Understanding the multidimensional neurodevelopmental outcomes in children after congenital Zika virus exposure.

Since 2016, international research groups have focused on assessing outcomes of children with in utero Zika virus (ZIKV) exposure. While the more severe outcomes of congenital Zika syndrome (CZS) occur in up to 10% of children with antenatal exposure, early findings among ZIKV-exposed children without CZS ages 0-5 years suggest that they may also have differences in multiple domains of neurodevelopment. Thus, longitudinal follow-up of all children with antenatal ZIKV exposure has been recommended. This review presents a summary of neurodevelopmental phenotypes of infants and children following antenatal ZIKV exposure. We present a multidimensional framework to understand child neurodevelopment from an interdisciplinary and whole-child perspective (International Classification of Functioning, Disability and Health model) and multi-domain ZIKV Outcome Toolboxes. The toolboxes are for clinicians, researchers, child educators, and others to implement longitudinal multi-domain neurodevelopmental assessments between ages 0-12 years. Recent innovations in telehealth and neuroimaging can help evaluate outcomes in ZIKV exposed children. The objective is to describe the multiple facets of neurodevelopmental focused care that can support the health, function, and well-being of children with antenatal ZIKV exposure. The research and clinical follow-up strategies are applicable to ZIKV and other congenital infectious or environmental exposures that can impact child neurodevelopment. IMPACT: International longitudinal cohort studies have revealed a range of differences in neurodevelopment among children with antenatal Zika virus (ZIKV) exposure. A multidimensional and whole-child framework is necessary to understand the neurodevelopment of children with antenatal ZIKV exposure in relation to family life, community participation, and environment. Multi-domain toolboxes that utilize parent questionnaires and child evaluations are presented. These toolboxes can be used internationally alongside telehealth, brain imaging, and other innovations to improve understanding of child outcomes.

Plasma Cell-free RNA Signatures of Inflammatory Syndromes in Children.

Inflammatory syndromes, including those caused by infection, are a major cause of hospital admissions among children and are often misdiagnosed because of a lack of advanced molecular diagnostic tools. In this study, we explored the utility of circulating cell-free RNA (cfRNA) in plasma as an analyte for the differential diagnosis and characterization of pediatric inflammatory syndromes. We profiled cfRNA in 370 plasma samples from pediatric patients with a range of inflammatory conditions, including Kawasaki disease (KD), Multisystem Inflammatory Syndrome in Children (MIS-C), viral infections and bacterial infections. We developed machine learning models based on these cfRNA profiles, which effectively differentiated KD from MIS-C - two conditions presenting with overlapping symptoms - with high performance (Test Area Under the Curve (AUC) = 0.97). We further extended this methodology into a multiclass machine learning framework that achieved 81% accuracy in distinguishing among KD, MIS-C, viral, and bacterial infections. We further demonstrated that cfRNA profiles can be used to quantify injury to specific tissues and organs, including the liver, heart, endothelium, nervous system, and the upper respiratory tract. Overall, this study identified cfRNA as a versatile analyte for the differential diagnosis and characterization of a wide range of pediatric inflammatory syndromes.

Neurodevelopmental Outcomes of Normocephalic Colombian Children with Antenatal Zika Virus Exposure at School Entry.

The long-term neurodevelopmental effects of antenatal Zika virus (ZIKV) exposure in children without congenital Zika syndrome (CZS) remain unclear, as few children have been examined to the age of school entry level. A total of 51 Colombian children with antenatal ZIKV exposure without CZS and 70 unexposed controls were evaluated at 4-5 years of age using the Behavior Rating Inventory of Executive Function (BRIEF), the Pediatric Evaluation of Disability Inventory (PEDI-CAT), the Bracken School Readiness Assessment (BSRA), and the Movement Assessment Battery for Children (MABC). The mean ages at evaluation were 5.3 and 5.2 years for cases and controls, respectively. Elevated BRIEF scores in Shift and Emotional Control may suggest lower emotional regulation in cases. A greater number of cases were reported by parents to have behavior and mood problems. BSRA and PEDI-CAT activity scores were unexpectedly higher in cases, most likely related to the COVID-19 pandemic and a delayed school entry among the controls. Although PEDI-CAT mobility scores were lower in cases, there were no differences in motor scores on the MABC. Of 40 cases with neonatal neuroimaging, neurodevelopment in 17 with mild non-specific findings was no different from 23 cases with normal neuroimaging. Normocephalic children with ZIKV exposure have positive developmental trajectories at 4-5 years of age but differ from controls in measures of emotional regulation and adaptive mobility, necessitating continued follow-up.

