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Using the Data Evaluation and Preparation for HIV-Exposed Uninfected Child Cohorts project's standardized child HIV exposure definitions, 64%, 64% and 90% of children exposed to HIV in utero could be classified as HIV-uninfected with moderate or high certainty at the ages of 1 and 3 years and at the time of first infectious disease hospitalization, respectively. These definitions can be applied retrospectively to routine datasets with linked mother-child data.
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INTRODUCTION: We evaluated associations of HIV and antiretroviral therapy (ART) with birth and maternal outcomes at a province-wide-level in the Western Cape, South Africa, in a recent cohort before dolutegravir-based first-line ART implementation. METHODS: This retrospective cohort study included pregnant people delivering in 2018-2019 with data in the Western Cape Provincial Health Data Centre which integrates individual-level data on all public sector patients from multiple electronic platforms using unique identifiers. Adverse birth outcomes (stillbirth, low birth weight (LBW), very LBW (VLBW)) and maternal outcomes (early and late pregnancy-related deaths, early and late hospitalizations) were compared by HIV/ART status and adjusted prevalence ratios (aPRs) calculated using log-binomial regression. RESULTS: Overall 171,960 pregnant people and their singleton newborns were included, 19% (Nâ=â32â015) identified with HIV. Amongst pregnant people with HIV (PPHIV), 60% (Nâ=â19â157) were on ART preconception, 29% (Nâ=â9276) initiated ART during pregnancy and 11% (Nâ=â3582) had no ART. Adjusted for maternal age, multiparity, hypertensive disorders and residential district, stillbirths were higher only for PPHIV not on ART [aPR 1.31 (95%CI 1.04-1.66)] compared to those without HIV. However, LBW and VLBW were higher among all PPHIV, with aPRs of 1.11-1.22 for LBW and 1.14-1.54 for VLBW. Pregnancy-initiated ART was associated with early pregnancy-related death (aPR 3.21; 95%CI 1.55-6.65), and HIV with or without ART was associated with late pregnancy-related death (aPRs 7.89-9.01). CONCLUSIONS: Even in the universal ART era, PPHIV experienced higher rates of LBW and VLBW newborns, and higher late pregnancy-related death regardless of ART status than pregnant people without HIV.
Subject(s)
HIV Infections , Pregnancy Complications, Infectious , Female , Pregnancy , Infant, Newborn , Humans , Pregnancy Complications, Infectious/drug therapy , Pregnancy Complications, Infectious/epidemiology , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/epidemiology , Retrospective Studies , South Africa/epidemiology , StillbirthABSTRACT
INTRODUCTION: With the scaling up of vertical HIV transmission prevention programmes, the HIV-related population profile of children in South Africa has shifted. We described temporal changes in HIV-related characteristics of children, aged ≤3 years (up to the third birthday), with infectious disease hospitalisations across the Western Cape province. METHODS: We used routinely collected electronic data to identify children born in the Western Cape with infectious disease hospital records for lower respiratory tract infections, diarrhoea, meningitis and tuberculous meningitis, from 2008 to 2021. Linked maternal and child unique identifiers were used to extract pregnancy, HIV-related, laboratory, pharmacy and hospitalisation data. We described temporal changes in child HIV exposure and acquisition status, timing of maternal HIV diagnosis and antiretroviral therapy (ART) start, infant exposure to maternal ART and timing thereof, and maternal CD4 and HIV viral load closest to delivery. We used logistic and multinomial regression to assess changes in characteristics between the Pre-Option B+ (2008-2013), Option B+ (2013-2016) and Universal ART periods (2016-2021). RESULTS: Among 52,811 children aged ≤3 years with hospitalisations, the proportion living with HIV dreased from 7.0% (2008) to 1.1% (2021), while those exposed to HIV and uninfected increased from 14.0% (2008) to 16.1% (2021) with a peak of 18.3% in 2017. Among mothers with HIV (n = 9873), the proportion diagnosed with HIV and starting ART before pregnancy increased from 20.2% to 69.2% and 5.8% to 59.0%, respectively, between 2008 and 2021. Children hospitalised during the Universal ART period had eight times higher odds (Odds Ratio: 8.41; 95% CI: 7.36-9.61) of exposure to maternal ART versus children admitted Pre-Option B+. Among mothers of children exposed to HIV and uninfected with CD4 records (n = 7523), the proportion with CD4 <350 cells/µl decreased from 90.6% (2008) to 27.8% (2021). CONCLUSIONS: In recent years, among children hospitalised with infectious diseases, there were fewer children with perinatally acquired HIV, while an increased proportion of those without HIV acquisition are exposed to maternal HIV and ART. There is a need to look beyond paediatric HIV prevalence and consider child exposure to HIV and ART among children without HIV, when assessing the HIV epidemic's impact on child health services.
