18th Apr 2019
The Children with HIV early antiretroviral trial (CHER) was aimed at investigating ART initiation strategies in infants and children in a resource limited setting in South Africa. The resulting cohort of infants followed up for a 36 months provided data on growth in anthropometric measurements, including head circumference that serves as a proxy measurement for brain size, especially before the age of two which is the period when almost all brain growth occurs. The aim of this analysis was to look at the impact of HIV infection and ART treatment on head circumference measurements, as a proxy for brain development, to assess the appropriateness of the WHO reference ranges for our cohort of healthy children, and to derive South African specific reference ranges using this cohort.
We adopted a broken-stick growth model for the head circumference profiles by including piecewise linear splines in a mixed effect model for the impact of the ART strategies on head circumference profiles over age. The LMS method was used to calculate z-scores using the WHO references ranges and the groups were compared with reference to these z-scores. Cohort specific percentiles and z-scores were calculated based on the Box-Cox Power distribution.
The model illustrated the positive effect of ART treatment with children on early ART catching up faster to the HIV- children than children on delayed ART. The latter group started catching up as the children start using ART at later ages.
Head circumference measurements for children included in the HIV-uninfected control groups were larger than expected based on WHO standards. Cohort specific derived reference ranges thus illustrated an upward adjustment of the percentile bands.