Maternal influenza infection during pregnancy impacts postnatal brain development in the rhesus monkey.
BACKGROUND
Maternal infection with influenza and other pathogens during pregnancy has been associated with increased risk for schizophrenia and neurodevelopmental disorders. In rodent studies, maternal inflammatory responses to influenza affect fetal brain development. However, to verify the relevance of these findings to humans, research is needed in a primate species with more advanced prenatal corticogenesis.


METHODS
Twelve pregnant rhesus monkeys were infected with influenza, A/Sydney/5/97 (H3N2), 1 month before term (early third trimester) and compared with 7 control pregnancies. Nasal swabs and blood samples confirmed viral shedding and immune activation. Structural magnetic resonance imaging was conducted at 1 year; behavioral development and cortisol reactivity were also assessed.


RESULTS
Maternal infections were mild and self-limiting. At birth, maternally derived influenza-specific immunoglobulin G was present in the neonate, but there was no evidence of direct viral exposure. Birth weight and gestation length were not affected, nor were infant neuromotor, behavioral, and endocrine responses. However, magnetic resonance imaging analyses revealed significant reductions in cortical gray matter in flu-exposed animals. Regional analyses indicated the largest gray matter reductions occurred bilaterally in cingulate and parietal areas; white matter was also reduced significantly in the parietal lobe.


CONCLUSIONS
Influenza infection during pregnancy affects neural development in the monkey, reducing gray matter throughout most of the cortex and decreasing white matter in parietal cortex. These brain alterations are likely to be permanent, given that they were still present at the monkey-equivalent of older childhood and thus might increase the likelihood of later behavioral pathology.
Short
Sarah J
SJ
Department of Psychology, Harlow Center for Biological Psychology, University of Wisconsin, Madison, Wisconsin, USA. sjshort@med.unc.edu
Lubach
Gabriele R
GR
Karasin
Alexander I
AI
Olsen
Christopher W
CW
Styner
Martin
M
Knickmeyer
Rebecca C
RC
Gilmore
John H
JH
Coe
Christopher L
CL
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development* / Q000276:immunology / Q000821:virology; D001921:Brain / Q000473:pathology*; D005260:Female; D006854:Hydrocortisone / Q000097:blood; D053122:Influenza A Virus, H3N2 Subtype; D008253:Macaca mulatta; D008297:Male; D009976:Orthomyxoviridae Infections / Q000150:complications* / Q000473:pathology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000473:pathology* / Q000821:virology; D011270:Pregnancy, Animal; D011297:Prenatal Exposure Delayed Effects
D006854:Hydrocortisone