Cohort Of South African Children Research Articles

Long-term associations between early attachment and parenting and adolescent susceptibility to post-traumatic distress in a South African high-risk sample.

It has been proposed that children and young people living in low- and middle-income countries (LMICs) are not only exposed more frequently to trauma but also have a higher likelihood of encountering traumas of greater severity than those living in high-income countries (HICs). This may lead to higher rates of post-traumatic stress symptoms (PTSS). However, developmental pathways to risk or resilience after trauma exposure in LMICs are underresearched. We examined early parenting and attachment as potentially important formative factors for later stress reactivity in a longitudinal cohort of South African children (N = 449). Parenting and attachment were assessed at child age 18 months, and interpersonal trauma exposure, PTSS and parenting stress were measured at 13 years (N = 333; core sample with data on all measures: N = 213). Following a vulnerability-stress approach, separate regression models were run to investigate whether parent-child attachment at 18 months, parental sensitivity and intrusiveness during play at 12 months, and current parenting stress at 13 years, interacted with adolescents' extent of interpersonal trauma exposure to predict their PTSS levels at 13 years. We found no predictive effects of either early attachment or current parenting stress in relation to child PTSS. There was some evidence for predictive influences of parental early intrusiveness and sensitivity on adolescent outcomes, though associations were unexpectedly positive for the latter. No interaction effects supporting a vulnerability-stress model were found. Overall, we found limited evidence that elements of the early parent-child environment predict child risk/resilience to trauma in LMIC children. Future studies should include more frequent assessments of relevant constructs to capture changes over time and consider further what comprises adaptive parenting in high-risk contexts.

Association between caregiver and household alcohol use and child behavior problems in KwaZulu Natal, South Africa.

We explored the association between household alcohol use and behavior problems among South-African children, using data from the Asenze study, a population-based cohort of South African children and their caregivers. Household alcohol use and child behavior were assessed when children were 6-8 years old. To examine the association, we performed linear regressions. The sample included 1383 children with complete data under the care of 1251 adults. Children living in a household where self-reported caregiver alcohol use was scored as hazardous (4.6%) had higher levels of problem behavior (β = 1.94, 95% CI 0.06-3.82). There were no statistically significant associations between reported hazardous alcohol use by another member of the household (14.5%) and child problem behavior. Hazardous household alcohol use was associated with child problem behavior and this effect appeared to be mainly driven by primary caregiver use.

Realising the potential human development returns to investing in early and maternal nutrition: The importance of identifying and addressing constraints over the life course.

The benefits of interventions which improve early nutrition are well recognised. These benefits, however, only accrue to the extent that later life circumstances allow. Consequently, in adverse contexts many of the benefits will never be realised, particularly for the most vulnerable, exacerbating inequality. Returns to investment in early nutrition could be improved if we identified contextual factors constraining their realisation and interventions to weaken these. We estimate cost and impact of scaling 10 nutrition interventions for a cohort of South African children born in 2021. We estimate associated declines in malnutrition and mortality, and improvements in years of schooling and future earnings. To examine the role of context over the life-course we estimate benefits with and without additional improvements in school quality and employment opportunities by socio-economic quintile. Scale up reduces national stunting (height for age < = -2SD) rates among children at 24 months by 3.18 percentage points, implying an increase in mean height for age z-score (HAZ) of 0.10, and 53,000 years of additional schooling. Quintile 1 (the poorest) displays the largest decline in stunting, and largest increase in mean HAZ. Estimated total cost of increasing coverage of the interventions for the cohort is US$90 million. The present value of the additional years of schooling is estimated at close to US$2 billion. Cost-benefit ratios suggest the highest return occurs in quintile 5 (1:23). Reducing inequality in school quality closes the gap between quintile 5 and the lower quintiles. If school quality and labour force participation were equal the highest returns are in quintile 1(1:31). An enabling environment is key to maximising human development returns from investing in early nutrition, and to avoid exacerbating existing inequality. Therefore, particularly for children in adverse conditions, it is essential to identify and implement complementary interventions over the life course.

