ANALYSIS OF THE BOVINE SPONGIFORM ENCEPHALOPATHY MATERNAL COHORT STUDY - EVIDENCE FOR DIRECT MATERNAL TRANSMISSION

In an initial exploratory analysis of the bovine spongiform encephalop athy (BSE) maternal cohort study data we demonstrate several confoundi ng effects in the study design. Given these effects, we assess a varie ty of statistical models to determine the relative contributions of di rect maternal transmission of the aetiological agent of BSE and of gen etic susceptibility to the observed maternally enhanced risk of BSE in the offspring of affected dams. To control for the substantial betwee n-herd variation in the risk of exposure to the BSE agent it is essent ial that analyses take into account the matched pair structure of the data. Maternal exposure is estimated to be most important in animals b orn within 150 days of disease onset in their dams. The analysis of a full survival likelihood model indicates that the hypothesis of matern al transmission with no genetic variation in susceptibility fits the d ata significantly better than the hypothesis of genetically variable s usceptibility with no maternal transmission. However, models incorpora ting both maternal transmission and genetically variable susceptibilit y fit the data significantly better than pure maternal transmission mo dels. 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 transmis sion of BSE is. at least in part, responsible for the significantly en hanced risk of BSE in the offspring of affected dams. Similar results indicating significant maternal transmission in the later stages of th e dam incubation period are obtained from the independent analysis of data on the dam-offspring relationships among confirmed BSE cases.