The Nutritional Burden of Cancer: Nutritional Status and Body Composition Differences Between Children with Acute Lymphoblastic Leukemia and their Siblings in Guatemala.

During treatment, children with acute lymphoblastic leukemia (ALL) gain fat mass and lose skeletal muscle mass. The great majority live in low- and middle-income countries with few studies of their body composition and none addressing the hypothesis that the disease itself contributes to nutritional morbidity. At diagnosis, children with ALL were compared to their siblings on socioeconomic status (SES). Nutritional status was assessed by mid-upper arm circumference (MUAC)-for-age Z scores and body composition by dual energy x-ray absorptiometry (DXA). Median SES scores for the patients (47.5) and their siblings (47.0) were very similar (P = 0.5). MUAC Z scores for patients aged >5 years were lower than for siblings (P < 0.001). On DXA siblings had a higher mean appendicular lean mass index Z score, a surrogate of skeletal muscle mass, than patients (P = 0.019). A logistic model to estimate the odds ratio (OR) of being severely/moderately under-nourished (classified by MUAC Z score) by SES revealed that, compared with siblings (n = 49), children with ALL (n = 60) had a higher probability of being under-nourished (OR 5.25, 95% CI 1.44-25.95, P = 0.02). The results support the hypothesis that children at diagnosis of ALL in Guatemala are more nutritionally depleted than their apparently healthy siblings.

Prepartum and postpartum mothers' and fathers' feelings of frustration in response to infant crying.

In this cross-sectional study performed in Canada, we evaluated the frustration levels of prepartum and postpartum mother and father couple-pairs. Our goal was to determine if there were differences in frustration levels between mothers and fathers while listening to prolonged infant crying, and further, how frustration levels might differ between prepartum and postpartum samples. Using two discrete groups, prepartum (Sample 1; N = 48) and postpartum (Sample 2; N = 44) mother and father couple-pairs completed 600 s of listening to audio-recorded infant cry sounds. Participants continuously reported their subjective frustration using a computerized Continuous Visual Analog Scale (CVAS). There was no significant difference in frustration responses between mothers and fathers across both prepartum and postpartum samples. Postpartum mothers and fathers experienced greater frustration than their prepartum counterparts, and frustration increased faster in postpartum couples compared to prepartum couples. Informing first-time parents of the universal experiences of frustration to prolonged crying bouts that are characteristic of their infant's early weeks of life may lead to greater understanding towards their infant, and perhaps decreased instances of harmful responses.

En este estudio transeccional, evaluamos los niveles de frustración de las parejas de mamás y papás antes y después del parto. Nuestro propósito fue determinar si hay diferencias entre mamás y papás en cuanto a los niveles de frustración mientras escuchan el prolongado llanto del infante, y cómo los niveles de frustración pudieran diferir entre grupos­muestra antes y después del parto. Usando dos grupos discretos, antes del parto (grupo­muestra 1; N = 48) y después del parto (grupo­muestra 2; N = 44), las parejas de mamás y papás completaron 600 segundos escuchando sonidos grabados en audio de llanto de infante. Los participantes continuamente reportaron su frustración subjetiva usando una escala análoga visual continua computarizada (CVAS). No hubo diferencia significativa en las respuestas de frustración entre mamás y papás a lo largo de los grupos­muestra tanto antes del parto como después del parto. Las mamás y papás en el grupo­muestra después del parto experimentaron mayor frustración que sus homólogos en el grupo­muestra antes del parto, y la frustración aumentó más rápido en las parejas del grupo­muestra después del parto tal como se les comparó con las parejas del grupo­muestra antes del parto. Estos resultados sugieren que las parejas primíparas posterior al parto están más propensas a experimentar considerables cantidades de frustración como respuesta al llanto del infante después que el bebé ha nacido. Informarles a los progenitores primerizos acerca de las experiencias generales de la frustración a los prolongados ataques de llanto que son característicos de las primeras semanas de vida de su infante pudiera llevar a una mayor comprensión hacia su infante y quizás disminuir las instancias de respuestas dañinas.

