Research Articles (Paediatrics and Child Health)

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Risk factors for developing intraventricular haemorrhage in very low-birthweight infants at Kalafong Provincial Tertiary Hospital, South Africa, 2019-2020
Mahlako-Lekalakala, Kgahliso; Paulse, Natalie (South African Medical Association, 2026-03-04)
BACKGROUND : Intraventricular haemorrhage (IVH) remains a major concern as a result of the high prevalence of preterm births globally. OBJECTIVES : To identify maternal and neonatal risk factors associated with IVH, and to assess its incidence and most frequently occurring grade in a population of very low-birthweight infants (VLBWIs) at Kalafong Provincial Tertiary Hospital, South Africa (SA). METHODS : This retrospective cohort study included all infants of birthweight <1 500 g admitted between 1 January 2019 and 31 December 2020. Associations between IVH and maternal and neonatal risk factors were analysed using Pearson’s χ2 test and Fisher’s exact test. Risk factors significantly associated with IVH were included in a binary logistic regression model to identify independent predictors. Risk factors significantly associated with IVH (p<0.05) corresponded to a 95% confidence level. RESULTS : IVH was diagnosed during the first week of life in 43 out of 127 VLBWIs who met the inclusion criteria. Hypoglycaemia remained the most significant independent risk factor after adjusting for potential confounders in the multivariable logistic regression: adjusted odds ratio 4.02 (95% confidence interval (CI) 1.52 - 10.64). The incidence of IVH was 33.9% (95% CI 25.7 - 42.1). Grade I IVH occurred in 83.7% of infants, grade II in 9.3% and grades III - IV in 7.0%. CONCLUSION : This study found an association between hypoglycaemia and IVH, but causality could not be established owing to the nature of the study. In this tertiary hospital in SA, a third of VLBWIs had IVH, mostly graded as mild.
Growth assessment of children and adolescents with type 1 diabetes mellitus at Steve Biko Academic Hospital in Pretoria, South Africa : a cross-sectional study of factors contributing to stunting
Badenhorst, C.J.; Rheeder, Paul; Karsas, Maria (South African Medical Association, 2026-03)
BACKGROUND : The continuous rise in the prevalence of type 1 diabetes mellitus (T1DM) places pressure on countries to increase the resources needed to manage patients adequately. Studies have documented an association socioeconomic status between poor glycaemic control and stunting, which poses a significant health concern. Minimal data are available on the prevalence of stunting in T1DM in South Africa. OBJECTIVE : To establish the prevalence of stunting in a population of paediatric T1DM patients and determine contributing factors. METHODS : A descriptive, cross-sectional study was conducted at the Paediatric Diabetes Clinic of the Steve Biko Academic Hospital, Pretoria. Data were collected from patient files, a questionnaire and the National Health Laboratory Service database. Stunting was defined as height-for-age Z-score (HAZ)<–2. RESULTS : Of the 169 recruited patients, 115 were included (56.5% female). The prevalence of stunting was 10.4%. The median haemoglobin A1c (HbA1c) was 11.8%. Stunting was significantly associated with poor glycaemic control (p=0.008), older age (p=0.039), presence of comorbidities (p=0.026), underweight (p=<0.001) and food insecurity (p=0.021). Genetic factors were also associated with stunting, specifically lower paternal height (p=0.006) and decreased mid-parental height Z-score (p=0.035). CONCLUSION : Stunting in children and adolescents with T1DM was associated with poor glycaemic control, nutritional and socioeconomic factors, comorbidities, older age and genetic factors. The results point to a multifactorial contribution to impaired growth. To promote growth in children with T1DM, a multidisciplinary approach is essential, with a focus on optimising glycaemic control, addressing nutritional status and food insecurity, managing comorbidities and monitoring growth against genetic potential regularly.
