Skeletal maturation in Zimbabwean children and adolescents and the impact of HIV

Abstract

HIV remains a significant global health challenge affecting 1.5 million children worldwide with just 57% accessing antiretroviral therapy (ART). HIV infection and its treatment are known to impact growth and development in children. Skeletal maturation is a crucial component of the overall growth and development and is affected by several factors which include genetic ancestry and environmental factors such as, chronic conditions, socio-economic deprivation, and nutrition. In Zimbabwe HIV, malnutrition, and poverty may all impact growth. Understanding factors that influence growth will help inform ways to mitigate poor growth and development, improving outcomes in later life.
Skeletal maturation is assessed as Bone age (BA), with the two most widely used methods being Greulich and Pyle (GP) and Tanner and Whitehouse 3 (TW3), both are based upon assessment of hand wrist radiographs. BA differs from chronological age (CA), which is calculated from the date of birth and does not account for an individual’s stage of growth. Until this study, skeletal maturation had not been assessed in Zimbabwean children nor in children living with HIV (CLWH) in Africa. No study had been conducted in an African population to determine the best method to use, nor to determine factors that influence the skeletal maturation process in CLWH, and no study had assessed BA longitudinally in CLWH. The aim of my thesis was to describe skeletal maturation in Zimbabwean children and adolescents living with and without HIV and determine whether HIV and other environmental and lifestyle factors were associated with differences between BA and CA at baseline and after follow-up. I also aimed to determine which method of BA assessment is appropriate for use in Zimbabwean children and adolescents.
I used data from the IMVASK (The Impact of vertical HIV infection on child and adolescent skeletal development) study conducted in Harare, Zimbabwe, which provided a cohort of 609 peripubertal children living with and without HIV aged 8-16 years. Participants were recruited from HIV clinics at Parirenyatwa and Sally Mugabe hospitals and schools within the same catchment area. Hand wrist radiographs were taken at baseline and at one year follow-up. I first assessed BA using the TW3 and GP method. I used Bland and Altman plots to test the agreement between BA by both methods and then with CA. I calculated the inter- and intra-rater reliability and precision. I then determined skeletal maturity deviation (SMD); the difference between BA and CA and compared differences in means by HIV status in males and females at baseline and follow-up. I used linear regression models to determine factors (weight for age z-scores, socioeconomic status, orphanhood, puberty, physical activity, vitamin D and calcium intakes) associated with SMD both at baseline and follow-up.
The TW3 method was the most precise and appropriate for use in Zimbabwean children and adolescents aged 8-16 years, as GP was biased by age. The two methods (TW3 and GP) did not give equal estimates of BA and therefore should not be used interchangeably. At baseline perinatally acquired HIV infection and being underweight were independently associated with delays in skeletal maturation in both males and females. After one-year follow-up female and male CLWH were still falling behind in skeletal maturation although the association was partially attenuated in males, suggesting that they were not catching up to their fellow HIV negative counterparts. In addition, in males being underweight and in females, lower levels of physical activity were associated with delays in skeletal maturation after one year. In CLWH, delays in initiating ART contributed to delays in skeletal maturation.
In conclusion, the TW3 method of BA assessment should be used in Zimbabwean children and adolescents aged 8-16years.My findings support the “test and treat” policy recommended by WHO programmes where ART is initiated regardless of disease or immunological stage. My results highlight the need for further research to support integration of nutritional and physical activity interventions into routine health care programmes for CLWH, to help improve growth and development.

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Identifiers

ORCID for Farirayi Nyakoko: orcid.org/0000-0002-5874-2045

ORCID for Kate Ward: orcid.org/0000-0001-7034-6750

ORCID for Cyrus Cooper: orcid.org/0000-0003-3510-0709

ORCID for Leo Westbury: orcid.org/0009-0008-5853-8096

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