Since the CCTR Pediatric Pilot Fund program began in 2008, these funds have been used to support a wide variety of research. Below are descriptions of the personnel and goals of each Pilot Fund project as stated at the time of the award.
2012 Pediatric Pilot Fund Recipients
Grace John-Stewart, MD, MPH, PhD, and Lisa Cranmer, MD, MPH
The effect of maternal immunity on infant vaccine response to BCG
Mycobacterial infection is a significant world-wide public health problem, with one third of the world’s population infected with tuberculosis (TB). BCG is the most widely used vaccine, but it has variable efficacy. In their pilot project, Drs. Grace John-Stewart and Lisa Cranmer will investigate whether maternal mycobacterial immunity diminishes infants’ vaccine response to BCG. Using a longitudinal cohort of mother–infant pairs in Kenya, the investigators will measure anti-mycobacterial cellular and humoral immunity prior to BCG at the birth and evaluate BCG immunogenicity among infants at 10 weeks. John-Stewart and Cranmer suggest that these results could better define the effect of maternal immunity on infant BCG response and could lead to an improved vaccine or an improved vaccine schedule.
Joseph Flynn, MD
Intravenous hydralazine for management of acute hypertension in children and adolescents
Acute severe hypertension in children typically requires treatment with an intravenous antihypertensive medication. One of the most commonly used is hydralazine. However, despite recommendations in the literature for use of IV hydralazine for such patients, there are no published clinicals trails or case series of IV hydralazine in children with acute severe hypertension, and therefore no evidence-based or FDA-endorsed pediatric doses available. Dr. Joseph Flynn and his research team will conduct a retrospective review of blood pressure response to individual does of IV hydralazine in hospitalized children with hypertension. The data generated from this study will help to develop improved dosing recommendations for IV hydralazine and inform the design of prospective, multi-center clinical trials to generate better-quality evidence. Thus, the results have the potential to improve the quality and safety of care of children with acute severe hypertension.
Ryan McAdams, MD
Is prolonged exposure to dexmedetomidine safe for neonates?
Dexmedetomidine (DEX) is a sedative medication that has reported to produce sedative effects without inducing significant respiratory depression. However, minimal data exists describing the pharmacokinetics, efficacy, safety or neuropathologic effects of prolonged exposure to DEX in infants. Dr. Ryan McAdams’ pilot project proposes to establish the pharmacokinetics of the DEX in neonates and to evaluate neuronal density, reactive astrogliosis and cell proliferation in specific regions of the brain after neonatal DEX treatment. The goal of this research is to provide evidence-based information that can improve the long-term intensive care of preterm infants and optimize their neurodevelopmental outcome.
Margaret Rosenfeld, MD, MPH
Novel home cough monitor in young children with cystic fibrosis: a pilot and feasibility study
Recent studies have demonstrated that cystic fibrosis (CF) begins in the first years of life. Therefore, there is a high level of interest in conducting clinical trials of early interventions to delay or present irreversible lung damage. Dr. Shwetak Patel and his research team at the University of Washington have recently developed a novel, fully automated cough sensor that has demonstrated feasibility and accuracy in ambulatory adults. In her pilot study, Dr. Margaret Rosenfeld will collaborate with Patel to assess the accuracy and feasibility of cough monitoring in CF patients from birth to 6 years of age and obtain longitudinal data in this age range necessary for the planning of future studies. This device could potentially serve as an important resource for clinical trials of disease-modifying therapies in children with CF.
Cate Pihoker, MD
Examining the role of vitamin D deficiency in diabetic kidney disease in children
Nearly a third of children with diabetes will develop diabetic kidney disease (DKD) as adults, the earliest sign of which is albuminuria (increased excretion of protein in urine). Several lines of evidence connect low vitamin D levels with albuminuria and DKD, including a recent clinical trial that demonstrated that supplementation with activated vitamin D reduces albuminuria in adults with DRD. This has not been studied in children. In her pilot project, Dr. Cate Pihoker and her research team will evaluate this association in two nationally representative cohorts for children. If the findings for adults hold true for children, vitamin D may be a cost-effective, low-side-effect tool for early intervention in the course of DKD in children.