First-year growth patterns of preterm infants receiving kangaroo mother care : associations with early life factors and 1-year anthropometry
Nel, Sanja; Feucht, Ute Dagma; Botha, Tanita; Arashi, Mohammad; Wenhold, Friedeburg Anna Maria (Springer, 2025-10-15)
BACKGROUND : This study characterises first-year growth patterns in a historical preterm infant cohort, and investigates associated early-life factors and 1-year anthropometry. METHODS : We analysed 322 South African preterm infants’ (mean 32.8 ± 2.4 weeks gestation) 1-year clinic records after kangaroo mother care discharge. Latent class trajectory modelling identified patterns of weight-for-age (WAZ), length-for-age (LAZ), weightfor-length (WLZ), and head circumference-for-age (HCZ) z-scores (Fenton 2013 Growth Chart; WHO Growth Standards, agecorrected). Z-score patterns were characterised as maintenance, faltering (progressively decreasing), gain (progressively increasing) or catch-up (rapidly increasing, exceeding birth z-score). Ordinal regression analysis investigated associations of early-life maternal/infant factors, birth weight, and early (until 50 weeks postmenstrual age) WAZ gain with growth patterns. One-year stunting (LAZ < -2), wasting (WLZ < -2) and overweight (body mass index-for-age z-score > +2) were compared. RESULTS : Best-fit models identified three WAZ and LAZ patterns (gradual gain, faltering, catch-up), three WLZ patterns (maintenance, faltering, catch-up) and two HCZ patterns (maintenance, gain). Most infants displayed maintenance, gradual gain or catch-up. Lower birth weight z-score (BWZ) was associated with LAZ catch-up (OR:8.33 (3.13–20.00)), WLZ faltering (OR:2.94 (1.69–5.00)) HCZ gain (OR:1.92 (1.23–3.13)), but lower odds of gradual WAZ gain (OR:0.36 (0.19–0.68)) and WAZ faltering (OR:0.56 (0.34–0.92)). Smaller early WAZ gains were associated with gradual WAZ gain (OR:2.27 (1.56–3.33)), WAZ faltering (OR:1.47 (1.11,1.96)), LAZ catch-up (OR:1.85 (1.25–2.70)), and LAZ faltering (OR:1.39 (1.09–1.75)). WAZ and WLZ faltering were both associated (p < 0.001) with 1-year stunting (45.5%, 23.5%) and wasting (21.8%, 10.3%). CONCLUSIONS : Most preterm infants had appropriate first-year growth. Lower BWZ was associated with WAZ and LAZ catch-up but WLZ faltering, and sub-optimal early WAZ growth with growth faltering.
The effects of in utero HIV and antiretroviral therapy exposure on infant T-cell and monocyte activation, function, and regulation of immune-modulatory pathways
Prinsloo, Andrea; Steel, Helen Carolyn; Feucht, Ute Dagmar; Rossouw, Theresa M. (Wiley, 2026-03)
Human immunodeficiency virus (HIV) infection is characterized by chronic, systemic immune activation. It is unclear how this affects the immune system of infants born to mothers living with HIV (MLWH). The current study assessed whether maternal HIV status and in utero antiretroviral therapy (ART) exposure impact infant T-cell and monocyte activation and regulation, as well as monocyte responsiveness to stimulation at birth and early infancy. T-cell and monocyte activation and expression of immune checkpoint molecules were characterized by means of flow cytometry. Pro- and anti-inflammatory cytokine/chemokine profiles were assessed using a suspension bead array assay. Seventy-one pregnant MLWH and 77 mothers not living with HIV (MNLWH) were recruited at 22 weeks’ gestation, and mother-infant pairs were followed until 6 months postpartum. MLWH had higher percentages of CD4+ and CD8+ T-cells expressing programmed cell death protein-1 (PD-1) and a higher percentage of regulatory T-cells (Tregs). HIV-exposed-but-uninfected (HEU) infants displayed disrupted CD4+ T-cell maturation with an increased number of CD8+ T-cells expressing PD-1 at the time of birth and increased T-cell exhaustion at 10 weeks of age. Higher levels of monocyte activation were observed in MLWH with increased numbers of classical (CL) monocytes expressing CCR2 and CD80. An increased percentage of CL monocytes expressing CCR2 and CD80 was noted in HEU infants at the time of birth, which persisted at 10 weeks of age. Significantly higher levels of C-reactive protein (CRP) and non-significantly higher levels of interleukin (IL)-6 and tumor necrosis factor-alpha were observed in MLWH, indicative of hyperactivated innate inflammation. HEU infants had persistently increased levels of IL-8 and transforming growth factor (TGF)-β1, and lower levels of IL-10, IFN-γ, and CRP. The latter might be secondary to cotrimoxazole use in the HEU infants while the altered cytokine levels might be indicative of altered immune programing. In summary, this cohort study showed that maternal HIV status has a transient effect on basal infant T-cell and monocyte activation, regulation, and monocyte responsiveness, which dissipates at 6 months of age, while altered cytokine levels persisted.
