How paediatric HIV services weathered the COVID-19 storm in Tshwane District, South Africa.

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.

Correction: Growth and the pubertal growth spurt in South African adolescents living with perinatally-acquired HIV infection.

[This corrects the article DOI: 10.1371/journal.pone.0262816.].

Adolescent maternal mortality at a district health services over a five year period in South Africa: A retrospective study.

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.

Infant growth by INTERGROWTH-21st and Fenton Growth Charts: Predicting 1-year anthropometry in South African preterm infants.

Post-natal growth influences short- and long-term preterm infant outcomes. Different growth charts, such as the Fenton Growth Chart (FGC) and INTERGROWTH-21st Preterm Post-natal Growth Standards (IG-PPGS), describe different growth curves and targets. This study compares FGC- and IG-PPGS-derived weight-for-postmenstrual age z-score (WZ) up to 50 weeks postmenstrual age (PMA50) for predicting 1-year anthropometry in 321 South African preterm infants. The change in WZ from birth to PMA50 (ΔWZ, calculated using FGC and IG-PPGS) was correlated to age-corrected 1-year anthropometric z-scores for weight-for-age (WAZ), length-for-age (LAZ), weight-for-length (WLZ) and BMI-for-age (BMIZ), and categorically compared with rates of underweight (WAZ < -2), stunting (LAZ < -2), wasting (WLZ < -2) and overweight (BMIZ > + 2). Multivariable analyses explored the effects of other early-life exposures on malnutrition risk. At PMA50, mean WZ was significantly higher on IG-PPGS (-0.56 ± 1.52) than FGC (-0.90 ± 1.52; p < 0.001), but ΔWZ was similar (IG-PPGS -0.26 ± 1.23, FGC -0.11 ± 1.14; p = 0.153). Statistically significant ΔWZ differences emerged among small-for-gestational age infants (FGC -0.38 ± 1.22 vs. IG-PPGS -0.01 ± 1.30; p < 0.001) and appropriate-for-gestational age infants (FGC + 0.02 ± 1.08, IG-PPGS -0.39 ± 1.18; p < 0.001). Correlation coefficients of ΔWZ with WAZ, LAZ, WLZ and BMIZ were low (r < 0.45), though higher for FGC than IG-PPGS. Compared with IG-PPGS, ΔWZ < -1 on FGC predicted larger percentages of underweight (42% vs. 36%) and wasting (43% vs. 39%) and equal percentages of stunting (33%), while ΔWZ > + 1 predicted larger percentages overweight (57% vs. 38%). Both charts performed similarly in multivariable analysis. Differences between FGC and IG-PPGS are less apparent when considering ΔWZ, highlighting the importance of assessing growth as change over time, irrespective of growth chart.

One-year anthropometric follow-up of South African preterm infants in kangaroo mother care: Which early-life factors predict malnutrition?

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.

Integrated growth assessment in the first 1000 d of life: an interdisciplinary conceptual framework.

OBJECTIVES: Prenatal growth affects short- and long-term morbidity, mortality and growth, yet communication between prenatal and postnatal healthcare teams is often minimal. This paper aims to develop an integrated, interdisciplinary framework for foetal/infant growth assessment, contributing to the continuity of care across the first 1000 d of life. DESIGN: A multidisciplinary think-tank met regularly over many months to share and debate their practice and research experience related to foetal/infant growth assessment. Participants' personal practice and knowledge were verified against and supplemented by published research. SETTING: Online and in-person brainstorming sessions of growth assessment practices that are feasible and valuable in resource-limited, low- and middle-income country (LMIC) settings. PARTICIPANTS: A group of obstetricians, paediatricians, dietitians/nutritionists and a statistician. RESULTS: Numerous measurements, indices and indicators were identified for growth assessment in the first 1000 d. Relationships between foetal, neonatal and infant measurements were elucidated and integrated into an interdisciplinary framework. Practices relevant to LMIC were then highlighted: antenatal Doppler screening, comprehensive and accurate birth anthropometry (including proportionality of weight, length and head circumference), placenta weighing and incorporation of length-for-age, weight-for-length and mid-upper arm circumference in routine growth monitoring. The need for appropriate, standardised clinical records and corresponding policies to guide clinical practice and facilitate interdisciplinary communication over time became apparent. CONCLUSIONS: Clearer communication between prenatal, perinatal and postnatal health care providers, within the framework of a common understanding of growth assessment and a supportive policy environment, is a prerequisite to continuity of care and optimal health and development outcomes.