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Acquired Immunodeficiency Syndrome , HIV Infections , Pregnancy Complications, Infectious , Infant , Pregnancy , Female , Child , Humans , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV Infections/diagnosis , Pregnancy Complications, Infectious/drug therapy , Pregnancy Complications, Infectious/epidemiology , South Africa/epidemiology , Mothers , Infectious Disease Transmission, Vertical/prevention & controlABSTRACT
INTRODUCTION: Studies have reported a higher risk of suboptimal neurodevelopment among children who are HIV-exposed uninfected (HEU) compared to children HIV-unexposed uninfected (HUU). Actual academic performance among school-aged children by HIV exposure status has not been studied. METHODS: Academic performance in Mathematics, Science, English, Setswana and overall among children enrolled in the Botswana-based FLOURISH study who were attending public primary school and ranging in age from 7.1 to 14.6 years were compared by HIV exposure status using a Cochran-Mantel-Haenszel test. Lower academic performance was defined as a grade of "C" or lower (≤60%). Unadjusted and adjusted logistic regression models were fit to assess for an association between HIV exposure and lower academic performance. RESULTS: Between April 2021 and December 2022, 398 children attending public primary school enrolled in the FLOURSH study, 307 (77%) were HEU. Median age was 9.4 years (IQR 8.9-10.2). Only 17.9% of children HEU were breastfeed versus 100% of children HUU. Among children HEU, 80.3% had foetal exposure to three-drug antiretroviral treatment, 18.7% to zidovudine only and 1.0% had no antiretroviral exposure. Caregivers of children HEU were older compared to caregivers of children HUU (median 42 vs. 36 years) and more likely to have no or primary education only (15.0% vs. 1.1%). In unadjusted analyses, children HEU were more likely to have lower overall academic performance compared to their children HUU (odds ratio [OR]: 1.96 [95% confidence interval (CI): 1.16, 3.30]), and lower performance in Mathematics, Science and English. The association was attenuated after adjustment for maternal education, caregiver income, breastfeeding, low birth weight and child sex (aOR: 1.86 [95% CI: 0.78, 4.43]). CONCLUSIONS: In this Botswana-based cohort, primary school academic performance was lower among children HEU compared to children HUU. Biological and socio-demographic factors, including child sex, appear to contribute to this difference. Further research is needed to identify modifiable contributors, develop screening tools to identify the risk of poor academic performance and design interventions to mitigate risk.
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Academic Performance , HIV Infections , Pregnancy Complications, Infectious , Pregnancy , Female , Humans , Child , Infant , Adolescent , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV Infections/prevention & control , Botswana/epidemiology , Breast Feeding , Zidovudine/therapeutic use , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/drug therapyABSTRACT
Despite the expanding digitisation of individual health data, informed consent for the collection and use of health data is seldom explicitly sought in public sector clinics in South Africa. This study aims to identify perceptions of informed consent practices for health data capture, access, and use in Gauteng and the Western Cape provinces of South Africa. Data collection from September to December 2021 included in-depth interviews with healthcare providers (n = 12) and women (n = 62) attending maternity services. Study findings suggest that most patients were not aware that their data were being used for purposes beyond the individualised provision of medical care. Understanding the concept of anonymised use of electronic health data was at times challenging for patients who understood their data in the limited context of paper-based folders and booklets. When asked about preferences for electronic data, patients overwhelmingly were in favour of digitisation. They viewed electronic access to their health data as facilitating rapid and continuous access to health information. Patients were additionally asked about preferences, including delivery of health information, onward health data use, and recontacting. Understanding of these use cases varied and was often challenging to convey to participants who understood their health data in the context of information inputted into their paper folders. Future systems need to be established to collect informed consent for onward health data use. In light of perceived ties to the care received, these systems need to ensure that patient preferences do not impede the content nor quality of care received.
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Electronics , Health Personnel , Pregnancy , Humans , Female , South Africa , Qualitative Research , Patient PreferenceABSTRACT
OBJECTIVES: We assessed the feasibility of an appropriately powered randomised trial by evaluating whether participants could be recruited and retained, and sought preliminary information on exclusive breastfeeding rates. SETTING: Primary healthcare facility, serving a rural community. PARTICIPANTS: Women initiating breast feeding within 24 hours of giving birth, on antiretroviral treatment and aged ≥18 years. INTERVENTIONS: We randomised mother-infant pairs to receive weekly text messaging encouraging exclusive breast feeding plus in-person individual motivational interviews post partum at weeks 2, 6 and 10, or standard infant feeding counselling. OUTCOME MEASURES: The feasibility endpoints included number of participants who consented to participate and number with complete evaluation of infant feeding practices at study visits. Exploratory endpoints included number of participants who exclusively breast fed at 24 weeks post partum and number of participants adhering to study protocol. RESULTS: Of 123 mothers screened, 52 participants consented for participation. We recruited an average of five participants per month over 11 months. Most participants were unemployed (75%), had some high school education (84%) and had disclosed their HIV status to someone close (88%). About 65% participants completed outcome evaluation at week 10, decreasing to 35% at week 24. Twenty participants had the week 24 visit planned between 20 March and August 2020, during COVID-19 lockdown. Of these, 4 completed the visit telephonically, 16 were lost to follow-up. Exclusive breastfeeding rate remained relatively high across both groups through week 24. The difference in exclusive breastfeeding rates between the intervention and control groups was minimal: rate difference 22.2% (95% CI -20.1% to 64.5%). CONCLUSIONS: With a large eligible target population, recruitment targets could be achieved for a large trial. Strategies to retain participants, such as remote monitoring and in-person follow-up visits, will be essential. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT02949713) and Pan African Clinical Trial Registry (PACTR201611001855404).
