Neurodevelopmental outcome of HIV-exposed but uninfected infants in the Mother and Infants Health Study, Cape Town, South Africa.

OBJECTIVES: To compare neurodevelopmental outcomes of HIV-exposed uninfected (HEU) and HIV-unexposed uninfected (HUU) infants in a peri-urban South African population. HEU infants living in Africa face unique biological and environmental risks, but uncertainty remains regarding their neurodevelopmental outcome. This is partly due to lack of well-matched HUU comparison groups needed to adjust for confounding factors. METHODS: This was a prospective cohort study of infants enrolled at birth from a low-risk midwife obstetric facility. At 12 months of age, HEU and HUU infant growth and neurodevelopmental outcomes were compared. Growth was evaluated as WHO weight-for-age, length-for-age, weight-for-length and head-circumference-for-age Z-scores. Neurodevelopmental outcomes were evaluated using the Bayley scales of Infant Development III (BSID) and Alarm Distress Baby Scale (ADBB). RESULTS: Fifty-eight HEU and 38 HUU infants were evaluated at 11-14 months of age. Performance on the BSID did not differ in any of the domains between HEU and HUU infants. The cognitive, language and motor scores were within the average range (US standardised norms). Seven (12%) HEU and 1 (2.6%) HUU infant showed social withdrawal on the ADBB (P = 0.10), while 15 (26%) HEU and 4 (11%) HUU infants showed decreased vocalisation (P = 0.06). There were no growth differences. Three HEU and one HUU infant had minor neurological signs, while eight HEU and two HUU infants had macrocephaly. CONCLUSIONS: Although findings on the early neurodevelopmental outcome of HEU infants are reassuring, minor differences in vocalisation and on neurological examination indicate a need for reassessment at a later age.

Favourable outcome in a child with symptomatic diagnosis of Glutaric aciduria type 1 despite vertical HIV infection and minor head trauma.

The first case of Glutaric aciduria Type 1(GA1) in an African child was reported in 2001. GA1 has a prevalence of 1:5000 in black South Africans. Although early diagnosis is essential for a favourable outcome, newborn screening is not routine in South Africa where an estimated 320,000 children have HIV infection. Neurodevelopmental delay and encephalopathy are complications of both HIV and GA1. In such a setting it is important to recognise that HIV and GA1 can occur simultaneously. We present an HIV-infected South African male child of Xhosa descent with macrocephaly who commenced combination antiretroviral therapy (ART) at 8 weeks of age in a clinical trial which included a neurodevelopmental sub-study. He developed short-lived focal seizures at 16 months after minor head trauma. Neurological examination was normal. Neuroimaging showed temporal lobe atrophy, subtle hyperintense signal change in the globus pallidus, and focal haemosiderosis in the right Sylvian fissure region. As findings were not in keeping with HIV encephalopathy, a urine metabolic screen was undertaken which suggested GA1. Genetic testing confirmed Arg293Trp mutation. He began L-carnitine and a low protein diet as a restricted diet was not practicable. At 21 months he developed pulmonary tuberculosis, requiring 6 months treatment. He did not develop any neurologic motor symptoms. Serial neurodevelopmental and neuropsychological test scores until 9 years were similar to healthy neighbourhood controls, except for mild language delay at 3½ years. Detection of GA1, probably facilitated through participation in a clinical trial, was pivotal for a favourable outcome. The concomitant use of ART and anti-tuberculous therapy in a child with GA1 appears safe.

Spastic diplegia in children with HIV encephalopathy: first description of gait and physical status.

AIM: The aim of this study was to explore the physical status and gait patterns of children with spastic diplegia secondary to human immunodeficiency virus encephalopathy (HIVE). METHOD: A cross-sectional study was conducted on children diagnosed with HIVE and spastic diplegia. Sociodemographic and clinical background information was obtained, followed by three-dimensional gait analysis (3DGA) and a physical examination including assessments of muscle tone, strength, motor control, contractures, and bony deformities of the lower extremities. RESULTS: Fourteen children (eight males, six females; mean age 5 y 8 mo [SD 9 mo], range 4 y 4 mo-6 y 10 mo) were studied. The cohort was divided into two groups based on distinctive gait patterns. Nine participants in group I showed only limited abnormalities. Group II displayed a more pathological gait pattern including stiff knee and equinus ankle abnormalities. Results of 3DGA, as with the physical examination outcomes, showed increased impairments from proximal to distal (except for hip extension). INTERPRETATION: This study provides a first description of distinctive gait patterns and related physical characteristics of children with HIVE and spastic diplegia. Further research is necessary.

Global COVID-19 childhood disability data coordination: A collaborative initiative of the International Alliance of Academies of Childhood Disability.

PURPOSE: The International Alliance of Academies of Childhood Disability created a COVID-19 Task Force with the goal of understanding the global impact of COVID-19 on children with disabilities and their families. The aim of this paper is to synthesize existing evidence describing the impact of COVID-19 on people with disabilities, derived from surveys conducted across the globe. METHODS: A descriptive environmental scan of surveys was conducted. From June to November 2020, a global call for surveys addressing the impact of COVID-19 on disability was launched. To identify gaps and overlaps, the content of the surveys was compared to the Convention on the Rights of the Child and the International Classification of Functioning, Disability and Health. RESULTS: Forty-nine surveys, involving information from more than 17,230 participants around the world were collected. Overall, surveys identified that COVID-19 has negatively impacted several areas of functioning - including mental health, and human rights of people with disabilities and their families worldwide. CONCLUSION: Globally, the surveys highlight that impact of COVID-19 on mental health of people with disabilities, caregivers, and professionals continues to be a major issue. Rapid dissemination of collected information is essential for ameliorating the impact of COVID-19 across the globe.