Comparison of Feeding Practices and Growth of Urbanized African Infants Aged 6-12 Months Old by Maternal HIV Status in Gauteng Province, South Africa.

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.

Immune and Metabolic Alterations in Children with Perinatal HIV Exposure.

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.

Association of Prenatal Placental Function with Anthropometry and Body Composition through 2 years of Age in South African Infants: The UmbiBaby Study.

BACKGROUND: Placental insufficiency negatively impacts fetal growth and body composition (BC), potentially affecting lifelong health. Placental insufficiency, detectable as an abnormal umbilical artery resistance index (UmA-RI) on Doppler ultrasonography, is highly prevalent in otherwise healthy South African pregnant women. Appropriate intervention reduces stillbirth and perinatal death, but research on long-term outcomes of surviving infants is lacking. OBJECTIVES: This study aimed to describe and compare anthropometry and BC during the first 2 y of life in a cohort of term-born infants with normal and abnormal prenatal UmA-RI. METHODS: Term-born infants (n = 81; n = 55 normal, n = 26 abnormal UmA-RI on third trimester Doppler screening) were followed up at 8-time points until age 2 y. Anthropometric measurements were taken, and FFM and FM were assessed by deuterium dilution. Age- and sex-specific z-scores were calculated for anthropometric indices, FM, FFM, FM index (FMI), and FFM index (FFMI) using appropriate reference data. Anthropometry and BC of infants with normal and abnormal UmA-RI were compared using an independent t-test or Mann-Whitney test. RESULTS: At most ages, group mean z-scores were <0 for length-for-age and FM and >0 for weight-for-length and FFM. Compared with infants with normal UmA-RI, infants with abnormal UmA-RI had significantly lower weight-for-age z-scores at birth (-0.77 ± 0.75 compared with -0.30 ± 1.10, P = 0.026), ages 10 wk to 9 mo (-0.4 ± 0.87 to -0.2 ± 1.12 compared with 0.3 ± 0.85 to 0.6 ± 1.09; P = 0.007-0.017) and 18 mo (-0.6 ± 0.82 compared with 0.1 ± 1.18; P = 0.037); length-for-age z-scores at ages ≤14 wk (-1.3 ± 1.25 to -0.9 ± 0.87 compared with -0.2 ± 1.04 to -0.1 ± 1.00; P = 0.004-0.021); and FFM-for-age z-scores at ages ≤9 mo (-0.1 ± 0.82 to 0.7 ± 0.71 compared with 0.7 ± 1.00 to 1.3 ± 0.85; P = 0.002-0.028). FFMI, percentage FFM, FM, percentage FM, and FMI showed no consistent significant differences. CONCLUSIONS: Infants with abnormal UmA-RI had lower weight-for-age and length-for-age z-scores, particularly at younger ages, with proportionally lower FFM but no consistent differences in percentage FFM and FFMI. These findings merit further investigation in larger cohorts.

Early Childhood Growth Parameters in South African Children with Exposure to Maternal HIV Infection and Placental Insufficiency.

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.

Identifying the High-Risk Fetus in the Low-Risk Mother Using Fetal Doppler Screening.

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<.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.

Early Reflections on Mphatlalatsane, a Maternal and Neonatal Quality Improvement Initiative Implemented During COVID-19 in South Africa.

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.

Cotrimoxazole guidelines for infants who are HIV-exposed but uninfected: a call for a public health and ethics approach to the evidence.

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.

A novel screening tool to predict severe acute malnutrition through automated monitoring of weight-for-age growth curves.

