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Ashburn Family Helps Push For Advances In CDH Research

by Erika Jacobson Moore

Looking back,

Looking back, Ashburn expectant mother Shannon Thomas first realized something might not be right with her son Brady at her 13-week appointment-although at the time she did not think much of it.

"Thirteen weeks is when they test for Down Syndrome," she said. "It normally takes a few minutes. Mine took an hour and a half."

But it wasn't until Thomas and her husband Collin Passieu went back for their 20-week check up, excited to learn their baby's sex, that they learned something was indeed wrong.

"The technician kept asking me to turn and move. It just dragged on and on," Thomas said. "We were so elated to be having a boy, but then we learned that he had a pretty significant hole in his diaphragm."

Brady was diagnosed in utero with a congenital diaphragmatic hernia, more commonly known as CDH, which occurs when the diaphragm, a thin strip of muscle that separates the abdomen from the chest cavity, does not form properly. When the diaphragm does not form properly, holes develop and the organs that are normally in the abdomen can be pushed, or herniated, through the opening into the chest cavity.

Thomas and Passieu were told that Brady's stomach had moved into his chest, but his liver was down.

"They told us it was important that his liver was down, because it is so large," Passieu said.

Because the abdominal organs move into the chest, the upper organs-the lungs and the heart-are displaced. Often babies who are born with CDH have other birth defects, the most common being the congenital heart defect. But since a number of hernias are discovered in utero, it is often difficult for parents to know exactly what the status of their child is. Such was the case with Thomas and Passieu.

"We were told he had no left lung," Thomas said of the diagnosis when she was still pregnant. After Brady was born doctors discovered it was not just his stomach, but his entire intestines and spleen that had moved into his chest. There was some better news, however. "He did have a left lung. It was just a bud stuck up by his collar bone."

Because of the seriousness of Brady's case, Thomas was transferred to Children's Hospital for care, and that was where her son was born, with the help of a doctor who specializes in high-risk delivery. Even with the specialized care, Brady was only given a 50 percent chance of survival.

But live he did, and at only five days old, he went through the first of many surgeries. "They pulled down everything they could," Thomas said. But because his body had grown without most of the lower organs where they were supposed to be, his abdomen was not large enough to take them all in at once. Instead his intestines had to be put back in slowly, allowing his abdomen to expand to accommodate them.

Brady, like many babies diagnosed with CDH, found himself with other medical issues stemming from his condition. He could not eat, and at 25 days old, the doctors learned his intestines were incomplete strictures, and they had to repair. He faced issues with his bilirubin levels, as his body could not break it down properly. He had four transfusions and doctors were talking about a transplant; all along he was having trouble getting enough nutrients. Soon he was being considered a "failure to thrive" case.

"It was just spiraling. It felt like one step forward and two steps back," Thomas said. "They called him astonishing. They couldn't believe was he was surviving."

And most importantly to the new parents, Brady's personality continued to shine through.

"He didn't cry. That was the amazing thing. He was smiling all the time," Passieu said, watching his son sitting in his high chair, teething on a toy in the couple's Ashburn home. Brady stopped chewing long enough to crack a large smile, proving his father's point. "They said he actually took CDH very well."

Like many parents of children diagnosed with CDH, Thomas and Passieu were constantly searching for any information they could find-research and information that could help them understand what had happened and was happening to their son. And like other parents, they found very little to help them.

"There's just not enough research," Thomas said. "That's why I want to be involved. It happened to my son. It could happen to anyone."

The Research Struggle

It is estimated that around one in 2,500 children is born with CDH. But every baby, the extent of their hernia and the medical issues stemming from it are different, and a large number of children diagnosed do not survive.

"Around 1,600 babies are born every year in the United States [with CDH]. And about 800 of them don't survive," Dawn Williamson, president and founder of CHERUBS, said. CHERUBS is the Association of Congenital Diaphragmatic Hernia Research, Awareness and Support, which Williamson founded in 1995 after her son was diagnosed.

