Regional adiposity and insulin sensitivity - interactions with menopause and HIV in middle-aged Black African women.

OBJECTIVE: To explore depot-specific functional aspects of adipose tissue, examining the putative role for menopause and HIV status on insulin sensitivity (SI) and beta-cell function in Black South African women. METHODS: Women (n = 92) from the Middle-Aged Soweto Cohort, including premenopausal HIV-negative (n = 21); premenopausal women living with HIV (WLWH; n = 11); postmenopausal HIV-negative (n = 42); postmenopausal WLWH (n = 18) underwent the following tests: body composition (dual energy x-ray absorptiometry); fasting bloods for sex hormones, inflammation and adipokines; frequently sampled intravenous glucose tolerance test for SI and beta-cell function (disposition index, DI); abdominal (aSAT) and gluteal subcutaneous adipose tissue (gSAT) biopsies for cell size and mRNA expression of adipokines, inflammation, and estrogen receptors [ER]. RESULTS: Depot-specific associations between gene expression and insulin parameters did not differ by HIV or menopause status. Pooled analysis showed significant models for SI (P = 0.002) and DI (P = 0.003). Higher SI was associated with lower leptin and CD11c expression in aSAT and higher adiponectin in gSAT. Higher DI was associated with higher aSAT and gSAT expression of adiponectin, LPL, ERα, and PPARγ, and lower leptin in aSAT. WLWH had higher expression of adiponectin and lower expression of leptin in both aSAT (P = 0.002 and P = 0.005) and gSAT (P = 0.004 and P = 0.002), respectively, and a larger proportion of smaller cells in aSAT (P < 0.001). CONCLUSION: Insulin sensitivity and beta cell function were distinctively associated with aSAT and gSAT. While menopause did not influence these relationships, HIV had a significant effect on adipose tissue, characterised by variations in cell size distribution and transcript levels within the depots.

Variability of polygenic prediction for body mass index in Africa.

BACKGROUND: Polygenic prediction studies in continental Africans are scarce. Africa's genetic and environmental diversity pose a challenge that limits the generalizability of polygenic risk scores (PRS) for body mass index (BMI) within the continent. Studies to understand the factors that affect PRS variability within Africa are required. METHODS: Using the first multi-ancestry genome-wide association study (GWAS) meta-analysis for BMI involving continental Africans, we derived a multi-ancestry PRS and compared its performance to a European ancestry-specific PRS in continental Africans (AWI-Gen study) and a European cohort (Estonian Biobank). We then evaluated the factors affecting the performance of the PRS in Africans which included fine-mapping resolution, allele frequencies, linkage disequilibrium patterns, and PRS-environment interactions. RESULTS: Polygenic prediction of BMI in continental Africans is poor compared to that in European ancestry individuals. However, we show that the multi-ancestry PRS is more predictive than the European ancestry-specific PRS due to its improved fine-mapping resolution. We noted regional variation in polygenic prediction across Africa's East, South, and West regions, which was driven by a complex interplay of the PRS with environmental factors, such as physical activity, smoking, alcohol intake, and socioeconomic status. CONCLUSIONS: Our findings highlight the role of gene-environment interactions in PRS prediction variability in Africa. PRS methods that correct for these interactions, coupled with the increased representation of Africans in GWAS, may improve PRS prediction in Africa.

Young women's social support networks during pregnancy in Soweto, South Africa.

BACKGROUND: Although studies from high-income countries have examined social support during pregnancy, it remains unclear what type of support is received by expectant mothers from low- and middle-income country settings. AIM: To explore young women's social support networks during pregnancy in Soweto, South Africa. SETTING: This study was undertaken in an academic hospital based in the Southwestern Townships (Soweto), Johannesburg, in Gauteng province, South Africa. METHODS: An exploratory descriptive qualitative approach was employed. Eighteen (18) young pregnant women were recruited using a purposive sampling approach. In-depth interviews were conducted, and data were analysed using inductive thematic analysis. RESULTS: Analysis of the data resulted in the development of two superordinate themes namely; (1) relationships during pregnancy and (2) network involvement. Involvement of the various social networks contributed greatly to the young women having a greater sense of potential parental efficacy and increased acceptance of their pregnancies. Pregnant women who receive sufficient social support from immediate networks have increased potential to embrace and give attention to pregnancy-related changes. CONCLUSION: Focusing on less-examined characteristics that could enhance pregnant women's health could help in the reduction of deaths that arise because of pregnancy complications and contribute in globally accelerating increased accessibility to adequate reproductive health.Contribution: This study's findings emphasise the necessity for policymakers and healthcare providers to educate the broader community about the importance of partner, family and peer support to minimise risks that may affect pregnancy care and wellbeing of mothers.

