Associations Between Early-Life Adversity, Ambient Air Pollution, and Telomere Length in Children.

OBJECTIVE: Examine the independent associations and interaction between early-life adversity and residential ambient air pollution exposure on relative buccal telomere length (rBTL). METHODS: Experiences of abuse, neglect, household challenges, and related life events were identified in a cross-sectional sample of children aged 1 to 11 years ( n = 197) using the 17-item Pediatric ACEs and Related Life Event Screener (PEARLS) tool. The PEARLS tool was analyzed both as a total score and across established domains (Maltreatment, Household Challenges, and Social Context). Ground-level fine particulate matter (PM 2.5 ) concentrations were matched to residential locations for the 1 and 12 months before biospecimen collection. We used multivariable linear regression models to examine for independent associations between continuous PM 2.5 exposure and PEARLS score/domains with rBTL. In addition, effect modification by PEARLS scores and domains on associations between PM 2.5 exposure and rBTL was examined. RESULTS: Study participants were 47% girls, with mean (standard deviation) age of 5.9 (3.4) years, median reported PEARLS score of 2 (interquartile range [IQR], 4), median 12-month prior PM 2.5 concentrations of 11.8 µg/m 3 (IQR, 2.7 µg/m 3 ), median 1-month prior PM 2.5 concentrations of 10.9 µg/m 3 (IQR, 5.8 µg/m 3 ), and rBTL of 0.1 (IQR, 0.03). Mean 12-month prior PM 2.5 exposure was inversely associated with rBTL ( ß = -0.02, 95% confidence interval = -0.04 to -0.01). Although reported PEARLS scores and domains were not independently associated with rBTL, we observed a greater decrement in rBTL with increment of average annual PM 2.5 as reported Social Context domain items increased ( p -interaction < .05). CONCLUSIONS: Our results suggest that adverse Social Context factors may accelerate the association between chronic PM 2.5 exposure on telomere shortening during childhood.

Increasing the uptake of Intermittent Preventive Treatment of malaria in pregnancy using Sulfadoxine-Pyrimethamine (IPTp-SP) through seasonal malaria chemoprevention channel delivery: protocol of a multicenter cluster randomized implementation trial in Mali and Burkina Faso.

BACKGROUND: The uptake of Intermittent Preventive Treatment of malaria in pregnancy using Sulfadoxine-Pyrimethamine (IPTp-SP) remains unacceptably low, with more than two-thirds of pregnant women in sub-Saharan Africa still not accessing the three or more doses recommended by the World Health Organisation (WHO). In contrast, the coverage of Seasonal Malaria Chemoprevention (SMC), a more recent strategy recommended by the WHO for malaria prevention in children under five years living in Sahelian countries with seasonal transmission, including Mali and Burkina-Faso, is high (up to 90%). We hypothesized that IPTp-SP delivery to pregnant women through SMC alongside antenatal care (ANC) will increase IPTp-SP coverage, boost ANC attendance, and increase public health impact. This protocol describes the approach to assess acceptability, feasibility, effectiveness, and cost-effectiveness of the integrated strategy. METHODS AND ANALYSIS: This is a multicentre, cluster-randomized, implementation trial of IPTp-SP delivery through ANC + SMC vs ANC alone in 40 health facilities and their catchment populations (20 clusters per arm). The intervention will consist of monthly administration of IPTp-SP through four monthly rounds of SMC during the malaria transmission season (July to October), for two consecutive years. Effectiveness of the strategy to increase coverage of three or more doses of IPTp-SP (IPTp3 +) will be assessed using household surveys and ANC exit interviews. Statistical analysis of IPT3 + and four or more ANC uptake will use a generalized linear mixed model. Feasibility and acceptability will be assessed through in-depth interviews and focus group discussions with health workers, pregnant women, and women with a child < 12 months. DISCUSSION: This multicentre cluster randomized implementation trial powered to detect a 45% and 22% increase in IPTp-SP3 + uptake in Mali and Burkina-Faso, respectively, will generate evidence on the feasibility, acceptability, effectiveness, and cost-effectiveness of IPTp-SP delivered through the ANC + SMC channel. The intervention is designed to facilitate scalability and translation into policy by leveraging existing resources, while strengthening local capacities in research, health, and community institutions. Findings will inform the local national malaria control policies. TRIAL REGISTRATION: Retrospectively registered on August 11th, 2022; registration # PACTR202208844472053. Protocol v4.0 dated September 04, 2023. Trail sponsor: University of Sciences Techniques and Technologies of Bamako (USTTB), Mali.