Mitochondrial DNA disorders in neuromuscular diseases in diverse populations
Gao, Fei; Schon, Katherine R.; Vandrovcova, Jana; Koken, Ozlem Yayıcı; Raga, Sharika; Naidu, Kireshnee; Schoonen, Maryke; Rani, Nimita; Tomaselli, Pedro; Baskar, Dipti; Kapapa, Musambo; Polat, Ipek; Wilson, Lindsay A.; Thangaraj, Kumarasamy; Yis, Uluc; Nandeesh, Bevinahalli N.; Bearden, David; Kvalsund, Michelle; Henning, Franclo; Vengalil, Seena; Nalini, Atchayaram; Sobreira, Claudia F.R.; Marques, Wilson; Topologlu, Haluk; Hanna, Michael G.; Yareeda, Sireesha; Vishnu, Venugopalan Y.; Van der Westhuizen, Francois H.; Smuts, Izelle; Meldau, Surita; Wilmshurst, Jo; Cavdarlı, Busranur; Heckmann, Jeannine; Chinnery, Patrick F.; Horvath, Rita (Wiley, 2025-08)
Neuromuscular features are common in mitochondrial DNA (mtDNA) disorders. The genetic architecture of mtDNA disorders in diverse populations is poorly understood. We analysed mtDNA variants from whole-exome sequencing data in neuromuscular patients from South Africa, Brazil, India, Turkey and Zambia. In 998 individuals, there were two definite diagnoses, two possible diagnoses and eight secondary findings. Surprisingly, common pathogenic mtDNA variants found in people of European ancestry were very rare. Whole-exome or -genome sequencing from undiagnosed patients with neuromuscular symptoms should be re-analysed for mtDNA variants, but the landscape of pathogenic mtDNA variants differs around the world.
Validating self-reported exclusive breastfeeding in Eswatini using stable isotope techniques
Simelane, Kwanele Siyabonga; Mhlanga, Tholakele; Mkhaliphi, Nhlakanipho Sandziso; Zwane, Siniketiwe; Dlamini, Glorious; Gadaga, Henry; Mulol, Helen; Coutsoudis, Anna (Public Library of Science, 2026-04-15)
Exclusive breastfeeding (EBF) prevalence at the population level is typically assessed through maternal or caregiver reports, which are prone to recall and social desirability biases. The deuterium oxide dose-to-mother (DTM) technique offers an objective alternative by administering a small amount of deuterium-labeled water to lactating mothers. This study compared the prevalence of EBF from maternal recall versus the DTM method in Eswatini and evaluated the strengths and limitations of both approaches in assessing infant feeding practices linked to malnutrition. A total of 102 mother-infant pairs were recruited from three regional hospitals and three health centers in Eswatini. EBF was assessed by maternal recall using the WHO 24-hour infant feeding recall method and objectively measured using the DTM stable isotope technique at three infant age intervals: 6 weeks to 2.4 months (n = 26), 2.5 to 4.0 months (n = 43), and 4.1 to 5.5 months (n = 33). Two cutoff values defined EBF status via the stable isotope method. Agreement between maternal recall and DTM measurements was analyzed using Kappa statistics. Maternal recall consistently overestimated EBF across all time points compared to the DTM method. Using Model 1 cutoffs, prevalences of EBF by maternal recall vs. DTM were 100% vs. 50% (≤2.4 months), 79.5% vs. 18.2% (2.5–4 months), and 71.9% vs. 18.8% (4.1–5.5 months). For Model 2, prevalences were 100% vs. 65.4%, 79.5% vs. 50%, and 71.9% vs. 43.8%, respectively. The difference between the two models is the cutoff that was used to determine EBF using the DTM method. Kappa analysis showed minimal agreement between methods at each time point. The DTM technique provides a more accurate and objective measure of EBF than maternal recall and is the gold standard for smaller sample studies. Maternal recall substantially overestimated exclusive breastfeeding prevalence, while the deuterium oxide technique yielded more reliable, objective assessments of infant feeding practices, highlighting the need to interpret recall data with caution due to overreporting.
