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Health disparities are defined on the basis of specific populations that, when compared to the general population, have a significant disparity on the rate of disease incidence, prevalence, morbidity, mortality, or survival. People that experience health disparities can be defined by multiple criteria. As the diversity of the United States broadens and increases, research on the origins and causes of health disparities becomes more important to support a healthy general population. Children are particularly sensitive to and vulnerable to health disparities due to the potentially life long consequences of events during periods of critical organ, intellectual and social development. The concept of health justice whereby each individual has the opportunity to realize their full health potential can only be realized with proper understanding and relevant data to frame practice, policy and actions. The National Children's Study (NCS) was a longitudinal birth cohort study designed to incorporate the principles of the Federal Collaboration on Health Disparities Research in consultation with subject matter experts, community representatives, and ongoing evaluation to ensure high quality and relevant data on factors that impact health outcomes. The NCS developed and tested a model of enrolling a diverse population, capturing and integrating data using a life course framework, constructing individual profiles, then aggregating individuals into groups based on profiles and outcomes. This approach is applicable to other longitudinal cohort studies.

Inherent to clinical research is the informed consent process, with the informed consent form (ICF), a key component of human participant protections. We wished to examine whether a shortened and simplified ICF, accompanied by an appendix, improved participant understanding of a study compared with a conventional ICF. A shortened ICF was developed from an existing conventional ICF for a neonatal study. Either the shortened or conventional ICF was randomly distributed to members of two parental advocacy groups. Participants answered survey questions about the form they received. Thirty-one out of forty-one (76%) parents in the shortened ICF and 28/41 (68%) in the conventional ICF group responded. Significantly more parents in the shortened ICF group found their form “short and to the point”. Although they also stated that the shortened ICF did not provide enough information, there were no significant differences between groups measuring the understanding of key study components. A shortened ICF did not impact the understanding of the clinical trial. It will be important to compare the shortened and conventional forms in actual clinical trials.

Purpose To summarise contemporary approaches to evaluating medicines in children, emphasizing topics that are often misunderstood by one or more stakeholder groups. Methods A narrative review that integrates the literature with experience in multiple settings. Findings Children and young people need specific approaches to research about drugs because of growth and development. Specific approaches include practicalities such as the volume, frequency and technique of blood samples, and recruitment, including consent by proxy decision-makers and assent by children/young people. The design of drug development programmes includes working with children/young people from an early stage and minimising the burden of research through careful design while optimizing the contribution of extant, high quality information (including extrapolation).Regulators, academics, the pharmaceutical industry and other communities are well-placed to support pediatric drug development. Regulatory challenges include legislation that drives the extension to children of medicines used in adults (rather than a focus on the needs of children) and diversity between jurisdictions. Academics can improve the impact of their work by ensuring that data can be used in drug development programmes after they have answered a well-defined study question. Pharmaceutical companies, and public research funders can promote good return on the investment made in research (including the investment made by children/young people) by supporting data management to allow data reuse. Implications a greater understanding of pediatric issues is relevant to diverse research communities that work to advance pharmacotherapy.

Vaccination during pregnancy is increasingly being used as an effective approach for protecting both young infants and their mothers from serious infections. Drawing conclusions from published studies in this area can be difficult because of the inability to compare vaccine trial results across different studies and settings due to the heterogeneity in the definitions of terms used to assess the safety of vaccines in pregnancy and the data collected in such studies.The guidelines proposed in this document have been developed to harmonize safety data collection in all phases of clinical trials of vaccines in pregnant women and apply to data from the mother, fetus and infant. Guidelines on the prioritization of the data to be collected is also provided to allow applicability in various geographic, cultural and resource settings, including high, middle and low-income countries.

