Childhood IQ, hearing loss, and maternal thyroid autoimmunity in the Baltimore Collaborative Perinatal Project.

BACKGROUND: Maternal thyroid autoantibodies during pregnancy have been implicated in neurodevelopmental delays, including early childhood cognitive deficits. We evaluated whether maternal autoantibodies to thyroid peroxidase (TPOaAbs) during late pregnancy were associated with childhood intelligence quotient (IQ) scores in their offspring and how the children's TPOaAb-associated sensorineural hearing loss (HL) might affect the result. METHODS: We evaluated banked third-trimester sera corresponding to 1,733 children for whom childhood cognitive test scores and audiology data were available. The mothers and their children participated in the National Institutes of Health (NIH)-sponsored Collaborative Perinatal Project (CPP) that ran from 1959 to 1974. RESULTS: A modest, statistically significant, effect of TPOaAbs on cognitive performance observed at 4 y of age lessened in both magnitude and P value by the age of 7 y. Children with sensorineural HL (SNHL) had lower IQ scores at both ages. CONCLUSION: Our data suggest that the reported effect of maternal TPOaAbs on IQ may involve early developmental delays or transient effects rather than permanent deficits. Reports associating TPOaAbs directly with IQ may reflect a portion with unexamined TPOaAb-associated SNHL. Whether the TPOaAb-associated SNHL is in the neurodevelopmental pathway of later cognitive delays or is independently associated with IQ requires investigation in other studies.

Infection and thyroid autoimmunity: A seroepidemiologic study of TPOaAb.

Infectious agents have been implicated as triggers of autoimmunity. Prospective epidemiologic studies of infection with specific pathogens and the subsequent elevation of specific autoantibodies are difficult and costly to conduct. As a result, a solid body of evidence regarding this theoretically intriguing connection remains to be accrued. We studied term sera from 1807 pregnancies in 1591 women for whom IgG status for cytomegalovirus, Epstein-Barr virus, herpes simplex virus type 1, herpes simplex virus type 2, and/or Toxoplasma gondii was available from prior analyses. We tested the sera (masked regarding infectious status) for autoantibodies to thyroid peroxidase (TPOaAb) and then unmasked and linked them. Adjusted for other cofactors, prior infection with T. gondii was associated significantly with the elevation of TPOaAb, whereas seropositivity for other infections was not. Negative and positive findings for suspected triggers of autoimmunity should be reported to build the evidentiary basis needed to advance our understanding of the disease process. The positive association observed between prior infection with T. gondii and the elevation of TPOaAb is supported by an almost simultaneous study. These findings require further investigation. We believe that if T. gondii is in fact confirmed to trigger or enhance a TPOaAb response, the most likely mechanism involved is the bystander effect.

Maternal thyroid autoantibodies during the third trimester and hearing deficits in children: an epidemiologic assessment.

Elevated maternal thyroid autoantibodies during pregnancy are linked to infertility, miscarriage, and neurodevelopmental deficits such as in cognitive function. It has not been established whether autoantibodies to thyroid peroxidase are associated with sensorineural hearing loss (SNHL). The authors tested stored third-trimester maternal serum specimens of 1,736 children for thyroid peroxidase autoantibodies (TPOaAb) by using an enzyme-linked immunosorbent assay technique. The children participated at the Baltimore, Maryland, site of the Collaborative Perinatal Project, which enrolled pregnant women in 1959-1965. An audiology examination was administered to the children at 8 years of age and was used to identify cases of SNHL. Compared with 4.3% of the other children, 22.7% of the children whose mothers had elevated TPOaAb (> or =62.5 IU/ml) had SNHL. The difference was significant after controlling for maternal race, age, and hypothyroidism (exact prevalence odds ratio = 7.5, 95% confidence interval: 2.4, 23.3). When a lower cutoff of TPOaAb > or =31.25 IU/ml was used, there continued to be an association with SNHL (exact prevalence odds ratio = 5.7, 95% confidence interval: 2.1, 15.6). The direction and magnitude of the association were similar when an alternative case definition of SNHL was used. These data suggest that antenatal exposure to maternal TPOaAb during the third trimester of pregnancy is associated with impaired auditory development.