Biological Burden of Adverse Childhood Experiences in Children.

OBJECTIVE: This study aimed to examine relationships between adverse childhood experiences (ACEs) and related life events and allostatic load (AL)-"wear and tear" from chronic stress-in a pediatric population. METHODS: Children were screened with the PEdiatric ACEs and Related Life Event Screener (PEARLS) tool, a 17-item questionnaire capturing experiences of abuse, neglect, household challenges, and related life events. Biological data were available for 207 participants, and AL was operationalized using clinical or empirical cutoff points across 4 physiological systems (i.e., cardiac, metabolic, inflammatory, neurologic). Covariate-adjusted multivariable regression models were used to examine associations between AL with adversity and health. RESULTS: Children (mean age = 6.5 years, range = 1-11 years) had an average AL score of 1.9 (standard deviation = 1.7), and a U-shaped relationship was observed with child's age. Continuous PEARLS and original ACE scores were not associated with AL. However, children with a reported PEARLS score of 1 to 2 or original ACEs score of 1 to 3 had 1.5 (incidence rate ratio [IRR] = 1.50, 95% confidence interval [CI] = 1.09-2.08) and 1.4 (IRR = 1.41, 95% CI = 1.08-1.84) times greater AL, respectively, compared with participants with none reported. In secondary analyses, caregiver mental illness was associated with higher child AL (adjusted IRR = 1.27, 95% CI = 1.01-1.58). AL was also associated with poorer perceived child general health (adjusted ß = -0.87, 95% CI = -1.58 to -0.15) and greater odds of child obesity (adjusted odds ratio = 1.51, 95% CI = 1.23-1.89). CONCLUSIONS: Measuring AL in a pediatric population requires careful consideration of age. Higher AL was associated with a greater number of reported adversities and worse child health.

Pediatric ACEs and related life event screener (PEARLS) latent domains and child health in a safety-net primary care practice.

BACKGROUND: Research examining the connections between individual adverse childhood experiences (ACEs) and how groupings of interrelated adversities are linked with subsequent health is scarce, limiting our understanding of risk during a period of rapid expansion of ACE screening in clinical practice. The study objective was to conduct a psychometric analysis to derive latent domains of ACEs and related life events and assess the association between each domain and health outcome. METHODS: Participants (3 months-11 years) were recruited from the University of California San Francisco Benioff's Children Hospital Oakland Primary Care Clinic. Children were screened with the Pediatric ACEs and Related Life Events Screener (PEARLS) (n = 340), which assessed 17 total ACEs and related life events, including forms of abuse, household challenges, and social risks. Domains were constructed using confirmatory factor analysis and associations between the three identified domains and 14 health outcomes were assessed using multivariable linear and logistic regression models. RESULTS: Three PEARLS domains were identified: Maltreatment (ω = 0.73, ɑ=0.87), Household Challenges (ω = 0.70, ɑ=0.82), and Social Context (ω = 0.55, ɑ=0.70). Measurement invariance was supported across both gender and screening format. All domains were associated with poorer general and behavioral health and stomachaches. Maltreatment and Social Context were additionally associated with eczema while only Social Context was associated with increased odds of reporting headaches and somatic symptoms. CONCLUSION: In an underserved, urban west-coast pediatric population, the PEARLS found three adversity domains of Maltreatment, Household Challenges, and Social Context that all had an independent statistically significant association with poorer child health. The results provide a timely and more nuanced representation of risk that can inform clinical practice and policy using more targeted resources and interventions.

A Caregiver-Child Intervention for Mitigating Toxic Stress ("The Resiliency Clinic"): A Pilot Study.

