determined clinically relevant attenuated executive function (%) along Homeostatic Model Assessment for Insulin Resistance (HOMA‐IR) values after recursive partitioning. Error bars represent 95% confidence intervals.
FIGURE 3
FIGURE 3
Graphical abstract of study rationale, methods, and key findings.
See this image and copyright information in PMC

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