Maternal noninfectious fever during pregnancy modulates offspring social behavior in rats: an exploratory study

Maternal fever and elevated interleukin-6 (IL-6) during labor are linked to higher risks of neonatal seizures and cerebral palsy. In rats, IL-6-induced maternal fever is associated with neonatal brain inflammation. This study tests the hypothesis that induced maternal noninfectious fever modulates social behavior in rat offspring.

Two groups of near-term pregnant rats (n=6/group) received systemic IL-6 and the intracerebroventricular prostaglandin E₁ (PGE₁) or vehicle solutions. Maternal core temperature was recorded and pups were delivered naturally. Sixteen offspring (n=8/group) underwent Crawley's behavioral sociability assessment at 4-5 months of age.

Injection with PGE₁ + IL-6 increased mean ± standard deviation (SD) core maternal temperature by 1.1 ± 0.3°C in the first hour compared to vehicle (P <0.001), with significant effect at 30, 60, and 90 minutes (P <0.05). Both groups preferred the social cue over the empty enclosure (F(1,14)=45.1, P <0.001), but their relative interest differed (Group x Side interaction: F(1,14)=5.1, P =0.033). Offspring of febrile mothers spent significantly less time (mean ± SD) sniffing the stranger rat's enclosure compared to controls (36.9 ± 15.8 vs. 56.3 ± 12.1 seconds, P =0.0154) indicating reduced sociability. However, both groups showed similar interest in social novelty, suggesting that recognition of a new social stimulus was unaffected.

Pups exposed to PGE₁ + IL-6 spent significantly less time than control pups exploring a new rat, suggesting decreased sociability. These results suggest a long-term effect of maternal fever and systemic noninfectious inflammation on offspring social behavior, highlighting the need for further research into the mechanisms underlying these neurodevelopmental changes.