Dans cette étude transversale nous avons évalué les niveaux de frustration des couples­paires mère et père avant et après la naissance. Notre but était de déterminer s'il existe des différences entres les mères et les pères dans leurs niveaux de frustration en entendant des pleurs de bébé prolongés et de quelle manière les niveaux pourraient différer entre les échantillons avant la naissance et après la naissance. En utilisant deux groupes discrets, avant la naissance (Echantillon 1; N = 48) et après la naissance (Echantillon 2; N = 44) les couples­paires mère et père ont écouté 600 seconds d'enregistrements de pleurs de bébés. Les participants ont fait état de leur frustration subjective en utilisant une échelle analogique visuelle continue informatisée (CVAS). Il s'est avéré n'y avoir aucune différence importante dans les réactions de frustration entre les mères et les pères au travers des échantillons à la fois avant l'accouchement et après l'accouchement. Ces résultats suggèrent que les coupes postpartum primipares sont plus à même de faire l'expérience de niveaux élevés de frustration en réaction aux pleurs du bébé une fois le bébé arrivé. Informer les parents qui sont parents pour la première fois des expériences universelles de frustration aux crises de pleurs prolongées qui caractérisent les premières semaines de la vie des bébés peut mener à une plus grande compréhension de leur bébé et peut­être à une baisse des case d réactions néfastes.

Effectiveness of nurse-home visiting in improving child and maternal outcomes prenatally to age two years: a randomised controlled trial (British Columbia Healthy Connections Project).

BACKGROUND: We investigated the effectiveness of Nurse-Family Partnership (NFP), a prenatal-to-age-two-years home-visiting programme, in British Columbia (BC), Canada. METHODS: For this randomised controlled trial, we recruited participants from 26 public health settings who were: <25 years, nulliparous, <28 weeks gestation and experiencing socioeconomic disadvantage. We randomly allocated participants (one-to-one; computer-generated) to intervention (NFP plus existing services) or comparison (existing services) groups. Prespecified outcomes were prenatal substance exposure (reported previously); child injuries (primary), language, cognition and mental health (problem behaviour) by age two years; and subsequent pregnancies by 24 months postpartum. Research interviewers were masked. We used intention-to-treat analyses. (ClinicalTrials.gov, NCT01672060.) RESULTS: From 2013 to 2016 we enrolled 739 participants (368 NFP, 371 comparison) who had 737 children. Counts for child injury healthcare encounters [rate per 1,000 person-years or RPY] were similar for NFP (223 [RPY 316.17]) and comparison (223 [RPY 305.43]; rate difference 10.74, 95% CI -46.96, 68.44; rate ratio 1.03, 95% CI 0.78, 1.38). Maternal-reported language scores (mean, M [SD]) were statistically significantly higher for NFP (313.46 [195.96]) than comparison (282.77 [188.15]; mean difference [MD] 31.33, 95% CI 0.96, 61.71). Maternal-reported problem-behaviour scores (M [SD]) were statistically significantly lower for NFP (52.18 [9.19]) than comparison (54.42 [9.02]; MD -2.19, 95% CI -3.62, -0.75). Subsequent pregnancy counts were similar (NFP 115 [RPY 230.69] and comparison 117 [RPY 227.29]; rate difference 3.40, 95% CI -55.54, 62.34; hazard ratio 1.01, 95% CI 0.79, 1.29). We observed no unanticipated adverse events. CONCLUSIONS: NFP did not reduce child injuries or subsequent maternal pregnancies but did improve maternal-reported child language and mental health (problem behaviour) at age two years. Follow-up of long-term outcomes is warranted given that further benefits may emerge across childhood and adolescence.

Vertebral Body Reshaping after Fractures: An Important Index of Recovery in Glucocorticoid-Treated Children.