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Cell Phone , HIV Infections , Motivational Interviewing , Text Messaging , Infant , Pregnancy , Female , Humans , Adolescent , Adult , Breast Feeding , South Africa , Feasibility Studies , HIV Infections/prevention & control , HIV Infections/drug therapy , Primary Health CareABSTRACT
INTRODUCTION: The global antiretroviral therapy era has led to a decline in the number of children newly acquiring HIV and an increase in the number of children who are HIV-exposed and uninfected (HEU). This shift has prompted extensive research focussing on health and survival outcomes of children who are HEU. Study findings, particularly in relation to adverse birth outcomes, have been disparate, inconclusive and have not always been generalisable. Thus, the objectives of this scoping review are (1) to identify and extract definitions used for the adverse birth outcome terms 'low birth weight', 'small for gestational age', 'stillbirth' and 'preterm birth'; (2) to compare the characteristics of studies from which birth outcome definitions were extracted by (a) temporal periods and (b) study country setting (high-income vs low-income and middle-income countries); (3) to use content analysis to map and describe the temporal and geographic distribution of the definitions used and construct a logical model of their evolution. METHODS AND ANALYSIS: The online databases of PubMed/MEDLINE, Scopus, Web of Science, Cochrane Library and CINHAL/EBSCOhost will be used to identify published and grey literature from 2011 to 2022 to identify definitions for the adverse birth outcome terms 'low birth weight', 'small for gestational age', 'stillbirth' and 'preterm birth'. A three-step process of (1) duplicate removal, (2) title and abstract screening and (3) full text screening will be used to select included studies. The extracted data will be used to conduct a comparative analysis, content analysis and construct a logic model. ETHICS AND DISSEMINATION: This review will be used to inform a consensus process around the development of harmonised definitions for the specified adverse birth outcomes. Our dissemination plan includes presentations, publications as well as the development infographics and a resource hub. The study is approved by the Human Research Ethics Committee of Stellenbosch University.
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HIV Infections , Pregnancy Complications , Premature Birth , Pregnancy , Infant, Newborn , Child , Female , Humans , Birth Weight , Pregnancy Complications/drug therapy , Stillbirth , HIV Infections/drug therapy , Anti-Retroviral Agents/therapeutic use , Premature Birth/epidemiology , Pregnancy Outcome/epidemiology , Review Literature as TopicABSTRACT
INTRODUCTION: Co-trimoxazole prophylaxis is recommended for children born to women with HIV to protect those who acquire HIV from opportunistic infections, severe bacterial infections and malaria. With scale-up of maternal antiretroviral therapy, most children remain HIV-exposed uninfected (HEU) and the benefits of universal co-trimoxazole are uncertain. We assessed the effect of co-trimoxazole on mortality and morbidity of children who are HEU. METHODS: We performed a systematic review (PROSPERO number: CRD42021215059). We systematically searched MEDLINE, Embase, Cochrane CENTRAL, Global Health, CINAHL Plus, Africa-Wide Information, SciELO and WHO Global Index Medicus for peer-reviewed articles from inception to 4th January 2022 without limits. Ongoing randomized controlled trials (RCTs) were identified through registries. We included RCTs reporting mortality or morbidity in children who are HEU receiving co-trimoxazole versus no prophylaxis/placebo. The risk of bias was assessed using the Cochrane 2.0 tool. Data were summarized using narrative synthesis and findings were stratified by malaria endemicity. RESULTS: We screened 1257 records and included seven reports from four RCTs. Two trials from Botswana and South Africa of 4067 children who are HEU found no difference in mortality or infectious morbidity in children randomized to co-trimoxazole prophylaxis started at 2-6 weeks of age compared to those randomized to placebo or no treatment, although event rates were low. Sub-studies found that antimicrobial resistance was higher in infants receiving co-trimoxazole. Two trials in Uganda investigating prolonged co-trimoxazole after breastfeeding cessation showed protection against malaria but no other morbidity or mortality differences. All trials had some concerns or a high risk of bias, which limited the certainty of evidence. DISCUSSION: Studies show no clinical benefit of co-trimoxazole prophylaxis in children who are HEU, except to prevent malaria. Potential harms were identified for co-trimoxazole prophylaxis leading to antimicrobial resistance. The trials in non-malarial regions were conducted in populations with low mortality potentially reducing generalizability to other settings. CONCLUSIONS: In low-mortality settings with few HIV transmissions and well-performing early infant diagnosis and treatment programmes, universal co-trimoxazole may not be required.
