Prenatal maternal inflammation and cognitive performance in offspring during late midlife.
5 affiliations
- 1Department of Psychology & Neuroscience, Temple University, USA.
- 2Department of Psychology, University of California, Berkeley, USA.
- 3Cousins Center for Psychoneuroimmunology, University of California, Los Angeles, USA.
- 4Child Health and Development Studies, Public Health Institute, USA.
- 5Department of Psychology & Neuroscience, University of Colorado, Boulder, USA.
Abstract
Higher levels of prenatal maternal inflammation (PNMI) have been associated with offspring psychiatric disorders characterized by cognitive changes, and alterations in cognitive ability during early stages of development. Investigations into the effects of PNMI exposure and timing on cognitive outcomes in offspring later in life are lacking. Thus, the current study aimed to assess whether PNMI exposure in the first two trimesters was associated with offspring cognitive performance in late midlife. Participants were 137 mother-offspring dyads from the Child Health and Developmental Studies (CHDS) cohort that had maternal first and second trimester (T1, T2) sera data for interleukin- (IL-) 6, IL-8, IL-1 receptor antagonist (RA), and soluble tumor necrosis factor receptor-II (sTNF-RII), and an offspring follow-up assessment during late midlife (ages 57-62). Offspring underwent a battery of cognitive tests assessing verbal memory, general cognitive ability, verbal IQ, executive control, attention, working memory, and fine motor functioning. After controlling for maternal education to account for postnatal cognitive advantage, we identified a significant association between higher T1 PNMI and better performance on tasks of executive control (IL-8, Trails B-A, p = .003) and working memory (sTNF-RII, Digit-Span [DS] Backwards, p = .014). We also found significant associations between higher T2 PNMI and poorer performance on executive control (IL-6, Trails B-A, p = .002), working memory (IL-6, DS Backwards, p = .018), verbal IQ (IL-6, Wechsler Test of Adult Reading [WTAR], p = .039), and verbal memory (IL-8, Long Delay-Free Recall [LD-FR], p = .001). Such timing-specific associations of PNMI suggest that early gestational inflammatory exposure may be protective for some cognitive capacities, whereas mid-gestational exposure, especially to IL-6, suggests risk for decreases in memory and several other cognitive domains measurable in offspring approximately six decades later.
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BibTeX
@article{hoffman2026prenatal,
title = {{Prenatal maternal inflammation and cognitive performance in offspring during late midlife.}},
author = {Linda J Hoffman and Emma C Smith and Madeline R Pike and Ann M Kring and Elizabeth C Breen and Barbara A Cohn and Piera M Cirillo and Nickilou Y Krigbaum and Ashby B Cogan and Bhakti P Patwardhan and Thomas M Olino and Ingrid R Olson and Lauren M Ellman},
journal = {Brain, behavior, \& immunity - health},
year = {2026},
month = oct,
doi = {10.1016/j.bbih.2026.101384},
url = {https://europepmc.org/article/MED/42927033},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Prenatal maternal inflammation and cognitive performance in offspring during late midlife.
AU - Linda J Hoffman
AU - Emma C Smith
AU - Madeline R Pike
AU - Ann M Kring
AU - Elizabeth C Breen
AU - Barbara A Cohn
AU - Piera M Cirillo
AU - Nickilou Y Krigbaum
AU - Ashby B Cogan
AU - Bhakti P Patwardhan
AU - Thomas M Olino
AU - Ingrid R Olson
AU - Lauren M Ellman
PY - 2026
DA - 2026/10/06
JO - Brain, behavior, & immunity - health
DO - 10.1016/j.bbih.2026.101384
UR - https://europepmc.org/article/MED/42927033
AB - Higher levels of prenatal maternal inflammation (PNMI) have been associated with offspring psychiatric disorders characterized by cognitive changes, and alterations in cognitive ability during early stages of development. Investigations into the effects of PNMI exposure and timing on cognitive outcomes in offspring later in life are lacking. Thus, the current study aimed to assess whether PNMI exposure in the first two trimesters was associated with offspring cognitive performance in late midlife. Participants were 137 mother-offspring dyads from the Child Health and Developmental Studies (CHDS) cohort that had maternal first and second trimester (T1, T2) sera data for interleukin- (IL-) 6, IL-8, IL-1 receptor antagonist (RA), and soluble tumor necrosis factor receptor-II (sTNF-RII), and an offspring follow-up assessment during late midlife (ages 57-62). Offspring underwent a battery of cognitive tests assessing verbal memory, general cognitive ability, verbal IQ, executive control, attention, working memory, and fine motor functioning. After controlling for maternal education to account for postnatal cognitive advantage, we identified a significant association between higher T1 PNMI and better performance on tasks of executive control (IL-8, Trails B-A, p = .003) and working memory (sTNF-RII, Digit-Span [DS] Backwards, p = .014). We also found significant associations between higher T2 PNMI and poorer performance on executive control (IL-6, Trails B-A, p = .002), working memory (IL-6, DS Backwards, p = .018), verbal IQ (IL-6, Wechsler Test of Adult Reading [WTAR], p = .039), and verbal memory (IL-8, Long Delay-Free Recall [LD-FR], p = .001). Such timing-specific associations of PNMI suggest that early gestational inflammatory exposure may be protective for some cognitive capacities, whereas mid-gestational exposure, especially to IL-6, suggests risk for decreases in memory and several other cognitive domains measurable in offspring approximately six decades later.
SN - 2666-3546
ER -