Effects of economic interventions on pediatric and adolescent HIV care outcomes: a systematic review.

Economic insecurity and poverty present major barriers to HIV care for young people. We conducted a systematic review of the current evidence for the effect of economic interventions on HIV care outcomes among pediatric populations encompassing young children, adolescents, and youth (ages 0-24). We conducted a search of PubMed MEDLINE, Cochrane, Embase, Scopus, CINAHL, and Global Health databases on October 12, 2022 using a search strategy curated by a medical librarian. Studies included economic interventions targeting participants <25 years in age which measured clinical HIV outcomes. Study characteristics, care outcomes, and quality were independently assessed, and findings were synthesized. Title/abstract screening was performed for 1934 unique records. Thirteen studies met inclusion criteria, reporting on nine distinct interventions. Economic interventions included incentives (n = 5), savings and lending programs (n = 3), and government cash transfers (n = 1). Study designs included three randomized controlled trials, an observational cohort study, a matched retrospective cohort study, and pilot intervention studies. While evidence is very limited, some promising findings were observed supporting retention and viral suppression, particularly for those with suboptimal care engagement or with detectable viral load. There is a need to further study and optimize economic interventions for children and adolescents living with HIV.

Pepea Pamoja:† Applying the Ecological Validity Framework to co-develop a wellbeing and behavioural training program for caregivers of young children with autism in low-resource settings of Kenya and the United States.

BACKGROUND: Autism is a complex neurodevelopmental disability with global prevalence of one in 100 individuals. Poor access to interventions in both under-resourced regions of high-income countries and low- and middle-income countries has deleterious effects on the health and wellbeing of individuals with autism and their families. Our objective was to utilize a reciprocal innovation framework and participatory methods to adapt and co-develop a culturally grounded group-based wellbeing and naturalistic developmental behavioural intervention (NDBI) training program for caregivers of young children with autism to be implemented in Kenya and rural Indiana. METHODS: This study was conducted within the Academic Model Providing Access to Healthcare (AMPATH) program. An evidence-informed Naturalistic Developmental Behavioral Intervention (NDBI) previously utilized in Indiana was adapted and iteratively refined using the Ecological Validity Framework (EVF) by a team of US and Kenyan disability experts. Key adaptations to the program were made across the EVF domains of language, persons, metaphors/content, concepts, goals, methods, and context. RESULTS: Substantial cultural adaptations were made to the NDBI following the EVF model, including the addition of traditional Kenyan cultural practices, use of narrative principles, and focus on daily routines over play. Pepea, the adapted program, involves 10 group sessions covering content in basic education on autism, positive caregiver coping strategies, and behavioural skills training to promote child communication and reduce challenging behaviour. Key adaptations for Pepea were integrated back into a US NDBI caregiver training program. CONCLUSIONS: This study fills a critical gap by detailing the adaptation process of a caregiver wellbeing and naturalistic developmental behavioural training program for caregivers of children with autism in low-resource settings. Our next steps are to report on mixed-methods outcomes from pilot implementation. Our long-term goal is to apply these insights to advance sustainable and scalable autism intervention services across the globe.

Ethical Aspects of Involving Adolescents in HIV Research: A Systematic Review of the Empiric Literature.

OBJECTIVE: To evaluate the ethics of involving adolescents in HIV research, we conducted a systematic review of the empiric literature. METHODS: Electronic databases Ovid Medline, Embase, and CINAHL were systematically searched using controlled vocabulary terms related to ethics, HIV, specified age groups, and empiric research studies. We reviewed titles and abstracts, including studies that collected qualitative or quantitative data, evaluated ethical issues in HIV research, and included adolescents. Studies were appraised for quality, data were extracted, and studies were analyzed using narrative synthesis. RESULTS: We included 41 studies: 24 qualitative, 11 quantitative, 6 mixed methods; 22 from high-income countries (HIC), 18 from low- or middle-income countries (LMIC), and 1 from both HIC and LMIC. Adolescent, parent, and community perspectives assert the benefits of involving minors in HIV research. Participants in LMIC expressed mixed views regarding parental consent requirements and confidentiality, given adolescents' both increasing autonomy and continued need for adult support. In studies in HIC, sexual or gender minority youth would not participate in research if parental consent were required or if there were confidentiality concerns. There was variation in the comprehension of research concepts, but adolescents generally demonstrated good comprehension of informed consent. Informed consent processes can be improved to increase comprehension and study accessibility. Vulnerable participants face complex social barriers that should be considered in study design. CONCLUSIONS: Data support the inclusion of adolescents in HIV research. Empiric research can inform consent processes and procedural safeguards to ensure appropriate access.