Impacts of heat exposure in utero on long-term health and social outcomes: a systematic review.

BACKGROUND: Climate change, particularly global warming, is amongst the greatest threats to human health. While short-term effects of heat exposure in pregnancy, such as preterm birth, are well documented, long-term effects have received less attention. This review aims to systematically assess evidence on the long-term impacts on the foetus of heat exposure in utero. METHODS: A search was conducted in August 2019 and updated in April 2023 in MEDLINE(PubMed). We included studies on the relationship of environmental heat exposure during pregnancy and any long-term outcomes. Risk of bias was assessed using tools developed by the Joanna-Briggs Institute, and the evidence was appraised using the GRADE approach. Synthesis without Meta-Analysis (SWiM) guidelines were used. RESULTS: Eighteen thousand six hundred twenty one records were screened, with 29 studies included across six outcome groups. Studies were mostly conducted in high-income countries (n = 16/25), in cooler climates. All studies were observational, with 17 cohort, 5 case-control and 8 cross-sectional studies. The timeline of the data is from 1913 to 2019, and individuals ranged in age from neonates to adults, and the elderly. Increasing heat exposure during pregnancy was associated with decreased earnings and lower educational attainment (n = 4/6), as well as worsened cardiovascular (n = 3/6), respiratory (n = 3/3), psychiatric (n = 7/12) and anthropometric (n = 2/2) outcomes, possibly culminating in increased overall mortality (n = 2/3). The effect on female infants was greater than on males in 8 of 9 studies differentiating by sex. The quality of evidence was low in respiratory and longevity outcome groups to very low in all others. CONCLUSIONS: Increasing heat exposure was associated with a multitude of detrimental outcomes across diverse body systems. The biological pathways involved are yet to be elucidated, but could include epigenetic and developmental perturbations, through interactions with the placenta and inflammation. This highlights the need for further research into the long-term effects of heat exposure, biological pathways, and possible adaptation strategies in studies, particularly in neglected regions. Heat exposure in-utero has the potential to compound existing health and social inequalities. Poor study design of the included studies constrains the conclusions of this review, with heterogenous exposure measures and outcomes rendering comparisons across contexts/studies difficult. TRIAL REGISTRATION: PROSPERO CRD 42019140136.

Cost-effectiveness of a complex continuum of care intervention targeting women and children: protocol for an economic evaluation of the Bukhali trial in South Africa.

INTRODUCTION: As nearly two-thirds of women presenting at their first antenatal visit are either overweight or obese in urban South Africa, the preconception period is an opportunity to optimise health and offset transgenerational risk of both obesity and non-communicable diseases. This protocol describes the planned economic evaluation of an individually randomised controlled trial of a complex continuum of care intervention targeting women and children in Soweto, South Africa (Bukhali trial). METHODS AND ANALYSIS: The economic evaluation of the Bukhali trial will be conducted as a within-trial analysis from both provider and societal perspectives. Incremental costs and health outcomes of the continuum of care intervention will be compared with standard care. The economic impact on implementing agencies (programme costs), healthcare providers, participants and their households will be estimated. Incremental cost-effectiveness ratios (ICERs) will be calculated in terms of cost per case of child adiposity at age years averted. Additionally, ICERs will also be reported in terms of cost per quality-adjusted life year gained. If Bukhali demonstrates effectiveness, we will employ a decision analytical model to examine the cost-effectiveness of the intervention over a child's lifetime. A Markov model will be used to estimate long-term health benefits, healthcare costs and cost-effectiveness. Probabilistic sensitivity analyses will be conducted to explore uncertainty and ensure robust results. An analysis will be conducted to assess the equity impact of the intervention, by comparing intervention impact within quintiles of socioeconomic status. ETHICS AND DISSEMINATION: The Bukhali trial economic evaluation has ethical approval from the Human Ethics Research Committee of the University of the Witwatersrand, Johannesburg, South Africa (M240162). The results of the economic evaluation will be disseminated in a peer-reviewed journal and presented at a relevant international conference. TRIAL REGISTRATION NUMBER: Pan African Clinical Trials Registry (PACTR201903750173871; https://pactr.samrc.ac.za).