Jerry Zimmerman, MD, PhD
Catabolism and morbidity after pediatric sepsis
Pediatric sepsis is a leading cause of childhood mortality worldwide. Sepsis is also likely an important cause of long term morbidity. However, the causes of long-term sepsis morbidity have been inadequately investigated. In his pilot project, Dr. Jerry Zimmerman and his research team will characterize the role of muscle catabolism on multi-dimensional fatigue and functional impairment among children hospitalized with severe sepsis. This knowledge of the role of muscle catabolism on long term physical outcomes following pediatric sepsis will facilitate the design of targeted intervention to help maximize functional outcomes among children surviving sepsis. It will also identify children who might benefit from early rehabilitation interventions following sepsis.
2011 Pediatric Pilot Fund Recipients
Scott Baker, MD, MS, and Abby Rosenberg, MD
Understanding resilience in parents of children with cancer
In their pilot project, Drs. Scott Baker and Abby Rosenberg will implement a cross-sectional study using both quantitative and qualitative instruments to assess overall resilience and psychological functioning among bereaved and non-bereaved parents of children with cancer. The research team will evaluate medical and psychosocial factors of resilience in both sets of parents. Results from this study will inform providers of the prevalence of various psychosocial outcomes among parents of children with cancer and will relate those findings to the medical experience. Ultimately, this research will direct future studies aimed at fostering resilient outcomes not only among parents, but also whole families facing pediatric cancer.
Janet Englund, MD, and Helen Chu, MD
Respiratory syncytial viral disease in Nepalese children: the effect of clean cook stove installation
Acute lower respiratory tract infection (ALRI) is the leading cause of childhood mortality globally, and respiratory syncytial virus (RSV) is an important viral pathogen in ALRI. There is recent evidence that household air pollution caused by indoor cook stoves using vegetable matter, cow dung and wood matter increases the risk of ALRI in children. In Drs. Janet Englund and Helen Chu's pilot project, study personnel will observe children with ALRI living in Nepal in families with and without clean cook stoves. The study team will perform weekly surveillance during the respiratory viral season for ALRI signs and symptoms in children ages 1 month to 36 months. They will collect nasopharyngeal swab specimens from the children during illness episodes both before and after a clean cook stove has been installed. This study will establish the baseline incidence, severity and duration of RSV illness in children in Nepalese households with traditional cook stoves and determine the impact of clean cook stoves in reduction of RSV illness.
Kelly Evans, MD
Sleep outcomes and airflow in Robin sequence (RS)
Craniofacial anomalies, such as Robin sequence (RS), are the leading cause of obstructive sleep apnea (OSA) in infants. In her pilot project, Dr. Kelly Evans will conduct overnight studies to measure sleep disturbance and sleep-impacted outcomes in five infants from birth to 6 months old with RS and five healthy infants. In addition to collecting standard phenotypic information, the study team will capture a three dimensional shape of the infants’ faces, allowing for more accurate assessment of craniofacial shape and systematic evaluation of relationships between facial structures. This collective data will provide Evans with information to characterize the nature and severity of OSA in infants with RS that can be used for further research.
Sangeeta Hingorani, MD, MPH
Assessment of endothelial function and hypertension in patients after hematopoietic cell transplant
Hematopoietic cell transplant (HCT) is an increasingly common treatment for many malignancies and some genetic disorders. Dr. Sangeeta Hingorani’s recent work has identified that at day 100 after this type of transplant, albuminuria and proteinuria are associated with an increased risk of chronic kidney disease (CKD), non-relapse and overall mortality. In the U.S., approximately 1,500 patients per year will develop proteinuria at day 100 and will die within the first year after transplant. The cause of this increase in mortality is unknown. In her pilot project, Hingorani and her team will evaluate whether endothelial dysfunction, a condition in which the endothelium (inner lining) of blood vessels do not function normally, predicts albuminuria and proteinuria at day 100. The information generated from this study will be used as preliminary data for further research in this patient population and to support the necessity for a targeted intervention trial.
