Language outcomes of preschool children who are HIV-exposed uninfected: An analysis of a South African cohort.

INTRODUCTION: There are approximately 16 million children who are HIV-exposed and uninfected (CHEU) worldwide. Studies suggest that CHEU are at risk for developmental impairment in infancy, particularly in language domains. However, there is limited research examining neurocognitive function in CHEU older than 2 years, including important pre-school years. This study aimed to investigate associations between HIV exposure without infection and neurocognitive outcomes and to determine risk factors for neurodevelopment in CHEU at age 3-4 years. METHODS: The Drakenstein Child Health Study is a South African population-based birth cohort which enrolled women in pregnancy with ongoing follow up. Neurocognitive outcomes were assessed in children at 3.5 years by trained assessors blinded to HIV status including general cognitive function, language, and memory, measured using the Kaufmann Assessment Battery for Children, Second Edition (KABC-II). Data were compared between CHEU and children who were HIV-unexposed uninfected (CHUU) using multivariable logistic and linear regression, including testing for effect modification; sex-stratified risk factor analyses were performed. RESULTS: A total of 497 children were included (97 [20%] CHEU; 400 [80%] CHUU; 50% male), with a mean age of 3.5 years (range 3.4-3.6). Groups had similar birth and household characteristics, although mothers of CHEU were older, on average. Overall, CHEU had lower expressive language scores compared to CHUU on unadjusted and adjusted analyses (effect size: -0.23 [95% CI -0.45, -0.01]). There were no group differences in general cognitive or memory function (p>0.05). On sex-stratified analyses, male CHEU were found to have higher odds of suboptimal cognitive development compared to male CHUU (aOR 2.28 [95% CI 1.06, 4.87], p = 0.034). Several other factors including birthweight, maternal education, maternal ART duration and HIV viral load during pregnancy were associated with cognition, memory, or expressive language outcomes in CHEU, dependent on child sex. INTERPRETATION: The findings suggest that perinatal HIV exposure continues to be associated with impaired language development across the preschool years, highlighting the importance of targeting early interventions to optimise language outcomes. Further, the results suggest the importance of demographic, biological and HIV-related variables influencing developmental outcomes in CHEU. The greater risk of suboptimal cognitive development in male CHEU requires investigation around sex-specific mechanisms.

Efficacy of a dialogic book-sharing intervention in a South African birth cohort: A randomized controlled trial.

OBJECTIVE: Evidence shows that dialogic book-sharing improves language development in young children in low-middle income countries (LMICs), particularly receptive and expressive language. It is unclear whether this intervention also boosts development of other neurocognitive and socio-emotional domains in children. Using a randomized controlled trial (RCT) nested in the Drakenstein Child Health Study (DCHS), a book-sharing intervention was implemented in caregivers of 3.5-year-old preschool children living in low-income South African communities. METHODS: 122 Caregivers and their children (mean age 3.5 years) were randomly assigned to an intervention group (n = 61) or waitlist control group (n = 61). A neurocognitive battery determined baseline receptive and expressive language, executive function, theory of mind, and behavior scores. RESULTS: No differences were observed between intervention and control groups on receptive and expressive language, or any of the neurocognitive or socio-emotional measures from baseline (3.5 years) to 4 months post-intervention administration (4 years). CONCLUSION: The benefits noted in prior literature of book-sharing in infants did not appear to be demonstrated at 4 months post-intervention, in children from 3.5 to 4 years of age. This suggests the importance of early intervention and emphasizes the need for further research on adaptation of book-sharing for older participants in a South African context. TRIAL REGISTRATION: retrospectively registered on 03/04/2022 PACTR202204697674974.

Externalizing behavior in preschool children in a South African birth cohort: Predictive pathways in a high-risk context.

Mental health problems often begin in early childhood. However, the associations of various individual and contextual risk factors with mental health in the preschool period are incompletely understood, particularly in low- to middle-income countries (LMICs) where multiple risk factors co-exist. To address this gap, we prospectively followed 981 children in a South African birth cohort, the Drakenstein Child Health Study, assessing pre-and postnatal exposures and risk factors. The predictive value of these factors for child mental health (assessed by the Child Behavior Checklist) was modeled using structural equation modeling. We identified two key pathways to greater externalizing behavior: (1) prenatal exposure to substances (alcohol and smoking) directly predicted increased externalizing behavior (ß = 0.24, p < 0.001); this relationship was partially mediated by an aspect of infant temperament (negative emotionality; ß = 0.05, p = 0.016); (2) lower socioeconomic status and associated maternal prenatal depression predicted more coercive parenting, which in turn predicted increased externalizing behavior (ß = 0.18, p = 0.001). Findings in this high-risk LMIC cohort cohere with research from higher income contexts, and indicate the need to introduce integrated screening and intervention strategies for maternal prenatal substance use and depression, and promoting positive parenting across the preschool period.