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Anti-Infective Agents , HIV Infections , Malaria , Infant , Female , Child , Humans , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use , HIV Infections/drug therapy , HIV Infections/prevention & control , Malaria/drug therapy , Malaria/prevention & control , Uganda , Anti-Infective Agents/therapeutic use , World Health Organization , Randomized Controlled Trials as TopicABSTRACT
Background: Children who are HIV-exposed uninfected (HEU), i.e., born to mothers living with HIV despite not acquiring HIV infection themselves, have increased morbidity and mortality. Data suggests that the breastmilk profile, and more specifically human milk oligosaccharide (HMO) composition, differ by maternal HIV status and may partly help explain this increased risk. We are currently conducting an HMO-based synbiotic randomized trial in breastfed children HEU, the MIGH-T MO study (ClinicalTrials.gov Identifier: NCT05282485), to assess the impact on health outcomes of children HEU. Here, we report our experience from a study of the feasibility and acceptability of a powder-based intervention given to breastfeeding children, conducted prior to the initiation of MIGH-T MO. Methods: 10 mothers living with HIV and their breastfeeding children HEU accessing care at Tygerberg Hospital, in Cape Town, South Africa were enrolled. A powder-based product, potato maltodextrin, was mixed with expressed breast milk and administered to the infants daily for 4 weeks. Data on feasibility, acceptability, adherence, and health outcomes were assessed at the enrollment visit and at the 4 week visit, along with weekly telephone calls. Results: 10 mother-infant pairs were enrolled in this study, with infant age ranging from 6-20 months of age. Among the mothers who met the eligibility criteria, all of them enrolled into the study suggesting high acceptability. While there was some Ioss-to-follow-up after the first visit, among the mothers who remained, there were no major feasibility concerns related to study procedures, product administration, adherence, tolerance, and health outcome assessment. Conclusion: Our pilot study demonstrated that a powder-based intervention for breastfeeding children HEU in South Africa is acceptable and feasible. This suggests potential feasibility and acceptability for other larger studies, including our ongoing MIGH-T MO study, that use similar powder-based interventions such as probiotics, prebiotics, or synbiotics, in breastfed infants from similar settings.
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OBJECTIVE: We evaluated the prevalence of de novo hypertensive disorders of pregnancy (dnHDP) in pregnant people with HIV (PPHIV) in the Western Cape Province, South Africa in 2018-2019 by HIV and antiretroviral therapy (ART) status. METHODS: All people with a pregnancy outcome from 1 January 2018 to 31 December 2019 in the Western Cape Provincial Health Data Centre (WCPHDC) were included. The WCPHDC integrates data from multiple electronic platforms according to unique identifiers. dnHDP was classified by ICD-10 code or first-time prescription of antihypertensive drugs less than 140âdays before delivery. Pregnant people with preexisting hypertension without superimposed preeclampsia/eclampsia were not considered to have dnHDP. Adjusted prevalence ratios (aPR) for dnHDP by HIV/ART status were calculated using Poisson regression with robust variance. RESULTS: Among 180 553 pregnant people studied, 13 677 (7.6%) had dnHDP and 33 978 (18.8%) were PPHIV. Among PPHIV, 11.3% ( N â=â3827) had no evidence of ART, 59.7% ( N â=â20 283) initiated ART preconception and 29.0% ( N â=â9868) had ART initiated during pregnancy. Compared to those without HIV (7.7%), dnHDP prevalence was lower in PPHIV with preconception [6.9%; aPR 0.78; 95% confidence interval (CI) 0.74-0.83] or pregnancy-initiated ART (7.0%; aPR 0.83; 95% CI 0.75-0.92) and higher in PPHIV without ART (9.8%; aPR 1.17; 95% CI 1.06-1.29) adjusted for maternal age, multiparity, multigestation pregnancy and preexisting hypertension. ART duration by delivery of at least 100âweeks versus pregnancy-initiated ART of 20-<40âweeks was protective (aPR 0.88; 95% CI 0.78-0.98). CONCLUSIONS: In the context of universal ART, these findings are reassuring for most PPHIV. ART was not associated with increased dnHDP prevalence and longer ART duration was protective.