PURPOSE: In this 6-year study we identified factors associated with spontaneous vertebral body reshaping in glucocorticoid (GC)-treated children with leukemia, rheumatic disorders, and nephrotic syndrome. METHODS: Subjects were 79 children (mean age 7.4 years) who had vertebral fracture (VF) evaluation on lateral spine radiographs at least 1 year after VF detection. VF were graded using the modified Genant semiquantitative method and fracture burden for individuals was quantified using the spinal deformity index (SDI; sum of grades from T4 to L4). RESULTS: Sixty-five children (82.3%) underwent complete vertebral body reshaping (median time from VF detection to complete reshaping 1.3 years by Cox proportional hazard modeling). Of 237 VF, the majority (83.1%) ultimately reshaped, with 87.2% reshaping in the thoracic region vs 70.7% in the lumbar region (P = .004). Cox models showed that (1) every g/m2 increase in GC exposure in the first year after VF detection was associated with a 19% decline in the probability of reshaping; (2) each unit increase in the SDI at the time of VF detection was associated with a 19% decline in the probability of reshaping [hazard ratio (HR) = 0.81; 95% confidence interval (CI) = 0.71, 0.92; P = .001]; (3) each additional VF present at the time of VF detection reduced reshaping by 25% (HR = 0.75; 95% CI = 0.62, 0.90; P = .002); and (4) each higher grade of VF severity decreased reshaping by 65% (HR = 0.35; 95% CI = 0.21, 0.57; P < .001). CONCLUSION: After experiencing a VF, children with higher GC exposure, higher SDI, more severe fractures, or lumbar VF were at increased risk for persistent vertebral deformity.

Factors Associated With Adolescent and Young Adult Females Attending a Fertility Consultation Within 30 Days of a Cancer Diagnosis in Ontario, Canada.

Purpose: To examine the factors associated with females attending a fertility consultation within 30 days of cancer diagnosis. Methods: This is a retrospective cohort study, including females, 15 to 39 years of age, diagnosed with cancer in Ontario, Canada. Administrative data were used from the Institute of Clinical and Evaluative Sciences for the period 2006 to 2019. A backward selection multivariate logistic regression was performed, with a primary outcome of fertility consultation within 30 days of diagnosis. Results: A total of 20,556 females were included in the study, with 7% having attended a fertility visit within 30 days of diagnosis. Factors associated with being more likely to attend included: not currently having children (odds ratio [OR] = 4.3; confidence interval [95% CI 3.6-5.1]), later years of diagnosis (OR = 3.2; 95% CI [2.8-3.8]), having undergone chemotherapy (OR = 3.6; 95% CI [3.0-4.3]) or radiation therapy (OR = 1.9; 95% CI [1.6-2.2]), and less marginalization within dependency quintiles (OR 1.4; 95% CI [1.1-1.7]). Having a cancer with lower risk to fertility (OR = 0.3; 95% CI [0.2-0.3]), death within a year of diagnosis (OR = 0.4; 95% CI [0.3-0.6]), and residing in a northern region of Ontario (OR = 0.3; 95% CI [0.2-0.4]) were associated with being less likely to attend. For sociodemographic factors, lower levels of income (OR = 0.5; 95% CI [0.4-0.6]) and marginalization with residential instability (OR = 0.6; 95% CI [0.5-0.8]) were associated with being less likely to attend a fertility consultation. Conclusions: Rates for attendance of female fertility consultations after a cancer diagnosis remain low, with disparities by both clinical and demographic factors.

Translation and cultural adaptation of the Health Utilities Preschool to Brazilian Portuguese

ABSTRACT Introduction: Health research is particularly important in low- and middle-income countries (LMICs), where improvements must be achieved with limited resources, and where the great majority of the world's population, especially children, live. Improvements in public health detection in Brazil have resulted in cancer becoming the most prevalent cause of death by disease in the group aged 1 to 19 years, hence, delivering cost-effective care to the group is a priority. Preference-based measures of health status and health-related quality of life (HRQL) integrate morbidity and mortality and provide utility scores for the estimation of quality-adjusted life years to be used in cost-effectiveness analyses and economic evaluation. The generic preference-based instrument Health Utilities - Preschool (HuPS) measures the health status of young children and is applicable to the age group 2 to 5 years, who carry the highest incidence of cancer in childhood. Methods: The translation of the HuPS classification system followed recommended protocols from published guidelines. Forward and backward translations were performed by a team of six qualified professionals and linguistic validation was undertaken with a sample of parents of preschool children. Main results: Initial disagreements on individual words occurring in 0.5-1.5% were resolved by consensus. A final version of the instrument was validated by the sample of parents. Conclusions: The translation and cultural adaptation of the HuPS into Brazilian Portuguese were accomplished as the first step in the validation of the HuPS instrument in Brazil.