Neurodevelopmental assessments used to measure preschoolers' cognitive development in Latin America: a systematic review.

OBJECTIVE: The objective of this study was to systematically review the standardized neurodevelopmental assessments used to study preschool-aged children's cognitive development in Spanish-speaking Latin America. METHODS: The authors systematically searched PubMed, PsycINFO, and ERIC databases for peer-reviewed articles from Spanish-speaking Latin American countries. Articles were included if they measured cognitive development among children aged 2-6 years using at least one standardized assessment tool; 97 articles were included and reviewed in accordance with PRISMA guidelines to assess their use of these tools. RESULTS: Ninety-seven studies across 13 countries used a total of 41 assessments to measure cognitive development; most widely used were the Wechsler intelligence scales (n = 46/97), particularly the Wechsler Preschool and Primary Scale of Intelligence and Wechsler Intelligence Scale for Children (n = 23 and 29, respectively). Other common assessments included the McCarthy Scales of Children's Abilities (n = 9), Raven's Progressive Matrices (n = 9), Child Neuropsychological Assessment (n = 8), and Peabody Picture Vocabulary Test (n = 7). In regions where normative data for a given assessment were unpublished, authors commonly used norms from the United States, Mexico, or Spain or did not report standard scores in their analyses. CONCLUSIONS: The wide range of tools used in these studies presents a challenge for generalizing results when measuring the neurodevelopment of Latin American preschool-aged children. The low availability of normative data for specific regions reveals concerns if some tools are culturally and linguistically appropriate even when Spanish is a common language, particularly in low-resource settings. Future work to forge greater consistency in the use of validated measures, clarity in reporting research methods, and publication of regional normative data would benefit the field.

Nucleic acid biomarkers of immune response and cell and tissue damage in children with COVID-19 and MIS-C.

Differential host responses in coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in children (MIS-C) remain poorly characterized. Here, we use next-generation sequencing to longitudinally analyze blood samples from pediatric patients with COVID-19 or MIS-C across three hospitals. Profiling of plasma cell-free nucleic acids uncovers distinct signatures of cell injury and death between COVID-19 and MIS-C, with increased multiorgan involvement in MIS-C encompassing diverse cell types, including endothelial and neuronal cells, and an enrichment of pyroptosis-related genes. Whole-blood RNA profiling reveals upregulation of similar pro-inflammatory pathways in COVID-19 and MIS-C but also MIS-C-specific downregulation of T cell-associated pathways. Profiling of plasma cell-free RNA and whole-blood RNA in paired samples yields different but complementary signatures for each disease state. Our work provides a systems-level view of immune responses and tissue damage in COVID-19 and MIS-C and informs future development of new disease biomarkers.

Positive and negative effects of the COVID-19 pandemic on families of young children in rural Colombia and implications for child outcome research.

BACKGROUND: The COVID-19 pandemic has impacted the lives of children and families worldwide. The objective of this study is to examine exposures and impact of the COVID-19 pandemic on preschool-aged children and caregivers in the Atlántico region of Colombia. METHODS: The COVID-19 Exposure and Family Impact Scales (CEFIS) questionnaire was administered in Fall 2021 to 63 caregivers of children in Sabanalarga, Colombia enrolled in a neurodevelopment study as healthy controls. The CEFIS assesses pandemic-related exposures/events and impact; higher scores indicate greater exposure and negative impact. Descriptive and correlation analyses among exposure and impact scores were conducted. RESULTS: Caregivers reported a mean (standard deviation[SD]) of 11.1 (3.2) among 25 COVID-19-related exposures/events; most common types included stay-at-home orders, school closures, disruptions to living conditions and income loss. Total number of events was correlated with higher caregiver (P < .001) and child distress (P = .002). However, the mean (SD) impact score of 2.0 (0.6) suggests a trend toward more positive impact than negative. Caregivers reported improvements to sleep, exercise and family interactions. Some caregivers (n = 21) qualitatively reported negative effects including unemployment, fear/anxiety and inability to visit family, and positive effects such as unification, family closeness and spending more time with children. CONCLUSIONS: This study highlights the importance of comprehensively exploring positive and negative impacts of COVID-19 and families' subsequent resilience and transformation. Using tools like the CEFIS, those seeking to mitigate negative impacts can contextualize data to better understand study outcomes and tailor services, resources and policy to families' unique needs. CEFIS data likely depend on timing, economic/public health resources and cultural values; future work should prioritize understanding the generalizability of CEFIS findings across samples.