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HIV Infections , Hypertension, Pregnancy-Induced , Pregnancy Complications, Infectious , Female , Pregnancy , Humans , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/epidemiology , Pregnancy Complications, Infectious/drug therapy , Pregnancy Complications, Infectious/epidemiology , Hypertension, Pregnancy-Induced/epidemiology , Pregnancy Outcome , South Africa/epidemiologyABSTRACT
INTRODUCTION: CHERISH is designed to establish a long-term sustainable system for measurement of in utero and postnatal exposures and outcomes in children who are HIV-exposed uninfected (HEU) and HIV-unexposed to compare survival, hospitalisation, growth and neurodevelopment in the Western Cape, South Africa. METHODS AND ANALYSIS: During 2022-2025, the CHERISH dynamic cohort is prospectively enrolling pregnant people with and without HIV at 24-36 weeks gestation from one urban and one rural community, following mother-child pairs, including children who are HEU (target N=1200) and HIV-unexposed (target N=600) for 3 years from the child's birth. In-person visits occur at enrolment, delivery, 12 months, 24 months and 36 months with intervening 3-monthly telephone data collection. Children and mothers without HIV are tested for HIV at all in-person visits. Data on exposures and outcomes are collected from routine standardised healthcare documentation, maternal interview, measurement (growth and neurodevelopment) at in-person visits and linkage to the Western Cape Provincial Health Data Centre (survival and hospitalisation). A priori adverse birth outcomes, advanced maternal HIV and maternal mental health are considered potential mediators of outcome disparities in children who are HEU and will be evaluated as such in multivariable models appropriate for each outcome. ETHICS AND DISSEMINATION: Mothers interested in joining the study are taken through a visual informed consent document for their and their child's participation, with the option to consent to anonymised de-identified data being contributed to a public data repository. All data is captured directly into an electronic database using alphanumeric identifiers devoid of identifying information. The cohort study is approved by Human Research Ethics Committees of Stellenbosch University (N20/08/084), University of Cape Town (723/2021) and Western Cape Government (WC_2021_09_007). Findings will be shared with participants, participating communities, local and provincial stakeholders, child health clinicians, researchers and policymakers at local, national and international forums and submitted for publication in peer-reviewed journals.
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HIV Infections , Pregnancy Complications, Infectious , Pregnancy , Female , Humans , Infant , Cohort Studies , Prospective Studies , ParturitionABSTRACT
INTRODUCTION: Children who are HIV-exposed uninfected (HEU), that is, children who do not acquire HIV infection despite being born to mothers with HIV, have a higher risk of mortality, infectious morbidity and growth deficits than children who are HIV-unexposed uninfected (HUU). Prior research has focused on breast feeding and has pointed to changes in human milk oligosaccharides (HMOs) associated with maternal HIV that may influence the infant microbiome and thereby lead to these adverse outcomes. However, to our knowledge, no study has attempted to intervene along this pathway to reduce the occurrence of the adverse outcomes in children HEU. We will conduct a double-blind, randomised trial of a synbiotic intervention, which combines an HMO and probiotic, in breastfed infants HEU in South Africa to evaluate whether this intervention has promise to reduce excess infectious morbidity and growth faltering compared with controls. METHODS AND ANALYSIS: One hundred and forty-four breastfed infants HEU, aged 4 weeks, will be 1:1 randomised to receive either a daily synbiotic or an identical-looking placebo through age 24 weeks. Infants will be followed until age 48 weeks and outcomes of infectious morbidity, growth and biological measurements (eg, microbiota, inflammation and metabolome) will be assessed. Analyses will follow intention-to-treat principles comparing the cohorts as randomised. Infants HEU will be compared across arms with respect to the occurrence of infectious morbidity and growth outcomes through 4-24 weeks and 4-48 weeks using appropriate parametric and non-parametric statistical tests. Additionally, an observational cohort of 40 breastfed infants HUU will be recruited as a comparator group with no intervention. ETHICS AND DISSEMINATION: Ethical approval for this study has been obtained from the ethics committees at Columbia University and Stellenbosch University. The findings will be disseminated in publications. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT05282485. SANCTR ID number: DOH-27-122021-6543.
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Communicable Diseases , HIV Infections , Pregnancy Complications, Infectious , Pregnancy , Child , Female , Infant , Humans , HIV Infections/epidemiology , Milk, Human , Morbidity , Oligosaccharides/therapeutic use , Randomized Controlled Trials as TopicABSTRACT
BACKGROUND: Children of foreign-born parents with vulnerable legal status, limited economic rights and exclusion from national social interventions may be at higher risk for severe acute malnutrition (SAM). We evaluated the relationship between parent status (foreign-born vs. South African) and outcomes for children with SAM admitted to a rural regional hospital in the Western Cape, South Africa. METHODS: A retrospective cohort study was conducted including children <5 years admitted to Worcester Provincial Hospital during 2015-17 with SAM (WHO weight-for-height Z score <-3, presence of nutritional oedema, mid-upper-arm-circumference of <11.5 cm or visible severe wasting). Exposures, including parent status, and outcomes including in-hospital death were determined from hospital and regional dietician records. RESULTS: Of 95 children included, 31 (33%) were of foreign-born and 64 (67%) of South African parents. Median (interquartile range) age at admission was 12 (8-18) vs. 10 (8-13) months in children of South African vs. foreign-born parents with no difference in preterm birth, concurrent illnesses or admission duration. Age, HIV status and breastfeeding practices were no different in foreign-born compared to South African mothers. In-hospital deaths occurred in 3/64 (5%) and 6/31 (19%) children of South African vs. foreign-born parents (p = 0.01). Children of foreign-born compared to South African parents had an odds ratio of 4.88 (95% CI 1.13-21.06) for in-hospital SAM-associated mortality. CONCLUSION: In this rural setting, 33% of children admitted with SAM were of foreign-born parents and experienced in-hospital SAM-associated mortality at least four times higher than children of South African parents. This illustrates the extreme vulnerability of these children.