Association of severe malaria with cognitive and behavioural outcomes in low- and middle-income countries: a meta-analysis and systematic review.

BACKGROUND: Malaria affects 24 million children globally, resulting in nearly 500,000 child deaths annually in low- and middle-income countries (LMICs). Recent studies have provided evidence that severe malaria infection results in sustained impairment in cognition and behaviour among young children; however, a formal meta-analysis has not been published. The objective was to assess the association between severe malaria infection with cognitive and behavioural outcomes among children living in LMICs. METHODS: Six online bibliographic databases were searched and reviewed in November 2022. Studies included involved children < 18 years of age living in LMICs with active or past severe malaria infection and measured cognitive and/or behaviour outcomes. The quality of studies was assessed. Definitions of severe malaria included cerebral malaria, severe malarial anaemia, and author-defined severe malaria. Results from all studies were qualitatively summarized. For studies with relevant data on attention, learning, memory, language, internalizing behaviour and externalizing behaviour, results were pooled and a meta-analysis was performed. A random-effects model was used across included cohorts, yielding a standardized mean difference between the severe malaria group and control group. RESULTS: Out of 3,803 initial records meeting the search criteria, 24 studies were included in the review, with data from 14 studies eligible for meta-analysis inclusion. Studies across sub-Saharan Africa assessed 11 cohorts of children from pre-school to school age. Of all the studies, composite measures of cognition were the most affected areas of development. Overall, attention, memory, and behavioural problems were domains most commonly found to have lower scores in children with severe malaria. Meta-analysis revealed that children with severe malaria had worse scores compared to children without malaria in attention (standardized mean difference (SMD) -0.68, 95% CI -1.26 to -0.10), memory (SMD -0.52, 95% CI -0.99 to -0.06), and externalizing behavioural problems (SMD 0.45, 95% CI 0.13-0.78). CONCLUSION: Severe malaria is associated with worse neuropsychological outcomes for children living in LMICs, specifically in attention, memory, and externalizing behaviours. More research is needed to identify the long-term implications of these findings. Further interventions are needed to prevent cognitive and behavioural problems after severe malaria infection. TRIAL REGISTRATION: This systematic review was registered under PROSPERO: CRD42020154777.

A psychometric evaluation of the NIH Toolbox fluid cognition tests adapted for Swahili and Dholuo languages in Kenyan children and adolescents.

OBJECTIVE: Our objective was to evaluate the psychometric properties of the culturally adapted NIH Toolbox African Languages® when used in Swahili and Dholuo-speaking children in western Kenya. METHOD: Swahili-speaking participants were recruited from Eldoret and Dholuo-speaking participants from Ajigo; all were <14 years of age and enrolled in primary school. Participants completed a demographics questionnaire and five fluid cognition tests of the NIH Toolbox® African Languages program, including Flanker, Dimensional Change Card Sort (DCCS), Picture Sequence Memory, Pattern Comparison, and List Sorting tests. Statistical analyses examined aspects of reliability, including internal consistency (in both languages) and test-retest reliability (in Dholuo only). RESULTS: Participants included 479 children (n = 239, Swahili-speaking; n = 240, Dholuo-speaking). Generally, the tests had acceptable psychometric properties for research use within Swahili- and Dholuo-speaking populations (mean age = 10.5; SD = 2.3). Issues related to shape identification and accuracy over speed limited the utility of DCCS for many participants, with approximately 25% of children unable to match based on shape. These cultural differences affected outcomes of reliability testing among the Dholuo-speaking cohort, where accuracy improved across all five tests, including speed. CONCLUSIONS: There is preliminary evidence that the NIH Toolbox ® African Languages potentially offers a valid assessment of development and performance using tests of fluid cognition in Swahili and Dholuo among research settings. With piloting underway across other diverse settings, future research should gather additional evidence on the clinical utility and acceptability of these tests, specifically through the establishment of norming data among Kenyan regions and evaluating these psychometric properties.

"If it benefits someone, it will be good:" perspectives on research participation from pregnant women living with HIV.