Longitudinal observational clinical data on pediatric patients in electronic format is becoming widely available. A new era of multi-institutional data networks that study pediatric diseases and outcomes across disparate health delivery models and care settings are also enabling an innovative collaborative rapid improvement paradigm called the Learning Health System. However, the potential alignment of routine clinical care, observational clinical research, pragmatic clinical trials, and health systems improvement requires a data infrastructure capable of combining information from systems and workflows that historically have been isolated from each other. Removing barriers to integrating and reusing data collected in different settings will permit new opportunities to develop a more complete picture of a patient’s care and to leverage data from related research studies. One key barrier is the lack of a common terminology that provides uniform definitions and descriptions of clinical observations and data. A well-characterized terminology ensures a common meaning and supports data reuse and integration. A common terminology allows studies to build upon previous findings and to reuse data collection tools and data management processes. We present the current state of terminology harmonization and describe a governance structure and mechanism for coordinating the development of a common pediatric research terminology that links to clinical terminologies and can be used to align existing terminologies. By reducing the barriers between clinical care and clinical research, a Learning Health System can leverage and reuse not only its own data resources but also broader extant data resources.

In 2009, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) established the Pediatric Terminology Harmonization Initiative to establish a core library of terms to facilitate the acquisition and sharing of knowledge between pediatric clinical research, practice, and safety reporting. A coalition of partners established a Pediatric Terminology Adverse Event Working Group in 2013 to develop a specific terminology relevant to international pediatric adverse event (AE) reporting. Pediatric specialists with backgrounds in clinical care, research, safety reporting, or informatics, supported by biomedical terminology experts from the National Cancer Institute’s Enterprise Vocabulary Services participated. The multinational group developed a working definition of AEs and reviewed concepts (terms, synonyms, and definitions) from 16 pediatric clinical domains. The resulting AE terminology contains >1000 pediatric diseases, disorders, or clinical findings. The terms were tested for proof of concept use in 2 different settings: hospital readmissions and the NICU. The advantages of the AE terminology include ease of adoption due to integration with well-established and internationally accepted biomedical terminologies, a uniquely temporal focus on pediatric health and disease from conception through adolescence, and terms that could be used in both well- and underresourced environments. The AE terminology is available for use without restriction through the National Cancer Institute’s Enterprise Vocabulary Services and is fully compatible with, and represented in, the Medical Dictionary for Regulatory Activities. The terminology is intended to mature with use, user feedback, and optimization.

Background The relationship between gestational weight gain (GWG) and childhood growth remains controversial. An examination on whether infant feeding practices mediate this relationship may improve our understanding of it. Methods We investigated whether the relationships among GWG, birth weight and childhood anthropometrics were mediated through infant feeding practices (breastfeeding duration and age at introduction of solid foods) in a cross-sectional multiethnic study of 1387 mothers and their children aged 0–5.9 years in the USA (2011–2012). Child anthropometrics included age-specific and sex-specific z-scores for weight-for-age (WAZ), height/length-for-age (HAZ), weight-for-height/length (WHZ) and body mass index-for-age (BMIZ); and ulnar length, a marker for limb growth. We used structural equation modelling to calculate standardised path coefficients and total, direct and indirect associations of GWG, birth weight and infant feeding practices with child anthropometrics. Results Maternal GWG had a positive indirect association with all anthropometrics mediated via birth weight, whereas longer breastfeeding duration reduced the positive associations of GWG and birth weight with WAZ, WHZ and BMIZ in non-Hispanics (β=−0.077, −0.064 and −0.106, respectively). Longer breastfeeding duration and introducing solid foods at a later age were positively associated with ulnar length (β=0.023 and 0.030, respectively) but not HAZ, suggesting a distinct association, for the first time, with limb growth. Conclusions Findings suggest that promoting longer breastfeeding duration among women with excessive GWG who had high birthweight newborns may mitigate the potential for their offspring to develop obesity. In addition, findings reinforce the importance of promoting appropriate GWG and preventing high birth weight, which are positively associated with childhood anthropometrics.

