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Background. Tuberculosis preventive therapy (TPT) offered to children who come into contact with infectious adult pulmonary tuberculosis (TB) cases is an important childhood TB prevention strategy. Objectives. To document paediatric TPT coverage as per South African national TB guidelines, to measure basic knowledge of TPT in adult TB patients and healthcare workers (HCWs), and to determine challenges in TPT delivery in eligible children. Methods. We conducted a descriptive, cross-sectional study at primary healthcare clinics in South-West Tshwane, Gauteng Province, South Africa (SA). Structured interviews were conducted with adult TB patients to obtain socio-demographic data, TB and HIV history, data on child contacts and TPT knowledge. A separate questionnaire probed HCWs' knowledge of TPT. Patient folders and the clinical process flow of adult TB cases and children on TPT were also assessed. Results. We interviewed 100 adult TB patients and identified 28 child contacts who were eligible for TPT, including six children (21%, n=6/28) on TPT, all HIV-uninfected and <5 years of age. Instability in household configuration was the most common reason for eligible children not having been brought to health facilities for assessment (57%; n=4/7). Almost all adult TB patients were aware of their TB diagnosis (98%; n=98/100), but only half (48%; n=48/100) had knowledge of their TB type, and 55% (n=6/11) of the adult TB patients with drug-resistant TB were aware of the drug resistance. In addition, we interviewed 71 HCWs, and more than one-third of HCWs (37%; n=26/71) were fully knowledgeable about paediatric TPT eligibility criteria, with 63% (n=45/71) unaware that HIV-infected children of all ages qualified for TPT after exposure. Conclusions. TPT provision in eligible child TB contacts in an urban district in SA was found to be suboptimal, especially for HIVinfected children. Instability in household configuration was an important reason for suboptimal TPT provision. Training of HCWs on paediatric TPT guidelines is required, together with knowledge sharing on TPT with the TB patients. [ABSTRACT FROM AUTHOR]

Marina White,1 Ute D Feucht,2– 4 Louise de Villiers du Toit,5 Theresa Rossouw,3– 5 Kristin L Connor1 1Health Sciences, Carleton University, Ottawa, Ontario, Canada; 2Paediatrics, University of Pretoria, Pretoria, Gauteng, South Africa; 3Research Centre for Maternal, Fetal, Newborn & Child Health Care Strategies, University of Pretoria, Pretoria, Gauteng, South Africa; 4Maternal and Infant Health Care Strategies Unit, South African Medical Council, Pretoria, Gauteng, South Africa; 5Department of Immunology, University of Pretoria, Pretoria, Gauteng, South AfricaCorrespondence: Kristin L ConnorDepartment of Health Sciences, Carleton University, Ottawa, Ontario, K1S5B6, CanadaEmail kristin.connor@carleton.caUte D FeuchtResearch Centre for Maternal, Fetal, Newborn & Child Health Care Strategies, University of Pretoria, Pretoria, Gauteng Province, 0002, South AfricaEmail ute.feucht@up.ac.zaAbstract: The Siyakhula study is an ongoing, observational cohort study in Pretoria, South Africa, that aims to understand how maternal HIV infection and perinatal environmental factors shape development and health in infants who are HIV-exposed (in utero and during breastfeeding) but remain uninfected themselves (HEU). The Siyakhula Collaborative Workshop, which took place at the Research Centre for Maternal, Fetal, Newborn & Child Health Care Strategies at Kalafong Hospital in Pretoria, South Africa on November 15– 16, 2018, brought together a group of international health scientists, clinicians, and stakeholders, including women with lived experience, to build capacity for research and training on the impact of HIV infection on women’s and infants’ health across geographical and disciplinary boundaries. The workshop sought to summarise the state of knowledge on the effects of being HEU on infant development and health in the first two years of life, identify gaps in existing research on modifiable exposures that may be associated with poor infant development, and develop ideas for novel research and interventions to lessen or prevent adverse health outcomes in pregnant or breastfeeding people living with HIV. These proceedings summarise the pre-workshop consensus process that was used to identify priority areas to discuss during small-group breakout sessions, as well as the themes and key challenges that emerged from these discussions during the workshop.Keywords: HIV, PMTCT, breastfeeding, growth, neurodevelopment, immune