Weight-for-age (WFA) growth faltering often precedes severe acute malnutrition (SAM) in children, yet it is often missed during routine growth monitoring. Automated interpretation of WFA growth within electronic health records could expedite the identification of children at risk of SAM. This study aimed to develop an automated screening tool to predict SAM risk from WFA growth, and to determine its predictive ability compared with simple changes in weight or WFA z-score. To develop the screening tool, South African child growth experts (n = 30) rated SAM risk on 100 WFA growth curves, which were then used to train an artificial neural network (ANN) to assess SAM risk from consecutive WFA z-scores. The ANN was validated in 185 children under five (63 SAM cases; 122 controls) using diagnostic accuracy methodology. The ANN's performance was compared with that of changes in weight or WFA z-score. Even though experts' SAM risk ratings of the WFA growth curves differed considerably, the ANN achieved a sensitivity of 73.0% (95% confidence interval [CI]: 60.3; 83.4), specificity of 86.1% (95% CI: 78.6; 91.7) and receiver-operating characteristic curve area of 0.795 (95% CI: 0.732; 0.859) during validation with real cases, outperforming changes in weight or WFA z-scores. The ANN, as an automated screening tool, could markedly improve the identification of children at risk of SAM using routinely collected WFA growth information.

Paediatric hospitalisations due to COVID-19 during the first SARS-CoV-2 omicron (B.1.1.529) variant wave in South Africa: a multicentre observational study.

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.

Growth and the pubertal growth spurt in South African adolescents living with perinatally-acquired HIV infection.

BACKGROUND: The majority children living with HIV infection now survive into adulthood because of effective antiretroviral therapy (ART), but few data exist on their growth during adolescent years. This study investigated growth patterns and evaluated factors associated with suboptimal growth in adolescents with perinatally-acquired HIV infection. METHODS: This retrospective cohort study included HIV-infected adolescents, aged 13 to 18 years, with at least 5 years of ART follow-up at a large HIV clinic in the Gauteng Province, South Africa. Weight-for-age Z-scores (WAZ), height-for-age Z-scores (HAZ) and body mass index (BMI)-for-age Z-scores were calculated using World Health Organization (WHO) growth standards. Growth velocity graphs were generated utilising the mean height change calculated at 6-monthly intervals, using all available data after ART initiation, to calculate the annual change. Other collected data included WHO HIV disease staging, CD4%, HIV viral loads (VLs), ART regimens and tuberculosis co-infection. RESULTS: Included were 288 children with a median age of 6.5 years (IQR 4.2;8.6 years) at ART initiation, and 51.7% were male. At baseline the majority of children had severe disease (92% WHO stages 3&4) and were started on non-nucleoside reverse transcriptase inhibitor-based regimens (79.2%). The median CD4% was 13.5% (IQR 7.9;18.9) and median HIV viral load log 5.0 (IQR 4.4;5.5). Baseline stunting (HAZ <-2) was prevalent (55.9%), with a median HAZ of -2.2 (IQR -3.1;-1.3). The median WAZ was -1.5 (IQR -2.5;-0.8), with 29.2% being underweight-for-age (WAZ <-2). The peak height velocity (PHV) in adolescents with baseline stage 3 disease was higher than for those with stage 4 disease. Being older at ART start (p<0.001) and baseline stunting (p<0.001) were associated with poorer growth, resulting in a lower HAZ at study exit, with boys more significantly affected than girls (p<0.001). CONCLUSIONS: Suboptimal growth in adolescents with perinatally-acquired HIV infection is a significant health concern, especially in children who started ART later in terms of age and who had baseline stunting and is more pronounced in boys than in girls.

The ability of continuous-wave Doppler ultrasound to detect fetal growth restriction.

BACKGROUND: Fetal growth restriction (FGR), defined as a fetus failing to reach its genetic growth potential, remains poorly diagnosed antenatally. This study aimed to assess the ability of continuous-wave Doppler ultrasound of the umbilical artery (CWD-UmA) to detect FGR in healthy women with low-risk pregnancies. METHODS AND FINDINGS: This prospective longitudinal descriptive cohort study enrolled infants born to low-risk mothers who were screened with CWD-UmA between 28-34 weeks' gestation; the resistance index (RI) was classified as normal or abnormal. Infants were assessed at 6, 10, 14 weeks, and 6 months postnatally for anthropometric indicators and body composition using the deuterium dilution method to assess fat-free mass (FFM). Neonates in the abnormal RI group were compared with those in the normal RI group, and neonates classified as small-for-gestational age (SGA) were compared with appropriate-for-gestational age (AGA) neonates. Eighty-one term infants were included. Only 6 of 26 infants (23.1%) with an abnormal RI value would have been classified as SGA. The abnormal RI group had significantly reduced mean FFM and FFM-for-age Z-scores at 6, 10, 14 weeks, and 6 months compared with the normal RI group (P<0.015). The SGA group's FFM did not show this consistent trend when compared to AGA FFM, being significantly different only at 6 months (P = 0.039). The main limitation of the study was the small sample size of the infant follow-up. CONCLUSIONS: Abnormal RI obtained from CWD-UmA is able to detect FGR and is considered a useful addition to classifying the neonate only by SGA or AGA at birth.