Paediatric HIV is a rapidly emerging disease in many resource-poor countries. Survival into adulthood is possible for HIV-infected children provided that they receive effective antiretroviral therapy (ART). Large trials comparing multiple regimens of ART in children of resource-poor countries have not been completed. Design of those trials will need to incorporate both lessons learned from trials completed in developed countries as well as unique aspects of the developing countries in which they are conducted. Trial design will necessarily include close attention to the endpoint, and in children, special consideration will need to be given to growth as a component of the endpoint--whether or not growth should be a component of the composite endpoint, and if so, how.

Purpose: To review the Food and Drug Administration (FDA) experience with approvals of new drugs for pediatric oncology and to discuss new regulatory initiatives directed at pediatric oncology. Methods: A retrospective review of FDA archival documents and the published literature. Results: More than 100 drugs have been approved by the Division of Oncology Drug Products of the FDA for the treatment of malignancies. Only 15 have pediatric use information in their labeling, which is less than 50% of the drugs commonly used in the treatment of pediatric malignancies. In the past 20 years, there have been six submissions to the FDA for pediatric oncology indications. To illustrate principles of the approval process, each submission is discussed. Conclusion: Potential reasons for a lack of New Drug Application submissions for pediatric oncology include the small pediatric oncology market compared with the adult oncology market and perceived barriers to performing studies in children. Reasons for failure to approve pediatric indications include small numbers of patients, lack of appropriate controls, and failure to demonstrate patient benefit. Approval criteria include the use of controlled trials, prospective data collection, and disease-appropriate end points. Regulatory initiatives to promote pediatric therapeutic development and product labeling are discussed.

Acute lymphoblastic leukemia (ALL) is the most common form of childhood cancer. The literature suggests multiple points of interaction between infant feeding patterns and leukemogenesis whereby diet may influence normal development of the immune system and levels of insulin-like growth factor 1 (IGF-1) in the serum. Thus the intent of the current study is to examine the association between infant feeding practices and age at introduction of solids, on risk of ALL. Incident cases of infant and childhood ALL (N=142, ages 0 to 14 years) were approached and enrolled in a case-control study at Texas Children's Cancer Center (TCCC). Controls (N=284) were recruited at TCCC and satellite clinics, as well as from participants in formative research for the National Children's Study in Houston, San Antonio and Austin, Texas. Cases and controls were frequency matched on age, sex, race and ethnicity. Differences in proportions of breast and bottle feeding between cases and controls were assessed by chi square test. Differences in the mean durations of feeding practices and age at introduction of solids were assessed by Student's t test. The odds ratios (OR) of ALL were calculated using multiple logistic regression analysis in two models with the infant feeding group (independent variables) characterized as follows and a reference group of exclusively breastfed: in the first model, ever formula fed; in the second model, exclusively fed formula or fed both breast milk and formula. A third addressed the effects of durations of breast and formula feeding and age at the introduction of solid foods on the odds of ALL. Each model was calculated before and after adjustment for race, ethnicity, child's age and maternal smoking during pregnancy. Cases started solid foods significantly later than controls. More mothers of cases than controls smoked during pregnancy. Compared to the controls, cases had longer duration of formula feeding, and upon analysis of the exclusive formula versus mixed breast and formula fed, mixed feeding groups had a longer duration of formula intake. In a preliminary multivariate model, each additional month of formula feeding was associated with a 16% (OR: 1.16, 95% CI 1.08-1.25) increased odds of ALL; and likewise each additional month of delaying the age at introduction of solids was also associated with a 14% (OR1.14, 95% CI: 1.04 -1.26) increased odds of ALL after adjustment for covariates. In this ethnically diverse population, duration of formula feeding and age at introduction of solid foods were directly associated with increased odds of ALL. Further research needs to address the factors influencing duration of formula feeding and delay in introduction of solids. Our results highlight the role of energy balance in early life as critical contributors to risk for pediatric ALL. Citation Format: Jeremy Schraw, Yong Q. Dong, Michael E. Scheurer, Steven Hirschfeld, M Fatih Okcu, Michele R. Forman. Longer formula feeding and later age at introduction of solids increase the odds ratio of pediatric acute lymphoblastic leukemia. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A102.