Analysis of the bovine spongiform encephalopathy maternal cohort study: Evidence for direct maternal transmission

In an initial exploratory analysis of the bovine spongiform encephalopathy (BSE) maternal cohort study data we demonstrate several confounding effects in the study design. Given these effects, we assess a variety of statistical models to determine the relative contributions of direct maternal transmission of the aetiological agent of BSE and of genetic susceptibility to the observed maternally enhanced risk of BSE in the offspring of affected dams. To control for the substantial between-herd variation in the risk of exposure to the BSE agent it is essential that analyses take into account the matched pair structure of the data. Maternal exposure is estimated to be most important in animals born within 150 days of disease onset in their dams. The analysis of a full survival likelihood model indicates that the hypothesis of maternal transmission with no genetic variation in susceptibility fits the data significantly better than the hypothesis of genetically variable susceptibility with no maternal transmission. However, models incorporating both maternal transmission and genetically variable susceptibility fit the data significantly better than pure maternal transmission models. Although genetic susceptibility cannot be excluded as the cause of the cohort study results in the absence of detailed genotyping, the analysis of these study data suggest that low level maternal transmission of BSE is. at least in part, responsible for the significantly enhanced risk of BSE in the offspring of affected dams. Similar results indicating significant maternal transmission in the later stages of the dam incubation period are obtained from the independent analysis of data on the dam-offspring relationships among confirmed BSE cases.