The Risks Posed by Prenatal and Perinatal Infection

Maternal illness continues to be one of the more significant challenges to the maintenance of pregnancy and to fetal well-being (McGregor et al, 1995). In addition to concerns about miscarriage and premature delivery, many bacteria and viruses can pose a grave threat to the fetus if they are able to infect placental tissues or transfer across the placenta. Rubella, syphilis, and toxoplasma are among the pathogens that were once prominent health hazards. Even the common herpes viruses, such as cytomegalovirus, which are normally benign when restricted to the maternal compartment, can have devastating effects on brain development if they reach the fetal compartment or if there is exposure during delivery or the early postpartum period (Barry et al, 2006; Revello and Gerna, 2002).

There has also been a long-standing suspicion that prenatal infections and obstetrical complications may play a role in certain neurodevel-opmental disorders and psychiatric conditions (Mednick et al, 1998). Viral infections have been implicated as possible causative agents for both autism and attention-deficit hyperactivity disorder (ADHD), although both of these pediatric conditions are obviously very complex and can be caused by other factors as well. Even more has been written about the possible involvement of prenatal infections as the reason for the brain dysfunction underlying schizophrenia (Brown, 2006; Byrne et al, 2007; Torrey and Torrey, 1979; Yolken et al, 1997). Concerns about exposure to influenza during pregnancy have been validated by support from animal models, at least after infection with more virulent strains (Shi et al, 2003,2005; Fatemi et al, 2008; Fortier et al, 2007). In both rat and mouse models of maternal influenza infection during pregnancy, there have been effects found on brain size, structure, cortical thickness, and monoamine neurochemistry.

If infection with influenza during pregnancy can really be harmful to fetal brain development, it is a more serious concern when virulent strains circulate at pandemic levels (Harris, 1919). Even in a typical year, up to 11% of pregnant women are infected with influenza at some point during gestation (Irving et al, 2000). Moreover, the offspring of infected pregnant women who are asthmatic are at greater risk because they are more likely to progress on to bacterial pneumonia (Hartert et al, 2003). However, the jury is still out on whether the more benign strains of influenza that commonly circulate, which cause just a transient illness and fever, are of equivalent concern. One particularly active area of research right now is on the mediating role of the increased proinflammatory cytokine activity during infection, because it can adversely alter placental functioning (Dammann and Leviton, 1997). Some cytokines, such as interleukin-6, can also cross the placenta and reach the fetus or stimulate fetal tissues to synthesize their own cytokines. If cytokines in fetal circulation get high enough, they can disrupt the proliferation of neurons, formation of dendrites, and the establishment of synaptic connections in the maturing brain (Lowe et al, 2008; Saito et al, 2009).

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