Pregnant women living with HIV (PWLHIV) are becoming increasingly involved in HIV research; however, the ethical concerns regarding their decision-making related to research participation are understudied. This qualitative study aimed to understand the perspectives and lived research experiences of PWLHIV, intending to identify important considerations to inform best practices. This study used semi-structured interviews (SSIs) of PWLHIV who participated in research studies in Eldoret, Kenya. All interviews were audio-recorded, transcribed, and translated. Qualitative analyses were performed, with line-by-line coding, constant comparison, axial coding, and triangulation to identify central concepts. Twelve PWLHIV participated. Overall, participants had positive experiences with HIV research. Most participants had difficulty distinguishing the differences between the research process and enhanced clinical care. They reported a willingness to participate in future HIV research studies and indicated altruism as the primary motivator. Participants identified their preferences and experiences with recruitment, consenting, reimbursement, and enrolment of infants in HIV research. The largest barrier for participating in HIV research was identified as a concern that participation would lead to HIV disclosure. By understanding the lived experiences of PWLHIV who participate in HIV research, future researchers can design studies and consenting processes to optimize ethical research practices.

'I bring her up with love:' Perspectives of caregivers of children with neurodevelopmental delays in western Kenya.

OBJECTIVE: This study aims to understand the challenges and perspectives of caregivers with neurodevelopmental delays (NDD) in rural Kenya. METHODS: Semi-structured interviews and the Affiliate Stigma Scale were administered to the primary caregivers of children with NDDs recruited from the communities near Eldoret, Kenya. Constant comparison and triangulation methods were used to inductively develop relevant themes and concepts. RESULTS: Sixteen caregivers participated. Challenges, which included hardships related to safety and supervision, challenging emotions and financial difficulties, were compounded by a lack of social support and community stigma towards these children. However, caregivers still felt deep love for their children, desired acceptance from the community and found sources of strength from faith and religious institutions. CONCLUSION: The study uncovered crucial insights into the perspectives of caregivers within this population and revealed a paucity of disability awareness and understanding within the community, possibly informing future programmes and intervention policies.

Evaluation of an ultrasensitive HRP2-based rapid diagnostic test for detection of asymptomatic Plasmodium falciparum parasitaemia among children in western Kenya.

BACKGROUND: Accurate detection of asymptomatic malaria parasitaemia in children living in high transmission areas is important for malaria control and reduction programmes that employ screen-and-treat surveillance strategies. Relative to microscopy and conventional rapid diagnostic tests (RDTs), ultrasensitive RDTs (us-RDTs) have demonstrated reduced limits of detection with increased sensitivity to detect parasitaemia in symptomatic individuals. In this study, the performance of the NxTek™ Eliminate Malaria P.f test was compared with traditional microscopy and quantitative polymerase chain reaction (qPCR) testing methods of detection for P. falciparum parasitaemia among asymptomatic children aged 7-14 years living in an area of high malaria transmission intensity in western Kenya. METHODS: In October 2020, 240 healthy children without any reported malaria symptoms were screened for the presence of P. falciparum parasitaemia; 120 children were randomly selected to participate in a follow-up visit at 6-10 weeks. Malaria parasitaemia was assessed by blood-smear microscopy, us-RDT, and qPCR of a conserved var gene sequence from genomic DNA extracted from dried blood spots. Sensitivity, specificity, and predictive values were calculated for field diagnostic methods using qPCR as the gold standard. Comparison of detectable parasite density distributions and area under the curve were also calculated to determine the effectiveness of the us-RDT in detecting asymptomatic infections with low parasite densities. RESULTS: The us-RDT detected significantly more asymptomatic P. falciparum infections than microscopy (42.5% vs. 32.2%, P = 0.002). The positive predictive value was higher for microscopy (92.2%) than for us-RDT (82.4%). However, false negative rates were high for microscopy and us-RDT, with negative predictive values of 53.7% and 54.6%, respectively. While us-RDT detected significantly more infections than microscopy overall, the density distribution of detectable infections did not differ (P = 0.21), and qPCR detected significantly more low-density infections than both field methods (P < 0.001, for both comparisons). CONCLUSIONS: Us-RDT is more sensitive than microscopy for detecting asymptomatic malaria parasitaemia in children. Though the detectable parasite density distributions by us-RDT in our specific study did not significantly differ from microscopy, the additional sensitivity of the us-RDT resulted in more identified asymptomatic infections in this important group of the population and makes the use of the us-RDT advisable compared to other currently available malaria field detection methods.

