Association of caregiver quality of care with neurocognitive outcomes in HIV-affected children aged 2–5 years in Uganda

Abstract: Children affected by HIV are at increased risk of developmental and neuropsychological disturbances due to direct effects of HIV on the brain and direct effects associated with living in poverty. Caregivers can play an important role, through quality caregiving, in mitigating the negative effect of these stressors. This study used baseline data from an ongoing caregiver training intervention trial to evaluate the association between quality of caregiver-child interactions and neurocognitive outcomes in rural HIV-infected and HIV-exposed but uninfected children in Uganda. We also assessed the extent to which caregiver distress moderated this relationship. Data on 329 caregiver-child dyads were collected between March 2012 and July 2014, when the children were between 2 and 5 years of age. Child outcomes include the Mullen Scales of Early Learning to assess general cognitive ability and the Color Object Association Test to assess immediate memory and total recall. Caregiving quality was assessed using the Home Observation for the Measurement of the Environment (HOME) total and subscale scores. Caregiver distress was assessed using the Hopkins Symptom Checklist. General linear regression models assessed the association between the HOME total and subscale scores and child outcomes, with interaction terms used to test moderation by caregiver distress. Total HOME scores were positively and significantly associated with Mullen scores of cognitive ability; HOME acceptance subscale scores were positively and significantly associated with immediate recall scores. No other associations were statistically significant. As hypothesized, there is a strong association between the HOME and Mullen scores of cognitive ability in our study population, such that children who were assessed as living in environments with more stimulation also presented with a higher level of general neurocognitive development. Our results support the view of program guidance for HIV-affected children that suggest family-oriented care with emphasis on parent-child relationships for optimal child development

Caregiver socioemotional health as a determinant of child wellâ being in schoolâ aged and adolescent Ugandan children with and without perinatal HIV exposure

ObjectiveCaregiver socioâ emotional attributes are major determinants of child wellâ being. This investigation in vulnerable schoolâ aged Ugandan children estimates relationships between children’s wellâ being and their caregiver’s anxiety, depression and social support.MethodsPerinatally HIVâ infected, HIVâ exposed uninfected and HIVâ unexposed Ugandan children and their caregivers were enrolled. Perinatal HIV status was determined by 18 months of age using DNAâ polymerase chainâ reaction test; status was confirmed via HIV rapid diagnostic test when children were 6â 18 years old. Five indicators of child wellâ being (distress, hopelessness, positive future orientation, esteem and quality of life (QOL)) and caregiversâ socioemotional status (depressive symptoms, anxiety and social support) were measured using validated, culturally adapted and translated instruments. Categories based on tertiles of each caregiver psychosocial indicator were defined. Linear regression analyses estimated percent differences (β) and corresponding 95% confidence intervals (CI) for child wellâ being in relation to caregiver’s psychosocial status.ResultsAs per tertile increment, caregiver anxiety was associated with 2.7% higher distress (95%CI:0.2%, 5.3%) and lower selfâ esteem/QOL (β = â 1.3%/â 2.6%; 95%CI: â 5.0%,â 0.2%) in their children. Child distress/hopelessness increased (β = 3.3%/7.6%; 95%CI:0.4%, 14.7%) and selfâ esteem/QOL decreased 2.3% (β = â 2.3%/â 4.4%; 95%CI: â 7.2%, â 1.3%) as per tertile increment in caregiver depression. Higher caregiver social support was associated with lower distress and higher positive outlook (β = 3%; 95%CI:1.4%, 4.5%) in their children. HIVâ infected/exposed children had most caregiver depressionâ related QOL deficit (β = â 5.2%/â 6.8%; 95%CI: â 12.4%, â 0.2%) and HIVâ unexposed children had most caregiver social supportâ related enhancements in positive outlook (β=4.5%; 95%CI:1.9%, 7.1%).ConclusionsCaregiver anxiety, depressive symptoms and low social support were associated with worse wellâ being in schoolâ aged and adolescent children. Improvement of caregiver mental health and strengthening caregiver social support systems may be a viable strategy for improving wellâ being of vulnerable children and adolescents in this setting.ObjectifLes attributs socioâ affectifs des responsables d’enfants sont des déterminants majeurs du bienâ être des enfants. Cette investigation menée auprès d’enfants ougandais vulnérables dâ âge scolaire a estimé les relations entre le bienâ être des enfants et l’anxiété, la dépression et le soutien social de leur responsable.MéthodesDes enfants ougandais infectés par le VIH de manière périnatale, exposés au VIH mais non infectés, et non exposés au VIH ainsi que leurs responsables ont été inscrits. Le statut VIH périnatal a été déterminé à lâ âge de 18 mois à l’aide du test de PCR de lâ ADN; le statut a été confirmé par un test de diagnostic rapide du VIH chez les enfants âgés de 6 à 18 ans. Cinq indicateurs du bienâ être de l’enfant (détresse, désespoir, orientation future positive, estime et qualité de vie (QV)), et le statut psychosocial des responsables (symptômes dépressifs, anxiété et soutien social) ont été mesurés à l’aide de méthodes validées, adaptées à la culture et respectées et d’outils traduits. Des catégories basées sur les tertiles de chaque indicateur psychosocial du responsable ont été définies. Des analyses de régression linéaire ont estimé les différences en pourcentage (β) et les intervalles de confiance (IC) à 95% correspondants pour le bienâ être de l’enfant par rapport au statut psychosocial de leurs responsables.RésultatsPar incrément de tertile, l’anxiété des responsables était associé à 2,7% de détresse plus élevé (IC95%: 0,2%, 5,3%) et de faible estime de soi/QV (β = â 1,3%/â 2,6%; IC95%: â 5,0%, â 0,2%) chez leurs enfants. La détresse et le désespoir des enfants augmentaient (β = 3,3%/7,6%; IC95%: 0,4%, 14,7%) et l’estime de soi/QV diminuait de 2,3% (β = â 2,3%/â 4,4%; IC95%: â 7,2%, â 1,3%) par incrément de tertile de la dépression chez le responsable. Un soutien social plus élevé des responsables était associé à une détresse moindre et à une perspective positive plus élevée (β = 3%; IC95%: 1,4%, 4,5%) chez leurs enfants. Les enfants infectés/exposés au VIH présentaient pour la plupart un déficit de QV lié à la dépression de leurs responsables (β = â 5,2%/â 6,8%; IC95%: â 12,4%, â 0,2%), et ceux non exposés au VIH présentaient pour la plupart des améliorations en perspective positive liées au soutien social de leurs responsables (β = 4,5%; IC95%: 1,9%, 7,1%).ConclusionsL’anxiété, les symptômes dépressifs et un faible soutien social du responsable étaient associés à un bienâ être précaire chez les enfants dâ âge scolaire et les adolescents. L’amélioration de la santé mentale des responsables et le renforcement des systèmes de soutien social pour les responsables peuvent constituer une stratégie viable pour améliorer le bienâ être des enfants et des adolescents vulnérables dans cette région.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149358/1/tmi13221.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149358/2/tmi13221_am.pd

