Prenatal maternal inflammation and cognitive performance in offspring during late midlife

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.