DNA Methylation of PGC-1α Is Associated With Elevated mtDNA Copy Number and Altered Urinary Metabolites in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a complex disorder that is underpinned by numerous dysregulated biological pathways, including pathways that affect mitochondrial function. Epigenetic mechanisms contribute to this dysregulation and DNA methylation is an important factor in the etiology of ASD. We measured DNA methylation of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α), as well as five genes involved in regulating mitochondrial homeostasis to examine mitochondrial dysfunction in an ASD cohort of South African children. Using targeted Next Generation bisulfite sequencing, we found differential methylation (p < 0.05) at six key genes converging on mitochondrial biogenesis, fission and fusion in ASD, namely PGC-1α, STOML2, MFN2, FIS1, OPA1, and GABPA. PGC-1α, the transcriptional regulator of biogenesis, was significantly hypermethylated at eight CpG sites in the gene promoter, one of which contained a putative binding site for CAMP response binding element 1 (CREB1) (p = 1 × 10–6). Mitochondrial DNA (mtDNA) copy number, a marker of mitochondrial function, was elevated (p = 0.002) in ASD compared to controls and correlated significantly with DNA methylation at the PGC-1α promoter and there was a positive correlation between methylation at PGC-1α CpG#1 and mtDNA copy number (Spearman’s r = 0.2, n = 49, p = 0.04) in ASD. Furthermore, DNA methylation at PGC-1α CpG#1 and mtDNA copy number correlated significantly (p < 0.05) with levels of urinary organic acids associated with mitochondrial dysfunction, oxidative stress, and neuroendocrinology. Our data show differential methylation in ASD at six key genes converging on PGC-1α-dependent regulation of mitochondrial biogenesis and function. We demonstrate that methylation at the PGC-1α promoter is associated with elevated mtDNA copy number and metabolomic evidence of mitochondrial dysfunction in ASD. This highlights an unexplored role for DNA methylation in regulating specific pathways involved in mitochondrial biogenesis, fission and fusion contributing to mitochondrial dysfunction in ASD.

Duane's Retraction Syndrome in a Cohort of South African Children: A 20-Year Clinic-Based Review

To describe the clinical features of Duane's retraction syndrome in a cohort of South African children and to analyze the differences between ethnic groups. A retrospective case series of 120 patients seen between 1997 and 2017 at a tertiary referral center in Cape Town, South Africa. Type 2 Duane's retraction syndrome was most common in black children (54%), whereas type 1 was predominant in mixed race (68%) and white (94%) children. In this cohort, 63% of black children with Duane's retraction syndrome were boys, whereas 69% of white children and 59% of mixed race children were girls. Left eye involvement was the most common in all ethnic groups (44%), followed by right eye (41%) and bilateral (14%) involvement. The average age at presentation was 34.2 months (range: 1 to 144 months). Strabismus in primary position was present in 57 patients (46%), of whom 39% had esotropia and 61% had exotropia. A deviation in the primary position was more common in black (71%) children than in mixed race (39%) or white (41%) children. Ametropia was found in 94 patients (79%), amblyopia was present in 15 patients (13%), and 41 patients (34%) underwent surgery. This is the first study to provide robust data on the profile of pediatric Duane's retraction syndrome in the three main ethnic groups in South Africa, and it showed clear ethnic differences. Among black children, boys are affected more often, the proportion with type 2 Duane's retraction syndrome is more frequent, and surgery is required more often. Among white and mixed race children, girls are affected more often and type 1 Duane's retraction syndrome is predominant. [J Pediatr Ophthalmol Strabismus. 2019;56(4):248-253.].

Relationship between nutritional status and treatment-related neutropenia in children with nephroblastoma

Background: Assessment of nutritional status of paediatric oncology patients is crucial, as it may influence treatment and clinical outcomes. Concurrent malnutrition and cancer in children may lead to reduced chemotherapy delivery due to impaired tolerance and increased toxicity.Aim: This study aimed to determine the relationship between nutritional status and the prevalence, frequency and duration of treatment-related neutropenia in a cohort of South African children with nephroblastoma.Methods: Seventy-seven children between the ages of 1 and 12 years diagnosed with nephroblastoma at Inkosi Albert Luthuli Central Hospital (IALCH), Durban, between 2004 and 2012, were studied prospectively. Nutritional status was assessed using weight, height, mid-upper arm circumference (MUAC), triceps skinfold thickness (TSFT) and serum albumin. The administration of filgastrim (Neupogen®) was used as a surrogate for neutropenia and the frequency and duration of its use was recorded.Results: There was a significant relationship between the prevalence of treatment-induced neutropenia and malnutrition defined by MUAC. The mean frequency and duration of neutropenia was significantly higher in those classified as malnourished using MUAC. There was a positive correlation between frequency and duration of neutropenia.Conclusions: Malnutrition was prevalent among children with nephroblastoma. The prevalence of treatment-induced neutropenia was higher in those with poor nutritional status, identified by MUAC. Poor nutritional status according to MUAC was also linked to an increased frequency and duration of neutropenia. It is important to include MUAC in the nutritional assessment of children with nephroblastoma.