Early Life Nutrition Factors and Risk of Acute Leukemia in Children: Systematic Review and Meta-Analysis.

Acute leukemia commonly occurs in young children with peak incidence at the age of 2-5 years. However, the etiology is still unclear and many preventable risk factors still deserve to be reviewed. The focus of this systematic review and meta-analysis is to summarize the evidence concerning early life nourishment (breastfeeding, early life diet), neonatal vitamin K administration and the risk of acute leukemia. All epidemiological studies published up to June 2023 and assessing diet-related risk factors for childhood acute leukemia were identified in two electronic databases (PubMed and Web of Science), with no limits on publication year or language. A total of 38 studies (37 case-control studies and 1 study with pooled analysis) were included. The published risk estimates were combined into a meta-analysis using the Generic Inverse Variance method. The current evidence shows that breastfeeding (yes vs. no) has a protective effect against acute lymphoblastic leukemia (odds ratio = 0.85; 95% CI, 0.76-0.94). Evidence related to the role of other studied factors (foods and supplements) is inconclusive. Further research into the potential role of diet in early life and the risk of acute leukemia is needed to develop prevention strategies at population level. Review Registration: PROSPERO registration no. CRD42019128937.

Sarcopenia in Children With Wilms Tumor: A Marker of Undernutrition Which May Impact Adversely on Clinical Outcomes.

The therapeutic approach to Wilms tumor (WT) is multidisciplinary and leads to significant patient impairment, increasing the risk of nutritional compromise and malnutrition. Children with cancer are vulnerable to sarcopenia which has been recognized as a negative impact of anticancer therapy. Recent studies have highlighted the reduction in the total psoas muscle area (TPMA) to be associated with a poor prognosis in many pediatric diseases, including cancer. This study aims to evaluate changes in the TPMA compartment during the treatment of children with WT. An observational, longitudinal, and retrospective study was undertaken in a single institution evaluating children (1 to 14 y, n=38) with WT between 2014 and 2020. TPMA was assessed by the analysis of previously collected, electronically stored computed tomography images of the abdomen obtained at 3 time points: diagnosis, preoperatively, and 1 year after surgery. For all patients, TPMA/age were calculated with a specific online calculator. Our data show a high incidence of sarcopenia (55.3%) at diagnosis which increased after 4 to 6 weeks of neoadjuvant chemotherapy (73.7%) and remained high (78.9%) 1 year after the surgical procedure. Using TPMA/age Z-score curves we have found significant and rapid muscle loss in children with WT, with little or no recovery in the study period.

Development of EPAT: An assessment tool for pediatric hematology/oncology training programs.

PURPOSE: In the absence of a standardized tool to assess the quality of pediatric hematology/oncology training programs, the Education Program Assessment Tool (EPAT) was conceptualized as a user-friendly and adaptable tool to evaluate and identify areas of opportunity, pinpoint needed modifications, and monitor progress for training programs around the world. METHODS: The development of EPAT consisted of three main phases: operationalization, consensus, and piloting. After each phase, the tool was iteratively modified based on feedback to improve its relevance, usability, and clarity. RESULTS: The operationalization process led to the development of 10 domains with associated assessment questions. The two-step consensus phase included an internal consensus phase to validate the domains and a subsequent external consensus phase to refine the domains and overall function of the tool. EPAT domains for programmatic evaluation are hospital infrastructure, patient care, education infrastructure, program basics, clinical exposure, theory, research, evaluation, educational culture, and graduate impact. EPAT was piloted in five training programs in five countries, representing diverse medical training and patient care contexts for proper validation of the tool. Face validity was confirmed by a correlation between the perceived and calculated scores for each domain (r = 0.78, p < .0001). CONCLUSIONS: EPAT was developed following a systematic approach, ultimately leading to a relevant tool to evaluate the different core elements of pediatric hematology/oncology training programs across the world. With EPAT, programs will have a tool to quantitatively evaluate their training, allowing for benchmarking with centers at the local, regional, and international level.

Reductions in Bone Mineral Density Are Apparent Early in Children With Prevalent Osteonecrosis Lesions Following Leukemia Therapy.