INTRODUCTION: Primary care-based interventions that promote nurturing caregiving relationships and early relational health may help mitigate toxic stress and promote resilience in children. This pilot study aims to: (1) describe a novel group-based, psychoeducational primary care intervention for children experiencing adverse childhood experiences (ACEs) ("The Resiliency Clinic"), (2) assess program feasibility and acceptability, and (3) explore effects on child/caregiver behavioral health. METHODS: Intervention design centered on promoting supportive caregiving, caregiver/child self-regulation and co-regulation and teaching evidence-based stress management tools. Program feasibility and acceptability were assessed through attendance data and caregiver focus groups. Behavioral health measures were obtained at baseline and 8-month follow-up. RESULTS: Of 101 eligible families, 38 (37.6%) enrolled and attended a median of 3.00 (mean = 2.95, sd = 1.75) out of 6 sessions. Caregivers reported high satisfaction and benefits including stress management tools and connection with staff and other parents. There were modest, statistically non-significant improvements in caregiver stress (d = 0.23) and child executive functioning (d = 0.27). DISCUSSION: In conclusion, a group intervention teaching supportive caregiving and stress mitigation is feasible and acceptable for many families in an urban federally qualified health center (FQHC) with a signal for modest improvements in behavioral health. Future program iterations will seek to address participation barriers and expand the intervention's capacity to promote early relational health.

Systematic review of pediatric health outcomes associated with childhood adversity.

BACKGROUND: Early detection of and intervention in childhood adversity has powerful potential to improve the health and well-being of children. A systematic review was conducted to better understand the pediatric health outcomes associated with childhood adversity. METHODS: PubMed, PsycArticles, and CINAHL were searched for relevant articles. Longitudinal studies examining various adverse childhood experiences and biological health outcomes occurring prior to age 20 were selected. Mental and behavioral health outcomes were excluded, as were physical health outcomes that were a direct result of adversity (i.e. abusive head trauma). Data were extracted and risk of bias was assessed by 2 independent reviewers. RESULTS: After identifying 15940 records, 35 studies were included in this review. Selected studies indicated that exposure to childhood adversity was associated with delays in cognitive development, asthma, infection, somatic complaints, and sleep disruption. Studies on household dysfunction reported an effect on weight during early childhood, and studies on maltreatment reported an effect on weight during adolescence. Maternal mental health issues were associated with elevated cortisol levels, and maltreatment was associated with blunted cortisol levels in childhood. Furthermore, exposure to childhood adversity was associated with alterations of immune and inflammatory response and stress-related accelerated telomere erosion. CONCLUSION: Childhood adversity affects brain development and multiple body systems, and the physiologic manifestations can be detectable in childhood. A history of childhood adversity should be considered in the differential diagnosis of developmental delay, asthma, recurrent infections requiring hospitalization, somatic complaints, and sleep disruption. The variability in children's response to adversity suggests complex underlying mechanisms and poses a challenge in the development of uniform diagnostic guidelines. More large longitudinal studies are needed to better understand how adversity, its timing and severity, and the presence of individual genetic, epigenetic, and protective factors affects children's health and development.

Adverse Childhood Experiences and Related Events are Associated with Asthma Symptoms in Children.

OBJECTIVE: To examine the association between adverse childhood experiences (ACEs) and related events and asthma symptom burden in children. METHODS: This is a cross-sectional study of baseline data from 147 participants with asthma from a cohort of children enrolled in the Pediatric ACEs Screening and Resiliency Study. Participants completed the PEdiatric ACEs and Related Life Events Screener (PEARLS) tool, a 17-item questionnaire, capturing 3 domains of childhood adversity-child maltreatment, household challenges, and social context. Asthma symptom burden was assessed using the International Study of Asthma and Allergies in Childhood core questionnaire, which asks participants to identify the presence and frequency of severe wheezing that limits speech, wheezing with exercise, nocturnal wheezing, and nocturnal cough in the last 12 months. Using multivariable logistical regression models, we examined the relationship between reported PEARLS and asthma symptoms. RESULTS: Of children with asthma, 86% reported at least 1 adversity, with 48% reporting 4 or more. The odds of severe wheeze limiting speech increased by 19% with each additional reported adversity captured by the PEARLS tool (95% confidence intervals (CI) 1.01-1.41). Increasing PEARLS scores were also associated with 16% increased odds of reporting wheeze with exercise (95% CI 1.03-1.31). Wheezing with exercise was associated with the household challenges domain (odds ratio (OR) 1.34; 95% CI 1.05-1.72), while severe wheeze limiting speech was associated with the social context domain (OR 1.75; 95%CI 1.02-3.02). CONCLUSIONS: Childhood adversities are associated with increased asthma symptom burden, suggesting the tool may be helpful in identifying children at risk for poorly controlled asthma.

