Prenatal infection A range of prenatal infective agents can impact on brain development.  While influenza was the focus of much research during the 1990s, the strength of the evidence of prenatal exposure to influenza is weak and inconsistent (McGrath and Castle, 1995). Other candidate viruses include rubella (Susser et al., 1999), coxsackievirus B (Rantakillio et al., 1997) and Borna virus (Salvatore et al., 1997). There are no robust data yet to either support or reject the theory that pre- or perinatal exposure to infection increases the risk of schizophrenia. However, until there are convincing data from well-designed and adequately powered studies, the viral theory should remain as a candidate risk factor. From the perspective of universal interventions, viral illness can be prevented by vaccinations, and there are now examples of public health interventions where mass vaccinations have eliminated certain viruses completely.  This is another area where the intervention cannot confidently be put forward for schizophrenia, but it has many other beneficial effects.

Nutritional factors There has been considerable interest in recent years about the impact of prenatal nutrition and various adult-onset disorders such as diabetes, cardiovascular disease and hypertension (Barker, 1992). Prenatal nutritional factors are biologically plausible risk-modifying factors for neurodevelopmental disorders (Brown et al., 1996). Susser and colleagues (1996) identified increased risk of schizophrenia in the offspring of women who were pregnant during a famine in the Netherlands during World War II.  While studies of the incidence of schizophrenia in developing nations (where poor nutrition is more prevalent) do not show higher rates, there remains the possibility that deficits in specific micronutrients may play a role. In a population-based study from Finland (Wahlbeck et al.,  2001),  the offspring of women with low late-pregnancy body mass index had an increased risk of schizophrenia. While we cannot assume that this variable was causally related to risk of schizophrenia in the offspring, it does open a window for possible intervention. Even in the absence of deficits, supplementing prenatal nutrition warrants consideration. For example, supplementing folate to women periconceptually is associated with a reduction in the incidence of neural tube defects in their offspring (Scott et al., 1994). Recent evidence from a randomized controlled trial of nutritional supplements for preterm infants found not only that cognitive outcomes (measured at age 7 years) were superior in the group allocated the enriched infant formulae but also this group had less cerebral palsy (Lucas et al., 1998). This study suggested that suboptimal nutrition during a critical period of brain growth could impair functional compensation in those sustaining an earlier brain insult. In summary, while the evidence implicating prenatal nutrition as a risk factor in schizophrenia is scant, it is another attractive candidate for universal intervention. Better maternal nutrition is safe, relatively cheap and could feasibly impact on a range of health outcomes. John McGrath
Queensland Centre for Schizophrenia Research, Wolston Park Hospital, Wacol, Australia

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