District Clinical Specialist Teams (DCSTs) are part of the primary healthcare re-engineering process in South Africa. These multidisciplinary clinical teams were established throughout the country in 2012, and their main role is reduction of maternal and childhood mortality and morbidity through improvement of service delivery at primary care level in their health districts. The Tshwane DCST is used as a case study to describe the challenges encountered in establishing the team within the complex district health system. On the other hand, the cross-disciplinary approach has proved itself a winning combination if the team shares a common vision and has a work plan to guide the priorities and facility support visits. Through their clinical expertise, and using extensive networking, DCSTs are well positioned in the health system to have a strong positive effect on child health. [ABSTRACT FROM AUTHOR]

Factors affecting the growth of HIV-exposed-uninfected (HEU) children are multi-factorial, with limited information available on the dietary intake from 6 months. This study compared the dietary intake, micronutrient composition of breastmilk, and growth of HEU and HIV-unexposed-uninfected (HUU) infants aged 6 and 12 months in an urban setting. A repeated cross-sectional study used structured questionnaires to collect socio-demographic, dietary intake, food group data, and anthropometric measurements in the Siyakhula study. The HEU (48%) and HUU (52%) infants were included (total n = 181). At 6 months, HEU infants had lower weight-for-age z-scores (WAZ) (-0.6 ± 1.1 vs. 0.1 ± 1.2; p < 0.001), length-for-age z-scores (-0.8 ± 1.4 vs. -0.1 ± 1.2; p < 0.001), and mid-upper-arm circumference-for-age z-scores (MUACAZ) (0.5 ± 1.1 vs. 1.0 ± 0.9; p < 0.001) than HUU infants. At 12 months, HEU infants had lower WAZ, MUACAZ, and weight-for-length z-scores compared to HUU infants (p < 0.05). Stunting was found at 6 (15%) and 12 (12%) months in HEU infants. The micronutrient composition of breastmilk fed to both groups was similar. Breastfeeding rates were lower in HEU than in HUU infants at 6 (49% vs. 64%; p = 0.005) and 12 (24% vs. 46%; p = 0.002) months. Less than 3% of HEU and HUU infants achieved minimal dietary diversity scores at 12 months. Dietary intake of fat was similar in all breastfed infants, but iron and vitamin B12 were higher in non-breastfed HEU infants at 12 months. HEU infants had lower breastfeeding rates than HUU infants. A lack of dietary diversity was found in all infants. Nutrition education and counselling in the complementary feeding phase are essential for optimal growth., (© 2024 The Author(s). Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Background: Globally, there is a significant gap in detailed neurodevelopmental data for infants under 3 months, despite 6 weeks being identified a critical milestone for neuro-behavioural development. Normative values and optimal scores for healthy infants at 6 and 10 weeks postnatally are lacking in many settings. In South Africa, the statutory neurodevelopmental assessments at these ages exclude notable characteristics of central nervous system maturation and limit opportunities to collect data of early developmental progress., Objectives: Our study aimed to assess developmental characteristics of healthy term infants aged 6 and 10 weeks using the Hammersmith Neonatal Neurological Examination (HNNE)., Method: A prospective longitudinal study was performed on 35 healthy term-born infants from low-risk pregnancies at 6 and 10 weeks' postnatal age in the Tshwane district. The statuses of infants' neurodevelopment in six domains were recorded using the HNNE. Optimality scores were derived from the raw scores of 34 items, using the 10th and 5th percentiles as cut-off points., Results: Evidences of neurodevelopmental advancements, particularly in posture, muscle tone and visual behaviour between 6 and 10 weeks were illustrated, and total examination optimality scores of 29.5 in 91% and 31.5 in 94% of infants were recorded at 6 and 10 weeks, respectively., Conclusion: This article provides data on the neurodevelopment characteristics of infants at and between 6- and 10-weeks post term ages., Clinical Implications: The findings support the viewpoint to identify important milestone characteristics during early screening., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article., (© 2024. The Authors.)