Targeting imported malaria through social networks: a potential strategy for malaria elimination in Swaziland.

BACKGROUND: Swaziland has made great progress towards its goal of malaria elimination by 2015. However, malaria importation from neighbouring high-endemic Mozambique through Swaziland's eastern border remains a major factor that could prevent elimination from being achieved. In order to reach elimination, Swaziland must rapidly identify and treat imported malaria cases before onward transmission occurs. METHODS: A nationwide formative assessment was conducted over eight weeks to determine if the imported cases of malaria identified by the Swaziland National Malaria Control Programme could be linked to broader social networks and to explore methods to access these networks. RESULTS: Using a structured format, interviews were carried out with malaria surveillance agents (6), health providers (10), previously identified imported malaria cases (19) and people belonging to the networks identified through these interviews (25). Most imported malaria cases were Mozambicans (63%, 12/19) making a living in Swaziland and sustaining their families in Mozambique. The majority of imported cases (73%, 14/19) were labourers and self-employed contractors who travelled frequently to Mozambique to visit their families and conduct business. Social networks of imported cases with similar travel patterns were identified through these interviews. Nearly all imported cases (89%, 17/19) were willing to share contact information to enable network members to be interviewed. Interviews of network members and key informants revealed common congregation points, such as the urban market places in Manzini and Malkerns, as well as certain bus stations, where people with similar travel patterns and malaria risk behaviours could be located and tested for malaria. CONCLUSION: This study demonstrated that imported cases of malaria belonged to networks of people with similar travel patterns. This study may provide novel methods for screening high-risk groups of travellers using both snowball sampling and time-location sampling of networks to identify and treat additional malaria cases. Implementation of a proactive screening programme of importation networks may help Swaziland halt transmission and achieve malaria elimination by 2015.

Screening for adverse childhood experiences in pediatrics: A randomized trial of aggregate-level versus item-level response screening formats.

BACKGROUND: While there is growing support for screening for Adverse Childhood Experiences (ACEs), rigorous evidence on the efficacy and preference of screening methods is needed. OBJECTIVE: To examine caregiver: (1) rates of disclosure of their child's exposure to ACEs using item-level response (each item can be endorsed) versus aggregate-level response (only total score reported) screening format, (2) associations between family demographic factors and disclosure by screening format, and (3) emotional reaction and experience of screening formats in a diverse, low-income pediatric population. METHODS: Caregiver participants (n = 367) were randomized to complete the Pediatric ACEs and Related Life Events Screener (PEARLS) tool, in an aggregate-level response vs item-level response format from 2016-2019. Select caregivers (n = 182) participated in debriefing interviews. T-test and chi-square analyses in 2019 compared PEARLS disclosure rates and reactions between the screening modalities. Regression models explored interactions with child characteristics. Thematic analysis of interview notes captured caregiver screening experience. RESULTS: PEARLS disclosure rates were significantly higher in the aggregate-level response compared to the item-level response screening arm (p <0.05). This difference was accentuated for children identified as black and/or male (p <0.05). Caregiver reactions to PEARLS screening were rarely negative in either screening format. Qualitative data demonstrated strong caregiver preference for the item-level response format; additional themes include provider relationship, fear with disclosure, and screening outcome expectations. CONCLUSION: While caregivers reported a preference for the item-level response format, the aggregate-level response screening format elicited higher disclosures rates particularly for children who are black or ma. TRIAL REGISTRATION: Clinical trial registry: NCT04182906.