Establish global nutrition research strategies: the meeting report of the First SIOP Nutrition Research Forum
Gala, Rajul M.; Schoeman, Judy; Iniesta, Raquel Revuelta; Van den Brink, Mirjam; Lovell, Amy L.; Huibers, Minke H.W. (MDPI, 2026-03)
Despite strong evidence linking nutritional status to treatment efficacy and survival in pediatric cancer, significant knowledge gaps and practice variation persist globally. On 24th October 2025, the International Society of Paediatric Oncology (SIOP) Nutrition Network, in collaboration with Prinsess Máxima Center for Paediatric Oncology and the International Initiative for Pediatrics and Nutrition (IIPAN), convened the first global SIOP Nutrition Network Research Forum. The forum brought together 54 international experts from high-income countries and low- and middle-income countries to define global nutrition research strategies for pediatric oncology. The forum addressed six emerging domains: body composition and treatment outcomes; microbiome, micronutrient status and metabolic health; prehabilitation and rehabilitation strategies; validation of nutritional assessment tools, guideline development for high-income settings; insights from international multicentric research initiatives—the International Atomic Energy Agency (IAEA), SIOP Nutrition Network, the Adapted Resource and Implementation Application (ARIA) guide nutrition portal, the International Collaboration on Nutrition in Cancer (ICONIC) WHO knowledge portal; and IIPAN and the World Cancer Research Fund (WCRF) for funding strategies. Delegates identified three priority working groups, namely prehabilitation optimization, pharmacokinetics, and advocacy, with each outlining collaborative nutrition research priorities for the next five years. This forum represents a critical point in pediatric oncology nutrition research as it established the first coordinated and internationally endorsed roadmap to bridge gaps in cancer care and ensure standard nutrition care worldwide. The research priorities and collaborations will help in creating evidence to improve cancer treatment and survival rate for children globally.
Severe, primary, and incidental COVID-19 in hospitalised children, South Africa : 2020-2023
Goga, Ameena Ebrahim; Ramraj, Trisha; Cloete, Jeane; Mawela, Dini; Waggie, Zainab; Archary, Moherndran; Chinniah, Kogielambal; Jeena, Prakash; Tabane, Nomakhuwa E.; Van Zyl, Riana; Reubenson, Gary; Strehlau, Renate; Feucht, Ute Dagmar; Reddy, Tarylee; Mchunu, Nobuhle; Cawood, Shannon; Zuhlke, Liesl; Webb, Kate; Zar, Heather J.; Donald, Kirsten A.; Scott, Christiaan; Morrow, Brenda M.; Aldersley, Thomas; Du Plessis, Nicolette Marie; Chetty, Terusha; Velaphi, Sithembiso; Dangor, Ziyaad; Moore, David P. (International Society of Global Health, 2026-01-30)
BACKGROUND : Knowledge gaps persist regarding paediatric COVID-19 clinical presentation, treatment and outcomes in high HIV prevalence settings, with low COVID-19 vaccine coverage. METHODS : An ambi-directional cohort study was conducted in 13 South African public sector hospitals. Hospitalised children with SARS-CoV-2 infection or post-infection syndrome were included. Main outcomes measures included severe disease and primary COVID-19 (hospitalisation for SARS-CoV-2 infection). RESULTS : There were 2363 SARS-CoV-2 positive children included (March 2020 through May 2023); median age 23.6 months (interquartile range (IQR) = 4.3–98.2 months). Excluding missing values, 1618 (68.9%) children had primary COVID-19; 1121 (69.3%) of these had severe primary COVID-19. In the primary COVID-19 group with data, 318 / 1588 (20.0%) received intensive or high care, 121/1285 (9.4%) received a blood transfusion and 48/1616 (3.0%) died. Multivariable analyses demonstrated that severe primary COVID-19 was 32% higher in children aged 29–365 days (adjusted Risk Ratio (aRR) = 1.32 (95% confidence interval (CI) = 1.13–1.55); reference: 0–28 days), 13% higher with one or more comorbidities (aRR = 1.13; CI = 1.05-1.22)), and 14–22% lower during the Beta, Delta and Omicron periods (reference: ancestral period). Amongst all hospitalised children with a positive SARS-CoV-2 test, severe disease was commoner in underweight children (aRR 1.09; CI = 1.02–1.17, P = 0.013)). Severe signs were commoner in children living with HIV (CLHIV), 88/121 (72.7%), vs. HIV uninfected 1320 / 2104 (62.7%), P = 0.026, and in antiretroviral therapy-naïve CLHIV, (37 / 41 (90.2%), vs. CLHIV on therapy 51 / 80 (63.8%), P = 0.002). CONCLUSIONS : In a high HIV prevalence country, approximately 70% of children with a positive SARS-CoV-2 test were hospitalised for COVID-19 treatment; almost 70% of these children were severely ill. Controlling for other factors, disease severity was highest in the hypothesised pre-immunity Ancestral period. HIV infection and delayed ART initiation were associated with severe signs. In such settings, strengthening general child health programmes to reduce underweight and prevent or treat paediatric HIV may reduce the severity of new diseases of pandemic proportion.