African multi-site 2-year neuropsychological study of school-age children perinatally infected, exposed, and unexposed to human immunodeficiency virus

CITATION: Boivin, M. J. et al. 2020. African Multi-Site 2-Year Neuropsychological Study of School-Age Children Perinatally Infected, Exposed, and Unexposed to Human Immunodeficiency Virus. Clinical infectious diseases, 71(7): e105–e114. doi:10.1093/cid/ciz1088The original publication is available at https://academic.oup.com/cid/Background Children living with human immunodeficiency virus (HIV) are at neuropsychological risk for cognitive and motor dysfunction. However, few prospective, multi-site studies have evaluated neuropsychological outcomes longitudinally among perinatally infected African children who received early antiretroviral treatment (ART). Methods We enrolled 611 children aged 5 to 11 years at 6 sites (South Africa [3], Zimbabwe, Malawi, Uganda). Of these, there were 246 children living with HIV (HIV+) who were initiated on ART before 3 years of age in a prior clinical trial comparing nevirapine to lopinavir/ritonavir (International Maternal Pediatric Adolescent Acquired Immunodeficiency Syndrome Clinical Trials [IMPAACT] P1060); 183 age-matched, exposed but uninfected (HEU) children; and 182 unexposed and uninfected (HUU) children. They were compared across 3 assessment time points (Weeks 0, 48, and 96) on cognitive ability (Kaufman Assessment Battery for Children, second edition [KABC-II]), attention/impulsivity (Tests of Variables of Attention [TOVA]), motor proficiency (Bruininks-Oseretsky Test, second edition [BOT-2]), and on the Behavior Rating Inventory of Executive Function (BRIEF). The cohorts were compared using linear mixed models, adjusting for site, child’s age and sex, and selected personal/family control variables. Results The HIV+ cohort performed significantly worse than the HEU and HUU cohorts for all KABC-II, TOVA, and BOT-2 performance outcomes across all 3 time points (P values < .001). The HUU and HEU cohorts were comparable. For the KABC-II planning/reasoning subtests, the HIV+ children showed less improvement over time than the HUU and HEU groups. The groups did not differ significantly on the BRIEF. Conclusions Despite initiation of ART in early childhood and good viral suppression at the time of enrollment, the HIV+ group had poorer neuropsychological performance over time, with the gap progressively worsening in planning/reasoning. This can be debilitating for self-management in adolescence.https://academic.oup.com/cid/article/71/7/e105/5649306?login=truePublishers versio