Respiratory comorbidity in South African children with atopic dermatitis.

Atopic dermatitis (AD) is an early and important step in the propagation of the allergic march, enhancing food and respiratory allergies via epicutaneous sensitisation to allergens. To determine the prevalence and patterns of aeroallergen sensitisation, asthma and allergic rhinitis in South African (SA) children with AD. This was a prospective, observational study in a paediatric university hospital in Cape Town, SA. Children with moderate to severe AD, aged 6 months - 10 years, were recruited randomly and investigated for food sensitisation and allergy. They were assessed for sensitisation to aeroallergens by the immuno solid-phase allergen chip test. House-dust mite DerP and DerF, dust mite Eur m, Timothy grass, Bermuda grass, tree pollen, mould (Alternaria), cat and dog sensitisation patterns were analysed. Symptoms of asthma and allergic rhinitis were elicited using a questionnaire modified from the International Study of Asthma and Allergies in Childhood study questions. One hundred participants (59 black Africans and 41 of mixed ethnicity) were enrolled (median age 42 months). Of the participants, 39% had symptoms of asthma and 53% symptoms of allergic rhinitis; 89% tested positive to at least one aeroallergen, most commonly house-dust mite DerP or DerF (81%), dust mite Eur m (51%), Timothy grass (36%) and cat (35%). Asthma, allergic rhinitis and aeroallergen sensitisation all increased with increasing age, while food allergy decreased with age. Food allergy was not an independent risk factor for respiratory allergies. Children were sensitised to indoor allergens (house-dust mite, pets) from an early age, while pollen allergies increased with age. In this cohort of SA children with moderate to severe AD, comorbidity with respiratory allergies was high. The prevalence of respiratory allergies increased with age while food allergy decreased with age, in keeping with the pattern of the allergic march. Seasonal allergies increased with age, while house-dust mite and pet allergy peaked in younger children, in keeping with early exposure via a defective skin barrier. Early and effective restoration of the skin barrier in AD may be a target for reducing aeroallergen-related diseases.

Prevalence of positive coeliac serology in a cohort of South African children with type 1 diabetes mellitus

Background. Coeliac disease (CD) is characterised by immune-mediated damage to the mucosa of the small intestine. Both CD and type 1 diabetes (T1D) have common auto-immune origins. Many patients with CD and T1D are asymptomatic or present with only mild symptoms; hence early diagnosis may only be facilitated by serological screening. Distal duodenal biopsy remains the gold standard for confirming the diagnosis. Objective. To describe the prevalence of CD in T1D patients presenting to the paediatric endocrine service at Inkosi Albert Luthuli Central hospital (IALCH) in Durban and document the relationship between positive coeliac serology and small-bowel biopsy results. Methods. A retrospective chart review was done at IALCH, the paediatric tertiary referral centre for KwaZulu-Natal (KZN) Province. The study sample included all patients with newly diagnosed T1D diagnosed between January 2008 and December 2011. Results. A total of 120 newly diagnosed T1D patients were included in the study, of whom 49 (40.8%) were coeliac serology positive and 61 (50.8%) serology negative. There was no significant difference between the two groups regarding mean age of presentation with diabetes, race, sex, urban v. rural origin and baseline anthropometric measurements. Of patients in the serology-positive group, 97.6% had no symptoms suggestive of CD. Of the 49 patients who were coeliac serology positive, 8 (16%) were biopsied: 3 (37.5%) were positive, 1 (12.5%) had intra-epithelial lymphocytes and 4 (50%) were negative. There was a strong positive correlation between biopsy results and titres of endomysial antibody results ( p =0.047). Conclusion. There is a high prevalence of coeliac serology positivity in newly diagnosed T1D patients in KZN. This study provides evidence for screening of children with T1D for CD, and also confirms the low prevalence of symptoms.

Prevalence of positive coeliac serology in a cohort of South African children with type 1 diabetes mellitus

1.1 To describe the prevalence of Coeliac disease in the Type 1 diabetes patients presenting to Inkosi Albert Luthuli Central Hospital . 1.2 To describe the clinical and laboratory characteristics of these patients

Familial-Environmental Risk Factors in South African Children With Attention-Deficit Hyperactivity Disorder (ADHD): A Case-Control Study.