Translation and Cultural Adaptation of NIH Toolbox Cognitive Tests into Swahili and Dholuo Languages for Use in Children in Western Kenya.

OBJECTIVES: Performing high-quality and reliable cognitive testing requires significant resources and training. As a result, large-scale studies involving cognitive testing are difficult to perform in low- and middle-income settings, limiting access to critical knowledge to improve academic achievement and economic production in these populations. The NIH Toolbox® is a collection of cognitive, motor, sensory, and emotional tests that can be administered and scored using an iPad® tablet, reducing the need for training and quality monitoring; and thus, it is a potential solution to this problem. METHODS: We describe our process for translation and cultural adaptation of the existing NIH Toolbox tests of fluid cognition into the Swahili and Dholuo languages for use in children aged 3-14 years in western Kenya. Through serial forward and back translations, cognitive interviews, group consensus, outside feedback, and support from the NIH Toolbox team, we produced translated tests that have both face validity and linguistic validation. RESULTS: During our cognitive interviews, we found that the five chosen tests (one each of attention, cognitive flexibility, working memory, episodic memory, and processing speed) were generally well understood by children aged 7-14 years in our chosen populations. The cognitive interviews informed alterations in translation as well as slight changes in some images to culturally adapt the tests. CONCLUSIONS: This study describes the process by which we translated five fluid cognition tests from the NIH Toolbox into the Swahili and Dholuo languages. The finished testing application will be available for future studies, including a pilot study for assessment of psychometric properties.

Retention in care and viral suppression in the PMTCT continuum at a large referral facility in western Kenya.

Medical records of pregnant and postpartum women living with HIV and their infants attending a large referral facility in Kenya from 2015 to 2019 were analyzed to identify characteristics associated with retention in care and viral suppression. Women were stratified based on the timing of HIV care enrollment: known HIV-positive (KHP; enrolled pre-pregnancy) and newly HIV-positive (NHP; enrolled during pregnancy). Associations with retention at 18 months postpartum and viral suppression (< 1000 copies/mL) were determined. Among 856 women (20% NHP), retention was 83% for KHPs and 53% for NHPs. Viral suppression was 88% for KHPs and 93% for NHPs, but 19% of women were missing viral load results. In a competing risk model, viral suppression increased by 18% for each additional year of age but was not associated with other factors. Overall, 1.9% of 698 infants with ≥ 1 HIV test result were HIV-positive. Tailored interventions are needed to promote retention and viral load testing, particularly for NHPs, in the PMTCT continuum.

Preventive Health Service Coverage Among Infants and Children at Six Maternal-Child Health Clinics in Western Kenya: A Cross-Sectional Assessment.

OBJECTIVES: Despite the substantial reduction of child mortality in recent decades, Kenya still strives to provide universal healthcare access and to meet other international benchmarks for child health. This study aimed to describe child health service coverage among children visiting six maternal and child health (MCH) clinics in western Kenya. METHODS: In a cross-sectional study of Kenyan children who are under the age of 5 years presenting to MCH clinics, child health records were reviewed to determine coverage of immunizations, growth monitoring, vitamin A supplementation, and deworming. Among 78 children and their caregivers, nearly 70% of children were fully vaccinated for their age. RESULTS: We found a significant disparity in full vaccination coverage by gender (p = 0.017), as males had 3.5 × higher odds of being fully vaccinated compared to females. Further, full vaccination coverage also varied across MCH clinic sites ranging from 43.8 to 92.9%. CONCLUSIONS FOR PRACTICE: Health service coverage for Kenyan children in this study is consistent with national and sub-national findings; however, our study found a significant gender equity gap in coverage at these six clinics that warrants further investigation to ensure that all children receive critical preventative services.

Ethical considerations for research involving pregnant women living with HIV and their young children: a systematic review of the empiric literature and discussion.