Malaria illness mediated by anaemia lessens cognitive development in younger Ugandan children

BACKGROUND: Asymptomatic falciparum malaria is associated with poorer cognitive performance in African schoolchildren and intermittent preventive treatment of malaria improves cognitive outcomes. However, the developmental benefits of chemoprevention in early childhood are unknown. Early child development was evaluated as a major outcome in an open-label, randomized, clinical trial of anti-malarial chemoprevention in an area of intense, year-round transmission in Uganda. METHODS: Infants were randomized to one of four treatment arms: no chemoprevention, daily trimethoprim–sulfamethoxazole, monthly sulfadoxine–pyrimethamine, or monthly dihydroartemisinin–piperaquine (DP), to be given between enrollment (4–6 mos) and 24 months of age. Number of malaria episodes, anaemia (Hb < 10) and neurodevelopment [Mullen Scales of Early Learning (MSEL)] were assessed at 2 years (N = 469) and at 3 years of age (N = 453); at enrollment 70 % were HIV-unexposed uninfected (HUU) and 30 % were HIV-exposed uninfected (HEU). RESULTS: DP was highly protective against malaria and anaemia, although trial arm was not associated with MSEL outcomes. Across all treatment arms, episodes of malarial illness were negatively predictive of MSEL cognitive performance both at 2 and 3 years of age (P = 0.02). This relationship was mediated by episodes of anaemia. This regression model was stronger for the HEU than for the HUU cohort. Compared to HUU, HEU was significantly poorer on MSEL receptive language development irrespective of malaria and anaemia (P = 0.01). CONCLUSIONS: Malaria with anaemia and HIV exposure are significant risk factors for poor early childhood neurodevelopment in malaria-endemic areas in rural Africa. Because of this, comprehensive and cost/effective intervention is needed for malaria prevention in very young children in these settings

Neruodevelopmental outcomes in pre-school children living with HIV-1 subtypes A and D in Uganda

Background: HIV is a neuropathogenic virus that may result in detrimental neurodevelopmental (ND) outcomes early in life. This is the first study to evaluate the effect of HIV-1 subtype on neurodevelopment of Ugandan preschool children. Methods: Neurodevelopment of 87 HIV-1 infected and 221 HIV exposed uninfected Ugandan children 1.8–4.9 years of age was assessed using 4 scales of the Mullen Scales of Early Learning (MSEL), 2 scales of the Color Object Association Test (COAT), and 1 score of the Early Childhood Vigilance Test. HIV-1 subtype was defined by phylogenetic analyses. General linear models were used to relate test scores to HIV-1 subtype (A versus D) while adjusting for relevant covariates. The scores were benchmarked against HIV exposed uninfected group to facilitate the interpretation. Results: Seventy-one percentage of children infected with subtype A versus 60% of children with subtype D were currently on antiretroviral therapy (P = 0.49). Children with HIV-1 subtype A infection were older when compared with subtype D (3.29 vs. 2.76 years, respectively, P = 0.03), but similar regarding sex, socioeconomic status, weight-for-age z-score, CD4+ and CD8+ (% and total), viral load. No statistically significant differences by HIV-1 subtype were observed in the MSEL, COAT and Early Childhood Vigilance Test. Differences ≥ 0.33 of the SD were observed for the MSEL Composite Score, Receptive Language (MSEL) and Total Memory (COAT). Conclusions: In contrast to previously reported differences in ND outcomes of school-age children by HIV-1 subtype, ND scores among preschool children were similar for subtypes A and D, with few potential differences on language production and memory outcomes that favored subtype A. Further investigation with larger sample sizes and longitudinal follow-up is neede

Neruodevelopmental Outcomes in Pre-School Children Living with HIV-1 Subtypes A and D in Uganda

