HIV‐stage, nutritional status, and child psychomotor development in resource‐poor settings – a causal web

Neurodevelopmental delay in infants with HIV infection and young children occurs in resource poor countries as well as more advantaged settings. It is well known that HIV disrupts central nervous system function by direct and indirect mechanisms. Furthermore, the relationship between HIV and neurodevelopmental outcome is often confounded by contexts associated with poorer child development, including extreme poverty or inadequate child nurturing, sometimes due to illness or death of the mother. Abubakar et al. report on slower psychomotor development in a group of children infected with HIV, (6to 35-months old), compared with uninfected children of HIV-positive mothers and to a reference population. Disease stage and weight-for-age independently predicted developmental scores. Furthermore, children at an advanced disease stage exhibited poorer development if their weight-for-age was low. This excellent crosssectional study took place in a rural district in Kenya at a time when antiretroviral therapies were not available. The investigators propose poor nutritional status as a potential marker to trigger developmental screening and psychomotor rehabilitation, when necessary, in resource-poor environments. Strengths of this study include the use of a validated developmental assessment tool created by the investigators for use in this population. They elegantly designed and executed this study with reliable measurements of weight and disease stage. Furthermore comparisons with a group of uninfected children of HIV-positive mothers add internal validity and partially address questions about the influence of context on development in children infected with HIV. The authors did not discuss the major limitation of this study related to its cross-sectional design. As in all crosssectional studies, it is impossible to determine temporal precedence in the complex relationships between disease stage, nutritional status, and developmental outcome. This severely limits our ability to make any conclusions related to best practice for screening for developmental delay in this very high-risk population. For example, malnutrition can contribute to advancing HIV ⁄AIDS disease stage and can even predict or lead to death. Conversely, advancing disease could lead to poorer nutrition by decreasing caloric intake in a debilitated child. Similarly, it is difficult to know the direction of effect in the association between nutritional status and developmental outcome. Children with neurodevelopmental decline may lose the ability to chew and swallow or their appetite may diminish. Some become too weak and debilitated to take adequate calories. On the other hand, malnutrition probably contributes to poorer psychomotor functioning. And finally, an earlier longitudinal study showed that poor psychomotor functioning (the outcome of Abubakar et al.’s study) was a predictor of HIV ⁄AIDS disease progression (a predictor in this study). The relationships between disease stage, nutritional status, and psychomotor development are likely to be intricately interrelated. The investigators conclude that infant and child weight might be used to plan intervention and follow-up related to psychomotor development in infants infected with HIV. This strategy could only be considered in the most resource-poor environments. In this study, the 31 children infected with HIV had significantly worse psychomotor developmental status (p<0.001) compared with the reference population and the HIV-exposed but uninfected group. However, not all infected with HIV children had abnormal developmental scores. Nonetheless, even those with normal scores must be regarded as high risk for future developmental delay. Therefore, in most contexts, it would be appropriate to provide developmental monitoring and psychomotor rehabilitation, when required, for all infants and young children who are HIV positive. In other words, HIV-positive status might be a more effective screening tool than low weight-for-age, as malnutrition is likely to occur later in the trajectory of psychomotor decline. Future studies employing a longitudinal design could begin to untangle the question of whether malnutrition in children with HIV is the prime determinant of developmental functioning, or whether advancing illness and debilitation might pre-date worsening nutrition. Furthermore, those with central nervous system involvement might have simultaneously worsening nutritional status and neurodevelopmental performance. Ideally, as the authors note, all infants and young children infected with HIV should receive nutritional support. Furthermore, it would be reasonable to provide developmental surveillance leading to early intervention in order to improve quality of life.