Food insecurity and coping strategies associate with higher risk of anxiety and depression among South African households with children.

OBJECTIVE: To investigate food insecurity and related coping strategies, and their associations with the risk of anxiety and depression, among South African households with children. DESIGN: Nationally representative cross-sectional study. Tools for assessing food insecurity, coping strategies, risk of anxiety and depression were assessed from the Community Childhood Hunger Identification Project, Coping Strategies Index, Generalised Anxiety Disorder-7 and Patient Health Questionnaire-9, respectively. We used ordered logistic regression to test associations of food insecurity and coping strategies with the risk of anxiety and depression. Moderating effects of each coping strategy were tested in the associations of food insecurity with anxiety and depression. SETTING: South Africa, post COVID-19 restrictions, May-June 2022. PARTICIPANTS: 1,774 adults, weighted to 20,955,234 households. RESULTS: Food insecurity prevalence was 23·7 % among households with children. All coping strategies were used to some extent, but relying on less preferred and less expensive foods was the most used strategy (85·5 % of food-insecure households). Moving to a higher level of food insecurity was associated with >1·6 greater odds of being in a higher risk of anxiety and depression. Sending a household member to beg for food was the strongest associated factor (OR = 1·7, P < 0·001). All coping strategies partly moderated (lessened) the associations of food insecurity with a higher risk of anxiety and depression. CONCLUSIONS: Food insecurity among households with children was high following the COVID-19 pandemic. Collaborative efforts between government, private sector and civil society to eradicate food insecurity should prioritise poorer households with children, as these populations are the most vulnerable.

Mobile Technology Use in Clinical Research Examining Challenges and Implications for Health Promotion in South Africa: Mixed Methods Study.

BACKGROUND: The use of mobile technologies in fostering health promotion and healthy behaviors is becoming an increasingly common phenomenon in global health programs. Although mobile technologies have been effective in health promotion initiatives and follow-up research in higher-income countries and concerns have been raised within clinical practice and research in low- and middle-income settings, there is a lack of literature that has qualitatively explored the challenges that participants experience in terms of being contactable through mobile technologies. OBJECTIVE: This study aims to explore the challenges that participants experience in terms of being contactable through mobile technologies in a trial conducted in Soweto, South Africa. METHODS: A convergent parallel mixed methods research design was used. In the quantitative phase, 363 young women in the age cohorts 18 to 28 years were contacted telephonically between August 2019 and January 2022 to have a session delivered to them or to be booked for a session. Call attempts initiated by the study team were restricted to only 1 call attempt, and participants who were reached at the first call attempt were classified as contactable (189/363, 52.1%), whereas those whom the study team failed to contact were classified as hard to reach (174/363, 47.9%). Two outcomes of interest in the quantitative phase were "contactability of the participants" and "participants' mobile number changes," and these outcomes were analyzed at a univariate and bivariate level using descriptive statistics and a 2-way contingency table. In the qualitative phase, a subsample of young women (20 who were part of the trial for ≥12 months) participated in in-depth interviews and were recruited using a convenience sampling method. A reflexive thematic analysis approach was used to analyze the data using MAXQDA software (version 20; VERBI GmbH). RESULTS: Of the 363 trial participants, 174 (47.9%) were hard to reach telephonically, whereas approximately 189 (52.1%) were easy to reach telephonically. Most participants (133/243, 54.7%) who were contactable did not change their mobile number. The highest percentage of mobile number changes was observed among participants who were hard to reach, with three-quarters of the participants (12/16, 75%) being reported to have changed their mobile number ≥2 times. Eight themes were generated following the analysis of the transcripts, which provided an in-depth account of the reasons why some participants were hard to reach. These included mobile technical issues, coverage issues, lack of ownership of personal cell phones, and unregistered number. CONCLUSIONS: Remote data collection remains an important tool in public health research. It could, thus, serve as a hugely beneficial mechanism in connecting with participants while actively leveraging the established relationships with participants or community-based organizations to deliver health promotion and practice.