Drakenstein Child Health Study (DCHS): investigating determinants of early child development and cognition.

INTRODUCTION: There is growing awareness that psychosocial risk and resilience factors in early life play a key role in influencing later health. Most work has been done in high-income settings, rather than low-income and middle-income countries (LMICs), where the majority of the global childhood population resides. The few studies with well-defined cohorts in LMICs have employed various methods and measures, making comparisons across studies challenging. This presentation describes the methodology for infant and child developmental measures used in the Drakenstein Child Health Study (DCHS), a multidisciplinary longitudinal birth cohort study in South Africa. METHODS AND ANALYSIS: We outline a multilevel approach combining a range of measures including parental reports, behaviour observations, clinician-administered scales and brain imaging. Using this approach, we aim at a longitudinal perspective of developmental, cognitive, socioemotional and neurophysiological outcomes in a birth cohort of children in an LMIC. ETHICS AND DISSEMINATION: The study was approved by the faculty of Health Sciences, Human Research Ethics Committee, University of Cape Town (401/2009), Stellenbosch University (N12/02/0002) and the Western Cape Provincial Health Research committee (2011RP45). DISCUSSION: Children in the DCHS develop in a context typical of many communities in South Africa and other LMICs. There is a critical need for research in LMICs to elucidate underlying factors that inform risk for, and resilience to, poor developmental outcomes in infants born into high-risk communities. Such work may inform effective intervention strategies appropriate to this context.

The Effects of Prenatal Alcohol Exposure on Episodic Memory Functioning: A Systematic Review.

OBJECTIVE: This paper systematically reviews the literature on the effects of prenatal alcohol exposure (PAE) on episodic memory. Specifically, the review focuses on recurring questions of whether memory deficits are consistent across memory domains, whether the impairments are consistent across the stages of episodic memory, and whether the impairments are primary episodic memory impairments or secondary to a global performance deficit or a higher order deficit. METHOD: In total, 33 relevant studies were identified through searches on electronic databases. Journal articles were limited to those that included human subjects and that were published in English-language journals. RESULTS: The vast majority of reviewed studies examined memory in school-aged children and adolescents. Twenty-three studies examined verbal memory and 19 studies examined visual-spatial memory. Although all of the reviewed studies examined encoding of new material, only 10 studies examined retention of the learned material over time. Ten studies controlled for IQ, either statistically or with matched controls, when analyzing memory task performance. CONCLUSION: In general, studies show that PAE results in impaired verbal and visual-spatial episodic memory performance in affected individuals and these impairments are unlikely to be secondary to a global impairment. However, impairments on some memory tests are specific to the encoding stage, whereas retention is relatively spared; suggesting that the episodic memory deficit might be influenced, at least in part, by higher order cognitive processes.

The fear-factor stress test: an ethical, non-invasive laboratory method that produces consistent and sustained cortisol responding in men and women.

We describe a method to administer a controlled, effective stressor to humans in the laboratory. The method combines the Trier Social Stress Test (TSST) and the Cold Pressor Test into a single, believable procedure called the Fear-Factor Stress Test (FFST). In the procedure, participants imagine auditioning for the reality television show Fear Factor. They stand before a video recorder and a panel of judges while (a) delivering a motivational speech, (b) performing a verbal arithmetic task, and (c) placing one hand into a bucket of ice water for up to 2 min. We measured subjective anxiety, heart rate, and salivary cortisol in three groups of young adults (n = 30 each, equal numbers of men and women): FFST, TSST, and Control (a placebo version of the FFST). Although the FFST and TSST groups were not distinguishable at the cortisol measure taken 5 min post-manipulation, at 35 min postmanipulation average cortisol levels in the TSST group had returned to baseline, whereas those in the FFST group continued to rise. The proportion of individual cortisol responders (≥ 2 nmol/l increase over baseline) in the TSST and FFST groups did not differ at the 5-min measure, but at the 35-min measure the FFST group contained significantly more responders. The findings indicate that the FFST induces a more robust and sustained cortisol response (which we assume is a marker of an HPA-axis response) than the TSST, and that it does so without increasing participant discomfort or incurring appreciably greater resource and time costs.