Xanthogranulomatous pyelonephritis in a child with autoimmune joint disease
Kriek, Pieter Willem; Karsas, Maria; Cloete, Jeane (Springer, 2025-11-06)
Xanthogranulomatous pyelonephritis is a rare condition in paediatric patients, mostly described in middle-aged female patients. We present a 7-year-old female with juvenile idiopathic arthritis, who was found to have a kidney mass with a concurrent Escherichia coli urinary tract infection. Surgical excision was done out of concern for possible malignancy. Histology confirmed the diagnosis of xanthogranulomatous pyelonephritis and persistent E. coli infection.
Management outcomes of South African children diagnosed with neuroblastoma in adolescence
Van Heerden, Jaques; Esterhuizen, Tonya; Du Plessis, Jan; Geel, Jennifer; Buchner, Ane; Van Zyl, Anel; Hendricks, Marc; Naidu, Gita; Van Emmenes, Barry; Vaithilingum, M.; Kruger, Mariana (Elsevier, 2025-03)
BACKGROUND : Neuroblastoma (NB) is an indolent disease in adolescents. Only 5 % of neuroblastoma diagnoses are made in adolescents and adults. Limited data exists on Africans of older age groups. OBJECTIVES : We aimed to compare the characteristics and outcomes of South African children ≥10 years diagnosed with NB with international reports. PATIENTS AND METHODS : Multicentric, retrospective data of South African patients (0–15 y) with NB diagnosed between January 2000 and December 2016 were analyzed. Clinical profiles and outcomes of adolescents (≥10 years) with NB were compared to those of the younger patients in our cohort. The outcomes of adolescents (≥10 years) with NB were compared with those reported in the global literature. RESULTS : Thirty adolescents with a male-to-female ratio of 1:0.6 were diagnosed with NB, constituting 6.5 % of all patients with NB. Metastatic disease at diagnosis was present in 24 (75 %), including lung metastases in 2 (6 %). Half of the patients presented with a raised lactate dehydrogenase (LDH) and/or ferritin and unfavorable pathology. Post-induction remission rates were higher in the adolescent group (33 %) compared to the 18–59 months (24.8 %) and 5–9.9 years (29.7 %) cohorts but less than the <18 months (47.2 %) cohort (p < 0.001). The adolescent group had the poorest five-year overall survival (20.9 %) compared to the children <18 months (39.0 %), 18–59 months (44.1 %), or 5–9.9 years old (63.5 %) (p < 0.001). CONCLUSIONS : Despite a favorable response rate to induction chemotherapy, the five-year overall survival of adolescents with NB is dismal in South Africa.
Population impact of South Africa's human papillomavirus (HPV) vaccination programme on HPV prevalence in adolescent girls with and without HIV : a repeat cross-sectional study
Machalek, Dorothy A.; Nyemba, Dorothy C.; Travill, Danielle; Petoumenos, Kathy; Mbulawa, Zizipho Z.A.; Naidoo, Ishana; Motshwane, Feni M.M.; Bamford, Lesley; Rees, Helen; Kaldor, John M.; Delany-Moretlwe, Sinead (Elsevier, 2026-04)
BACKGROUND : A school-based human papillomavirus (HPV) vaccination programme providing protection against types 16 and 18 of HPV was introduced in South Africa in 2014 for Grade 4 girls (aged ≥9 years), achieving 87% coverage among learners with at least one of the two recommended doses. We evaluated the programme's impact on HPV prevalence among adolescent girls in a setting of high HIV prevalence. METHODS : In this repeat cross-sectional study, girls aged 17–18 years were invited from 15 primary health-care clinics in four provinces (Free State, Gauteng, Mpumalanga, and North West) of South Africa to provide a self-collected vaginal sample for HPV testing (AnyPlex II HPV28, Seegene, Seoul, South Korea). A survey done from June 19 to Dec 11, 2019, estimated baseline (pre-vaccine) HPV prevalence. A repeat survey done from Feb 16 to Dec 6, 2023, estimated HPV prevalence in a group eligible for the vaccination programme (post-vaccine). Vaccination status was assessed through district registers and self-reported data. The primary outcome was the impact of the HPV vaccination programme, measured as the relative reduction in HPV prevalence between the two birth cohorts using generalised linear regression (estimating adjusted prevalence ratios), overall and by HIV status. FINDINGS : Of 2470 participants enrolled, 819 girls were recruited for the pre-vaccine survey (248 living with HIV) and 1538 for the post-vaccine survey (295 living with HIV). Prevalence of HPV vaccine types HPV-16 and HPV-18 declined by 83%, from 21·6% (177 of 819 participants) in the pre-vaccine group to 3·2% (49 of 1538 participants) in the post-vaccine group (adjusted prevalence ratio 0·17, 95% CI 0·12–0·24; p<0·0001). A similar reduction was observed among those living with HIV, with prevalence decreasing from 29·4% (73 of 248 participants) in the pre-vaccine group to 4·4% (13 of 295 participants) in the post-vaccine group (adjusted prevalence ratio 0·18, 95% CI 0·10–0·32; p<0·0001). No significant reductions were noted for other HPV types, except HPV-31 and HPV-45, which is consistent with cross-protection. INTERPRETATION : In this large-scale evaluation of South Africa's two-dose HPV vaccination programme, we observed impacts similar to those seen with three-dose programmes in high-income settings, including equivalent impacts among adolescent girls living with HIV. These findings underscore the substantial population-level benefits of high-coverage routine HPV vaccination in a high-HIV-burden setting.