Adverse Childhood Experiences, Outcomes, and Interventions.

Adverse childhood experiences (ACEs) are stressful or traumatic events that children experience before age 18 years. Studies have linked exposure to ACEs and negative health, and developmental and behavioral outcomes. Screening in pediatric medical settings provides a clear opportunity for early detection, intervention, and treatment. Providing anticipatory guidance on healthy relationships, sleep, exercise, nutrition, mindfulness, and nature is essential. Pediatric medical providers must screen and intervene. Primary care is the ideal setting for ACE screening because interacting with children and their families at regular intervals can allow patients and providers to develop a trusting relationship.

Pediatrics adverse childhood experiences and related life events screener (PEARLS) and health in a safety-net practice.

BACKGROUND: Adverse Childhood Experiences (ACEs) are associated with behavioral, mental, and clinical outcomes in children. Tools that are easy to incorporate into pediatric practice, effectively screen for adversities, and identify children at high risk for poor outcomes are lacking. OBJECTIVE: To examine the relationship between caregiver-reported child ACEs and related life events with health outcomes. PARTICIPANTS AND SETTING: Participants (0-11 years) were recruited from the University of California San Francisco Benioff's Children Hospital Oakland Primary Care Clinic. There were 367 participants randomized. METHODS: Participants were randomized 1:1:1 to item-level (item response), aggregate-level (total number of exposures), or no screening for ACEs (control arm) with the PEdiatric ACEs and Related Life Event Screener (PEARLS). We assessed 10 ACE categories capturing abuse, neglect, and household challenges, as well as 7 additional categories. Multivariable regression models were conducted. RESULTS: Participants reported a median of 2 (IQR 1-5) adversities with 76 % (n = 279) reporting at least one adversity; participants in the aggregate-level screening arm, on average, disclosed 1 additional adversity compared to item-level screening (p = 0.01). Higher PEARLS scores were associated with poorer perceived child general health (adjusted B = -0.94, 95 %CI: -1.26, -0.62) and Global Executive Functioning (adjusted B = 1.99, 95 %CI: 1.51, 2.46), and greater odds of stomachaches (aOR 1.14; 95 %CI: 1.04-1.25) and asthma (aOR 1.08; 95 %CI 1.00, 1.17). Associations did not differ by screening arm. CONCLUSION: In a high-risk pediatric population, ACEs and other childhood adversities remain an independent predictor of poor health. Increased efforts to screen and address early-life adversity are necessary.

Review of Tools for Measuring Exposure to Adversity in Children and Adolescents.

Exposure to childhood adversity can result in negative behavioral and physical health outcomes due to potential long-term embedding into regulatory biological processes. Screening for exposure to adversity is a critical first step in identifying children at risk for developing a toxic stress response. We searched PubMed, PsycArticles, and CINAHL for studies published between January 1, 2012, and December 31, 2016, as well as other sources, to identify potential tools for measuring cumulative adversity in children and adolescents. We identified 32 tools and examined them for adversity categories, target population, administration time, administration qualifications and method, and reliability and validity. We also created a list of recommended tools that would be feasible for use by pediatric practitioners in most types of practice. This review provides a starting point for mobilizing screening in pediatric settings, highlighting the challenges with existing tools, and potential issues in the development and evaluation of future tools.

Ameliorating the biological impacts of childhood adversity: A review of intervention programs.

Childhood adversity negatively impacts the biological development of children and has been linked to poor health outcomes across the life course. The purpose of this literature review is to explore and evaluate the effectiveness of interventions that have addressed an array of biological markers and physical health outcomes in children and adolescents affected by adversity. PubMed, CINAHL, PsychInfo, Sociological Abstracts databases and additional sources (Cochrane, WHO, NIH trial registries) were searched for English language studies published between January 2007 and September 2017. Articles with a childhood adversity exposure, biological health outcome, and evaluation of intervention using a randomized controlled trial study design were selected. The resulting 40 intervention studies addressed cortisol outcomes (n = 20) and a range of neurological, epigenetic, immune, and other outcomes (n = 22). Across institutional, foster care, and community settings, intervention programs demonstrated success overall for improving or normalizing morning and diurnal cortisol levels, and ameliorating the impacts of adversity on brain development, epigenetic regulation, and additional outcomes in children. Factors such as earlier timing of intervention, high quality and nurturant parenting traits, and greater intervention engagement played a role in intervention success. This study underlines progress and promise in addressing the health impacts of adversity in children. Ongoing research efforts should collect baseline data, improve retention, replicate studies in additional samples and settings, and evaluate additional variables, resilience factors, mediators, and long-term implications of results. Clinicians should integrate lessons from the intervention sciences for preventing and treating the health effects of adversity in children and adolescents.