Measuring post-traumatic stress after childbirth: a review and critical appraisal of instruments.

BACKGROUND: Addressing psychological trauma after childbirth requires accurate measurement of its prevalence, risk factors, and outcomes using validated instruments that distinguish perceptions of traumatic birth, subclinical post-traumatic stress (PTS) symptoms, and symptoms meeting a diagnostic threshold. OBJECTIVE: The purpose of this study was to review literature on psychological trauma following childbirth and appraise instruments that measure postpartum PTS. METHODS: In January 2020, the authors searched for and evaluated peer-reviewed studies that quantitatively measured PTS following hospital-based live births in the United States, United Kingdom, Canada, Australia, Norway, Sweden, and Switzerland; 37 articles were selected and evaluated. RESULTS: Levels of post-traumatic stress disorder were most commonly measured, followed by PTS symptoms. Diagnostic instruments suggested lower PTS prevalence estimates than those screening for or assessing PTS symptoms. Community samples yielded lower prevalence estimates than samples recruited from the internet or settings specifically addressing mental health. Measurement sooner after birth yielded higher estimates. CONCLUSION: Study design, sample characteristics, instruments, and timing of measurements likely impact postpartum PTS prevalence estimates. Variation in these characteristics make it difficult to draw conclusions on the prevalence of postpartum PTS. Researchers should consider the appraisal of measurement tools presented here and use rigorous study methodology when studying traumatic birth experiences and evaluating interventions.

Neurodevelopment in infants with antenatal or early neonatal exposure to SARS-CoV-2.

BACKGROUND: Antenatal and neonatal viral exposure may put the developing brain at risk for abnormal neurodevelopment. A clinical program at Children's National Hospital provides detailed follow-up of infants with in utero or neonatal SARS-CoV-2 exposure. AIMS: To determine impact of early SARS-CoV-2 exposure on neurodevelopment. STUDY DESIGN: We performed a prospective observational study of infant evaluations between 3/2020 and 11/2021. Demographics, pregnancy and birth details, SARS-CoV-2 data, specialty consultations, and NICU records were extracted from infants' medical records. Infants had neurologic exams and developmental screening with Ages and Stages Questionnaire (ASQ). Correlations between SARS-CoV-2 exposure type and neurodevelopmental outcomes were analyzed. SUBJECTS: Thirty-four infants evaluated in the SARS-CoV-2 follow-up program. OUTCOME MEASURES: Abnormal neurologic exams or ASQ scores near or below suggested cut-offs. RESULTS: Infants received up to three evaluations. Most (28/34; 82 %) were exposed in utero - 16 to symptomatic mothers (IU-S) and 12 to asymptomatic mothers (IU-A). Six were exposed only as a neonate. IU-S had abnormal neurologic exams at mean (SD) age 112 (24) days and ASQ scores near or below cut-offs for all domains more frequently than IU-A or neonatally exposed infants. IU-S were more likely to score below any ASQ cutoff compared to IU-A (P = .04); differences were significant for Fine Motor (P = .01) and Personal-Social (P = .02) domains. CONCLUSIONS: Early SARS-CoV-2 exposure may impact neurodevelopment, especially among infants exposed in utero to symptomatic gestational parents. Vaccination and other precautions to reduce early-in-life infection may protect against neurodevelopmental delays. Children with early SARS-CoV-2 exposure should have additional longitudinal screening for neurodevelopmental delays.

The use of community-based interventions in reducing morbidity from the psychological impact of conflict-related trauma among refugee populations: a systematic review of the literature.

With large numbers of refugee arrivals and numerous barriers to accessing services it is especially important that resources are efficiently and effectively directed to address the health needs of refugees. Ten databases were utilised to conduct the review, returning 156 titles which were assessed for validity based on specified criteria. The 14 critically appraised articles included in this review consist of experimental research and discussions on best practice. Articles consistently demonstrated the benefit of community-based mental health service in improving mental health outcomes. Themes of cultural awareness, language, setting, and post-migration stressors emerged across the articles. In addition, the studies also point to the gaps in research of a longitudinal nature and ones that deal with scattered populations post migration. Community-based interventions proved valuable for improving the mental health of refugees. However, additional interventions and evaluations are required to draw consistent and conclusive judgments on best practice in dealing with refugee mental health issues.