Characterization of early viral populations in infants acquiring HIV through perinatal and breastmilk transmission : a review of what is currently known and the gaps that need to be addressed to guide passive HIV immunization of breastfeeding infants
Giorgi, Elena E.; Abrahams, Melissa-Rose; Fouda, Genevieve; John-Stewart, Grace; Goga, Ameena Ebrahim; Mullins, James I.; Permar, Sallie R.; Janes, Holly; Martin, Troy M. (Bentham Science Publishers, 2025-09)
Newborns represent only 1% of the population. Yet, HIV vertical transmissions represent 10% of all new infections globally, even though antiretroviral therapy (ART) has been shown to reduce the risk of vertical transmission to less than 2%. While vaccines still represent the most efficient and cost-effective intervention to eradicate new infections, HIV immunogens that can effectively elicit broad-spectrum protection are still at least a decade away. In contrast, passive immunization with broadly neutralizing antibody (bnAb) combinations has the potential to provide a more immediate pathway to HIV prophylaxis. Early-phase infant trials are underway to establish the safety and pharmacokinetics of bnAb combinations selected for their potency against viruses acquired via adult transmissions. However, the specific characteristics and phenotypic differences of vertically transmitted viruses in infants compared to those in adults remain uncertain, including their susceptibility to known broadly neutralizing antibodies (bnAbs). We review the current knowledge of vertically transmitted HIV viruses, including their genetics and phenotypic features. Differences in immunity between adults and infants lead us to hypothesize that distinct selection and evolutionary pressures act on the virus at the time of transmission and during the early phases of infection, and these may in turn affect the choice of bnAb combinations needed for protection against vertical transmission of HIV.
An epigenetic perspective on neonatal encephalopathy with suspected hypoxic ischaemic encephalopathy
Mistry, Priyal; Mellet, Juanita; Durandt, Chrisna; Smuts, Izelle; Pepper, Michael Sean (BioMed Central, 2026-01-22)
Neonatal encephalopathy with suspected hypoxic ischaemic encephalopathy (NESHIE) is a neurological disorder caused by oxygen deprivation and limited blood flow to a neonate's brain. Although various antenatal and perinatal factors have been identified, their precise role in NESHIE pathogenesis remains unclear. The pathophysiology involves multiple molecular pathways that can be explored using a multi-omics approach, including epigenetics. Epigenetics involves heritable changes in gene expression without altering the DNA sequence, encompassing chemical modifications to DNA and histone proteins, as well as changes mediated by non-coding RNAs (ncRNAs). These epigenetic changes regulate gene expression and can be influenced by environmental factors, offering crucial insights into gene regulation and disease mechanisms. This review examines the role of epigenetic mechanisms in NESHIE, focusing on the modulation of hypoxia-inducible factor-1 alpha (HIF-1α) and ncRNA during hypoxic conditions. Additionally, epigenetic-mediated foetal programming may shed light on how maternal and antenatal risk factors contribute to NESHIE susceptibility. Understanding these epigenetic signatures could advance biomarker discovery and the development of novel therapeutic strategies for NESHIE.
