Socioeconomic status and global variations in the incidence of neuroblastoma: call for support of population‐based cancer registries in low‐middle–income countries

Global variations in the incidence of pediatric cancers have been described; however, the causes of such differences are not known. We investigated the relationship between the incidence of embryonal tumors and human development index on a global scale. Increasing incidence of neuroblastoma correlates significantly with an increasing index of human development, with greater incidence among countries with high socioeconomic development, in apparent contrast to the incidence of retinoblastoma. While more data are needed to corroborate this observation, our findings suggest new avenues for etiological research and serve as a call for support of population‐based cancer registries in low–middle‐income countries.     

Congenital diaphragmatic hernia: The role of multi-institutional collaboration and patient registries in supporting best practice

Among congenital malformations, congenital diaphragmatic hernia (CDH) is distinguished by its relatively low occurrence rate, need for resource intensive, integrated multidisciplinary care, and widespread variation in practice and outcome. Although randomized controlled trials (RCTs) are considered the gold standard for generating evidence, they are poorly suited to the study of a condition like CDH due to challenges in illness severity adjustment, unpredictability in clinical course and the impact limitations of studying a single intervention at a time. An alternative to RCTs for comparative effectiveness research for CDH is the patient registry, which aggregates multi-institutional condition-specific patient level data into a large CDH-specific database for the dual purposes of collaborative research and quality improvement across participating sites. This article discusses patient registries from the perspective of structure, data collection and management, and privacy protection that guide the use of registry data to support collaborative, multidisciplinary research. Two CDH-specific registries are described as illustrative examples of the “value proposition” of registries in improving the evidence basis for best practices for CDH.     

Turner's syndrome in Italy: familial characteristics, neonatal data, standards for birth weight and for height and weight from infancy to adulthood

In 1990, the Italian Study Group for Turner's Syndrome (ISGTS) undertook a nationwide survey, involving the retrospective collection of cross-sectional data and longitudinal growth profiles of 772 girls with Turner's syndrome born between 1950 and 1990. The study was carried out in 29 pediatric endocrinological centers. In this first report, the familial characteristics and neonatal data of Turner girls are described, compared to those of the general population, and related to postnatal somatic development. Furthermore, charts for birth weight and growth standards for height and weight from infancy to adulthood are presented (these are the first charts based on a large sample from the Mediterranean area). The main findings were: (1) incidence of Turner births increases with parental age or parity; (2) most of the neonates are small for dates; (3) girls with normal birth weight tend to be both taller and heavier than girls with low birth weight during the whole growth period; and (4) a 10-cm difference in midparental height leads to a 6.5-cm difference in adult stature.     

Tumor biology,biomarkers, and liquid biopsy in pediatric renal tumors

The expansion of knowledge regarding driver mutations for Wilms tumor (WT) and malignant rhabdoid tumor of the kidney (MRT) and various translocations for other pediatric renal tumors opens up new possibilities for diagnosis and treatment. In addition, there are growing data surrounding prognostic factors that can be used to stratify WT treatment to improve outcomes. Here, we review the molecular landscape of WT and other pediatric renal tumors as well as WT prognostic factors. We also review incorporation of circulating tumor DNA/liquid biopsies to leverage this molecular landscape, with potential use in the future for distinguishing renal tumors at the time of diagnosis and elucidating intratumor heterogeneity, which is not well evaluated with standard biopsies. Incorporation of liquid biopsies will require longitudinal collection of multiple biospecimens. Further preclinical research, identification and validation of biomarkers, molecular studies, and data sharing among investigators are crucial to inform therapeutic strategies that improve patient outcomes.     

Data standards in pediatric oncology: Past,present, and future

In this commentary, we highlight the central role that data standards play in facilitating data-driven efforts to advance research in pediatric oncology. We discuss the current state of data standards for pediatric oncology and propose five steps to achieve an improved future state with benefits for clinicians, researchers, and patients.     

Newly developed WHO growth standards: Implications for demographic surveys and child health programs

Objective To compare estimates of undernutrition based on the World Health Organization (WHO) Child Growth Standards (‘WHO standards’) and the National Center for Health Statistics NCHS/WHO international growth reference (‘NCHS reference’), and discuss implications for child health programs and reporting of prevalence of underweight in demographic surveys. Methods A cross-sectional study was carried out in 20 Anganwadi centers under Primary Health Centre, Anji. Total of 1491 under-six year children attending the Anganwadi centers were studied for nutritional status. Nutritional status was analyzed by NCHS standards by using EPI_INFO 6.04 software package and also by newly introduced WHO Child Growth Standards by Anthro 2005 software package. Chi-square test was used to compare the results. Results According to WHO standards, the prevalence of underweight and severe underweight for children 0–6 year was 47.4% and 16.9% respectively. By NCHS reference, the overall prevalence of underweight and severe underweight for children 0–6 years was 53% and 15% respectively. The prevalence of underweight as assessed by WHO standards was significantly lower when compared with the assessment based on NCHS reference (p<0.01). But, WHO standards gave higher prevalence of severe underweight than NCHS reference though the difference was not statistically significant (p>0.05). Conclusion In the light of newly developed WHO Child growth standards, all the nutrition-related indicators in demographic surveys like NFHS should now be derived using the WHO standards. There is need to reanalyze NFHS-I and NFHS-II data using WHO standards and findings should be made available so that it becomes comparable and trends over the years can be studied.     