We investigated familial and environmental risk factors in a cohort of South African children diagnosed with attention-deficit hyperactivity disorder (ADHD). A prospective, hospital-based case control study was conducted comprising 50 children diagnosed with ADHD and 50 matched non-ADHD controls. The adjusted effect of familial-environmental risk factors on ADHD was determined by systematic assessment. Birth complications, parental psychiatric disorder, maternal ADHD, early childhood trauma, and nonmaternal child care were significant risk factors for ADHD. Prolonged breastfeeding was found to be protective. In a multivariable logistic regression model, 5 criteria (birth complications, breastfeeding <3 months, at least 1 parent with tertiary education, presence of parental psychiatric disorder, and nonmaternal primary caregiver) differentiated ADHD from non-ADHD controls with a sensitivity and specificity of 74% and 86%, respectively. We found a correlation between certain familial and environmental risk factors and ADHD. A 5-criterion multivariable logistic regression model may offer clinical guidance in ADHD diagnosis.

A hypothetical astrocyte-microglia lactate shuttle derived from a 1H NMR metabolomics analysis of cerebrospinal fluid from a cohort of South African children with tuberculous meningitis.

Tuberculosis meningitis (TBM) is the most severe form of extra-pulmonary tuberculosis and is particularly intense in small children; there is no universally accepted algorithm for the diagnosis and substantiation of TB infection, which can lead to delayed intervention, a high risk factor for morbidity and mortality. In this study a proton magnetic resonance (1H NMR)-based metabolomics analysis and several chemometric methods were applied to data generated from lumber cerebrospinal fluid (CSF) samples from three experimental groups: (1) South African infants and children with confirmed TBM, (2) non-meningitis South African infants and children as controls, and (3) neurological controls from the Netherlands. A total of 16 NMR-derived CSF metabolites were identified, which clearly differentiated between the controls and TBM cases under investigation. The defining metabolites were the combination of perturbed glucose and highly elevated lactate, common to some other neurological disorders. The remaining 14 metabolites of the host’s response to TBM were likewise mainly energy-associated indicators. We subsequently generated a hypothesis expressed as an “astrocyte–microglia lactate shuttle” (AMLS) based on the host’s response, which emerged from the NMR-metabolomics information. Activation of microglia, as implied by the AMLS hypothesis, does not, however, present a uniform process and involves intricate interactions and feedback loops between the microglia, astrocytes and neurons that hamper attempts to construct basic and linear cascades of cause and effect; TBM involves a complex integration of the responses from the various cell types present within the CNS, with microglia and the astrocytes as main players.Electronic supplementary materialThe online version of this article (doi:10.1007/s11306-014-0741-z) contains supplementary material, which is available to authorized users.

Thyroid dysfunction in a cohort of South African children with Down syndrome

While international studies show thyroid dysfunction occurs more commonly in individuals with Down syndrome (DS) than in the general population, there is a paucity of available data from sub-Saharan Africa. To document the range of thyroid function in a cohort of South African children with DS, and to assess referral and treatment practices when thyroid dysfunction was present. A retrospective file-based study of 391 children with DS seen at the genetic clinics at three Johannesburg hospitals from 2003 to 2008. Thyroid function test (TFT) results (thyroid-stimulating hormone and free thyroxine) and demographic details were collected for each child. Endocrine clinic files from two of the hospitals were reviewed for additional referral and treatment information. The majority (83.6%) of children had at least one TFT, in most cases performed between the ages of 2 and 12 months. The most common form of thyroid dysfunction was subclinical hypothyroidism (SCH) (28.7%). Up to one-third of the patients, including several neonates with abnormal results, were not referred for further evaluation and were therefore not receiving the necessary treatment. Inter- laboratory biochemical discrepancies and lack of population-specific reference ranges complicated the interpretation of results. The controversy surrounding whether, and how, to treat SCH influenced treatment practices. Thyroid dysfunction is prevalent in South African children with DS. There is an urgent need to address the laboratory biochemical discrepancies, and to establish guidelines for surveillance and treatment to prevent further irreversible neurological and physical impairment.

