**4. Seroprevalence studies in mothers and newborns**

The possible transplacental transmission of *T. gondii* has attracted considerable attention in seroprevalence studies. Maternal infection during the first or second trimester of pregnancy can lead to severe problems in the offspring, including intracranial calcifications, chorio‐ retinitis, blindness, deafness, hydrocephaly, microcephaly, mental retardation, psychomo‐ tor retardation, pancytopenia, or epilepsy. The timing of the transmission is an influential factor: early maternal infection less frequently affects the fetus but is associated with a more severe congenital toxoplasmosis that may result in intrauterine death and miscarriages, while later maternal infection (third trimester) increases the risk of affecting the fetus but is associated with offspring who are asymptomatic [17]. Complications, possibly including schizophrenia, can appear decades later in patients with initially undetected infection due to its reactivation [59].

This type of study can be classified into two groups: those on the presence of antibodies in pregnant women and the development of schizophrenia in their offspring; those on the pres‐

ence of antibodies in newborns and their later development of schizophrenia. Among the for‐ mer, Brown et al. [60] and Blomström et al. [61] demonstrated associations between increased anti‐*Toxoplasma* IgG levels in pregnant mothers and risk of schizophrenia in their offspring, although other researchers published discrepant results [62]. Xiao et al. [63] observed a signif‐ icant association between the presence of maternal antibodies against type I *T. gondii* (but not against types II or III) and the onset of psychotic disorders in the offspring. Among the latter group of studies, Mortensen et al. [59] demonstrated that newborn levels of anti‐*T. gondii* IgG levels (from the mother) were significantly higher in individuals who developed schizophre‐ nia in adulthood.

Published data suggest that schizophrenia risk in offspring is associated with persistent maternal infection by *T. gondii* but is not directly related to acute maternal infection [64]. If this were the case, a significant association could be expected between the presence of IgM in the serum of mothers and/or newborns and the presence of the disease, which has not been demonstrated [60]. However, this relationship may be masked by the low frequency of anti‐*Toxoplasma* IgM detection in pregnant women [24, 65].

As noted above, increased maternal IgG levels can cross the placenta (unlike IgM antibod‐ ies) and may damage fetal brain development by molecular mimicry [60, 64]. However, the presence of maternal IgG may indicate a reactivation of latent infection due to the impact of immune system disorders on protozoan replication control during pregnancy [66]; hence, brain development could also be impaired by transplacental transmission and/or the passage of inflammatory cytokines to the fetus [67, 68].

The majority of schizophrenic patients do not have anti‐*Toxoplasma* antibodies, and the major‐ ity of seropositive patients are not schizophrenic. Therefore, *T. gondii* would only explain a minority of cases. Other factors under investigation that may explain why only some parasit‐ ized individuals develop schizophrenia include genetic susceptibility, the infective genotype of the parasite, the existence of different infection pathways, and the timing of toxoplasmosis onset [20, 33, 63].