Background HIV is a neuropathogenic virus that may result in detrimental neurodevelopmental (ND) outcomes early in life. This is the first study to evaluate the effect of HIV-1 subtype on neurodevelopment of Ugandan pre-school children. Methods Neurodevelopment of 87 HIV-1 infected and 221 HIV exposed uninfected (HEU) Ugandan children aged 1.8 to 4.9 years was assessed using four scales of the Mullen Scales of Early Learning (MSEL), two scales of the Color Object Association Test (COAT), and one score of the Early Childhood Vigilance Test (ECVT). HIV-1 subtype was defined by phylogenetic analyses. General linear models were used to relate test scores to HIV-1 subtype (A versus D) while adjusting for relevant covariates. The scores were benchmarked against HEU group to facilitate the interpretation. Results Seventy-one percent of children infected with subtype A vs. 60% of children with subtype D were currently on antiretroviral therapy (ART) (p=0.49). Children with HIV-1 subtype A infection were older when compared to subtype D (3.29 vs. 2.76 years, respectively, p=0.03), but similar regarding sex, socioeconomic status, weight-for-age z-score, CD4+ and CD8+ (% and total), viral load. No statistically significant differences by HIV-1 subtype were observed in the MSEL, COAT, and ECVT. Differences ≥0.33 of the standard deviation were observed for the MSEL Composite Score, Receptive Language (MSEL), and Total Memory (COAT). Conclusions In contrast to previously reported differences in ND outcomes of school-aged children by HIV-1 subtype, ND scores among pre-school children were similar for subtypes A and D, with few potential differences on language production and memory outcomes that favored subtype A. Further investigation with larger sample sizes and longitudinal follow-up is needed

Nutritional and Immunological Correlates of Memory and Neurocognitive Development Among HIV-Infected Children Living in Kayunga, Uganda.

Objective: To identify the nutritional and immunological correlates of memory and neurocognitive development as measured by the Mullen Scales of Early Learning (MSEL) and by the Color Object Association Test (COAT) among children in Uganda. Design: This analysis uses baseline data collected between 2008 and 2010 from 119 HIV-infected children aged 1–6 years, participating in a randomized controlled trial of an interventional parenting program in Kayunga, Uganda. Methods: Peripheral blood draws were performed to determine immunological biomarkers. Unadjusted and adjusted linear regression models were used to relate MSEL and COAT scores to sociodemographic characteristics, weight-for-age Z scores (WAZs), antiretroviral therapy status, and immunological biomarkers. Results: In the final analysis, 111 children were included. Lower levels of CD4+ CD38+ T cells (P = 0.04) were associated to higher immediate and total recall scores (P = 0.04). Higher levels of CD8+ HLA-DR+ T cells were associated with higher total recall score (P = 0.04) of the COAT. Higher CD4+ CD38+ HLA-DR+ T cells levels were associated with higher gross motor scores of the MSEL (P = 0.02). WAZ was positively correlated to visual reception, fine motor, expressive language, and composite score of the MSEL. Conclusions: Overall, WAZ was a stronger predictor of neurocognitive outcomes assessed by the MSEL. CD4+ CD38+ T cells were more specifically associated with memory-related outcomes. Future research should include immunological markers and standardized neurocognitive tests to further understand this relationship

Neuropsychological benefits of computerized cognitive rehabilitation training in Ugandan children surviving severe malaria: A randomized controlled trial

Background Computerized cognitive rehabilitation training (CCRT) may be beneficial for alleviating persisting neurocognitive deficits in Ugandan severe malaria survivors. We completed a randomized controlled trial of CCRT for both severe malaria and non-malaria cohorts of children. Methods 150 school-age severe malaria and 150 non-malaria children were randomized to three treatment arms: 24 sessions of Captain’s Log CCRT for attention, working memory and nonverbal reasoning, in which training on each of 9 tasks difficulty increased with proficiency; a limited CCRT arm that did not titrate to proficiency but randomly cycled across the simplest to moderate level of training; and a passive control arm. Before and after 2 months of CCRT intervention and one year following, children were tested with the Kaufman Assessment Battery for Children, 2nd edition (KABC-II), computerized CogState cognitive tests, the Behavior Rating Inventory for Executive Function (BRIEF), and the Achenbach Child Behavior Checklist (CBCL). Results Malaria children assigned to the limited-CCRT intervention arm were significantly better than passive controls on KABC-II Mental Processing Index (P = 0.04), Sequential Processing (working memory) (P = 0.02) and the Conceptual Thinking subtest (planning/reasoning) (P = 0.02). At one year post-training, the limited CCRT malaria children had more rapid CogState card detection (attention) (P = 0.02), and improved BRIEF Global Executive Index (P = 0.01) as compared to passive controls. Non-malaria children receiving CCRT significantly benefited only on KABC-II Conceptual Thinking (both full- and limited-CCRT; P \u3c 0.01), CogState Groton maze chase and learning (P \u3c 0.01), and CogState card identification (P = 0.05, full CCRT only). Improvements in KABC-II Conceptual Thinking planning subtest for the non-malaria children persisted to one-year follow-up only for the full-CCRT intervention arm. Conclusion For severe malaria survivors, limited CCRT improved attention and memory outcomes more than full CCRT, perhaps because of the greater repetition and practice on relevant training tasks in the absence of the performance titration for full CCRT. There were fewer significant cognitive and behavior benefits for the non-malaria children, with the exception of the planning/reasoning subtest of Conceptual Thinking, with stronger full- compared to limited-CCRT improvements persisting to one-year follow-up