Development and implementation of a pediatric adverse childhood experiences (ACEs) and other determinants of health questionnaire in the pediatric medical home: A pilot study.

Adverse Childhood Experiences (ACEs) are associated with poor health outcomes, underlining the significance of early identification and intervention. Currently, there is no validated tool to screen for ACEs exposure in childhood. To fill this gap, we designed and implemented a pediatric ACEs questionnaire in an urban pediatric Primary Care Clinic. Questionnaire items were selected and modified based on literature review of existing childhood adversity tools. Children twelve years and under were screened via caregiver report, using the developed instrument. Cognitive interviews were conducted with caregivers, health providers, and clinic staff to assess item interpretation, clarity, and English/Spanish language equivalency. Using a rapid cycle assessment, information gained from the interviews were used to iteratively change the instrument. Additional questions assessed acceptability of screening within primary care and preferences around administration. Twenty-eight (28) caregivers were administered the questionnaire. Cognitive interviews conducted among caregivers and among 16 health providers and clinic staff resulted in the changes in wording and addition of examples in the items to increase face validity. In the final instrument, no new items were added; however, two items were merged and one item was split into three separate items. While there was a high level of acceptability of the overall questionnaire, some caregivers reported discomfort with the sexual abuse, separation from caregiver, and community violence items. Preference for methods of administration were split between tablet and paper formats. The final Pediatric ACE and other Determinants of Health Questionnaire is a 17-item instrument with high face validity and acceptability for use within primary care settings. Further evaluation on the reliability and construct validity of the instrument is being conducted prior to wide implementation in pediatric practice.

Effective program management: a cornerstone of malaria elimination.

Effective program management is essential for successful elimination of malaria. In this perspective article, evidence surrounding malaria program management is reviewed by management science and malaria experts through a literature search of published and unpublished gray documents and key informant interviews. Program management in a malaria elimination setting differs from that in a malaria control setting in a number of ways, although knowledge and understanding of these distinctions are lacking. Several core features of successful health program management are critical to achieve elimination, including effective leadership and supervision at all levels, sustained political and financial commitment, reliable supply and control of physical resources, effective management of data and information, appropriate incentives, and consistent accountability. Adding to the complexity, the requirements of an elimination program may conflict with those of a control regimen. Thus, an additional challenge is successfully managing program transitions along the continuum from control to elimination to prevention of reintroduction. This article identifies potential solutions to these challenges by exploring managerial approaches that are flexible, relevant, and sustainable in various cultural and health system contexts.

Review of mass drug administration for malaria and its operational challenges.

Mass drug administration (MDA) was a component of many malaria programs during the eradication era, but later was seldomly deployed due to concerns regarding efficacy and feasibility and fear of accelerating drug resistance. Recently, however, there has been renewed interest in the role of MDA as an elimination tool. Following a 2013 Cochrane Review that focused on the quantitative effects of malaria MDA, we have conducted a systematic, qualitative review of published, unpublished, and gray literature documenting past MDA experiences. We have also consulted with field experts, using their historical experience to provide an informed, contextual perspective on the role of MDA in malaria elimination. Substantial knowledge gaps remain and more research is necessary, particularly on optimal target population size, methods to improve coverage, and primaquine safety. Despite these gaps, MDA has been used successfully to control and eliminate Plasmodium falciparum and P. vivax malaria in the past, and should be considered as part of a comprehensive malaria elimination strategy in specific settings.