Department of Psychology, Harlow Center for Biological Psychology, University of Wisconsin, Madison, Wisconsin, USA.
Biol Psychiatry. 2010 May 15;67(10):965-73. doi: 10.1016/j.biopsych.2009.11.026. Epub 2010 Jan 15.
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.
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.
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.
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.
母体在怀孕期间感染流感和其他病原体与精神分裂症和神经发育障碍的风险增加有关。在啮齿动物研究中，母体对流感的炎症反应会影响胎儿大脑发育。然而，为了验证这些发现与人类的相关性，需要在具有更先进产前皮质发生的灵长类物种中进行研究。
12 只怀孕的恒河猴在足月前 1 个月（妊娠晚期）感染了流感病毒 A/Sydney/5/97（H3N2），并与 7 例对照妊娠进行比较。鼻拭子和血液样本证实了病毒脱落和免疫激活。在 1 岁时进行结构磁共振成像；还评估了行为发育和皮质醇反应性。
母体感染轻微且自行限制。在出生时，新生儿中存在母体来源的流感特异性免疫球蛋白 G，但没有直接的病毒暴露证据。出生体重和妊娠时间不受影响，婴儿的神经运动、行为和内分泌反应也不受影响。然而，磁共振成像分析显示，暴露于流感的动物的皮质灰质明显减少。区域分析表明，双侧扣带回和顶叶区域的灰质减少最大；顶叶的白质也明显减少。
怀孕期间的流感感染会影响猴子的神经发育，使大部分皮层的灰质减少，并减少顶叶皮层的白质。鉴于这些脑改变在猴子相当于儿童后期仍然存在，因此可能会增加以后出现行为病理学的可能性，这些改变很可能是永久性的。
