The primary mission of the Florida Neonatal Neurologic Network is to spread current state of the art care for babies with brain injuries to the outstanding medical centers throughout the state of Florida. The network represents a long term commitment to help babies with brain injuries. The network is designed to mimic the highly successful Children’s Oncology Group model which has drastically improved the outcome of children with leukemia.
Building the Network
The first phase of FN3 will consist of a network of Level III-IV NICUs in north-central Florida including:
- Gainesville (UFHealth)
- Tampa (Tampa General Hospital, St. Joseph’s Hospital)
- Jacksonville (UFHealth at Jacksonville and Baptist-Wolfson Children Hospital)
- St. Petersburg (All Children’s Hospital)
- Orlando (Florida Hospital and Winnie Palmer Hospital)
This phase will develop a centralized registry at the University of Florida, initiate hypothermia programs at all participating centers and construct a biological specimen library. The initial phase will allow us to understand any potential roadblocks to forming the network.
After the initial phase is complete, the network will be spread to the entire state of Florida.
Touching the Future
After formation of the network, the group will perform innovative clinical trials to help develop future therapies for babies with brain injuries. The group will use the same design as the Children’s Oncology Group where babies with brain injury will be randomized to receive emerging therapies.
Clinical Research at FN3 – Why the Network Is Needed
Current clinical research model
Current research models use either a single center or multiple centers to enroll patients to evaluate potential new therapies. The first drawback is the lack of long term relationships between the centers after the trials are completed. Often times the enrolling center or centers do not continue to study additional treatments in the patient population in which the research was performed. Even when long term relationships exist between multiple centers, the group does not have a strategy to continue to rapidly enroll patients for other therapies and accumulate data for mining. Building the infrastructure for studying neonatal brain injury and maintaining that singular focus within the proposed FN3 consortium is a unique strength of our proposal which could lead to fast-tracking progress in this very difficult area. This model is similar to the Children’s Oncology Group model.
Children’s Oncology Group model
Historically, children’s cancer was difficult to treat because no single center would have adequate patient volumes with a particular tumor, especially when one considers varying stages of the tumor. Neonatal HIE matches this model because no center has large numbers of these patients, and the degree of injury at presentation is variable. The Children’s Oncology Group (COG) offers an attractive model to treat neonates with HIE. The oncology group assigns patients to a particular treatment arm based on the type and severity of disease. Using this approach, COG members have increased the cancer cure rate for children from less than 10 percent in the 1950s to nearly 80 percent at present, in COG member hospitals 19. To help develop new ways to treat children’s cancer, COG members submit diagnostic, treatment and follow-up data to the COG Research Data Center. Because the data from many patients are combined, clinical trials obtain results more rapidly and new treatments are developed hundreds of times faster 19. A similar approach to neonates with HIE may speed the progression of discovery of therapeutic interventions, especially when the group is cohesive and comfortable working together.
The FN3 Model
FN3 is designed to be a hybrid of the above models drawing on the strengths of a multicenter network to generate adequate patient numbers and combining this with the building of an infrastructure to specifically support trials in neonatal brain injury. The network will build an organized patient registry as part of the needed infrastructure for clinical trials focused on neonatal brain injury—a model similar to the COG.
We believe that this approach is novel for treating neurologic disorders. The network will enroll all neonates with mild, moderate and severe HIE. Demographic data, maternal information, birth history and clinical course, including follow-up developmental evaluations, will be recorded in the database. This is very similar to the multicenter trial design and the COG. Future grant applications will randomize patients to various treatment regimens. This is very similar to the COG model. Serum samples will also be processed for metabolomic and proteomic data which will foster the development of powerful biomarker tools to predict the pattern of injury and provide prognostic information. Other investigators will be able to access the database and potentially access serum samples as part of the data sharing plan. Future studies would include seeking gene-specific risks to add to the prediction model. With these results, treatment regimens may be refined in the future to individualized care based on the pattern of neurologic injury and the genotype of the patient to improve outcomes.
Clinical Trials & Publications
The purpose of this study is to create a detailed medical and sample database of infants born with HIE. Both the medical information and the samples are de-identified. Any future studies performed with the data and samples will receive Institutional Review Board (IRB) approval.
Hypoxic-Ischemic Encephalopathy (HIE) occurs in 20 per 1000 births. Only 47% of neonates treated with the state of the art therapy (induced systemic hypothermia) have normal outcomes. Therefore, other promising therapies that potentially work in synergy with hypothermia to improve neurologic outcomes need to be tested.
This study will test the safety and efficacy of an infusion of a baby’s own (autologous) umbilical cord blood as compared with placebo in babies born with history and signs of hypoxic-ischemic brain injury.
We aimed to determine if minimal enteral nutrition (MEN) during hypothermia in patients with hypoxic-ischemic encephalopathy was associated with a reduced duration of parenteral nutrition, time to full oral feeds, and length of stay, but would not be associated with increased systemic inflammation or feeding complications.