BACKGROUND: The proper and ethical inclusion of PWLHIV and their young children in research is paramount to ensure valid evidence is generated to optimize treatment and care. Little empirical data exists to inform ethical considerations deemed most critical to these populations. Our study aimed to systematically review the empiric literature regarding ethical considerations for research participation of PWLHIV and their young children. METHODS: We conducted this systematic review in partnership with a medical librarian. A search strategy was designed and performed within the following electronic databases: Ovid MEDLINE, Embase and CINAHL. We screened titles and abstracts using the following inclusion criteria: (1) a study population of PWLHIV or children under 5 years of age; and (2) collection of qualitative or quantitative data regarding ethics of research participation. Excluded were reviews, commentaries, policy statements, clinical care-related ethics concerns, abstracts, case studies, or studies unrelated to HIV research. Studies were appraised for quality, data were extracted, and studies were qualitatively analyzed using a principle-based ethical framework within the Belmont Report. RESULTS: Of the 7470 titles identified, 538 full-text articles were reviewed for eligibility and only three articles met full criteria for inclusion within this review. While we allowed for inclusion of studies involving young children born to mothers with HIV, only articles focused on PWLHIV were identified. Within the results of these studies, four themes emerged: (1) adequacy of informed consent; (2) consideration of paternal involvement; (3) balancing risks; and (4) access to research and treatment. A strength of this review is that it included perspectives of international research investigators, community leaders, and male partners. However, only two studies collected empiric data from PWLHIV regarding their experiences participating in research CONCLUSION: Researchers and funding agencies should be aware of these considerations and appreciate the value of and critical need for formative research to ensure clinical trials involving PWLHIV promote ethical, well-informed research participation and, ultimately, improve care outcomes. More research is needed to create a comprehensive ethical framework for researchers when conducting studies with PWLHIV.

Interventions for developmental delays in children born to HIV-infected mothers: a systematic review.

Children born to HIV-infected mothers have worse developmental outcomes compared to HIV-unexposed children. However, little is known about interventions to improve developmental outcomes in this population. This study systematically reviews the literature on interventions to improve development in children born to HIV-infected mothers. We systematically searched the following electronic bibliographic databases: Ovid MEDLINE, Embase, PsycINFO, Education Resources Information Center, and the Cochrane Database of Systematic Reviews. Studies were selected on the basis of defined inclusion criteria and excluded if antiretroviral medication was the only intervention. Titles, abstracts, and full texts were assessed by 2 independent reviewers. Data were collected on characteristics of the study design, intervention, and developmental outcomes measured. Risk of bias and strength of evidence were assessed on all included articles. Our search resulted in 11,218 records. After our initial review, 43 records were appraised in their entirety and 9 studies met all inclusion criteria. Six were performed in sub-Saharan Africa, while the remaining 3 were performed in the United States. Eight were randomized-controlled trials and one was a retrospective chart review. Four studies focused on caregiver-training, 2 studied massage therapy, and the remaining studies focused on maternal vitamin supplementation, video-based cognitive therapy, or center-based interventions. Massage therapy had the most consistent improvements in the domains measured, while caregiver training and cognitive therapy interventions had limited benefits. The center-based intervention showed no benefit. Only 3 studies had a low risk of bias, and 4 studies had good strength of evidence. Most studies found some benefit. However, these findings are limited by the quality of the study designs, small sample size, and heterogeneity of the interventions and assessments used to measure outcomes. There is a critical need for the creation of evidence-based interventions to promote development in this vulnerable population.

Tablet-based disclosure counselling for HIV-infected children, adolescents, and their caregivers: a pilot study.

BACKGROUND: Overwhelmed, under-trained medical staff working in resource-limited settings need efficient resources for HIV disclosure counselling. The objective of this study was to describe providers' experiences using tablet computers for disclosure-related counselling with HIV-infected children and their caregivers in western Kenya, with additional perspectives from adolescents. METHODS: A qualitative study design was implemented at three HIV clinics in western Kenya (Bumala, Busia and Port Victoria) within the Academic Model Providing Access to Healthcare (AMPATH) partnership. Twenty-one healthcare providers involved with paediatric disclosure were recruited and enrolled in the study. Initial interviews focused on understanding current disclosure practices and barriers. Tablets containing disclosure-related resources were distributed. Resources included short narrative videos created in this context to highlight issues relevant to child HIV disclosure. RESULTS: Providers reported tablets improved disclosure, child participation, and medication adherence. All reported that reviewing materials increased their knowledge and comfort with disclosure. The most frequently used materials were the narrative videos and an animated video explaining the importance of medication adherence. Time was a major barrier for using the tablet. Clinician self-education persisted at one-year follow-up. Adolescents expressed enjoyment from viewing the tablet resources and had a better understanding of the importance of medication adherence. CONCLUSIONS: Tablet computers containing resources for disclosure are an acceptable and potentially effective resource to help providers support families with disclosure. Further work is needed to train the clinical providers in using the resources in a developmentally appropriate manner, and to develop new resources on adolescent-specific and HIV-related topics.