Osteonecrosis (ON) is a serious complication of childhood acute lymphoblastic leukemia. We determined the prevalence of osteonecrotic lesions in our patient population by a one-time multisite magnetic resonance imaging (MRI) more than 1 year following leukemia therapy. MRI findings were evaluated in relationship to clinical factors (including longitudinal changes in bone mineral density [BMD]). Eighty-six children enrolled in the Steroid Associated Osteoporosis in the Pediatric Population (STOPP) study were evaluated for ON at 3.1 ± 1.3 years following therapy. Thirty children had a total of 150 confirmed ON lesions (35%). Lumbar spine (LS) BMD Z-scores (mean ± SD) were low at diagnosis and similar between patients with and without ON (-1.09 ± 1.53 versus -1.27 ± 1.25, p = 0.549). LS BMD Z-scores declined from baseline to 12 months in children with ON (-0.31 ± 1.02) but not in those without (0.13 ± 0.82, p = 0.035); the hip BMD Z-scores from baseline to 24 months declined in both groups, but to a greater extent in those with ON (-1.77 ± 1.22) compared to those without (-1.03 ± 1.07, p = 0.045). At the time of the MRI, mean total hip and total body (TB) BMD Z-scores were lower in children with ON (hip -0.98 ± 0.95 versus -0.28 ± 1.06, p = 0.010; TB -1.36 ± 1.10 versus -0.48 ± 1.50, p = 0.018). Pain occurred in 11/30 (37%) with ON versus 20/56 (36%) without, p = 0.841. In multivariable models, older age at diagnosis (odds ratio [OR] 1.57; 95% confidence interval [CI], 1.15-2.13; p = 0.004), and hip BMD Z-score at MRI (OR 2.23; 95% CI, 1.02-4.87; p = 0.046) were independently associated with ON. Overall, one-third of children demonstrated ON after leukemia therapy. Those with ON had greater reductions in spine and hip BMD Z-scores in the first 1 and 2 years of therapy, respectively. Older age and lower hip BMD Z-scores at MRI were significantly associated with prevalent, off-therapy ON. These data assist in identifying children at risk of ON. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

The international scandal of defective asparaginase: A blight on children with cancer.

Acute lymphoblastic leukemia is the commonest form of cancer in children and adolescents worldwide, and asparaginase is an essential component of successful chemotherapy for this disease associated with long-term survival rates often exceeding 90% in high-income countries. Demonstrably defective preparations of asparaginase, distributed from China and India, increase the burden of morbidity and mortality, reducing attainable survival rates. This adverse outcome is enabled by inadequate regulation and oversight, especially in resource-poor settings in low- and middle-income countries where the great majority of children and adolescents with cancer live. The pediatric oncology community must rise to the challenge.

Development and Validation of an Indicator for Oncofertility Care in Ontario, Canada, for Adolescents and Young Adults with Cancer.

Introduction: There is a lack of metrics to monitor and evaluate fertility care in adolescents and young adults with cancer. This study evaluated the indicator "proportion of cases attending a fertility consult visit ≤30 days from diagnosis of cancer" using the National Quality Forum (NQF) criteria. Methods: This was a retrospective cohort study using administrative data available through the Institute of Clinical Evaluative Sciences in Ontario, Canada. Cases were included if they were diagnosed with a cancer between January 2005 and December 2019, and aged 15-39 years. Fertility consultations were identified by Ontario Health Insurance Plan Claims Database (OHIP) diagnostic codes 628 and 606.Validity was assessed by examining expected differences in the proportion of fertility consults within clinical and demographic factors using chi-square tests. Reliability was assessed by comparing fertility consult visits identified using OHIP diagnostic codes with consults identified using visits to physicians in a registered specialty, using Pearson's correlation coefficient. Results: The population was composed of 39,977 cases, with 6524 (16.3%) having attended a fertility consult. For diagnostic years 2016-2019, differences in the proportion of cases receiving their first fertility consult within 30 days of diagnosis were observed for sex, age, cancer type, hospital type, Local Health Integration Unit, and region (p < 0.001). There was no correlation between the time from diagnosis to fertility consult and time from diagnosis to the first visit to a fertility-related specialty (r = 0.11; p = 0.002). Conclusion: The indicator examined in this article adhered to the criteria described by the NQF, providing a possible metric for reporting on oncofertility care.