Expanding the human gut microbiome atlas of Africa.

Population studies are crucial in understanding the complex interplay between the gut microbiome and geographical, lifestyle, genetic, and environmental factors. However, populations from low- and middle-income countries, which represent ~84% of the world population, have been excluded from large-scale gut microbiome research. Here, we present the AWI-Gen 2 Microbiome Project, a cross-sectional gut microbiome study sampling 1,803 women from Burkina Faso, Ghana, Kenya, and South Africa. By intensively engaging with communities that range from rural and horticultural to urban informal settlements and post-industrial, we capture population diversity that represents a far greater breadth of the world's population. Using shotgun metagenomic sequencing, we find that study site explains substantially more microbial variation than disease status. We identify taxa with strong geographic and lifestyle associations, including loss of Treponema and Cryptobacteroides species and gain of Bifidobacterium species in urban populations. We uncover a wealth of prokaryotic and viral novelty, including 1,005 new bacterial metagenome-assembled genomes, and identify phylogeography signatures in Treponema succinifaciens. Finally, we find a microbiome signature of HIV infection that is defined by several taxa not previously associated with HIV, including Dysosmobacter welbionis and Enterocloster sp. This study represents the largest population-representative survey of gut metagenomes of African individuals to date, and paired with extensive clinical biomarkers, demographic data, and lifestyle information, provides extensive opportunity for microbiome-related discovery and research.

Final 192-Week Efficacy and Safety Results of the ADVANCE Trial, Comparing 3 First-line Antiretroviral Regimens.

Background: ADVANCE compared 3 World Health Organization-recommended first-line regimens in participants with HIV who were antiretroviral naive. Methods: This randomized, open-label, noninferiority trial enrolled participants living with HIV with no antiretroviral exposure in the previous 6 months to 1 of the following arms: tenofovir alafenamide (TAF) / emtricitabine (FTC) + dolutegravir (DTG) (2 tablets), tenofovir disoproxil fumarate (TDF) / FTC + DTG (2 tablets), or a fixed-dose combination of TDF / FTC / efavirenz (EFV) (1 tablet). We report the final safety and efficacy data up to 192 weeks. Results: Repeat consent from the original 351 participants randomized to each arm was obtained from 230 participants (66%) in the TAF/FTC + DTG arm, 209 (60%) in the TDF/FTC + DTG arm, and 183 (52%) in the TDF/FTC/EFV arm. At 192 weeks, 213 (61%) of the original 351 participants in the TAF/FTC + DTG arm, 195 (56%) in the TDF/FTC + DTG arm, and 172 (49%) in the TDF/FTC/EFV arm had confirmed RNA <50 copies/mL, with low virologic failure in all groups and no significant integrase inhibitor mutations in any arm. Mean weight gain was 8.9 kg (SD, 7.1) in the TAF/FTC + DTG arm, 5.9 kg (SD, 7.1) in the TDF/FTC + DTG arm, and 3.2 kg (SD, 8.1) in the TDF/FTC/EFV arm at 192 weeks from baseline and was greatest among women, those taking TAF, and those with lower baseline CD4 counts. The weight trajectory slowed after week 96. There were few clinical events and minor laboratory changes and differences among arms after 96 weeks. There were no significant differences in treatment-emergent hypertension or pregnancy outcomes by arm. Conclusions: High viral suppression was seen across arms, with no resistance to DTG. Weight gain continued but slowed after 96 weeks, with few clinical events or laboratory changes.

A qualitative analysis of community health worker perspectives on the implementation of the preconception and pregnancy phases of the Bukhali randomised controlled trial.

