TY - JOUR
T1 - Maternal Immune Activation and Child Brain Development
T2 - A Longitudinal Population-Based Multimodal Neuroimaging Study
AU - Suleri, Anna
AU - White, Tonya
AU - de Witte, Lot
AU - Gigase, Frederieke
AU - Cecil, Charlotte A.M.
AU - Jaddoe, Vincent W.V.
AU - Breen, Michael
AU - Hillegers, Manon H.J.
AU - Muetzel, Ryan L.
AU - Bergink, Veerle
N1 - © 2024 Society of Biological Psychiatry
PY - 2025/2
Y1 - 2025/2
N2 - BackgroundMaternal immune activation (MIA) has been hypothesized to have an adverse effect on child neurodevelopment, but only a few neuroimaging studies have been performed to date, mostly in neonates. In this population-based cohort study, we investigated the association between MIA and multiple neuroimaging modalities depicting brain development from childhood to adolescence.MethodsWe used data of mother-child pairs from the Generation R Study. To define our exposure, we measured interleukin (IL) 1β, IL-6, IL-17a, IL-23, interferon gamma, and C-reactive protein at 2 time points during pregnancy. Because levels of these 5 cytokines were highly correlated, we were able to compute a cytokine index. We used multiple brain imaging modalities as outcomes, including global and regional measures of brain morphology (structural magnetic resonance imaging, volume; n = 3295), white matter microstructure (diffusion magnetic resonance imaging, fractional anisotropy and mean diffusivity; n = 3267), and functional connectivity (functional magnetic resonance imaging, graph theory measures, and network-level connectivity; n = 2914) in the children at ages 10 and 14 years. We performed mixed effects models using child’s age as a continuous time variable.ResultsWe found no significant effect of time on any neuroimaging outcomes in children over time, and there was no time × MIA interaction. These associations were similar for the cytokine index, C-reactive protein, and individual cytokines. We observed no evidence for differential effects of timing of prenatal MIA or child sex after multiple testing correction.ConclusionsIn this longitudinal population-based study, we found no evidence for an association between MIA and child brain development in the general population. Our findings differ from previous research in neonates that have shown structural and functional brain abnormalities after MIA.
AB - BackgroundMaternal immune activation (MIA) has been hypothesized to have an adverse effect on child neurodevelopment, but only a few neuroimaging studies have been performed to date, mostly in neonates. In this population-based cohort study, we investigated the association between MIA and multiple neuroimaging modalities depicting brain development from childhood to adolescence.MethodsWe used data of mother-child pairs from the Generation R Study. To define our exposure, we measured interleukin (IL) 1β, IL-6, IL-17a, IL-23, interferon gamma, and C-reactive protein at 2 time points during pregnancy. Because levels of these 5 cytokines were highly correlated, we were able to compute a cytokine index. We used multiple brain imaging modalities as outcomes, including global and regional measures of brain morphology (structural magnetic resonance imaging, volume; n = 3295), white matter microstructure (diffusion magnetic resonance imaging, fractional anisotropy and mean diffusivity; n = 3267), and functional connectivity (functional magnetic resonance imaging, graph theory measures, and network-level connectivity; n = 2914) in the children at ages 10 and 14 years. We performed mixed effects models using child’s age as a continuous time variable.ResultsWe found no significant effect of time on any neuroimaging outcomes in children over time, and there was no time × MIA interaction. These associations were similar for the cytokine index, C-reactive protein, and individual cytokines. We observed no evidence for differential effects of timing of prenatal MIA or child sex after multiple testing correction.ConclusionsIn this longitudinal population-based study, we found no evidence for an association between MIA and child brain development in the general population. Our findings differ from previous research in neonates that have shown structural and functional brain abnormalities after MIA.
UR - http://www.scopus.com/inward/record.url?scp=85213943689&partnerID=8YFLogxK
U2 - 10.1016/j.bpsc.2024.10.013
DO - 10.1016/j.bpsc.2024.10.013
M3 - Article
C2 - 39491788
AN - SCOPUS:85213943689
SN - 2451-9022
VL - 10
SP - 222
EP - 235
JO - Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
JF - Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
IS - 2
ER -