Role of Maternal Diet in the Risk of Childhood Acute Leukemia: A Systematic Review and Meta-Analysis.

Many studies have investigated the etiology of acute leukemia, one of the most common types of cancer in children; however, there is a lack of clarity regarding preventable risk factors. This systematic review and meta-analysis aimed to summarize the current evidence regarding the role of maternal dietary factors in the development of childhood leukemia. All epidemiological studies published until July 2022 that evaluated maternal dietary risk factors for childhood acute leukemia were identified in two electronic databases (PubMed and Web of Science) without limits of publication year or language. A total of 38 studies (1 prospective cohort study, 34 case-control studies and 3 studies with pooled analysis) were included. The published risk estimates were combined into a meta-analysis, using the Generic Inverse Variance method. The maternal consumption of fruits (two or more daily servings vs. less) was inversely associated with acute lymphoblastic leukemia (odds ratio = 0.71; 95% CI, 0.59-0.86), whereas maternal coffee intake (higher than two cups per day vs. no consumption) was associated with an increased risk of acute lymphoblastic leukemia (odds ratio = 1.45; 95% CI, 1.12-1.89). Despite these findings, more high-quality research from cohort studies and the identification of causal factors are needed to develop evidence-based and cost-effective prevention strategies applicable at the population level. Review Registration: PROSPERO registration no. CRD42019128937.

Translation and cultural adaptation of the Health Utilities Preschool to Brazilian Portuguese.

INTRODUCTION: Health research is particularly important in low- and middle-income countries (LMICs), where improvements must be achieved with limited resources, and where the great majority of the world's population, especially children, live. Improvements in public health detection in Brazil have resulted in cancer becoming the most prevalent cause of death by disease in the group aged 1 to 19 years, hence, delivering cost-effective care to the group is a priority. Preference-based measures of health status and health-related quality of life (HRQL) integrate morbidity and mortality and provide utility scores for the estimation of quality-adjusted life years to be used in cost-effectiveness analyses and economic evaluation. The generic preference-based instrument Health Utilities - Preschool (HuPS) measures the health status of young children and is applicable to the age group 2 to 5 years, who carry the highest incidence of cancer in childhood. METHODS: The translation of the HuPS classification system followed recommended protocols from published guidelines. Forward and backward translations were performed by a team of six qualified professionals and linguistic validation was undertaken with a sample of parents of preschool children. MAIN RESULTS: Initial disagreements on individual words occurring in 0.5-1.5% were resolved by consensus. A final version of the instrument was validated by the sample of parents. CONCLUSIONS: The translation and cultural adaptation of the HuPS into Brazilian Portuguese were accomplished as the first step in the validation of the HuPS instrument in Brazil.

Safety and Efficacy of Alendronate to Treat Osteopenia in Children During Therapy for Acute Lymphoblastic Leukemia: A Retrospective Cohort Study of Sequential Outcomes.

BACKGROUND: Low bone mineral density is encountered in children with acute lymphoblastic leukemia (ALL) before, during, and after treatment. Prior experience with alendronate, an oral bisphosphonate, demonstrated high tolerability and evident clinical efficacy. However, concerns have been expressed about the long-term safety and utility of such agents in children. PROCEDURE: Sixty-nine children with ALL received alendronate for a mean of 87 weeks after dual-energy radiograph absorptiometry. Dual-energy radiograph absorptiometry was repeated following the completion of alendronate, and 5 to 9 years later in a subgroup of 32 children. Lumbar spine areal bone mineral density (LS aBMD) Z scores were obtained. RESULTS: The mean LS aBMD Z score rose from -1.78 to-0.47 ( P <0.0001). There was a modest median loss of LS aBMD subsequently in the 32 subjects on long-term follow-up. Almost 80% (N=172) of the children remain in continuous complete remission at a mean of 14.5 years from diagnosis. Of those who received alendronate, which was almost uniformly well tolerated, 7/69 (10.3%) relapsed compared with 19/89 (21.3%) who did not receive the drug. DISCUSSION: Alendronate appears to be well tolerated and moderately effective in osteopenic children with ALL. Whether it offers protection against relapse of leukemia needs further study.