Community health workers (CHWs) play an important role in health systems in low- and middle-income countries, including South Africa. Bukhali is a CHW-delivered intervention as part of a randomised controlled trial, to improve the health trajectories of young women in Soweto, South Africa. This study aimed to qualitatively explore factors influencing implementation of the preconception and pregnancy phases of Bukhali, from the perspective of the CHWs (Health Helpers, HHs) delivering the intervention. As part of the Bukhali trial process evaluation, three focus group discussions were conducted with the 13 HHs employed by the trial. A thematic approach was used to analyse the data, drawing on elements of a reflexive thematic and codebook approach. The following six themes were developed, representing factors impacting implementation of the HH roles: interaction with the existing public healthcare sector; participant perceptions of health; health literacy and language barriers; participants' socioeconomic constraints; family, partner, and community views of trial components; and the HH-participant relationship. HHs reported uses of several trial-based tools to overcome implementation challenges, increasing their ability to implement their roles as planned. The relationship of trust between the HH and participants seemed to function as one important mechanism for impact. The findings supported a number of adaptations to the implementation of Bukhali, such as intensified trial-based follow-up of referrals that do not receive management at clinics, continued HH training and community engagement parallel to trial implementation, with an increased emphasis on health-related stigma and education. HH perspectives on intervention implementation highlighted adaptations across three broad strategic areas: navigating and bridging healthcare systems, adaptability to individual participant needs, and navigating stigma around disease. These findings provide recommendations for the next phases of Bukhali, for other CHW-delivered preconception and pregnancy trials, and for the strengthening of CHW roles in clinical settings with similar implementation challenges. Trial registration: Pan African Clinical Trials Registry; PACTR201903750173871, Registered March 27, 2019.

The role of a community health worker-delivered preconception and pregnancy intervention in achieving a more positive pregnancy experience: the Bukhali trial in Soweto, South Africa.

BACKGROUND: A patient-centered, human-rights based approach to maternal care moves past merely reducing maternal mortality and morbidity, towards achieving a positive pregnancy experience. When evaluating an intervention, particularly in the context of the complex challenges facing maternal care in South Africa, it is therefore important to understand how intervention components are experienced by women. We aimed to qualitatively explore (i) factors influencing the pregnancy and postpartum experience amongst young women in Soweto, South Africa, and (ii) the influence of Bukhali, a preconception, pregnancy, and early childhood intervention delivered by community health workers (CHWs), on these experiences. METHODS: Semi-structured, in-depth interviews were conducted with 15 purposively sampled participants. Participants were 18-28-year-old women who (i) were enrolled in the intervention arm of the Bukhali randomized controlled trial; (ii) were pregnant and delivered a child while being enrolled in the trial; and (iii) had at least one previous pregnancy prior to participation in the trial. Thematic analysis, informed by the positive pregnancy experiences framework and drawing on a codebook analysis approach, was used. RESULTS: The themes influencing participants' pregnancy experiences (aim 1) were participants' feelings about being pregnant, the responsibilities of motherhood, physical and mental health challenges, unstable social support and traumatic experiences, and the pressures of socioeconomic circumstances. In terms of how support, information, and care practices influenced these factors (aim 2), four themes were generated: acceptance and mother/child bonding, growing and adapting in their role as mothers, receiving tools for their health, and having ways to cope in difficult circumstances. These processes were found to be complementary and closely linked to participant context and needs. CONCLUSION: Our findings suggest that, among women aged 18-28, a CHW-delivered intervention combining support, information, and care practices has the potential to positively influence women's pregnancy experience in South Africa. In particular, emotional support and relevant information were key to better meeting participant needs. These findings can help define critical elements of CHW roles in maternal care and highlight the importance of patient-centred solutions to challenges within antenatal care. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR201903750173871, 27/03/2019.

Explainable Early Prediction of Gestational Diabetes Biomarkers by Combining Medical Background and Wearable Devices: A Pilot Study With a Cohort Group in South Africa.