"For something to be as common as CDH and not to have been heard of by the common person is hard. It's hard to get research done," Williamson said. "There just isn't the funding for it. We're the first and largest charity for CDH. We help families in 38 counties but our budget is $35,000 a year."

Williamson also noted that children with CDH, when out of the hospital, don't appear any different than any other child. "They are not walking billboards for awareness," she said. So, awareness is where CHERUBS is partially focused, with the other parts being research and support for parents of CDH babies, and the children themselves.

Passieu found CHERUBS the night before Brady was scheduled to be born, and it became a God-send for his family. CHERUBS knew of neonatal intensive care nurses at Children's Hospital who could help.

"I had to go to work and then go straight to the hospital until almost midnight, but I still couldn't be there the whole time," Passieu said. "So it was helpful for [the nurse] to be there with her."

Thomas said that is the best thing about CHERUBS-it is made up of families and parents who have been through, or are going through, what new parents of CDH babies are. One of the big things Williamson makes sure is done for any new parent of a CDH baby is to have a tote bag delivered with things like stuffed animals, blankets and disposable cameras, which most new parents might not think of in the face of medical emergencies.

"They have booklets of stories about other parents and other babies," Thomas said, noting she found it helpful to realize she, and Brady were not going through anything alone. Williamson said the tote bag also includes a "baby book" about CDH babies explaining the medical terms to parents in a way they can understand.

"A lot of the medical terminology goes over their heads," Williamson said.

For those who are actively working in the lab and in the medical community on CDH, funding is a major issue because, even with one in 2,500 births, the defect is still uncommon-especially when compared with other diseases currently under study, like cancer.

"It is still a rare problem. So the National Institutes of Health and other funding agencies have not viewed it as a priority," Dr. Kevin P. Lally, one of the top researchers and pediatric surgery chairman at the University of Texas Health Science Center in Houston, said.

"Part of how granting can work is someone has an interest and they create a need. But if there is no money; no research. There has not been a national focus around [CDH]. It's an ongoing problem."

Lally said researchers have applied to the March of Dimes and other funding sources, with no success, and added that it might take a big name coming out in support to see anything done. He noted Danny Thomas was the impetus behind St. Jude Children's Research Hospital, and Jerry Lewis brought the attention to muscular dystrophy through his telethon.

One of the few studies that is actively researching CDH and its cause is the DHREAMS Study at Columbia University Medical Center in New York City. The study is focused on understanding the potential genetic basis for CDH, and is being headed by principal investigator Dr. Wendy Chung.

"One of the questions parents ask me is what does this mean for the future of my child? They want to understand the long-term health and well being impacts," Chung said. "One of the frustrating things is we don't always know the answer to that question. We want to try and give better information to the families about that, and if we can find out what caused it we might be better able to understand the long-term impacts."

The study that eventually became DHREAMS began at Columbia eight years ago, and three-and-a-half years ago it received funding from the National Institutes of Health. To date there are 150 families like Thomas' participating, but Chung said they will take as many as are willing to be involved.

"I think we were fortunate," Chung said of DHREAMS funding. "I think the general concern is, because thankfully [CDH] is not very common, and the budget at NIH, and the entire government, is very severe." She noted that only 8 percent of applications for funding actually receive money, and that biomedical research in particular is very difficult to obtain. "We were fortunate to get funding for a disease that is not necessarily in the forefront of people's minds but is for a constituency that can't vote."

There is a Congressional bill being pushed by CHERUBS to designate federal funding to CDH research, and Williamson is hopeful that it will find a strong sponsor in Congress.

"There is an astronomical amount of money being spent for these kids after they are born for healthcare. It would save so much money if it would stop it from happening. If we could better diagnose them before they are born," she said.

Indeed, money is often tight for families with children who have CDH, between hospital stays and surgeries, to medical equipment like ECMOs, or extracorporeal membrane oxygenation machines. Often one parent cannot work so the child can receive round-the-clock care.

"Money is difficult," Thomas acknowledged, saying they have been working with Medicaid since January. "It is difficult to make them understand."