Associations of adverse maternal experiences and diabetes on postnatal maternal depression and child social-emotional outcomes in a South African community cohort.

Previous literature has identified associations between diabetes during pregnancy and postnatal maternal depression. Both maternal conditions are associated with adverse consequences on childhood development. Despite an especially high prevalence of diabetes during pregnancy and maternal postnatal depression in low- and middle-income countries, related research predominates in high-income countries. In a South African cohort with or without diabetes, we investigated associations between adverse maternal experiences with postnatal maternal depression and child social-emotional outcomes. South African mother-child dyads were recruited from the Bishop Lavis community in Cape Town. Participants consisted of 82 mother-child dyads (53 women had GDM or type 2 diabetes). At 14-20 months postpartum, maternal self-report questionnaires were administered to assess household socioeconomic status, food insecurity, maternal depressive symptoms (Edinburgh Postnatal Depression Scale (EPDS)), maternal trauma (Life Events Checklist), and child social-emotional development (Brief Infant Toddler Social Emotional Assessment, Ages and Stages Questionnaires: Social-Emotional, Second Edition). Lower educational attainment, lower household income, food insecurity, living without a partner, and having experienced physical assault were each associated with postnatal maternal depressive symptoms and clinical maternal depression (EPDS ≥ 13). Maternal postnatal depression, lower maternal educational attainment, lower household income, household food insecurity, and living in a single-parent household were each associated with child social-emotional problems. Stratified analyses revealed maternal experiences (education, income, food insecurity, trauma) were associated with postnatal maternal depressive symptoms and child social-emotional problems only among dyads with in utero exposure to diabetes. Women with pre-existing diabetes or gestational diabetes in LMIC settings should be screened for health related social needs to reduce the prevalence of depression and to promote child social-emotional development.

Diagnostic accuracy of the Molteno Adapted Scale for developmental delay in South African toddlers.

Background: There is currently a great need in South Africa for culturally appropriate neurodevelopmental screening measures in order to facilitate early identification of neurodevelopmental problems in children. Neurodevelopmental screening has the potential to decrease the burden at health-care facilities as it is time, resource and cost effective. Aim: To assess the use of the Molteno Adapted Scale (MAS), a locally developed screening measure, to suggest an optimal cut-off score and investigate its accuracy in detecting developmental delays. Method: The MAS was assessed by evaluating three components: accuracy, efficacy and usefulness. For each of 136 participants, MAS scores were compared with dichotomised scores from the Griffiths Mental Development Scales (GMDS). Receiver operating characteristic (ROC) curves were generated to determine the accuracy of the MAS in identifying developmental delay defined by the GMDS. Sensitivity, specificity and predictive values were calculated for potential MAS cut-off scores. Results: The MAS had an excellent area under the ROC curve, indicating good test accuracy. A developmental quotient of 83 was identified as optimal for screening purposes, with acceptable sensitivity (71.4%) and specificity (90.7%) as well as predictive values (29.4% positive predictive value and 98.3% negative predictive value) for developmental delay on the GMDS. Conclusion: The present study provides preliminary evidence supporting the use of the MAS for screening.

Neurocognitive and functional impairment in adult and paediatric tuberculous meningitis.

In those who survive tuberculous meningitis (TBM), the long-term outcome is uncertain; individuals may suffer neurocognitive, functional and psychiatric impairment, which may significantly affect their ability to lead their lives as they did prior to their diagnosis of TBM. In children who survive, severe illness has occurred at a crucial timepoint in their development, which can lead to behavioural and cognitive delay. The extent and nature of this impairment is poorly understood, particularly in adults. This is in part due to a lack of observational studies in this area but also inconsistent inclusion of outcome measures which can quantify these deficits in clinical studies. This leads to a paucity of appropriate rehabilitative therapies available for these individuals and their caregivers, as well as burden at a socioeconomic level. In this review, we discuss what is known about neurocognitive impairment in TBM, draw on lessons learnt from other neurological infections and discuss currently available and emerging tools to evaluate function and cognition and their value in TBM. We make recommendations on which measures should be used at what timepoints to assess for impairment, with a view to optimising and standardising assessment of neurocognitive and functional impairment in TBM research.

Early antiretroviral therapy improves neurodevelopmental outcomes in infants.

OBJECTIVES: To evaluate the effect of early versus deferred antiretroviral therapy (ART) on the neurodevelopment of infants from Cape Town participating in the Children with HIV Early Antiretroviral Therapy (CHER) trial. DESIGN: HIV-infected infants were randomized to early (<3 months) or deferred ART. HIV-uninfected infants (HIV-exposed and HIV-unexposed) provide background data. METHODS: Neurological examination and Griffiths Mental Development Scales (GMDS) were administered between 10-16 months of age by testers blind to HIV status and randomized allocation. Mean quotients were compared using paired Student's t-tests. RESULTS: Sixty-four infants on early ART and 26 on deferred ART (of potential 77 and 38 respectively on CHER trial) were assessed at median age 11 months (range 10-16). On the GMDS, all scores were lower in the deferred arm and the General Griffiths and Locomotor Scores were significantly lower: mean (SD) =100.1 (13.8) vs. 106.3 (10.6) P=0.02; and 88.9 (16.3) vs. 97.7 (12.5), P<0.01, respectively. Children with HIV who received early ART performed as well as children without HIV except on the Locomotor subscale. Both infected and uninfected mean GMDS scores were within the average range. CONCLUSION: Infants initiated on early ART have significantly better Locomotor and general scores on the GMDS at median age 11 months compared to infants on deferred ART, despite careful monitoring and ready access to ART in the latter.