This study aims to explore the potential of Internet of Things (IoT) devices and explainable Artificial Intelligence (AI) techniques in predicting biomarker values associated with GDM when measured 13-16 weeks prior to diagnosis. We developed a system that forecasts biomarkers such as LDL, HDL, triglycerides, cholesterol, HbA1c, and results from the Oral Glucose Tolerance Test (OGTT) including fasting glucose, 1-hour, and 2-hour post-load glucose values. These biomarker values are predicted based on sensory measurements collected around week 12 of pregnancy, including continuous glucose levels, short physical movement recordings, and medical background information. To the best of our knowledge, this is the first study to forecast GDM-associated biomarker values 13 to 16 weeks prior to the GDM screening test, using continuous glucose monitoring devices, a wristband for activity detection, and medical background data. We applied machine learning models, specifically Decision Tree and Random Forest Regressors, along with Coupled-Matrix Tensor Factorisation (CMTF) and Elastic Net techniques, examining all possible combinations of these methods across different data modalities. The results demonstrated good performance for most biomarkers. On average, the models achieved Mean Squared Error (MSE) between 0.29 and 0.42 and Mean Absolute Error (MAE) between 0.23 and 0.45 for biomarkers like HDL, LDL, cholesterol, and HbA1c. For the OGTT glucose values, the average MSE ranged from 0.95 to 2.44, and the average MAE ranged from 0.72 to 0.91. Additionally, the utilisation of CMTF with Alternating Least Squares technique yielded slightly better results (0.16 MSE and 0.07 MAE on average) compared to the well-known Elastic Net feature selection technique. While our study was conducted with a limited cohort in South Africa, our findings offer promising indications regarding the potential for predicting biomarker values in pregnant women through the integration of wearable devices and medical background data in the analysis. Nevertheless, further validation on a larger, more diverse cohort is imperative to substantiate these encouraging results.

Comparing a range of potassium-enriched low sodium salt substitutes to common salt: Results of taste and visual tests in South African adults.

BACKGROUND AND AIMS: Potassium-enriched low sodium salt substitutes (LSSS), which replace a proportion of sodium chloride (NaCl) with potassium chloride (KCl), have been shown to reduce blood pressure and offer a potential solution to address the high burden of hypertension in South Africa. However, it is unknown which proportions of KCl in LSSS are acceptable. We compared the taste and visual acceptability of various LSSS in South African adults. METHODS AND RESULTS: Fifty-six adults underwent double-blind taste and visual tests of four LSSS (35%KCl/65%NaCl; 50%KCl/50%NaCl; 66%KCl/34%NaCl; 100%KCl) in comparison to 100%NaCl (common salt). Participants scored each product by taste ranking, taste perception and likeliness to use. Participants then visually inspected the five products and attempted to identify which was which. Almost half (45 %) of participants ranked the taste of 50%KCl/50 %NaCl as fantastic or really good. Furthermore, 62 % of participants liked and would be happy to use the 50 %KCl/50 %NaCl or felt this tasted like common salt. Only 12 % rated the 100%KCl highly for taste, and over half reported being unlikely to use this. Most participants (57.3 % and 36.4 %) were able to visually identify 100%NaCl and 100%KCl, while identification of other blends was generally poor. Responses were similar for 35%KCl/65%NaCl and 66%KCl/34%NaCl throughout. CONCLUSION: Our findings suggest that the taste of the 50%KCl salt substitute would be well tolerated by South African adults, most of which could not visually differentiate between this salt substitute and common salt.

Integrated health system intervention aimed at reducing type 2 diabetes risk in women after gestational diabetes in South Africa (IINDIAGO): a randomised controlled trial protocol.

INTRODUCTION: South Africa has a high prevalence of gestational diabetes mellitus (GDM; 15%) and many of these women (48%) progress to type 2 diabetes mellitus (T2DM) within 5 years post partum. A significant proportion (47%) of the women are not aware of their diabetes status after the index pregnancy, which may be in part to low postnatal diabetes screening rates. Therefore, we aim to evaluate a intervention that reduces the subsequent risk of developing T2DM among women with recent GDM. Our objectives are fourfold: (1) compare the completion of the nationally recommended 6-week postpartum oral glucose tolerance test (OGTT) between intervention and control groups; (2) compare the diabetes risk reduction between control and intervention groups at 12 months' post partum; (3) assess the process of implementation; and (4) assess the cost-effectiveness of the proposed intervention package. METHODS AND ANALYSES: Convergent parallel mixed-methods study with the main component being a pragmatic, 2-arm individually randomised controlled trial, which will be carried out at five major referral centres and up to 26 well-baby clinics in the Western Cape and Gauteng provinces of South Africa. Participants (n=370) with GDM (with no prior history of either type 1 or type 2 diabetes) will be recruited into the study at 24-36 weeks' gestational age, at which stage first data collection will take place. Subsequent data collection will take place at 6-8 weeks after delivery and again at 12 months. The primary outcome for the trial is twofold: first, the completion of the recommended 2-hour OGTT at the well-baby clinics 6-8 weeks post partum, and second, a composite diabetes risk reduction indicator at 12 months. Process evaluation will assess fidelity, acceptability, and dose of the intervention. ETHICS AND DISSEMINATION: Ethics approval has been granted from University of Cape Town (829/2016), University of the Witwatersrand, Johannesburg (M170228), University of Stellenbosch (N17/04/032) and the University of Montreal (2019-794). The results of the trial will be disseminated through publication in peer-reviewed journals and presentations to key South African Government stakeholders and health service providers. PROTOCOL VERSION: 1 December 2022 (version #2). Any protocol amendments will be communicated to investigators, Human Ethics Research Committees, trial participants, and trial registries. TRIAL REGISTRATION NUMBER: PAN African Clinical Trials Registry (https://pactr.samrc.ac.za) on 11 June 2018 (identifier PACTR201805003336174).

