INCORPORATING CORRELATIONS BETWEEN MEASUREMENTS INTO THE ESTIMATION OF AGE-RELATED REFERENCE RANGES

An LMS-based maximum likelihood method of fitting age-related referenc e ranges is extended to incorporate non-independent measurements by in cluding the matrix of the correlations between standard normalized rep eat measurements into the likelihood. The likelihood is maximized via iterative re-estimation of the correlation structure and the reference range parameters until convergence is achieved. The correlation struc ture is explicitly modelled and the extent to which the estimated cent iles depend on the adequacy with which the correlation structure is mo delled is investigated, The method is illustrated using CD4 counts of uninfected children born to HIV-1 infected women. This data set consis ts of 5063 CD4 counts taken from 745 children at irregular ages betwee n birth and 10 years of age. The data exhibited a strong correlation s tructure with correlations decreasing with increasing time between mea surements and being lower for younger measurement ages. However, incor poration of the correlation had little effect on the choice of model f or the median or on the fitted centiles or their precision. (C) 1998 J ohn Wiley & Sons, Ltd.