Objective: To determine the trend in adolescent maternal deaths and deliveries over a period of 5 years and 9 months (July 2014-March 2020) at the Ekurhuleni Health District in South Africa., Methods: The present study was a retrospective review and secondary data analysis using data from the District Health Information System and clinical oversight data from the District Clinical Specialist Team. The study population was adolescent pregnant women aged 10-19 years who died at health facilities. Descriptive and inferential statistics were used for analysis., Results: There was a total of 12 559 adolescent deliveries. Adolescent birth rate was lower than that of sub-Saharan Africa. Adolescent deaths (n = 37) contributed to around 8% of the total maternal deaths. Deliveries (97%) and deaths (98%) were most common among women aged 15-19 years. Six (16%) women had a repeat pregnancy. A total of 21 (57%) had booked for antenatal care. There were few antenatal visits (mean 4 ± SD 2.1). The main three causes of death were hypertension (35%) followed by hemorrhage (24%) and suicide (14%). Postpartum deaths (62%) were significantly (chi-square test, P = 0.02) higher than antepartum deaths (38%). The majority (73%) of newborns were born alive which was significantly (chi-square test, P = 0.002) higher than those which were stillborn (27%)., Conclusion: The main challenges were the high number of adolescent deliveries, repeat pregnancies, and preventable causes of death. Multidisciplinary collaboration involving obstetricians, midwives, pediatricians, school health services, social workers and psychologists is indispensable for comprehensive management, prioritizing pregnancy prevention among this vulnerable group., (© 2024 The Author(s). International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Background: The coronavirus disease 2019 (COVID-19) pandemic disrupted paediatric HIV services across South Africa. Shortly before COVID-19, updated national HIV guidelines were released., Objectives: This study describes COVID-19's impact on paediatric HIV services in Tshwane District, South Africa., Method: A retrospective review of National Institute for Communicable Diseases and District Health Information System data for Tshwane District from April 2019 to March 2022. Data included: Early Infant Diagnosis (EID), HIV viral load (VL) and CD4 monitoring and HIV management among children (< 15 years) living with HIV (CLHIV). Pre-pandemic (2019/2020) and pandemic periods (2020/2021, 2021/2022) were compared., Results: Year-on-year, HIV testing improved at 10 weeks, 6 months, and 18 months, whereas birth testing decreased. HIV EID case rates were 485 (2019/2020), 410 (2020/2021) and 454 (2021/2022). HIV EID test positivity was 0.77% - 1.2%. Antiretroviral treatment initiation declined from 2019/2020 to 2020/2021, but improved in 2021/2022.Initial HIV VL and CD4 testing declined, with HIV VL testing increasing in 2021/2022, and CD4 testing further declining. HIV VL suppression rate among CLHIV ranged from 69% to 73%., Conclusion: Initially, COVID-19 resulted in reduced paediatric HIV services as children disengaged from care. Indicators eventually recovered to proximate pre-pandemic levels; however, compensatory increases did not occur. Thus, some children may not have returned to care., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article., (© 2024. The Authors.)