Lally noted, however, that passing a bill does not ensure a step forward in funding levels.

"It has to be followed by a funding line. There would have to be a congressional mandate," he said, adding that while he would like to see something like that happen, "I think that is highly unlikely."

The Steps Forward

Like many doctors who have devoted time and effort to CDH patients and research, Lally and Chung came to know the defect through patients. And at the time they first saw CDH patients, there was little hope for survival.

In the 1990s, Lally was heading a program in San Antonio that worked with ECMO machines, and a girl was brought in with CDH. "The only thing we could do is put her on ECMO. We had a CDH baby on ECMO, and I had never done that before. It turned out that not many people had," he said. "The issue of, does she have a survivable problem, that really started my interest in CDH."

Now ECMO is used on a number of CDH babies who have lung problems stemming from the condition, and has been credited partially with the uptick in survival rates.

As part of his decades-long work on CDH, Lally developed and runs the CDH registry, which includes data on more than 6,000 cases across the country and internationally. Lally said the low numbers served as the impetus for the registry.

"When we created the registry, the problem was that while it is not that uncommon, the per-center numbers are going to be very low. Fifteen to 20 cases a year is a high number. To get 100 patients for a series would take five years," he said. "The problem was that single institutional data was all that was available. And treatments changed quickly especially in the 1990s, so you had a moving treatment target and a relatively uncommon problem per institution."

Lally's ultimate goal with the registry is to determine if there is an optimal way to treat and help children born with CDH. By observing what is happening at the centers on the registry, more can be learned about the disease and what treatments appear to work.

"What we can get to the centers then is risk-adjusted outcomes. That helps from a quality improvement standpoint," Lally said.

Lally said that no matter how much research and work is done, a 100 percent survival rate is unlikely. But things have improved in the last decade, he said, pointing to the 72 percent survival rate of registry participants. As the survival rate increases, Lally said, so does the focus on how to improve the quality of life for the children as they grow up. That is a fairly new area of research, as there are few children who 10-15 years ago made it to their teenage years or adulthood.

"We'd like to link a standard post-natal follow-up between multiple centers," Lally said.

As for the cause of CDH, Chung said there have been some interesting preliminary findings from the DHREAMS study-namely that in approximately 10 percent of the children there is micro-dilution or duplications, in laymen's terms, parts that are missing or extra within their DNA.

"In a way that make sense," Chung said. "Those are the children that tend to do worse."

In the past year, the study also has begun looking at familial CDH, where more than one member of a family has the defect. While it is not very common, particularly in multi-generational families because older CDH babies were not living to their childbearing years, the fact that there is any correlation between siblings or cousins indicates there might be a genetic link.

To help determine the cause, DHREAMS researchers have begun using exome sequencing, which isolates and sequences all exons, or the coding portions of the genes that tell the body how to grow and develop. The hope is that sequencing will help researchers determine what genetic mutations might be causing CDH, Chung said.

Researchers in all aspects of CDH also are committed to working together, and to getting information out to parents like Thomas and Passieu, who are facing unending questions. Each year CHERUBS hosts a conference for parents and researchers, where parents can share stories and find support, and researchers can share the information that has become available. It also is an opportunity for researchers to gather blood samples for research, Williamson said.

"For a lot of these families the first time they ever meet another family with a CDH baby is at one of our get-togethers or our conference," Williamson said.

Talking, she said, is important for these families. It certainly has been for Thomas.

"It is great to have that resource," she said. "If I need anything I can talk to her," she added about Williamson.

And given Brady's rough start in the world, there is a lot still to be done. Doctors have given him a three-month developmental delay, and so he works with an occupational therapist. He isn't crawling yet, but at nine months is sitting up. He was recently diagnosed with epilepsy, and has had some brain volume loss.

But it is his smile that shines through, and makes him seem like any other happy nine-month old boy, learning about the world, and working to make his way in it.

"The doctor told me, in your lifetime you will never know why this happened," Thomas said, holding Brady. "But my hope is we will know in his lifetime."