Infant growth and body composition from birth to 24 months: are infants developing the same?

BACKGROUND: Given the importance of infancy for establishing growth trajectories, with later-life health consequences, we investigated longitudinal body composition among infants from six economically and ethnically diverse countries. METHODS: We recruited mother-infant dyads using the WHO Multicenter Growth Reference Study criteria. We measured fat-free mass (FFM) in 1393 (49% female) infants from birth to 6 months of age (Australia, India, and South Africa; n = 468), 3-24 months of age (Brazil, Pakistan, South Africa, and Sri Lanka; n = 925), and derived fat mass (FM), fat mass index (FMI), and fat-free mass index (FFMI). Height-for-age (HAZ), weight-for-age (WAZ), and weight-for-length (WHZ) Z-scores were computed. Sex differences were assessed using a t-test, and country differences using a one-way analysis of covariance. We further compared subsamples of children with average (-0.25 > HAZ < +0.25), below-average (≤-0.25) and above-average (≥+0.25) HAZ. RESULTS: HAZ performed well between 0 and 6 months, but less so between 3 and 24 months. The stunting prevalence peaked at 10.3% for boys and 7.8% for girls, at 24 months. By 24 months, girls had greater FMI (10%) than boys. There were significant differences in FFM (both sexes in all countries) and FM (Brazilian boys, Pakistani and South African girls) by 24 months of age between infants with average, above-average, and below-average HAZ. CONCLUSION: In a multi-country sample representing more ideal maternal conditions, body composition was heterogeneous even among infants who exhibited ideal length. Having a mean HAZ close to the median of the WHO standard for length reduced FFM between-country heterogeneity but not FM, suggesting that other factors may influence adiposity.

Genome-wide association study meta-analysis of blood pressure traits and hypertension in sub-Saharan African populations: an AWI-Gen study.

Most hypertension-related genome-wide association studies (GWASs) focus on non-African populations, despite hypertension (a major risk factor for cardiovascular disease) being highly prevalent in Africa. The AWI-Gen study GWAS meta-analysis for blood pressure (BP)-related traits (systolic and diastolic BP, pulse pressure, mean-arterial pressure and hypertension) from three sub-Saharan African geographic regions (N = 10,775), identifies two novel genome-wide significant signals (p < 5E-08): systolic BP near P2RY1 (rs77846204; intergenic variant, p = 4.95E-08) and pulse pressure near LINC01256 (rs80141533; intergenic variant, p = 1.76E-08). No genome-wide signals are detected for the AWI-Gen GWAS meta-analysis with previous African-ancestry GWASs (UK Biobank (African), Uganda Genome Resource). Suggestive signals (p < 5E-06) are observed for all traits, with 29 SNPs associating with more than one trait and several replicating known associations. Polygenic risk scores (PRSs) developed from studies on different ancestries have limited transferability, with multi-ancestry PRS providing better prediction. This study provides insights into the genetics of BP variation in African populations.

Exploring the national prevalence of mental health risk, multimorbidity and the associations thereof: a repeated cross-sectional panel study.

