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Maternal Prenatal Immune Activation Associated with Brain Tissue Microstructure and Metabolite Concentrations in Newborn Infants

Abstract

Few human studies have assessed the association of prenatal maternal immune activation (MIA) with measures of brain development and psychiatric risk in newborn offspring. Our goal was to identify the effects of MIA during the 2nd and 3rd trimesters of pregnancy on newborn measures of brain metabolite concentrations, tissue microstructure, and motor development. This was a prospective longitudinal cohort study conducted with nulliparous pregnant women who were aged 14 to 19 years and recruited in their 2nd trimester, as well as their children who were followed through 14 months of age. MIA was indexed by maternal interleukin-6 (IL-6) and C-reactive protein (CRP) in both trimesters of pregnancy. Primary outcomes included: (1) newborn brain metabolite concentrations as ratios to creatine (N-acetylaspartate (NAA)/creatine (Cr) and choline (Cho)/Cr) measured using Magnetic Resonance Spectroscopy; (2) newborn fractional anisotropy and mean diffusivity, measured using Diffusion Tensor Imaging; and (3) indices of motor development, assessed prenatally and postnatally at ages 4- and 14-months. Maternal IL-6 and CRP levels associated significantly with both metabolites in the putamen, thalamus, insula, and the internal capsule. Maternal IL-6 associated significantly with fractional anisotropy in the putamen, caudate, thalamus, insula, and precuneus, and with mean diffusivity in the inferior parietal and middle temporal gyrus. CRP associated significantly with fractional anisotropy in the thalamus, insula, and putamen. Significant associations were found in common regions across imaging modalities, though the direction of associations differed by immune marker. In addition, both maternal IL-6 and CRP (in both trimesters) prenatally associated significantly with offspring motor development at 4- and 14-months of age. The left thalamus mediated effects of IL-6 on postnatal motor development. These findings demonstrate that levels of MIA in mid- to late pregnancy in a generally healthy sample associate with tissue characteristics in newborn brain regions that primarily support motor integration and coordination, as well as behavioral regulation. Those brain effects may contribute to differences in motor development.

Citing Articles

Maternal Immune Activation and Child Brain Development: A Longitudinal Population-Based Multimodal Neuroimaging Study.

Suleri A, White T, de Witte L, Gigase F, Cecil C, Jaddoe V Biol Psychiatry Cogn Neurosci Neuroimaging. 2024; 10(2):222-235.

PMID: 39491788 PMC: 11805671. DOI: 10.1016/j.bpsc.2024.10.013.

References
1.
Bilbo S, Barrientos R, Eads A, Northcutt A, Watkins L, Rudy J . Early-life infection leads to altered BDNF and IL-1beta mRNA expression in rat hippocampus following learning in adulthood. Brain Behav Immun. 2007; 22(4):451-5. DOI: 10.1016/j.bbi.2007.10.003. View

2.
Chumbley J, Worsley K, Flandin G, Friston K . Topological FDR for neuroimaging. Neuroimage. 2009; 49(4):3057-64. PMC: 3221040. DOI: 10.1016/j.neuroimage.2009.10.090. View

3.
Malkova N, Yu C, Hsiao E, Moore M, Patterson P . Maternal immune activation yields offspring displaying mouse versions of the three core symptoms of autism. Brain Behav Immun. 2012; 26(4):607-16. PMC: 3322300. DOI: 10.1016/j.bbi.2012.01.011. View

4.
Patterson P . Immune involvement in schizophrenia and autism: etiology, pathology and animal models. Behav Brain Res. 2009; 204(2):313-21. DOI: 10.1016/j.bbr.2008.12.016. View

5.
Brown A, Hooton J, Schaefer C, Zhang H, Petkova E, Babulas V . Elevated maternal interleukin-8 levels and risk of schizophrenia in adult offspring. Am J Psychiatry. 2004; 161(5):889-95. DOI: 10.1176/appi.ajp.161.5.889. View