Research Review: Crossing syndrome boundaries in the search for brain endophenotypes

The inherent imprecision of behavioral phenotyping is the single most important factor contributing to the failure to discover the biological factors that are involved in psychiatric and neurodevelopmental disorders (e.g., Bearden & Freimer, 2006 ). In this review article we argue that in addition to an appreciation of the inherent complexity at the biological level, a rather urgent task facing behavioral scientists involves a reconsideration of the role that clinical syndromes play in psychological theorizing, as well as in research into the biological basis of cognition and personality. Syndrome heterogeneity, cross-syndrome similarities and syndrome comorbidities question the relevance of syndromes to biological research. It is suggested that the search for brain endophenotypes, intermediate between genes and behavior, should be based on cross-syndrome, trait classification. Cohort selection should rest on behavioral homogeneity, enabling, when necessary, syndrome heterogeneity.     

Prenatal nutrition supplementation and growth biomarkers in preadolescent Bangladeshi children: A birth cohort study

Little is known about the usefulness of biomarkers to study the influence of prenatal nutrition supplementation in improving child growth. Anthropometry is not always straightforward to understand how nutrition might impact growth, especially in settings with high rates of malnutrition and infections. We examined the effects of prenatal supplementation on growth and growth biomarkers and the relationship between anthropometric measures and growth biomarkers of children at 4.5 and 9 years of age. Children were enrolled from a longitudinal cohort, where mothers were randomized into daily supplementation with either early-food (≤9 gestation week [GW]) or usual-food (~20 GW) (608 kcal 6 days/week); they were further randomized to receive 30-mg or 60-mg iron with 400-μg folic acid, or multiple micronutrients (MM) in rural Bangladesh. Anthropometric data were collected from mothers at GW8 and children at 4.5 (n = 640) and 9 years (n = 536). Fasting blood was collected from children at each age. Early-food supplementation showed reduced stunting and underweight at 4.5 and 9 years age respectively compared to usual-food. Prenatal supplementations did not have any effect on growth biomarkers except for STAT5b expression which was lower in the early-food compared to the usual-food group (β = ?0.21; 95 CI% = ?0.36, ?0.07). Plasma concentrations of 25-hydroxy vitamin D and calcium were both inversely associated with weight-for-age and body mass index-for-age Z-scores at 9 years, particularly in early-food and MM groups. Although there was minimal effect on child growth by prenatal supplementations, the associations of biomarkers with anthropometric indices were predominantly driven by timing of food or MM supplementations.     

The World Health Organization child growth standards: expected implications for clinical and epidemiological research

In 2006 and 2007, the World Health Organization (WHO) released two sets of child growth standards (World Health Organization, WHO Child Growth Standards. Methods and development. Length/height-for-age, weight-for-age, weight-for-length, weight-for-height and body mass index-for-age. WHO, Geneva, 2006; World Health Organization, WHO Child Growth Standards: Methods and Development. Head circumference-for-age, arm circumference-for-age, triceps skinfold-for-age and subscapular skinfold-for-age. WHO, Geneva, 2007) to replace the National Center for Health Statistics references (Hamill et al., National Center for Health Statistics, Vital and Health Statistics Series 11, No 165, 1977) as an international tool for growth and nutritional assessment. This paper explores the scope of implications for future anthropometric research, highlighting foreseeable effects on the choice of research questions, choice of nutritional indices, training of measurers, and issues of internal and external validity of research results. The conclusion drawn is that the introduction of the WHO child growth standards is expected to have wide implications for growth and nutrition research. The full scope of this effect will gradually become clear while researchers, similar to health care workers, make the transition to using the new standards, re-evaluate results of past approaches, and explore the uses and functional validity of the standards, including those for indices that were not previously available.     

Editorial: Biomarkers in precision medicine for mental illnesses

Precision medicine and biomarker development have become the prevailing paradigm for mental health research. Despite its conceptual elegance and dominance as a research framework, precision medicine has a very limited track record of demonstrable success thus far for mental illnesses, due in varying degrees to the complexity of both the brain and the pathophysiology of mental illnesses, which limits our ability to develop, replicate, and validate biomarkers for use in enhancing clinical care for mental illnesses, especially in high-risk and complex clinical populations. Research and funding priorities should integrate biomarker development and precision medicine interventions that target the robust behavioral, environmental, and social determinants that we know are important for population-based mental health.