In some contexts children of foreign-born parents may experience vulnerable legal status putting them at higher risk for food insecurity and severe malnutrition in their early years of life, compared to children of native-born parents. In a rural region of the Western Cape of South Africa, we observed that children of foreign-born parents were four times more likely to die of malnutrition than children of South African parents. This was so even though these children did not display other expected risk factors for malnutrition such as being born preterm, not breastfeeding or being HIV-exposed. To achieve the Sustainable Developmental Goals, policy makers and healthcare systems will need to cater for all children in the country, including asylum seekers and children of foreign-born parents. The South African Constitution and Refugee Act are in support of this. However, the findings of this study illustrate the extent of vulnerability of children living in South Africa born to foreign-born parents and calls for an evaluation of the services made available to support their health and well-being.
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Malnutrition , Premature Birth , Severe Acute Malnutrition , Infant, Newborn , Child , Female , Humans , Infant , South Africa/epidemiology , Retrospective Studies , Hospital Mortality , Severe Acute Malnutrition/epidemiology , Hospitals, RuralABSTRACT
BACKGROUND: Preeclampsia is a considerable cause of maternal and infant morbidity and mortality. Although its etiology is unknown, preeclampsia has been described as a state of exaggerated maternal inflammatory response. Therefore, it has been hypothesized that preeclampsia would occur less commonly in states of immune deficiency. OBJECTIVE: This study aimed to compare the prevalence of treated and untreated HIV infections among preeclamptic cases and controls, determine infant outcomes, and evaluate the association between HIV and preeclampsia after adjusting for known predictor variables, including maternal age, gravidity, body mass index, and smoking. STUDY DESIGN: This case-control study investigated the association between preeclampsia and HIV infection using secondary data from an unrelated study. We defined preeclamptic cases as pregnant women who were normotensive until 20 weeks of gestation and thereafter had at least 1 high blood pressure measurement either before or at delivery and proteinuria, defined as protein excretion of ≥300 mg within 24 hours or >2 protein on dipstick urinalysis. The prevalence of HIV infection was compared between cases and controls. Multivariate logistic regression analysis was used to assess the association between preeclampsia and potential confounding variables and reported using odds ratios and 95% confidence intervals. RESULTS: There were 571 cases with preeclampsia and 596 normotensive controls included in this study. The median age was 27 years for cases and 26 years for controls (P=.008). Most participants (69%) had ≥2 previous pregnancies with no difference between the cases and controls (P=.176). Overall, 43% of the participants were obese, with a mean body mass index of 29 (interquartile range, 24.5-34.2), with higher proportions of women who were overweight and obese in the group with preeclampsia (P=.031). The prevalence of HIV was significantly lower in cases than in controls (24% vs 30%, respectively; P=.014). Compared with 16% of infants born preterm to normotensive controls, 48% of infants were born preterm born to women with preeclampsia (P<.001). Compared with 14% of infants born with low birthweight to normotensive controls, 53% of infants were born with low birthweight to women with preeclampsia (P<.0001). Untreated HIV infection was negatively associated with preeclampsia (unadjusted odds ratio, 0.330; 95% confidence interval, 0.197-0.552; P<.0001), whereas factors associated with preeclampsia were advanced maternal age (odds ratio, 1.673; 95% confidence interval, 1.209-2.316; P=.002) and obesity (odds ratio, 1.611; 95% confidence interval, 1.023-2.537; P=.040). After adjusting for maternal age, gravidity, smoking, and body mass index in the multivariate regression, only obesity remained significantly associated with preeclampsia (adjusted odds ratio, 1.624; 95% confidence interval, 1.024-2.575; P=.039). CONCLUSION: Before the large-scale rollout of antiretroviral therapy in a setting with a high burden of HIV and preeclampsia, untreated HIV infection was found to have a protective effect against preeclampsia. The protective effect against preeclampsia was not apparent for HIV infection treated with antiretroviral therapy.
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INTRODUCTION: As new antiretrovirals (ARVs), including long-acting ARVs for treatment and prevention, are approved and introduced, surveillance during pregnancy must become the safety net for evaluating birth outcomes, especially those that are rare and require large numbers of observations. Historically, drug pharmacovigilance in pregnancy has been limited and fragmented between different data sources, resulting in inadequate data to assess risk. The International Maternal Pediatric Adolescent AIDS Clinical Trials Network and World Health Organization convened a Workshop which reviewed strengths and weaknesses of existing programs and discussed an improved framework to integrate existing safety data sources and promote harmonization and digitalization. DISCUSSION: This paper highlights that although robust sources of safety data and surveillance programs exist, key challenges remain, including unknown denominators, reporting bias, under-reporting (e.g. in voluntary registries), few data sources from resource-limited settings (most are in North America and Europe), incomplete or inaccurate data (e.g. within routine medical records). However, recent experiences (e.g. with safety signals) and current innovations (e.g. electronic record use in resource-limited settings and defining adverse outcomes) provide momentum and building blocks for a new framework for active surveillance of ARV safety in pregnancy. A public health approach should be taken using data from existing sources, including registries of pregnancy ARV exposure and birth defects; observational surveillance and cohort studies; clinical trials; and real-world databases. Key facilitators are harmonization and standardization of outcomes, sharing of materials and tools, and data linkages between programs. Other key facilitators include the development of guidance to estimate sample size and duration of surveillance, ensuring strategic geographic diversity, bringing partners together to share information and engaging the community of women living with HIV. CONCLUSIONS: Looking ahead, critical steps to safely introduce new ARVs include (1) adopting harmonized standards for measuring adverse maternal, birth and infant outcomes; (2) establishing surveillance centres of excellence in areas with high HIV prevalence with harmonized data collection and optimized electronic health records linking maternal/infant data; and (3) creating targets and evaluation goals for reporting progress on implementation and quality of surveillance in pregnancy. The platform will be leveraged to ensure that appropriate contributions and strategic actions by relevant stakeholders are implemented.