Effectiveness of cross-cultural education for medical residents caring for burmese refugees.

BACKGROUND: Limited resources are available to educate health professionals on cultural considerations and specific healthcare needs of Burmese refugees. The objective of this study was to determine the effectiveness of a module focused on cross-cultural considerations when caring for Burmese refugees. METHODS: A brief educational module using anonymously tracked pre- and post-intervention, self-administered surveys was developed and studied. The surveys measured pediatric and family medicine residents' knowledge, attitudes, and comfort in caring for Burmese refugees. Paired t-tests for continuous variables and Fisher's exact tests for categorical variables were used to test pre- and post-intervention differences. We included open-ended questions for residents to describe their experiences with the Burmese population. RESULTS: The survey was available to 173 residents. Forty-four pre- and post-intervention surveys were completed (response rate of 25%). Resident comfort in caring for Burmese increased significantly after the module (P = 0.04). Resident knowledge of population-specific cultural information increased regarding ethnic groups (P = 0.004), appropriate laboratory use (P = 0.04), and history gathering (P = 0.001). Areas of improved resident attitudes included comprehension of information from families (P = 0.03) and length of time required with interpreter (P = 0.01). Thematic evaluation of qualitative data highlighted four themes: access to interpreter and resources, verbal communication, nonverbal communication, and relationship building with cultural considerations. DISCUSSION: A brief intervention for residents has the potential to improve knowledge, attitudes, and comfort in caring for Burmese patients. Interventions focused on cultural considerations in medical care may improve cultural competency when caring for vulnerable patient populations.

EXPLORING HEALTHCARE PERSPECTIVES OF BURMESE CHIN REFUGEES.

The objective of this study was to understand the Burmese Chin refugees' experiences with and perspectives on the United States healthcare system. Using a mixed-methods study design, a survey was distributed and focus groups were conducted. Thirty-seven surveys were completed. Five major themes emerged from the focus group discussions: time, language barriers, relationships with healthcare providers, traditional medicine, and adolescents'roles in their community. Refugee healthcare perspectives give health providers insights on how to work towards providing culturally appropriate care.

Care of the Child Perinatally Exposed to Human Immunodeficiency Virus.

Substantial progress in preventing vertical human immunodeficiency virus (HIV) transmission has led to a dramatic decline in new pediatric HIV infections. Alongside this success, a growing population of children who are HIV-exposed but uninfected face unique health challenges due to a variety of risk factors. Recommendations for healthcare providers caring for this population include optimizing and integrating general and HIV-related care for both mother and child through comprehensive care packages. Further research and multidisciplinary approaches are needed to address the long-term health implications for this vulnerable population.

Understanding the need for pediatric neurodevelopmental services among households in western Kenya: A population-based study.

Introduction: Existing estimates of rates of childhood disability in Kenya are based on data with important limitations. Individual-level data on childhood disability at the local level is also lacking, leaving critical knowledge gaps for clinical and programmatic development. Objectives: We aimed to estimate the rates of children at-risk for disability, examine the external factors related to risk of childhood disability, and gain a better understanding of the challenges experienced by children at-risk for disabilities and their families within western Kenya. Methods: We conducted a small, cross-sectional randomized community survey to assess the rates of childhood disability across six administrative locations in Uasin Gishu County, Kenya, and to understand the experiences of these children and their caretakers. Results: Rate of childhood disability in Uasin Gishu county was estimated to be 5%, with the most common disabilities being mood disorders. Caretakers reported several barriers to accessing treatment for their children at-risk of having disabilities, including financial concerns and lack of transportation. Conclusions: Our findings suggest a need for improved access to care in this region, including addressing significant barriers to accessing care such as stigma and socioeconomic challenges. These community-level data will inform the development of future infrastructure and programming for this population.

Impact of Maternal Viral Suppression on Growth Patterns for HIV-Exposed Uninfected Infants in Kenya.