Objective and methods: South Africans were affected by the COVID-19 pandemic and resultant economic hardships. As a result, mental health within this region may have worsened. Therefore, using large scale nationally representative data, we repeated the cross-sectional panel study to investigate mental health risk post COVID-19 to explore mental health and multimorbidity and to examine the relationship between adverse childhood experiences (ACEs) and comorbid health conditions in South African adults (aged 18 years and older). Results: Post-pandemic, 26.2, 17.0, and 14.8% of the South African respondents reported being probably depressed, anxious and had suffered high exposure to early life adversity, respectively. Nationally, the prevalence of mental health across the country remained alarmingly high when compared to Panel 1. The prevalence of multimorbidity (2 or more chronic morbidities) among the South African population was reported at 13.9%, and those with 2 or more morbidities were found to have increased odds of early adversity, irrespective of differing socio-demographics. Furthermore, early adversity was also associated with multimorbidity partly via mental health. Conclusion: This repeated cross-sectional national study reiterated that the prevalence of mental health across South African adults aged 18 years and older is widespread. Mental health remains worryingly high post-pandemic where more than a quarter of respondents are probably depressed, nearly one in every five respondents are anxious, and 14.8% reported high exposure ACEs. Public health interventions need to be upscaled with efforts to reduce the incidence of early adversity that may have the ability to lower adverse health outcomes and mental ill-health in adulthood.

Navigating relationship dynamics, pregnancy and fatherhood in the Bukhali trial: a qualitative study with men in Soweto, South Africa.

BACKGROUND: South Africa has a complex range of historical, social, political, and economic factors that have shaped fatherhood. In the context of the Bukhali randomised controlled trial with young women in Soweto, South Africa, a qualitative study was conducted with the male partners of young women who had become pregnant during the trial. This exploratory study aimed to explore individual perceptions around relationship dynamics, their partner's pregnancy, and fatherhood of partners of young women in Soweto, South Africa. METHODS: Individual, in-depth interviews were conducted with male partners (fathers, n = 19, 25-46 years old) of Bukhali participants. A thematic approach was taken to the descriptive and exploratory process of analysis, and three final themes and subthemes were identified: (1) relationship dynamics (nature of relationship, relationship challenges); (2) pregnancy (feelings about the pregnancy, effect of the pregnancy on their relationship, providing support during pregnancy; and 3) fatherhood (view of fatherhood, roles of fathers, influences on views and motivation, challenges of fatherhood). RESULTS: While most male participants were in a committed ("serious") relationship with their female partner, less than half of them were cohabiting. Most reported that their partner's pregnancy was not planned, and shared mixed feelings about the pregnancy (e.g., happy, excited, shocked, nervous), although their views about fatherhood were overwhelmingly positive. Many were concerned about how they would economically provide for their child and partner, particularly those who were unemployed. Participants identified both general and specific ways in which they provided support for their partner, e.g., being present, co-attending antenatal check-ups, providing material resources. For many, the most challenging aspect of fatherhood was having to provide financially. They seemed to understand the level of responsibility expected of them as a father, and that their involvement and presence related to love for and connection with their child. Participants' responses indicated that there were some changes in the norms around fatherhood, suggesting that there is a possibility for a shift in the fatherhood narrative in their context. CONCLUSIONS: These findings suggest that the complex array of factors influencing fatherhood in South Africa continue to play out in this generation, although promising changes are evident.

'We were not allowed to gather even for Christmas.' Impact of COVID-19 on South African young people: Exploring messaging and support.

COVID-19 prevention measures including lockdowns, school closures, and restricted movement disrupted young people's lives. This longitudinal qualitative study conducted in Soweto, South Africa aimed to explore young people's knowledge and perceptions of COVID-19, vaccination, and the impact of infections. A convenience sample of 30 young black people (n = 15 men; n = 15 women, aged 16-21 years) from Soweto participated in 24 focus group discussions (FGDs), conducted in six phases - each phase had four FGDs stratified by gender and age. Young people's understanding of COVID-19 deepened throughout the study, however, did not always translate into adherence (following the government's COVID-19 prevention measures). Although deemed inadequate, TV and radio were preferred over internet COVID-19 information. Parents, teachers, and schools were trusted sources of information. Vaccines and limited access to information attributed to low-risk perception, while new COVID-19 variants attributed to high-risk perception. A low-risk perception and conspiracy theories contributed to non-adherence (disregarding COVID-19 preventative measures provided by the government), particularly among young men. Accessing reliable information that considers young people's lives and their living context is important. Communities, scientists, and policymakers must learn from the COVID-19 experience and implement localised preventive strategies for education, awareness, and economic support in future emergencies.