Understanding the Impact of Maternal HIV Infection on the Health and Well-Being of Mothers and Infants in South Africa: Siyakhula Collaborative Workshop Report.

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.

Healthcare without borders: A cross-sectional study of immigrant and nonimmigrant children admitted to a large public sector hospital in the Gauteng Province of South Africa.

BACKGROUND: Human migration is a worldwide phenomenon that receives considerable attention from the media and healthcare authorities alike. A significant proportion of children seen at public sector health facilities in South Africa (SA) are immigrants, and gaps have previously been noted in their healthcare provision. The objective of the study was to describe the characteristics and differences between the immigrant and SA children admitted to Kalafong Provincial Tertiary Hospital (KPTH), a large public sector hospital in the urban Gauteng Province of SA. METHODS AND FINDINGS: A cross-sectional study was conducted over a 4-month period during 2016 to 2017. Information was obtained through a structured questionnaire and health record review. The enrolled study participants included 508 children divided into 2 groups, namely 271 general paediatric patients and 237 neonates. Twenty-five percent of children in the neonatal group and 22.5% in the general paediatric group were immigrants. The parents/caregivers of the immigrant group had a lower educational level (p < 0.0001 neonatal and paediatric), lower income (neonatal p < 0.001; paediatric p = 0.024), difficulty communicating in English (p < 0.001 neonatal and paediatric), and were more likely residing in informal settlements (neonatal p = 0.001; paediatric p = 0.007) compared to the SA group. In the neonatal group, there was no difference in the number of antenatal care (ANC) visits, type of delivery, gestational age, and birth weight. In the general paediatric group, there was no difference in immunisation and vitamin A supplementation coverage, but when comparing growth, the immigrant group had more malnutrition compared to the SA group (p = 0.029 for wasting). There was no difference in the prevalence of maternal human immunodeficiency virus (HIV) infection, with equally good prevention of mother-to-child transmission (PMTCT) coverage. There was also no difference in reported difficulties by immigrants in terms of access to healthcare (neonatal p = 0.379; paediatric p = 0.246), although a large proportion (10%) of the neonates of immigrant mothers were born outside a medical facility. CONCLUSIONS: Although there were health-related differences between immigrant and SA children accessing in-hospital care, these were fewer than expected. Differences were found in parental educational level and socioeconomic factors, but these did not significantly affect ANC attendance, delivery outcomes, immunisation coverage, HIV prevalence, or PMTCT coverage. The immigrant population should be viewed as a high-risk group, with potential problems including suboptimal child growth. Health workers should advocate for all children in the community they are serving and promote tolerance, respect, and equal healthcare access.

Mother-to-child transmission of Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis in HIV-infected pregnant women in South Africa.

BACKGROUND: Sexually transmitted infections (STIs) can be transmitted from mother to neonate. We determined the frequency of mother-to-child transmission (MTCT) of Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis to the newborn nasopharynx. METHODS: This study was nested in a cohort study of etiologic testing versus syndromic management for STIs among pregnant women living with human immunodeficiency virus in South Africa. Mothers were tested for STIs using the GeneXpert platform within 60 days after delivery. Nasopharyngeal swabs were obtained from newborns of mothers with a positive STI test; these were then tested by Xpert® on the same day based on the maternal STI diagnosis. RESULTS: We tested nasopharyngeal swabs from 85 STI-exposed newborns; 74 (87%) were tested within 2 weeks after birth (median five; range 2-12 days). MTCT frequency of any STI was 30/74 (41%); 43% (23/53) for C. trachomatis, 29% (2/7) for N. gonorrhoeae, and 24% (6/25) for T. vaginalis. Also, 4/11 (36%) swabs obtained between 14 and 60 days after delivery tested positive for STI. CONCLUSIONS: There was a high frequency of MTCT of STIs to the nasopharynx of newborns in our setting. The impact of nasopharyngeal colonization and the benefits of STI testing on newborn health remain to be determined.