Background and Objective: Children born to mothers living with human immunodeficiency virus (HIV) are at risk for poor health outcomes but data characterizing these associations are limited. Our objective was to determine the impact of maternal viral suppression on growth patterns and malnutrition for infants who are HIV-exposed but uninfected (HEU). Methods: We conducted a retrospective cohort analysis of clinical data for infants who were HEU and their mothers (September 2015 - March 2019) in Kenya. Infants were stratified based on maternal viral suppression status (≥ or <1000 copies/mL); t-tests were used to compare groups. Growth indicators were evaluated with Chi-square, Fisher's exact, and area under the curve. Moderate-to-severe underweight status, stunting, and wasting were defined by weight-for-age (WFA), height-for-age (HFA), and weight-for-height (WFH), z-scores ≤2, and were used to define malnutrition. Multivariate logistic regression analyses were performed to evaluate potential associations with malnutrition indicators between WFH and HFA. Results: Among 674 infants who were HEU, 48.7% were male and 85.0% had mothers who were virally suppressed. The median age at first and last clinic visits was 1.5 and 16.4 months, respectively. WFA and HFA z-scores over time differed by sex, and WFA and HFA differed based on maternal viral suppression (P < 0.05). Male infants had higher adjusted odds for stunted status, and as children aged, they had slightly increased odds of becoming underweight or stunted. Maternal viral suppression and timing of maternal antiretroviral therapy initiation in relation to the prevention of vertical transmission (PVT) enrollment did not significantly affect malnutrition indicators. Conclusion and Global Health Implications: Maternal viral suppression status was not associated with increased odds of more severe malnutrition indicators in children who were HEU. However, overall growth patterns over time, measured by z-scores of growth indicators, did differ based on maternal viral suppression status, and to a lesser degree, by gender.

Pharmacovigilance in Pregnancy Studies, Exposures and Outcomes Ascertainment, and Findings from Low- and Middle-Income Countries: A Scoping Review.

INTRODUCTION: Pharmacovigilance (PV), or the ongoing safety monitoring after a medication has been licensed, plays a crucial role in pregnancy, as clinical trials often exclude pregnant people. It is important to understand how pregnancy PV projects operate in low- and middle-income countries (LMICs), where there is a disproportionate lack of PV data yet a high burden of adverse pregnancy outcomes. We conducted a scoping review to assess how exposures and outcomes were measured in recently published pregnancy PV projects in LMICs. METHODS: We utilized a search string, secondary review, and team knowledge to review publications focusing on therapeutic or vaccine exposures among pregnant people in LMICs. We screened abstracts for relevance before conducting a full text review, and documented measurements of exposures and outcomes (categorized as maternal, birth, or neonatal/infant) among other factors, including study topic, setting, and design, comparator groups, and funding sources. RESULTS: We identified 31 PV publications spanning at least 24 LMICs, all focusing on therapeutics or vaccines for infectious diseases, including HIV (n = 17), tuberculosis (TB; n = 9), malaria (n = 7), pertussis, tetanus, and diphtheria (n = 1), and influenza (n = 3). As for outcomes, n = 15, n = 31, and n = 20 of the publications covered maternal, birth, and neonatal/infant outcomes, respectively. Among HIV-specific publications, the primary exposure-outcome relationship of focus was exposure to maternal antiretroviral therapy and adverse outcomes. For TB-specific publications, the main exposures of interest were second-line drug-resistant TB and isoniazid-based prevention therapeutics for pregnant people living with HIV. For malaria-specific publications, the primary exposure-outcome relationship of interest was antimalarial medication exposure during pregnancy and adverse outcomes. Among vaccine-focused publications, the exposure was assessed during a specific time during pregnancy, with an overall interest in vaccine safety and/or efficacy. The study settings were frequently from Africa, designs varied from cohort or cross-sectional studies to clinical trials, and funding sources were largely from high-income countries. CONCLUSION: The published pregnancy PV projects were largely centered in Africa and concerned with infectious diseases. This may reflect the disease burden in LMICs but also funding priorities from high-income countries. As the prevalence of non-communicable diseases increases in LMICs, PV projects will have to broaden their scope. Birth and neonatal/infant outcomes were most reported, with fewer reporting on maternal outcomes and none on longer-term child outcomes; additionally, heterogeneity existed in definitions and ascertainment of specific measures. Notably, almost all projects covered a single therapeutic exposure, missing an opportunity to leverage their projects to cover additional exposures, add scientific rigor, create uniformity across health services, and bolster existing health systems. For many publications, the timing of exposure, specifically by trimester, was crucial to maternal and neonatal safety. While currently published pregnancy PV literature offer insights into the PV landscape in LMICs, further work is needed to standardize definitions and measurements, integrate PV projects across health services, and establish longer-term monitoring.