Bridging gaps in mitochondrial disease diagnosis : the role of advanced biomarker discovery
Makwikwi, Tendai; Schoonen, Maryke; Smuts, Izelle; Van der Westhuizen, Francois H. (Springer, 2026-01)
Mitochondrial disease (MD) is associated with dysfunction of the oxidative phosphorylation (OXPHOS) system and represents one of the most frequently occurring inherited neuromuscular diseases. Like many rare diseases, MD is characterised by striking clinical heterogeneity, resulting from its unique bi-genomic aetiology and multi-system involvement of energy-dependent tissues. Despite four decades of genetic discoveries and the advent of omics-driven insights into genes, mutations, and phenotypes, achieving an early and accurate diagnosis remains challenging—even within advanced diagnostic settings. A reliable genetic diagnosis for MD requires specialised clinical expertise capable of recognising population-specific phenotypes, providing access to genomic diagnostic services, and interpreting local genotype–phenotype correlations. However, these resources remain unevenly distributed, limiting diagnostic yield and equity. Research output and diagnostic infrastructure for MD are disproportionately concentrated in high-income countries. This imbalance persists even though ~ 84% of the global population resides in low- and middle-income countries (LMICs), where access to MD diagnostics, research infrastructure, and specialised care remains limited. Recent World Health Organisation (WHO) and International Classification of Diseases (ICD-11) initiatives have acknowledged these disparities, emphasising the need for improved diagnostic access, laboratory capacity, and data-sharing mechanisms [4,5,6,7]. Nevertheless, the diagnostic capacity divide remains substantial. A major contributor to the diagnostic gap in MD is the absence of reliable biomarkers that enable early detection, disease monitoring, and assessment of therapeutic efficacy. The lack of validated biomarkers restricts both diagnostic precision and therapeutic development.
Maternal phenotype, infant size and breast milk composition in women living with HIV
Gilfillan, Marlene; Wenhold, Friedeburg Anna Maria; Mulol, Helen; Feucht, Ute Dagmar (Wiley, 2025-07)
The impact of maternal factors on the size of HIV‐exposed‐uninfected (HEU) infants and breast milk composition is poorly understood. Anthropometry, bio‐electrical impedance, haemoglobin and HIV viral load data of women living with HIV (WLWH) and without HIV (WLWOH) were compared and related to their infants' anthropometric Z‐scores and breast milk macronutrients 6 weeks and 6 months postnatally. At both time points, WLWH (6‐week: n = 83; 6‐month: n = 63) had lower reactance (measure of body cell mass) (6‐week: p = 0.016; 6‐month: p < 0.001), phase angle (PhA) (measure of cell health) (6‐week: p = 0.001; 6‐month: p = 0.002) and haemoglobin (6‐week: p = 0.002; 6‐month: p = 0.004) than WLWOH (6‐week: n = 90; 6‐month: n = 73). HEU infants had lower weight‐for‐age Z‐scores (WAZ) (6‐week: p = 0.010; 6‐month: p = 0.005). Breast milk composition did not differ between groups. At 6 weeks, HEU infants had lower head circumference‐for‐age Z‐scores (HCAZ) (p = 0.014). Bivariate regression demonstrated maternal HIV predicted lower infant WAZ (ß = −0.442; p = 0.011) and HCAZ (ß = −0.445; p = 0.014). Maternal body mass index (BMI) and mid‐upper arm circumference were positively associated with breast milk protein content (ß = 0.018; p = 0.014 and ß = 0.025; p = 0.002, respectively). At 6 months (bivariate regression) maternal HIV predicted lower infant WAZ (ß = −0.609; p = 0.005) and length‐for‐age Z‐scores (ß = −0.741; p = 0.018). Higher maternal BMI and PhA were associated with higher infant WAZ (ß = 0.622; p = 0.015 and ß = 0.055; p = 0.017, respectively). On multivariable analysis, maternal HIV remained a predictor of lower WAZ (ß = −0.568; p = 0.024). In conclusion, maternal HIV infection and phenotype predict the size of infants and breast milk composition up to 6 months postnatally.
Exploring infant size and body composition at 18 months : an ambidirectional peri‐urban South African cohort study
Mulol, Helen; Nel, Sanja; Wenhold, Friedeburg Anna Maria; Feucht, Ute Dagmar (Wiley, 2025-04)
The first 1000 days of life lay the foundations for subsequent growth. This ambidirectional study, including prenatal, perinatal and postnatal factors, aimed to identify exposure variables affecting body size and composition and corresponding Z‐score outcomes at age 18 months in infants born to women at low risk of adverse pregnancy outcomes in a peri‐urban area of South Africa. Prenatal factors (maternal age, HIV status, anthropometry, parity, food insecurity and umbilical artery resistance index Z‐score (UmA‐RIAZ) as a measure of placental function, with higher UmA‐RIAZ indicating poorer placental function); perinatal factors (infant sex, gestational age and birth anthropometry) and postnatal factors (infant feeding) were included as exposure variables, with infant anthropometry and body composition at 18 months as outcomes. Simple linear regression analysis was used to investigate associations between exposure variables and infant outcomes, and variables with p < 0.10 were included in the subsequent multiple regression analyses. Multiple regression analysis showed that higher UmA‐RIAZ predicted lower birthweight [−0.11 kg (95% CI: −0.17, −0.04 kg)], birthweight‐for‐age Z‐score [−0.24 (95% CI: −0.39, −0.09)] and 18‐month infant length [−0.9 cm (95% CI: −1.4, −0.4 cm)] and length‐for‐age Z‐score [−0.28 (95% CI: −0.45, −0.11)]. Maternal HIV infection predicted reduced 18‐month infant length‐for‐age Z‐score [−0.46 (95% CI: −0.83, −0.09)]. Household food insecurity predicted reduced fat‐free mass‐for‐age Z‐score at 18 months [−0.27 (95% CI: −0.51, −0.03)]. Infant anthropometry and body composition outcomes, therefore, are greatly affected by pre‐ and postnatal nutrition‐related factors, such as placental insufficiency in utero and household food insecurity, with long‐term consequences including stunting, which impact the individual, future generations and society.
