Related Experiment Video
Updated: Jul 10, 2025
Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats
Published on: November 20, 2015
Placental inflammatory cytokines mRNA expression and preschool children's cognitive performance: a birth cohort study
Jixing Zhou1,2,3,4, Juan Tong1,2,3,4, Xue Ru1,2,3,4
1Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, Hefei, 230032, China.
Insights
High levels of placental inflammatory cytokines, including IL-8, IL-6, TNF-α, and IFN-γ, were linked to lower cognitive performance in preschoolers. This suggests the intrauterine placental immune environment impacts offspring intellectual development, particularly in boys.
Area of Science:
- Reproductive immunology
- Developmental neuroscience
- Pediatric health
Background:
- The maternal-fetal interface's immunologic environment influences fetal brain development.
- Limited epidemiological data exists on placental inflammatory cytokines and offspring cognitive function.
Purpose of the Study:
- To investigate the association between placental inflammatory cytokine mRNA expression and cognitive performance in preschoolers.
- To explore the impact of the intrauterine immune milieu on child intellectual development.
Main Methods:
- Utilized real-time quantitative polymerase chain reaction (RT-qPCR) to measure placental mRNA levels of IL-8, IL-6, TNF-α, and IFN-γ.
- Assessed cognitive development in preschoolers using the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV).
- Employed multiple linear regression and restricted cubic spline models for statistical analysis in the Ma'anshan birth cohort (MABC) of 1665 mother-child pairs.
Main Results:
- Elevated placental mRNA expression of IL-8, IL-6, TNF-α, and IFN-γ was significantly associated with lower full-scale intelligence quotient (FSIQ) in preschoolers.
- Higher IL-8 and IL-6 correlated with lower fluid reasoning index (FRI), while higher IFN-γ was linked to lower working memory index (WMI).
- An integrated index of pro-inflammatory cytokines negatively correlated with FSIQ and its sub-dimensions; these associations were more pronounced in boys.
Conclusions:
- Found evidence linking low cognitive performance to high placental inflammatory cytokine expression (IL-8, IL-6, TNF-α, IFN-γ).
- Highlights the potential importance of the intrauterine placental immune status in determining offspring cognitive development.
- Suggests sex-specific influences of placental inflammation on cognitive outcomes.
Background:
The immunologic milieu at the maternal-fetal interface has profound effects on propelling the development of the fetal brain. However, accessible epidemiological studies concerning the association between placental inflammatory cytokines and the intellectual development of offspring in humans are limited. Therefore, we explored the possible link between mRNA expression of inflammatory cytokines in placenta and preschoolers' cognitive performance.
Methods:
Study subjects were obtained from the Ma'anshan birth cohort (MABC). Placental samples were collected after delivery, and real-time quantitative polymerase chain reaction (RT-qPCR) was utilized to measure the mRNA expression levels of IL-8, IL-1β, IL-6, TNF-α, CRP, IFN-γ, IL-10, and IL-4. Children's intellectual development was assessed at preschool age by using the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV). Multiple linear regression and restricted cubic spline models were used for statistical analysis.
Results:
A total of 1665 pairs of mother and child were included in the analysis. After adjusting for confounders and after correction for multiple comparisons, we observed that mRNA expression of IL-8 (β = - 0.53; 95% CI, - 0.92 to - 0.15), IL-6 (β = - 0.58; 95% CI, - 0.97 to - 0.19), TNF-α (β = - 0.37; 95% CI, - 0.71 to - 0.02), and IFN-γ (β = - 0.31; 95% CI, - 0.61 to - 0.03) in the placenta was negatively associated with preschoolers' full scale intelligence quotient (FSIQ). Both higher IL-8 and IL-6 were associated with lower children's low fluid reasoning index (FRI), and higher IFN-γ was associated with lower children's working memory index (WMI). After further adjusting for confounders and children's age at cognitive testing, the integrated index of six pro-inflammatory cytokines (index 2) was found to be significantly and negatively correlated with both the FSIQ and each sub-dimension (verbal comprehension index (VCI), visual spatial index (VSI), FRI, WMI, processing speed index (PSI)). Sex-stratified analyses showed that the association of IL-8, IFN-γ, and index 2 with children's cognitive development was mainly concentrated in boys.
Conclusions:
Evidence of an association between low cognitive performance and high expression of placental inflammatory cytokines (IL-8, IL-6, TNF-α, and IFN-γ) was found, highlighting the potential importance of intrauterine placental immune status in dissecting offspring cognitive development.
More Related Videos
07:13Induction of Maternal Immune Activation in Mice at Mid-gestation Stage with Viral Mimic PolyI:C
Published on: March 25, 2016
08:50A Murine Model of Fetal Exposure to Maternal Inflammation to Study the Effects of Acute Chorioamnionitis on Newborn Intestinal Development
Published on: June 24, 2020
Related Concept Videos
01:29Environmental Influences on Intelligence
01:30Information Processing Approach