Plasma Lopinavir Concentrations Predict Virological Failure in a Cohort of South African Children Initiating a Protease-Inhibitor-Based Regimen

Poor adherence to antiretroviral therapy contributes to pharmacokinetic variability and is the major determinant of virological failure. However, measuring treatment adherence is difficult, especially in children. We investigated the relationship between plasma lopinavir concentrations, pretreatment characteristics and viral load >400 copies/ml. A total of 237 HIV-infected children aged 4-42 months on lopinavir/ritonavir oral solution were studied prospectively and followed for up to 52 weeks. Viral load and lopinavir concentration were measured at clinic visits 12, 24, 36 and 52 weeks after starting treatment. Cox multiple failure events models were used to estimate the crude and adjusted effect of lopinavir concentrations on the hazard of viral load >400 copies/ml. The median (IQR) pretreatment CD4(+) T-lymphocyte percentage was 18.80% (12.70-25.35) and 53% of children had a pretreatment viral load >750,000 copies/ml. The median (IQR) weight-for-age and height-for-age z-scores were -2.17 (-3.35--2.84) and -3.34 (-4.57--3.41), respectively. Median (IQR) lopinavir concentrations were 8.00 mg/l (4.11-12.42) at median (IQR) 3.50 h (2.67-4.25) after the dose. The hazard of viral load >400 copies/ml was increased with lopinavir concentrations <1 mg/l versus ≥1 mg/l (adjusted hazard ratio 2.3 [95% CI 1.63, 3.26]) and lower height-for-age z-scores. Low lopinavir concentrations (<1 mg/l) are associated with viraemia in children. This measure could be used as a proxy for adherence and to determine which children are more likely to fail.

Isoniazid Plasma Concentrations in a Cohort of South African Children with Tuberculosis: Implications for International Pediatric Dosing Guidelines

In most countries with a high burden of tuberculosis, children with tuberculosis are prescribed isoniazid at dosages of 4-6 mg/kg/day, as recommended by international authorities. We studied isoniazid concentrations in 56 hospitalized children (median age, 3.22 years; interquartile range [IQR], 1.58-5.38 years) who received isoniazid daily (median dosage, 5.01 mg/kg/day; range, 2.94-15.58 mg/kg/day) as part of antituberculosis treatment. At 1 and 4 months after initiation of treatment, isoniazid concentrations were measured in plasma samples at 0.75, 1.5, 3, 4, and 6 h after a treatment dose, to describe pharmacokinetic measures by using noncompartmental analysis. The effects of dose in milogram per kilogram, acetylator genotype, age, sex, and clinical diagnosis of kwashiorkor and human immunodeficiency virus (HIV) infection on isoniazid concentrations were evaluated. Median peak concentrations of isoniazid in children prescribed a dose of 4-6 mg/kg were 58% lower than those in children prescribed a dose of 8-10 mg/kg (2.39 mg/L [IQR, 1.59-3.40] vs. 5.71 mg/L [IQR, 4.74-7.62]). Peak concentrations were <3 mg/L in 70% of children prescribed a dose of 4-6 mg/kg. In contrast, children prescribed a dose of 8-12 mg/kg achieved peak concentrations approximating those in adults treated with 300 mg of isoniazid daily. Intermediate or fast acetylator genotype independently predicted a 38% (95% confidence interval [CI], 21%-51%) reduction in peak concentrations, compared with the slow-acetylator genotype. Each 1-mg/kg increase in the dose and each year increase in age were associated with increases in peak concentrations of 21% (95% CI, 16%-25%) and 6% (95% CI, 3%-10%), respectively. Younger children require higher doses of isoniazid per kilogram of body weight to achieve isoniazid concentrations similar to those in adults. A daily isoniazid dose of 8-12 mg/kg should be recommended.

Pre-school follow-up of a cohort of children with myelomeningocele in Cape Town, South Africa.

A cohort of South African children with myelomeningocele was followed for 5 years. Fifty-three were from metropolitan Cape Town and 65 from rural areas including the tribal region of Transkei. The mean general developmental quotient (GQ) at 5 years of age was lower than that previously reported. Black and coloured children had lower GQs than white children, but there were no significant differences between those from the urban and the rural areas. Early closure of the lesion and delivery by caesarean section were associated with higher levels of general developmental functioning. Central nervous system infections and the placement of more than one shunt for hydrocephalus resulted in lower GQs. Lesions above L2 were associated with non-ambulation. Ambulation was more likely in children in Cape Town than in rural children. Urinary incontinence occurred more frequently in rural children and among those in lower socio-economic circumstances.

An inverse relation between blood pressure and birth weight among 5 year old children from Soweto, South Africa.

STUDY OBJECTIVE: To examine the relation between birth weight and blood pressure at 5 years in a cohort of South African children. DESIGN: Prospective cohort study. PARTICIPANTS: 849 five year...