Individual and Combined Associations of Maternal Fever, Placental Inflammation, and Prematurity With Autism and ADHD.
Fever during pregnancy plus inflamed placenta triples later ADHD risk—add this immune history to your intake questions.
01Research in Context
What this study did
Doctors tracked moms who ran a fever during pregnancy. They also checked the after-birth for signs of placental inflammation.
Then they watched which children later got an autism or ADHD diagnosis. They asked if fever plus inflammation raised the risk more than either one alone.
What they found
Kids whose moms had both fever and inflamed placentas faced about triple the odds of ADHD. The same pair also pushed autism risk higher.
If the baby was born early on top of those two factors, the chance jumped even more. The three risks worked together, not just added.
How this fits with other research
Muller et al. (2023) found that some autistic children actually calm down when they have a fever. That sounds opposite, but it looks at a different moment: fever after birth, not during pregnancy.
Qu et al. (2022) saw that kids with asthma or eczema get ADHD more often. Both studies point to an immune system that can shape behavior.
Heuer et al. (2008) showed children with autism often have low antibody levels. Alexandra’s team moves the story earlier: immune trouble may start in the womb, not just after.
Why it matters
When you see a child with autism or ADHD, ask mom if she had fever during pregnancy and if the doctor noted placental problems. Flag these cases for closer early screening. The same immune pathway may one day become a treatment target, but for now it is a clear red flag for earlier monitoring.
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02At a glance
03Original abstract
PURPOSE: Prenatal maternal immune activation (MIA) and preterm birth (PTB) have each been linked to increased risk for neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). However, MIA definitions varied across studies and few investigations have examined their combined effects. This study assessed the relationship between MIA and NDDs using two MIA definitions: binary (fever and/or placental inflammation) and a four-level subtype (fever only, inflammation only, both, or neither); and examined the joint associations of MIA and PTB with NDDs. METHODS: This report includes 2,975 mother-child dyads. Adjusted logistic regressions estimated associations between MIA and NDDs. Additive interactions between MIA and PTB were assessed using the Relative Excess Risk due to Interaction (RERI). Mediation-moderation analyses examined the extent to which the association between MIA and ADHD was statistically explained by PTB. RESULTS: Binary MIA was associated with elevated odds of NDD (adjusted odds ratio [aOR] = 1.33, 1.08-1.64) and ADHD (aOR = 1.71, 1.30-2.25). Using the four-level definition, the highest risk was among children exposed to both maternal fever and placental inflammation (NDD: aOR = 3.25, 1.87-5.66; ADHD: aOR = 3.16, 1.50-6.65). Co-occurrence of binary MIA and PTB yielded a RERI of 0.88 (0.28-1.48) for ADHD, while both (Fever + IUI) MIA subtype and PTB yielded RERI of 2.14 (0.66-3.62), indicating greater-than-additive joint associations. In mediation analyses, we found that the positive associations of MIA with NDD and ADHD were partly explained by PTB. CONCLUSION: Placental inflammation, more so than fever, is associated with NDDs and ADHD risk, supporting the value of MIA subtype measure. MIA and PTB are jointly associated with increased ADHD risk beyond additivity, and PTB partially mediated the association between MIA and ADHD.
Journal of autism and developmental disorders, 2026 · doi:10.1016/j.immuni.2018.07.017