Sarah Ringold, MD, and Anne Stevens, MD, PhD
Is there a link between prophyromonas gingivalis infection and juvenile idiopathic arthritis?
In their pilot project, Drs. Sarah Ringold and Anne Stevens will test the hypothesis that exposure to Porphyromonas gingivalis, a bacteria associated with periodontitis/gingivitis, is a trigger for polyarticular juvenile idiopathic arthritis (JIA). Evidence suggests that P. gingivalis may trigger rheumatoid arthritis (RA) via mimicry, a process where antibodies to this bacteria cross-react with certain proteins found in joint tissue. Although polyarticular JIA is believed to share a cause with adult RA, it is not yet clear whether P. gingivalis plays a similar role in the JIA pathogenesis. In this study, investigators will measure the levels of cross-reactive antibodies of children with JIA and the association between the levels of these antibodies and clinically assessed JIA disease activity. These data will pave the way for additional research on the relationship between periodontal disease and JIA, hopefully leading to a better understanding of the etiology of JIA and novel treatment strategies. Peggy Lee, BDS, MSD, PhD, in the Division of Dentistry at the University of Washington School of Medicine, is also a co-investigator on the project.
Klane White, MD
Identifying access barriers in children with developmental dysplasia of the hip
Developmental dysplasia of the hip (DDH) is a fairly common pediatric orthopedic disorder. While early detection and treatment of DDH is critical for the best chances of obtaining a well-functioning, pain-free hip joint into adulthood, there continue to be ongoing cases of delayed presentation of DDH patients at Seattle Children’s Orthopedic Clinic. In his pilot project, Dr. Klane White and his research team will conduct a study to identify different factors that may be contributing to the delayed patient visits to a pediatric orthopedic specialist. White will use the results to do educational outreach to address healthcare providers for children who are “at risk” of missed DDH diagnoses. Co-investigators on the project include Vivian Bompadre, PhD, and Antoinette Lindberg, MD, both in the Division of Orthopedics at Seattle Children’s.
2010 Pediatric Pilot Fund Recipients
Yuk Law, MD
Effect of remote ischemic preconditioning in children undergoing cardiac surgery
In his pilot project, Dr. Yuk Law will investigate the use of remote ischemic preconditioning (RIPC) as a simple and practical intervention that could reduce the risk of post-operative cardiac and renal dysfunction in children undergoing open heart surgery. RIPC is a noninvasive treatment that involves using a tourniquet to squeeze the extremities prior to cardiac surgery. Results of the pilot study will be useful in applying for larger-scale funding for full-scale clinical and translational research in this area.
Sarah Ringold, MD, MS
Development of a pediatric-specific disease activity index for juvenile idiopathic arthritis
In her pilot project, Dr. Sarah Ringold will use a previously collected dataset of children with juvenile idiopathic arthritis (JIA) to perform principal component analyses and factor analyses that will be used in development of a standardized pediatric-specific composite disease activity index for JIA. The results of this study will provide key data about which variables will be included in the index and their respective weights, thus setting directions for the design of future studies to test additional properties of the index and incorporate data collected via consensus methodology.
Julie Brown, MD, MPH
A controlled trial evaluating pediatric lumbar puncture success using the Compass™, a compact quantitative pressure transducer
In her pilot project, Dr. Julie Brown will study the effectiveness of the Compass™ Lumbar Puncture, a new digital pressure-measuring device specifically designed for use during lumbar puncture. Lumbar punctures (LPs) are common procedures in the pediatric emergency department, most involving infants younger than four months of age. However, many patients require multiple attempts and some LPs are unsuccessful. Julie expects that the Compass device will improve the likelihood of first attempt LP success and will decrease the total amount of time required to perform an LP. These benefits may translate into a reduction of traumatic LPs in the clinical population, leading to fewer unnecessary hospital admissions and decreased use of antibiotics.
