Children's Hospital Colorado
Changing the outcomes for families, one discovery at a time.

Changing the outcomes for families, one discovery at a time.

Research & Innovation

LEADER In EXIT Procedure for Treatment of Complex Fetal Heart Block
OVER $25 Million in Research Funding
FIRST to use Nifedipine for TTTS

Clinical Research

Role of vascular/cardiac biomarkers in amniotic fluid of patients with Twin-Twin Transfusion Syndrome (TTTS)
Purpose: To identify proteins in amniotic fluid that could lead to an earlier diagnosis and improved treatment for TTTS.
Primary Investigator: Dr. Timothy Crombleholme

TTTS1: A cluster randomized controlled trial comparing a conservative management approach and primary laser surgery in stage 1 TTTS
Purpose: An international, randomized trial of stage 1 TTTS pregnancies to compare observation vs. primary laser surgery.
Primary Investigator: Dr. Timothy Crombleholme

Indications for delivery for twin-twin transfusion after SFLP
Purpose: Multicenter trial including NAFTNet members to collect information about timing and indications for delivery following the Selective Fetoscopic Laser Photocoagulation (SFLP) procedure.
Primary Investigator: Dr. Michael V. Zaretsky

Assessment of fetal cardiac function in twin-to-twin transfusion syndrome
Purpose: To learn more about how the heart works in twins who have been diagnosed with twin-to-twin transfusion syndrome as evaluated by a fetal cardiologist.
Primary Investigator: Dr. Lisa Howley

MOMS Plus
Purpose: To collect outcomes data on all women undergoing prenatal or postnatal myelomeningocele (spina bifida) closure, as well as to collect medical information on the child for up to six years. Data will also be submitted to the NAFTNet MOMS database.
Primary Investigator: Dr. Timothy Crombleholme

DHREAMS: Diaphragmatic Hernia Research & Exploration; Advancing Molecular Science
Purpose: Large, multicenter trial to learn more about genes and family history can affect this disease as well as following affected children for five years to study neurodevelopmental outcomes.
Primary Investigator: Dr. Timothy Crombleholme
Partnering Research Institutions: Columbia University Medical Center (lead site); University of Nebraska Children’s Hospital & Medical Center; Monroe Carell Jr. Children’s Hospital; Cincinnati Children’s Hospital; CS Mott Children’s Hospital; Children’s Hospital of Pittsburgh; St. Louis Children’s Hospital; Children’s Hospital of Wisconsin; North Shore Long Island Jewish Hospital; and Cairo University Hospital.

Advancing clinical research in pediatric surgery: an observational study of infants with congenital diaphragmatic hernia
Purpose: To collect data from 90 centers in 10 countries around the world, to learn more about the natural history of congenital diaphragmatic hernia so that appropriate treatments can potentially be identified.
Primary Investigator: Dr. Timothy Crombleholme

Echocardiographic criteria for timing of congenital diaphragmatic hernia repair
Purpose: To evaluate the standardization of the decision to perform CDH repair using echocardiography.
Primary Investigator: Dr. Timothy Crombleholme and Dr. Jason Gien
Partnering Research Institute: Cincinnati Children’s Hospital

Heart Sounds at Home: prospective maternal surveillance of SSA positive pregnancies using a hand-held fetal heart rate monitor
Purpose: To determine whether the use of fetal heart rate monitors in the ambulatory setting will successfully detect the earliest onset of antibody-mediated AV heart block.
Primary Investigator: Dr. Bettina Cuneo
Website: http://heartsoundsathome.com/ 

Prospective identification of long QT syndrome in fetal life
Purpose: To collect medical information about the type of Long QT syndrome identified, EKG and genetic testing after the affected baby is born. Also to look for and identify long QT syndrome in babies before they are born. Identifying long QT syndrome (a heart rhythm disorder) before birth could prevent some stillbirths, sudden infant death syndrome and childhood deaths.
Primary Investigator: Dr. Bettina Cuneo
Website: http://fetallqts.com

International Fetal Cardiac Registry
Purpose: To gather clinical information about pregnant women who are referred to CHCO for echocardiograms as well as prenatal and postnatal information about the baby. 
Primary Investigator: Dr. Lisa Howley

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Basic Science Research

Primary Investigator: Dr. Timothy Crombleholme and Dr. Nicholas Behrendt
Purpose: Congenital bladder outlet obstruction is a devastating condition that can lead to severe morbidity in childhood. The high bladder pressure and ensuing anhydramnios can lead to kidney failure requiring dialysis or transplant, irreversible bladder scarring, urinary incontinence, lung hypoplasia and limb deformities. The current established method of treating bladder outlet obstruction in utero focuses on creating a shunt between the fetal bladder and the amniotic cavity in order to decompress the bladder and increase the fluid volume around the fetus. This procedure is usually done with the Harrison shunt -- a small pig-tailed catheter placed under ultrasound or fetoscopic guidance. This treatment is known to have certain limitations as the shunt can be dislodged, sometimes necessitating multiple shunts per pregnancy.

Dr. Crombleholme and his research group are using an ovine model of bladder outlet obstruction to test a new type of vesico-amniotic shunt. The research group believes the characteristics of this new shunt will mean a reduced chance of displacement and allow urine to flow out of the obstructed bladder, at lower pressure, than the current shunt.

The new shunt has been successfully tested in a pilot study. The project has now moved into the comparative phase; testing the new shunt against the Harrison shunt, in a twin pregnancy ovine model.

Primary Investigator: Dr. Timothy Crombleholme
Purpose: Interuterine growth restriction is the failure of fetuses to reach their normal growth potential, leading to small size at birth. This growth restriction can be caused by nutritional, maternal, or environmental factors. There is no effective treatment for intrauterine growth restriction except early delivery of the pregnancy for nutritional supplementation.