Background: Preterm infants often have poor short- and long-term growth. Kangaroo mother care supports short-term growth, but longer-term outcomes are unclear., Methods: This study analysed longitudinally collected routine clinical data from a South African cohort of preterm infants (born <37 weeks gestation) attending the outpatient follow-up clinic of a tertiary-level hospital (Tshwane District, South Africa) for 1 year between 2012 and 2019. At 1 year, small-for-gestational age (SGA) and appropriate-for-gestational age (AGA) infants were compared with regard to age-corrected anthropometric z-scores (weight-for-age [WAZ], length-for-age [LAZ], weight-for-length [WLZ] and BMI-for-age [BMIZ]) and rates of underweight (WAZ < -2), stunting (LAZ < -2), wasting (WLZ < -2) and overweight (BMIZ> + 2). Multiple regression analysis was used to investigate associations between maternal/infant characteristics and rates of underweight, stunting, wasting and overweight., Results: At 1 year, compared with AGA infants (n = 210), SGA infants (n = 111) had lower WAZ (-1.26 ± 1.32 vs. -0.22 ± 1.24, p < 0.001), LAZ (-1.50 ± 1.11 vs. -0.60 ± 1.06, p < 0.001), WLZ (-0.66 ± 1.31 vs. 0.11 ± 1.24, p < 0.001) and BMIZ (-0.55 ± 1.31 vs. 1.06 ± 1.23, p < 0.001), despite larger WAZ gains from birth (+0.70 ± 1.30 vs. +0.05 ± 1.30, p < 0.001). SGA infants had significantly more stunting (34.2% vs. 9.1%; p < 0.001), underweight (31.2% vs. 7.2%; p < 0.001) and wasting (12.6% vs. 4.3%, p = 0.012), with no difference in overweight (4.5% vs. 7.7%, p = 0.397). In multiple regression analysis, birth weight-for-GA z-score more consistently predicted 1-year malnutrition than SGA., Conclusion: Preterm-born SGA infants remain more underweight, stunted and wasted than their preterm-born AGA peers at 1 year, despite greater WAZ gains. Interventions for appropriate catch-up growth especially for SGA preterm infants are needed., (© 2024 The Authors Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

Appropriate feeding practices are protective against malnutrition and poor growth. We compared feeding practices and growth in HIV-exposed-uninfected (HEU) and HIV-unexposed-uninfected (HUU) between 6-12 months of age in urbanized African infants in South Africa. A repeated cross-sectional analysis was used to determine differences in infant feeding practices and anthropometric measures by HIV exposure status at 6, 9, and 12 months in the Siyakhula study. The study included 181 infants (86 HEU; 95 HUU). Breastfeeding rates were lower in HEU vs. HUU infants at 9 (35.6% vs. 57.3%; p = 0.013) and 12 months (24.7% vs. 48.0%; p = 0.005). Introduction to early complementary foods was common (HEU = 16.2 ± 11.0 vs. HUU = 12.8 ± 9.3 weeks; p = 0.118). Lower weight-for-age Z-scores (WAZ) and head circumference-for-age Z-scores (HCZ) were found in HEU infants at birth. At 6 months, WAZ, length-for-age Z-scores (LAZ), HCZ, and mid-upper-arm circumference-for-age Z-scores (MUACAZ) were lower in HEU vs. HUU infants. At 9 months, lower WAZ, LAZ, and MUACAZ were found in HEU vs. HUU infants. At 12 months, lower WAZ, MUACAZ, and weight-for-length Z-scores (-0.2 ± 1.2 vs. 0.2 ± 1.2; p = 0.020) were observed. HEU infants had lower rates of breastfeeding and poorer growth compared to HUU infants. Maternal HIV exposure affects the feeding practices and growth of infants.

With the global rollout of mother-to-child prevention programs for women living with HIV, vertical transmission has been all but eliminated in many countries. However, the number of children who are exposed in utero to HIV and antiretroviral therapy (ART) is ever-increasing. These children who are HIV-exposed-but-uninfected (CHEU) are now well recognized as having persistent health disparities compared to children who are HIV-unexposed-and-uninfected (CHUU). Differences reported between these two groups include immune dysfunction and higher levels of inflammation, cognitive and metabolic abnormalities, as well as increased morbidity and mortality in CHEU. The reasons for these disparities remain largely unknown. The present review focuses on a proposed link between immunometabolic aberrations and clinical pathologies observed in the rapidly expanding CHEU population. By drawing attention, firstly, to the significance of the immune and metabolic alterations observed in these children, and secondly, the impact of their healthcare requirements, particularly in low- and middle-income countries, this review aims to sensitize healthcare workers and policymakers about the long-term risks of in utero exposure to HIV and ART.