Luke Hoffman, MD, PhD, and Daniel Wolter, PhD
Community-level physiologic profiling: a novel method for studying chronic, polymicrobial infections
In their pilot project, Drs. Luke Hoffman and Daniel Wolter will use cutting-edge techniques known collectively as community-level physiologic profiling (CLPP) as a novel approach for studying the behavior of cystic fibrosis (CF) multispecies infections. Hoffman and Wolter recently developed new CLPP methods to probe multispecies consortia of microbes and will apply these new techniques to test the metabolic properties and antibiotic susceptibilities of intact microbial communities from chronically infected CF airways. This study should give these researchers sufficient preliminary data to apply for a larger translational grant, which they hope to use to show that this tool will be clinically useful in identifying more effective therapeutic regimens for CF patients.
Ann Vander Stoep, PhD, and Molly Adrian, PhD
Genetic influences on co-occurring depression and conduct problems in adolescence
In their pilot project, Drs. Ann Vander Stoep and Molly Adrian will collect DNA from adolescents participating in an epidemiological study to investigate genetic associations with combined depression and conduct problems. They will compare subjects with comorbid depression and conduct problems to adolescents suffering from depression without comorbid conduct problems, as well as those without psychopathology. This pilot research will lay the ground work for future genetic studies and investigations of gene-environment interactions likely to be involved in the etiology of depression and conduct problems.
2009 Pediatric Pilot Fund Recipients
Richard Hopper, MD
Measurement of nasal morphological changes following use of the Seattle Alar Molding (SAM) device in infants born with unilateral complete cleft lip deformities
In his pilot project, Dr. Richard Hopper is evaluating the clinical effectiveness of the Seattle Alar Molding (SAM) device, a patent-pending novel invention. The SAM device is used on infants with unilateral cleft lip and palate (UCLP) who are undergoing presurgical molding in preparation for primary cleft lip repair and rhinoplasty. Hopper will refine the prototype for clinical efficacy and compare the changes in nasal morphology associated with SAM treatment with the nasal changes occurring over the same time period in patients undergoing traditional molding treatment. This pilot study will perform initial evaluation of the SAM device, which is intended to optimize long-term nasal symmetry and function in children with UCLP.
Danielle Zerr, MD, MPH, and Emily Martin, PhD
Natural history of bocavirus in young infants
In their pilot, Dr. Danielle Zerr and Emily Martin will test Human bocavirus (HBoV) with a new salivary assay they have developed. By defining the illness characteristics associated with HBoV detection in a birth cohort, more detailed specific studies can be conducted to look at HBoV disease in high- risk populations such as children with cancer or immunosuppression. By testing salivary samples with their HBoV assay, the investigators will be able to obtain the detailed longitudinal data that is necessary to define the association between HBoV and disease and to understand the implications of an HBoV-positive result in a clinical setting.
Jonathan Perkins, DO
Identification of biomarkers associated with propranolol induced infantile hemangioma regression
In his pilot project, Dr. Jonathan Perkins will examine the effect of propranolol on infantile hemangiomas (IH), proliferative endotherial cell tumors, which are the most common pediatric head and neck tumors. Rapidly expanding IH can impair vision and breathing during infancy and early childhood. Propranolol has been effective in reducing IH size and IH-associated complications. Perkins will compare genotypically matched IH tissue gene expression before and after propranolol treatment to IH tumors that are treated with standard therapy. The proposed project will add to the understanding of how beta adrenergic blockade stops tumor growth and induces tumor regression.
Nathalia Jimenez, MD, MPH
Effects of polymorphisms in the μ-opioid receptor and UDP-glucuronosyltransferase genes on analgesic response and side effects to morphine in Latino and non-Latino pediatric patients
In her pilot project, Dr. Nathalia Jimenez will analyze the role of genetic factors on occurrence of morphine side effects in Latino and non-Latino pediatric patients. A preliminary analysis of a study on morphine pharmacokinetics and pharmacodynamics found significant differences in the occurrence of side effects between these two groups. This study will provide preliminary data for future studies on the role of genetic variation on morphine effect in different ethnic populations. It will also increase the current knowledge on genetic variability in the response to morphine and other opioids for all patients regardless of the racial or ethnic background.
