Neurodevelopmental and behavioural outcome of the HIV-exposed uninfected infant and child

Springer, Priscilla Estelle (2020-03)

Thesis (PhD)--Stellenbosch University, 2020.

Thesis

ENGLISH ABSTRACT: The first 1000 days of life represents a crucial phase for cognitive, language and emotional development. Indeed, early childhood development provides a foundation for educational and vocational success. Early screening and detection of developmental delay is therefore important, as timely intervention can improve school readiness. The human immunodeficiency virus (HIV) pandemic has been identified as a contributor to early developmental delay in low-and middle-income countries. In South Africa, successful vertical HIV-transmission prevention programmes have led to a substantial decrease in mother-to-child transmission rates. As a result, approximately one in four newborns are HIV-exposed but uninfected (HEU). However, the impact of both HIV exposure and anti-retroviral therapy on neurodevelopmental outcomes of HEU infants remains poorly understood. In particular, few prospective studies have combined developmental and behavioural assessments from infancy to early childhood. In response to this knowledge gap, a pilot study was performed to explore the feasibility of using the Griffiths Mental Development Scales to assess outcome in HEU compared to HIV-unexposed uninfected (HUU) infants. Following the initial pilot phase, mother-infant dyads were better matched for home language, cultural and maternal social characteristics and we extended infant assessments to include cognitive, motor, language and behavioural domains using the Bayley Scales of Infant and Toddler Development-3rd edition (BSID), as well as the Alarm Distress Baby Scale. The BSID was repeated at two-year follow-up, and behaviour was assessed using the Strengths and Difficulties Questionnaire. Despite similar performance in BSID motor, language and cognitive domains, more behavioural problems were reported by mothers of HUU children at 2-3 years old. Childhood stunting was associated with poorer motor and behavioural outcome, irrespective of HIV exposure. Based on initial findings, we further explored the use of the Molteno Adapted Scale (MAS) screening tool, and its correlations with the BSID at 11-14 months and 2-3 years of age in our study cohort. There was moderate correlation between the major domains of these tests; however, we were unable to test the diagnostic accuracy of the MAS, as too few participants had significant developmental delays. There was also increased discrepancy in scores of the assessment tools at the lower and upper ranges of the spectrum, which could potentially lead to under-identification of children at risk for delay. Lastly, we assessed the diagnostic accuracy of the Goodenough Drawing test screening tool (DAP) in a group of at-risk children at five years of age. The diagnostic accuracy of the DAP was sufficiently promising to justify its use as a research tool to detect visuo-perceptual and fine motor delay. High attrition rates and a small sample size were important limitations in our study. However, a major strength lies in the observation of the need for developmental surveillance and support for all children regardless of HIV exposure, especially those from socio-economically disadvantaged communities. Our findings could help South African policy makers justify initiatives encouraging multi-sectoral collaboration such as the Framework for Nurturing Care, aligning with both the fourth Sustainable Development Goal and the National Development Plan for 2030, which aims to “leave no child behind”.

AFRIKAANSE OPSOMMING: Die eerste 1 000 dae van ’n mens se lewe is ’n deurslaggewende fase vir kognitiewe, taal- en emosionele ontwikkeling. Vroeë kinderontwikkeling bied trouens ’n grondslag vir opvoedkundige en beroepsukses. Vroeë sifting en die identifisering van ontwikkelingsagterstande is gevolglik belangrik, aangesien tydige ingryping skoolgereedheid kan verbeter. Menslike immuniteitsgebrekvirus- (MIV) infeksie is as ’n bydraer tot agterstande in vroeë ontwikkeling geïdentifiseer in lae- en midde-linkomste-lande. In Suid-Afrika het suksesvolle vertikale MIVoordragvoorkomingsprogramme tot ’n aansienlike afname in moeder-kind-oordragkoerse gelei. Ongeveer een uit elke vier pasgeborenes is gevolglik MIV-blootgestelde dog onbesmette babas (sogenaamde HEU’s). Die invloed van MIV-blootstelling en antiretrovirale behandeling op HEUbabas se neuro-ontwikkelingsuitkomste word egter steeds nie behoorlik verstaan nie. In die besonder kombineer weinig beoogde studies ontwikkelings- en gedragsevaluerings vanaf babatyd tot die vroeë kinderjare. Na aanleiding van hierdie kennisgaping is ’n loodstudie onderneem om die haalbaarheid van die gebruik van die Griffiths Mental Development Scales by die evaluering van uitkomste in HEU’s met uitkomste in MIV-nieblootgestelde babas (sogenaamde HUU’s) te vergelyk. Ná afloop van die loodsfase is moeder-baba-diades beter gepaar volgens huistaal, kulturele en moederlike sosiale kenmerke, terwyl ons baba-evaluerings uitgebrei het om kognitiewe, motoriese, taal- en gedragsdomeine aan die hand van die derde uitgawe van die Bayley Scales of Infant and Toddler Development® (BSID), asook die Alarm Distress Baby Scale in te sluit. Die BSID is in ’n tweejaaropvolgtoets herhaal, terwyl gedrag aan die hand van die “Strengths and Difficulties Questionnaire” geëvalueer is. Ondanks soortgelyke prestasies in die BSID- motoriese, taal- en kognitiewe domein, het moeders van HUU-kinders op 2- tot 3-jarige ouderdom meer gedragsprobleme gerapporteer. Belemmerde groei by kinders is met ’n swakker motoriese en gedragsuitkoms in verband gebring, ongeag blootstelling aan die MIV. Op grond van die aanvanklike bevindings, het ons verder die gebruik van die “Molteno Adapted Scale- (MAS-)” siftingsinstrument en die korrelasies daarvan met die BSID op 11 tot 14 maande en 2 tot 3 jaar in ons studiekohort ondersoek. Daar was matige korrelasie tussen hierdie toetse se belangrikste domeine. Ons kon egter nie die diagnostiese akkuraatheid van eersgenoemde groep toets nie, aangesien te min deelnemers beduidende ontwikkelingsagterstande ervaar het. Daar was ook groter afwykingsverskille in die tellings van die evalueringsinstrumente vir die onderste en boonste reikwydtes van die spektrum, wat moontlik tot die onderidentifikasie van kinders wat aan die risiko van agterstande blootgestel is, kan lei. Laastens het ons die diagnostiese akkuraatheid van die “Goodenough–Harris Drawing Test” (DAP) siftingsinstrument in ’n groep van vyfjarige risikokinders beoordeel. Die diagnostiese akkuraatheid van die DAP was belowend genoeg om die gebruik daarvan as ’n navorsingsinstrument te regverdig, met die oog op die opsporing van visueelperseptuele en fynmotoriese agterstande. Hoë afslytingskoerse en ’n klein steekproefgrootte was belangrike beperkings in ons studie. ’n Belangrike sterk punt lê egter in die observasie van die behoefte aan ontwikkelingsbewaking en - steun vir alle kinders, ongeag hul blootstelling aan MIV, veral dié uit sosio-ekonomies benadeelde gemeenskappe. Ons bevindings kan Suid-Afrikaanse beleidmakers help met die motivering van inisiatiewe ter bevordering van multisektorale samewerking, soos die Raamwerk vir Sorgsame Versorging, wat strook met die vierde Volhoubaarheidsontwikkelingsdoelwit (SDG) en met die Nasionale Ontwikkelingsplan vir 2030, wat wil verseker dat “geen kind agterweë gelaat word nie”.

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