Maternal HIV exposure and intrauterine growth restriction (IUGR) due to placental insufficiency both carry major risks to early child growth. We compared the growth outcomes of children aged 18 months who had abnormal umbilical artery resistance indices (UmA-RI), as a marker of placental insufficiency, with a comparator group of children with normal UmA-RI during pregnancy, as mediated by maternal HIV infection. The cross-sectional study included 271 children, grouped into four subgroups based on HIV exposure and history of normal/abnormal UmA-RI, using available pregnancy and birth information. Standard procedures were followed to collect anthropometric data, and z-scores computed as per World Health Organization growth standards. Lower length-for-age z-scores (LAZ) were observed in children who were HIV-exposed-uninfected (CHEU) (-0.71 ± 1.23; p = 0.004) and who had abnormal UmA-RI findings (-0.68 ± 1.53; p < 0.001). CHEU with abnormal UmA-RI had lower LAZ (-1.3 ± 1.3; p < 0.001) and weight-for-age z-scores (WAZ) (-0.64 ± 0.92; p = 0.014) compared to the control group. The prevalence of stunting was 40.0% in CHEU with abnormal UmA-RI and 16.0% in CHEU with normal UmA-RI ( p < 0.001; p = 0.016, respectively). In conclusion, maternal HIV exposure and placental insufficiency are independent risk factors for childhood stunting, with this risk potentiated when these two risk factors overlap.

Despite global progress in reducing maternal and neonatal mortality and stillbirths, much work remains to be done to achieve the Sustainable Development Goals. Reports indicate that coronavirus disease (COVID-19) disrupts the provision and uptake of routine maternal and neonatal health care (MNH) services and negatively impacts cumulative pre-COVID-19 achievements. We describe a multipartnered MNH quality improvement (QI) initiative called Mphatlalatsane, which was implemented in South Africa before and during the COVID-19 pandemic. The initiative aimed to reduce the maternal mortality ratio, neonatal mortality rate, and stillbirth rate by 50% between 2018 and 2022. The multifaceted design comprises QI and other intervention activities across micro-, meso-, and macrolevels, and its area-based approach facilitates patients' access to MNH services. The initiative commenced 6 months pre-COVID-19, with subsequent adaptation necessitated by COVID-19. The initial focus on a plan-do-study-act QI model shifted toward meeting the immediate needs of health care workers (HCWs), the health system, and health care managers arising from COVID-19. Examples include providing emotional support to staff and streamlining supply chain management for infection control and personal protection materials. As these needs were addressed, Mphatlalatsane gradually refocused HCWs' and managers' attention to recognize the disruptions caused by COVID-19 to routine MNH services. This gradual reprioritization included the development of a risk matrix to help staff and managers identify specific risks to service provision and uptake and develop mitigating measures. Through this approach, Mphatlalatsane led to an optimization case using existing resources rather than requesting new resources to build an investment case, with a responsive design and implementation approach as the cornerstone of the initiative. Further, Mphatlalatsane demonstrates that agile and context-specific responses to crises such as the COVID-19 pandemic can mitigate such threats and maintain interventions to improve MNH services., (© Odendaal et al.)