Subject(s)
Anti-Retroviral Agents/adverse effects , Breast Feeding , Adolescent , Anti-Retroviral Agents/therapeutic use , Child , Cohort Studies , Europe , Female , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV Infections/prevention & control , Humans , Infant , North America , PregnancyABSTRACT
PURPOSE: The Western Cape Pregnancy Exposure Registry (PER) was established at two public sector healthcare sentinel sites in the Western Cape province, South Africa, to provide ongoing surveillance of drug exposures in pregnancy and associations with pregnancy outcomes. PARTICIPANTS: Established in 2016, all women attending their first antenatal visit at primary care obstetric facilities were enrolled and followed to pregnancy outcome regardless of the site (ie, primary, secondary, tertiary facility). Routine operational obstetric and medical data are digitised from the clinical stationery at the healthcare facilities. Data collection has been integrated into existing services and information platforms and supports routine operations. The PER is situated within the Provincial Health Data Centre, an information exchange that harmonises and consolidates all health-related electronic data in the province. Data are contributed via linkage across a unique identifier. This relationship limits the missing data in the PER, allows validation and avoids misclassification in the population-level data set. FINDINGS TO DATE: Approximately 5000 and 3500 pregnant women enter the data set annually at the urban and rural sites, respectively. As of August 2021, >30 000 pregnancies have been recorded and outcomes have been determined for 93%. Analysis of key obstetric and neonatal health indicators derived from the PER are consistent with the aggregate data in the District Health Information System. FUTURE PLANS: This represents significant infrastructure, able to address clinical and epidemiological concerns in a low/middle-income setting.
Subject(s)
Pregnant Women , Prenatal Care , Delivery of Health Care , Female , Humans , Infant, Newborn , Pregnancy , Pregnancy Outcome/epidemiology , Registries , South Africa/epidemiologyABSTRACT
INTRODUCTION: For the growing number of children with in utero and postpartum exposure to HIV and/or antiretrovirals, it is unclear which exposures or risk factors play a significant role in predicting worse neurodevelopmental outcomes. This protocol describes a prospective longitudinal cohort study of infants born to mothers living with HIV and those born to mothers without HIV. We will determine which risk factors are most predictive of child neurodevelopment at 24 months. We aim to create a risk assessment tool to help predict which children are at risk for worse neurodevelopment outcomes. METHODS AND ANALYSIS: This study leverages an existing Kenyan cohort to prospectively enrol 500 children born to mothers living with HIV and 500 to those without HIV (n=1000 total) and follow them from birth to age 24 months. The following factors will be measured every 6 months: infectious morbidity and biological/sociodemographic/psychosocial risk factors. We will compare these factors between the two groups. We will then measure and compare neurodevelopment within children in both groups at 24 months of age using the Child Behaviour Checklist and the Bayley Scales of Infant and Toddler Development, third edition. Finally, we will use generalised linear mixed modelling to quantify associations with neurodevelopment and create a risk assessment tool for children ≤24 months. ETHICS AND DISSEMINATION: The study is approved by the Moi University's Institutional Research and Ethics Committee (IREC/2021/55; Approval #0003892), Kenya's National Commission for Science, Technology and Innovation (NACOSTI, Reference #700244) and Indiana University's Institutional Review Board (IRB Protocol #110990). This study carries minimal risk to the children and their mothers, and all mothers will provide written consent for participation in the study. Results will be disseminated to maternal child health clinics within Uasin Gishu County, Kenya and via papers submitted to peer-reviewed journals and presentation at international conferences.