Margarett Shnorhavorian, MD, MPH, FAAP, FACS
Genes involved in male reproductive tract anomalies and the risk of testis cancer: a candidate genetic polymorphism study
In her pilot project, Dr. Margarett Shnorhavorian will test the testicular dysgenesis syndrome (TDS) theory that proposes that testicular germ cell tumors (TGCT), undescended testes (UDT) and hypospadias have a common etiology. The goal of this study is to identify genetic risk factors of TGCT by evaluating variations in the genes for two conditions, UDT and hypospadia, which are hypothesized to be part TDS. These findings will provide evidence for or against the TDS theory as well as establish a basis for targeted screening and prevention strategies for TGCT.
2008 Pediatric Pilot Fund Recipients
Eric J. Chow, MD, MPH
Glucocorticoid pharmacogenetics and obesity after childhood ALL therapy
In his pilot project, Dr. Eric Chow is examining a cohort of 200 pediatric patients who have been treated for childhood acute lymphoblastic leukemia (ALL). He will be looking at the role played by high-dose glucocorticoids – such as prednisone and dexamethasone – given to children who have been treated for ALL, in producing an elevated risk of obesity. Results of this research may help identify those children with ALL who would benefit most from early interventions to reduce future obesity and insulin resistance.
Christian L. Roth, MD
Pilot study of functional magnetic resonance brain imaging in patients with hypothalamic obesity
In his pilot project, Dr. Christian Roth is examining patients with hypothalamic obesity. Using an established functional magnetic imaging (fMRI) protocol, he is observing food-related responses of brain centers involved in appetite control. The goals are to establish a project identifying neuroendocrine and behavioral mechanisms that lead to overeating and weight gain in patients with medial hypothalamic brain lesions and to establish interdisciplinary fMRI studies at Seattle Children’s Hospital in the field of neuroendocrine disorders of energy homeostasis.
Sheela Sathyanarayana, MD, MPH
Phthalate exposure and potential health outcomes in the neonatal intensive care unit
Dr. Sheela Sathyanarayana’s pilot project is looking at the use of phthalate – a synthetic chemical used to make plastics flexible – in medical products. She is measuring urinary phthalate concentrations in infants at the Swedish Neonatal Intensive Care Unit in Seattle, where efforts are under way to change to equipment that is free of di-ethylhexyl phthalate. For the study, infants will be randomized to phthalate-containing medical equipment or phthalate-free medical equipment to determine if significant exposure differences exist. Data gathered in this study will be invaluable in future research efforts to determine the impact of endocrine-disrupting chemicals on infant health and development.
Thor A. Wagner, MD
Novel microcapillary immunoassay methodology to enable point-of-care infant HIV-1 diagnosis
Dr. Thor Wagner’s project is motivated by the observation that 50% of all children with HIV die before they are diagnosed. His pilot project seeks to explore a novel, high-sensitivity, microcapillary approach to infant HIV-1 diagnosis, with the goal of enabling an affordable point-of-care diagnostic test for infant HIV. If successful, this approach might be applicable to diagnostic testing for other infectious diseases in low-resource settings.
Danielle M. Zerr, MD, MPH
Emerging MDR in pediatric Enterobacteriaceae infections
Dr. Danielle Zerr’s pilot project looks at emerging multidrug resistance and aims to characterize the associations between clinical factors, bacterial strain background, intrinsic virulence, plasmid structure and broad spectrum β-lactam resistance in pediatric E. coli isolates. The results will serve as preliminary data for a multicenter grant application to describe national molecular and epidemiological trends in pediatric plasmid-borne broad-spectrum β-lactam resistance in Enterobacteriaceae bacteria.