WHO first recommended cotrimoxazole prophylaxis for all infants who are HIV-exposed but uninfected (HEU) in 2000, given the ability of this treatment to prevent mortality from pneumocystis pneumonia in adults living with HIV. Over the last 21 years, evidence has been generated from the use of cotrimoxazole prophylaxis in infants who are HEU, including two randomised controlled trials, which have shown no clinical benefit and an increase in antibiotic resistance and microbiome dysbiosis. Additionally, improvements in health care over the last two decades in terms of antiretroviral treatment and prophylaxis for mothers and infants, and notably improved vaccination programmes, have substantially reduced the risk of HIV transmission and the overall morbidity and mortality of infants who are HEU from pneumonia and diarrhoeal diseases. Here, we highlight these changes in health care alongside the unchanged cotrimoxazole prophylaxis guidelines and call for a change in these guidelines on the basis of a public health and ethics approach., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Identifying the high-risk fetus in the low-risk pregnant mother (LRM) is a neglected area of research. Fetal growth restriction (FGR) is a major cause of stillbirths, especially in low- and middle-income countries (LMICs). FGR is very poorly detected particularly in healthy pregnant women classified as low risk. Umbiflow is an inexpensive continuous-wave Doppler ultrasound (CWDU) apparatus that is suitable for use by low-level health care providers for screening low-risk pregnant populations. It can easily detect umbilical artery blood flow in the cord, which correlates well with placental function, and poor placental function correlates well with FGR.Use of CWDU to screen an LMIC population of more than 7,000 LRMs has demonstrated a high prevalence of abnormal umbilical artery flow of 13%, and absent end-diastolic flow, which is associated with end-stage placental disease, was found in 1.2%. This is 10 times higher than previously reported in high-income countries. Screening with CWDU together with a standard protocol managing those pregnancies with abnormal placental blood flow resulted in a 43% reduction in stillbirths (risk ratio: 0.57; 95% confidence interval=0.29, 0.85) in this LRM population. Further, follow-up of infants who had abnormal umbilical artery blood flow showed that these infants had significantly less fat-free mass at ages 6 weeks, 10 weeks, 14 weeks, and 6 months, than those with normal umbilical artery blood flow (P&lt;.015), confirming that CWDU was able to detect true FGR.Thus, screening with CWDU can detect the fetus at risk of stillbirth, and infants likely to have suboptimal growth and development postnatally. Screening with CWDU in LRMs opens the door to a step change in preventing stillbirths in LMICs., (© Feucht et al.)

Background: South Africa reported a notable increase in COVID-19 cases from mid-November, 2021, onwards, starting in Tshwane District, which coincided with the rapid community spread of the SARS-CoV-2 omicron (B.1.1.529) variant. This increased infection rate coincided with a rapid increase in paediatric COVID-19-associated admissions to hospital (hereafter referred to as hospitalisations)., Methods: The Tshwane Maternal-Child COVID-19 study is a multicentre observational study in which we investigated the clinical manifestations and outcomes of paediatric patients (aged ≤19 years) who had tested positive for SARS-CoV-2 and were admitted to hospital for any reason in Tshwane District during a 6-week period at the beginning of the fourth wave of the COVID-19 epidemic in South Africa. We used five data sources, which were: (1) COVID-19 line lists; (2) collated SARS-CoV-2 testing data; (3) SARS-CoV-2 genomic sequencing data; (4) COVID-19 hospitalisation surveillance; and (5) clinical data of public sector COVID-19-associated hospitalisations among children aged 13 years and younger., Findings: Between Oct 31 and Dec 11, 2021, 6287 children and adolescents in Tshwane District were recorded as having COVID-19. During this period, 2550 people with COVID-19 were hospitalised, of whom 462 (18%) were aged 19 years or younger. The number of paediatric cases was higher than in the three previous SARS-CoV-2 waves, uncharacteristically increasing ahead of adult hospitalisations. 75 viral samples from adults and children in the district were sequenced, of which 74 (99%) were of the omicron variant. Detailed clinical notes were available for 138 (75%) of 183 children aged ≤13 years with COVID-19 who were hospitalised. 87 (63%) of 138 children were aged 0-4 years. In 61 (44%) of 138 cases COVID-19 was the primary diagnosis, among whom symptoms included fever (37 [61%] of 61), cough (35 [57%]), shortness of breath (19 [31%]), seizures (19 [31%]), vomiting (16 [26%]), and diarrhoea (15 [25%]). Median length of hospital stay was 2 days [IQR 1-3]). 122 (88%) of 138 children with available data needed standard ward care and 27 (20%) needed oxygen therapy. Seven (5%) of 138 children were ventilated and four (3%) died during the study period, all related to complex underlying copathologies. All children and 77 (92%) of 84 parents or guardians with available data were unvaccinated to COVID-19., Interpretation: Rapid increases in paediatric COVID-19 cases and hospitalisations mirror high community transmission of the SARS-CoV-2 omicron variant in Tshwane District, South Africa. Continued monitoring is needed to understand the long-term effect of the omicron variant on children and adolescents., Funding: South African Medical Research Council, South African Department of Science & Innovation, G7 Global Health Fund., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)