Subject(s)
HIV Infections , Pregnancy Complications, Infectious , Child Development , Child, Preschool , Female , HIV Infections/complications , HIV Infections/epidemiology , Humans , Infant , Kenya/epidemiology , Longitudinal Studies , Mothers , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Prospective StudiesABSTRACT
INTRODUCTION: Adolescents living with HIV are subject to multiple co-morbidities, including growth retardation and immunodeficiency. We describe growth and CD4 evolution during adolescence using data from the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) global project. METHODS: Data were collected between 1994 and 2015 from 11 CIPHER networks worldwide. Adolescents with perinatally acquired HIV infection (APH) who initiated antiretroviral therapy (ART) before age 10 years, with at least one height or CD4 count measurement while aged 10-17 years, were included. Growth was measured using height-for-age Z-scores (HAZ, stunting if <-2 SD, WHO growth charts). Linear mixed-effects models were used to study the evolution of each outcome between ages 10 and 17. For growth, sex-specific models with fractional polynomials were used to model non-linear relationships for age at ART initiation, HAZ at age 10 and time, defined as current age from 10 to 17 years of age. RESULTS: A total of 20,939 and 19,557 APH were included for the growth and CD4 analyses, respectively. Half were females, two-thirds lived in East and Southern Africa, and median age at ART initiation ranged from <3 years in North America and Europe to >7 years in sub-Saharan African regions. At age 10, stunting ranged from 6% in North America and Europe to 39% in the Asia-Pacific; 19% overall had CD4 counts <500 cells/mm3 . Across adolescence, higher HAZ was observed in females and among those in high-income countries. APH with stunting at age 10 and those with late ART initiation (after age 5) had the largest HAZ gains during adolescence, but these gains were insufficient to catch-up with non-stunted, early ART-treated adolescents. From age 10 to 16 years, mean CD4 counts declined from 768 to 607 cells/mm3 . This decline was observed across all regions, in males and females. CONCLUSIONS: Growth patterns during adolescence differed substantially by sex and region, while CD4 patterns were similar, with an observed CD4 decline that needs further investigation. Early diagnosis and timely initiation of treatment in early childhood to prevent growth retardation and immunodeficiency are critical to improving APH growth and CD4 outcomes by the time they reach adulthood.
Subject(s)
HIV Infections , Adolescent , Adult , CD4 Lymphocyte Count , Child , Child, Preschool , Cohort Studies , Female , Growth Disorders/epidemiology , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , Income , MaleABSTRACT
In countries with high human immunodeficiency virus (HIV) prevalence, up to 30% of pregnant women are living with HIV, with fetal exposure to both HIV and antiretroviral therapy during pregnancy. In addition, pregnant women without HIV but at high risk of HIV acquisition are increasingly receiving HIV preexposure antiretroviral prophylaxis (PrEP). Investments are being made to establish and follow cohorts of children to evaluate the long-term effects of in utero HIV and antiretroviral exposure. Agreement on a key set of definitions for relevant exposures and outcomes is important both for interpreting individual study results and for comparisons across cohorts. Harmonized definitions of in utero HIV and antiretroviral drug (maternal treatment or PrEP) exposure will also facilitate improved classification of these exposures in future observational studies and clinical trials. The proposed definitions offer a uniform approach to facilitate the consistent description and estimation of effects of HIV and antiretroviral exposures on key child health outcomes.
Subject(s)
Anti-HIV Agents , HIV Infections , Pre-Exposure Prophylaxis , Pregnancy Complications, Infectious , Anti-HIV Agents/adverse effects , Anti-Retroviral Agents/therapeutic use , Child , Female , HIV , HIV Infections/prevention & control , Humans , Infectious Disease Transmission, Vertical/prevention & control , Pregnancy , Pregnancy Complications, Infectious/drug therapyABSTRACT
BACKGROUND: Infants born HIV-exposed yet remain uninfected (HEU) are at increased risk of poorer growth and health compared to infants born HIV-unexposed (HU). Whether maternal antiretroviral treatment (ART) in pregnancy ameliorates this risk of poorer growth is not well understood. Furthermore, whether risks are similar across high burden HIV settings has not been extensively explored. METHODS: We harmonized data from two prospective observational studies conducted in Cape Town, South Africa, and Lusaka, Zambia, to compare weight-for-age (WAZ), length-for-age (LAZ) and weight-for-length (WLZ) Z-scores between infants who were HEU and HU, converting infant anthropometric measures using World Health Organisation Growth Standards adjusted for age and sex. Linear mixed effects models were fit to identify risk factors for differences in anthropometrics at 6-10 weeks and 6 months by infant HIV exposures status and by timing of exposure to maternal ART, either from conception or later in gestation. RESULTS: Overall 773 mother-infant pairs were included across two countries: women living with HIV (WLHIV), 51% (n = 395) with 65% on ART at conception and 35% initiating treatment in pregnancy. In linear mixed effects models, WAZ and WLZ at 6-10 weeks were lower among infants who were HEU vs HU [ß = - 0.29 (95% CI: - 0.46, - 0.12) and [ß = - 0.42 (95% CI: - 0.68, - 0.16)] respectively after adjusting for maternal characteristics and infant feeding with a random intercept for country. At 6 months, LAZ was lower [ß = - 0.28 CI: - 0.50, - 0.06)] among infants who were HEU, adjusting for the same variables, with no differences in WAZ and WLZ. Within cohort evaluations identified different results with higher LAZ among infants who were HEU from Zambia at 6-10 weeks, [ß = + 0.34 CI: + 0.01, + 0.68)] and lower LAZ among infants who were HEU from South Africa [ß = - 0.30 CI: - 0.59, - 0.01)] at 6 months, without other anthropometric differences at either site. CONCLUSION: Infant growth trajectories differed by country, highlighting the importance of studying contextual influences on outcomes of infants who were HEU.