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Updated: Jul 25, 2025

Induction of Maternal Immune Activation in Mice at Mid-gestation Stage with Viral Mimic PolyI:C
Published on: March 25, 2016
Fetal inflammatory response and risk for psychiatric disorders
Blake Gibson1, Eli Goodfriend2, Yongqi Zhong3
1University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Insights
Children born with placental inflammation, known as fetal inflammatory syndrome (FIRS), face a higher risk of developing childhood neuropsychiatric disorders. Early detection and monitoring are crucial for these at-risk children.
Area of Science:
- Neuroscience
- Developmental Pediatrics
- Obstetrics
Background:
- Maternal intrauterine environment and placental health significantly influence fetal brain development and neuropsychiatric disorder risk.
- Childhood-onset neuropsychiatric disorders are increasingly linked to inflammatory processes.
Purpose of the Study:
- To investigate the association between fetal inflammatory syndrome (FIRS), characterized by placental inflammation, and the incidence of neuropsychiatric disorders in children.
- To identify specific neuropsychiatric conditions associated with FIRS.
Main Methods:
- Retrospective cohort study utilizing electronic medical records from a 19-year period.
- Included 4851 children with FIRS (chorionic vasculitis and/or funisitis) and 31,927 controls.
- Follow-up for at least 5 years to assess primary outcome (neuropsychiatric disorders) and secondary outcomes (medications, hospitalizations).
Main Results:
- Children with FIRS demonstrated a significantly higher likelihood of developing neuropsychiatric disorders (OR=1.21, CI 95% [1.09, 1.35]).
- Increased risks were observed for autism spectrum disorder (OR=1.35), ADHD (OR=1.27), conduct disorder (OR=1.50), and PTSD (OR=2.46).
- Adjustments were made for maternal psychiatric history, substance use, and anti-inflammatory drug prescriptions.
Conclusions:
- Placental inflammation (FIRS) is associated with an increased risk of childhood neuropsychiatric disorders.
- Findings highlight the importance of the intrauterine environment in neurodevelopmental outcomes.
- Implications for enhanced research, early detection, monitoring, and treatment strategies for affected children.
Abstract:
Inflammation contributes to numerous neuropsychiatric disorders, especially those that first appear in childhood. Maternal intrauterine environment, including the placenta, has a role in brain development and risk for neuropsychiatric disorders. This study examines the link between fetal inflammatory syndrome (FIRS), which is placental inflammation in the peri-partem period, and neuropsychiatric disorders during childhood.This is a retrospective cohort study using data from electronic medical records over a 19-year period at one women's hospital. The study includes 4851 children born with placentas meeting criteria for and 31,927 controls identified with normal placentas born during the same period. To be diagnosed with FIRS placenta must contain chorionic vasculitis and/or funisitis. Children had to be in study period for at least 5 years. The primary outcome of the study is incidence of neuropsychiatric disorders during childhood. The secondary outcomes were psychiatric medications prescribed, and psychiatric hospitalizations and treatment. Children born to placentas meeting criteria for FIRS were more likely to be diagnosed with neuropsychiatric disorders (OR = 1.21, CI 95% [1.09,1.35]). Specifically, they were more likely to be diagnosed with autism spectrum disorder (OR = 1.35, CI 95% [1.08, 1.67]), ADHD (OR = 1.27, CI 95% [1.07, 1.49]), conduct disorder (OR = 1.50, CI 95% [1.24, 1.81]), PTSD (OR = 2.46. CI 95% [1.21, 5.04]), adjusting for maternal history of psychiatric disorders, intra-partem substance use, and prescriptions of anti-inflammatory drugs. Children born with placental inflammation are at an increased risk to develop neuropsychiatric disorders. This has profound implications for future research, and early detection, monitoring, and treatment in these children.
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