Besides problems of prematurity and small size at birth, intrauterine growth restriction also makes the baby susceptible to diseases such as obesity, diabetes, and high blood pressure as it matures into adulthood. Currently, we are investigating both sides of this story. First, we are investigating target therapeutics which can promote the growth of the fetus before birth. Second, we are investigating how these therapies alter the fetus' susceptibility to metabolic disease as it grows into adulthood.

Primary Investigator: Dr. Timothy Crombleholme and Dr. Jason Gien
Purpose: Postnatal survival depends upon the ability of the pulmonary circulation to undergo rapid and dramatic developmental changes in blood flow due to vasodilation during the first minutes after birth. Failure of the pulmonary circulation to successfully achieve or sustain this vasodilation causes severe hypoxemia in cardiopulmonary disorders that constitute persistent pulmonary hypertension (PPHN). Currently, Dr. Dodson’s work focuses on understanding the relationship between the altered biomechanics of blood flow in the pulmonary arteries to the changes that occur within the endothelial cells and extracellular matrix of the vascular wall.  Dr. Dodson’s expertise in studying the pathobiology of PPHN is to develop novel therapeutic targets in the treatment of PPHN in newborns

Primary Investigator: Dr. Kenneth Liechty   
Purpose: Heart attacks, also known as a myocardial infarction, are sustained by more than 1 million Americans per year. Procedures such as angioplasty or coronary artery bypass surgery are successful in large subsets of patients, however, there is still a subset of patients where there is not an adequate treatment. Myocardial infarctions in adults causes scar formation of the heart muscle which is the result of collagen accumulating at the site of the injury causing hardening of the tissue of the heart muscle.  However, unlike the adult scenario, the fetus is able to regenerate the heart muscle following a myocardial infarction resulting in restoration of normal heart function.

Fetal wounds also tend to heal without a scar and with limited inflammation. Dr. Liechty’s work focuses on understanding the cellular mechanisms that play key roles into the ability for the fetus to regenerate the heart. Debunking these cellular mechanisms that play key roles will aid in the development of potential treatments to prevent heart failure following a heart attack in the adult. 
Reference materials: Mammalian Fetal Cardiac Regeneration After Myocardial Infarction Is Associated With Differential Gene Expression Compared With the Adult

Primary Investigator: Dr. Kenneth Liechty  
Purpose: Skin and tendons wounds are the result of injury to either the skin or tendon. These injuries can be the result of traumas, surgery, burns, elective surgeries, or even immobility following an injury.  Scar tissue is weaker than normal tissue and can cause impairments to the affected areas of skin or tendon. People with diabetes have particular skin healing impairments due to their condition which can causes prolonged healing and can even lead to amputation. Interestingly, fetal small skin and tendon wounds heal scarlessly with restoration of normal skin and tendon architecture.

Large fetal wounds do not tend to heal scarlessly, similar to the adult scenario, but small fetal wounds heal scarlessly. Dr. Liechty’s team uses the fetal model, to understand the cellular mechanisms differences between the fetal scenario and the adult scenario. Understanding the relationship between the fetal small wounds and larger wounds will allow for future therapeutics in the adult scenario. Especially understanding the mechanism of inflammation in the diabetic scenario will lead to improvement in would healing in those suffering from diabetes and offer better therapies to wound healing. 

Primary Investigator: Dr. Rony Marwan    
Purpose: Neural tube defects have profound effects not only anatomically, but functionally, emotionally and psychologically. Neural tube defects also have large financial burden not only upon the affected families but the health care system as well. Although there has been a decrease in neural tube defects such as spina bifida with the improvements in prenatal care, there is a lack of knowledge of the basic biological mechanisms to develop novel medical treatments to treat these defects.

Currently one of the types of neural tube defect called of spina bifida aperta, which is an open neural tube defect, requires surgery at 24 week gestation to improve postnatal needs of shunts and reduce the negative effects of exposed neural elements in utero. However operation in utero introduces its own risk to the mother and fetus and damage to the neural elements has still occurred. Dr. Marwan’s work is focused on understanding the biomechanisms responsible for neural tube closure which will be a key in developing alternate therapies to treat those affected by neural tube defects. Also improving surgical methods with alternate biomaterials to either treat the defect at an earlier stage of gestation or act as a therapeutic agent that can treat the defect will improve prenatal outcomes.

Primary Investigator: Timothy Crombleholme, M.D.

Myelomeningocele (MMC), a common form of spina bifida, occurs when a section of the neural tube that runs along the spine fails to close, leaving the spinal cord exposed. The consequences are severe: contact with amniotic fluid causes nerve damage, loss 
of sensation, sometimes paralysis.

Twenty years ago, about 80 percent of babies born with MMC needed a cerebral shunt to aid drainage. However, now fetal surgeons at Children's Hospital Colorado have become the first in the world to use 3D printing to prefabricate MMC patches in advance of surgery, based on 3D computer models assembled from fetal MRI.

Learn more about how 3D printing helps treat severe cases of spina bifida.

The preeminent source on fetal care.

Widely regarded as the gold standard source of information in the field, Fetology: Diagnosis and Management of the Fetal Patient (2nd edition) by Dr. Timothy Crombleholme and colleagues, Director of CFCC, and colleagues, is a comprehensive examination of the diagnosis and treatment of fetal conditions within pediatric surgery and maternal-fetal medicine.

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Volumes and Outcomes

Our goal is for every family to receive optimal high-value, compassionate health care. As a result of our multidisciplinary approach, we are proud to report some of the best outcomes in the nation. See our Volumes and Outcomes Summary.


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