Perspective : radiotherapy and body composition: unmet meeds in low- and middle-income countries
Murphy-Alford, Alexia J.; Grossberg, Aaron J.; Baracos, Vickie E.; Barbar, Maha; Bauer, Judy; Bennett, Jonathan P.; Fidarova, Elena; Fuller, Clifton D.; Loser, Anastassia; Moreno, Amy C.; Patra, Anurima; Puttaswamy, Deepa; Rosenthal, David, I.; Schoeman, Judy; Anacak, Yavuz (Elsevier, 2026-01)
Radiotherapy plays a vital role in cancer treatment, yet its effects on patients’ nutritional status can precipitate muscle loss, with significant implications for treatment tolerance and outcomes. Evidence from high-income countries increasingly links radiation-induced muscle loss to adverse clinical outcomes. In contrast, low- and middle-income countries face a stark evidence gap, despite the heightened vulnerability of cancer patients in these settings due to delayed diagnosis, limited access to care, and high rates of co-morbidities. This paper highlights the critical gaps in nutritional care for radiotherapy patients in low- and middle-income countries. STATEMENTS OF SIGNIFICANCE : Radiotherapy can affect body composition and consequently clinical outcomes, yet evidence from low- and middle-income countries remains limited despite heightened risks from delayed care and comorbidities. This perspective argues that generating context-specific body composition data and building evidence for integrating nutrition into radiotherapy services are critical steps to optimize treatment and improve survivorship in resource-limited settings.
Increasing access to pediatric allogeneic hematopoietic stem cell transplantation in South Africa
Hendricks, Candice Laverne; Brittain, David; Davidson, Alan; Novitzky, Nicolas; Du Toit, Justin Rudolph; Thomson, Jackie; Reynders, David; Geel, Jennifer Ann; Naidu, Gita; Mellet, Juanita; Durandt, Chrisna; West, Erna; Ingram, Charlotte; Verburgh, Estelle; Pepper, Michael Sean (Wiley, 2026)
Current pediatric allogeneic hematopoietic stem cell transplantation (HSCT) services in South Africa do not meet the substantial demand in the country. The factors leading to this paucity are multifactorial, including a limited number of appropriate donors on our local registries, inadequate identification and referral of appropriate patients, long distances to travel to health facilities, socioeconomic inequality, and inadequate infrastructure and clinical expertise for the number of transplants required. We describe a model for a large HSCT unit that caters to insured and uninsured patients in order to ensure equitable access, and which is in line with the WHO health system building blocks. The scale at which transplantation will be achieved will allow for the development of local skills and expertise, which can be decentralized in the future to further improve HSCT access.
Feeding profit : how the food and drinks industry (FDI) is one of the key drivers of the global epidemic of childhood overweight and obesity
Spencer, Nick; Mercer, Raul Gerardo; Rajmil, Luis; Lake, Lori; Kraus De Camargo, Olaf; Ezeonu, Thecla; Olatunya, Oladele Simeon; Oguda, Lulu; Tsitsika, Artemis; Iwamoto, Azusa; Rohloff, Peter (BMJ Publishing Group, 2026-01)
No abstract available.
Guest editorial
Van Niekerk, Andre (Allergy Society of South Africa, 2025-03)
Many short courses (bursts) of oral corticosteroids (OCS) are commonly prescribed for indicated and non-indicated conditions. These bursts are perceived to be safe and are usually given by prescription for less than 14 days at a time. The global corticosteroid market was USD 5.7 billion in 2023, and with a projected annual growth rate of 4.6% across all regions, reflects its widespread use. Published data of OCS use in South Africa are difficult to find, yet parents of children attending a clinic for immune deficiencies frequently report repetitive prescriptions.

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