Malaria illness mediated by anaemia lessens cognitive development in younger Ugandan children.

Background Asymptomatic falciparum malaria is associated with poorer cognitive performance in African schoolchildren and intermittent preventive treatment of malaria improves cognitive outcomes. However, the developmental benefits of chemoprevention in early childhood are unknown. Early child development was evaluated as a major outcome in an open-label, randomized, clinical trial of anti-malarial chemoprevention in an area of intense, year-round transmission in Uganda. Methods Infants were randomized to one of four treatment arms: no chemoprevention, daily trimethoprim–sulfamethoxazole, monthly sulfadoxine–pyrimethamine, or monthly dihydroartemisinin–piperaquine (DP), to be given between enrollment (4–6 mos) and 24 months of age. Number of malaria episodes, anaemia (Hb \u3c 10) and neurodevelopment [Mullen Scales of Early Learning (MSEL)] were assessed at 2 years (N = 469) and at 3 years of age (N = 453); at enrollment 70 % were HIV-unexposed uninfected (HUU) and 30 % were HIV-exposed uninfected (HEU). Results DP was highly protective against malaria and anaemia, although trial arm was not associated with MSEL outcomes. Across all treatment arms, episodes of malarial illness were negatively predictive of MSEL cognitive performance both at 2 and 3 years of age (P = 0.02). This relationship was mediated by episodes of anaemia. This regression model was stronger for the HEU than for the HUU cohort. Compared to HUU, HEU was significantly poorer on MSEL receptive language development irrespective of malaria and anaemia (P = 0.01). Conclusions Malaria with anaemia and HIV exposure are significant risk factors for poor early childhood neurodevelopment in malaria-endemic areas in rural Africa. Because of this, comprehensive and cost/effective intervention is needed for malaria prevention in very young children in these settings

Association of caregiver quality of care with neurocognitive outcomes in HIV-affected children aged 2–5 years in Uganda

Children affected by HIV are at increased risk of developmental and neuropsychological disturbances due to direct effects of HIV on the brain and direct effects associated with living in poverty. Caregivers can play an important role, through quality caregiving, in mitigating the negative effect of these stressors. This study used baseline data from an ongoing caregiver training intervention trial to evaluate the association between quality of caregiver–child interactions and neurocognitive outcomes in rural HIV-infected and HIV-exposed but uninfected children in Uganda. We also assessed the extent to which caregiver distress moderated this relationship. Data on 329 caregiver–child dyads were collected between March 2012 and July 2014, when the children were between 2 and 5 years of age. Child outcomes include the Mullen Scales of Early Learning to assess general cognitive ability and the Color Object Association Test to assess immediate memory and total recall. Caregiving quality was assessed using the Home Observation for the Measurement of the Environment (HOME) total and subscale scores. Caregiver distress was assessed using the Hopkins Symptom Checklist. General linear regression models assessed the association between the HOME total and subscale scores and child outcomes, with interaction terms used to test moderation by caregiver distress. Total HOME scores were positively and significantly associated with Mullen scores of cognitive ability; HOME acceptance subscale scores were positively and significantly associated with immediate recall scores. No other associations were statistically significant. As hypothesized, there is a strong association between the HOME and Mullen scores of cognitive ability in our study population, such that children who were assessed as living in environments with more stimulation also presented with a higher level of general neurocognitive development. Our results support the view of program guidance for HIV-affected children that suggest family-oriented care with emphasis on parent–child relationships for optimal child development