NICHD Research Aims to Understand and Treat CDH
CDH, which affects about 1 in every 3,8001 babies born in the United States, occurs in the womb when the diaphragm doesn’t develop normally. A hole, thin area, or underdeveloped muscles in the diaphragm allow the organs in the abdomen to move into the chest cavity, crowding out the heart and lungs and limiting proper lung development.
Infants with CDH are born facing significant life-threatening breathing problems and other difficulties related to organ position and lung development. Of babies born with CDH, survival rates are low and long-term health problems are likely.
Although CDH is a very serious condition that requires immediate intervention at or before birth, more infants born with CDH are surviving, likely because of research advances, earlier detection, and improved surgical treatments.
Research is improving our understanding of CDH and the molecular and genetic factors that play a role in the condition. The activities are also opening possibilities for screening, prevention, and treatment of CDH. Select a link below to learn more.
NICHD Research on CDH
CDH is often detected during a routine ultrasound during pregnancy, or immediately after birth when the infant experiences life-threatening breathing difficulties. In some cases, babies born with CDH have a bluish tint to their skin due to a lack of oxygen. In addition, infants born with CDH2 are more likely to have chronic gastro esophageal reflux disease, lung disease, and failure to thrive. These infants may also have neurological deficits and skeletal abnormalities, such as scoliosis.
CDH can also occur as part of a broader syndrome, such as Cornelia de Lange Syndrome (CdLS). Characteristics of CdLS include CDH, low birth weight, small head size, and intellectual and developmental delays.
The primary treatment for CDH is surgical repair. In most cases, the surgeon guides the organs back to their proper locations, creating space for the lungs to continue to grow, and closes the hole in the diaphragm. In some cases, if the hole is quite large, or if the infant’s diaphragm is lacking muscle on one side of the diaphragm, the surgeon will use additional tissue to patch the hole.
Currently, it is standard practice to do the surgical treatment shortly after the baby is born. However, an experimental surgical procedure called fetal endoscopic tracheal occlusion—which involves inserting a balloon into the abdominal hole while the fetus is still in the womb—is being evaluated for its effect on CDH-related outcomes. To date, studies of the prenatal surgery have shown mixed results.3 As a result of improved surgical techniques and earlier detection, survival of newborns with CDH has increased to about 67%2 from less than 50% a few decades ago.
Ongoing studies indicate that long-term health outcomes for infants with CDH may depend on how well the lungs were are ready to function at birth, whether the infant has conditions that affect other parts of the body, and whether there are complications related to the surgical treatment. Recent research suggests that infant outcomes are better when the infant is first stabilized using gentle ventilation therapy before performing any kind of surgical repair.2
NICHD Research on CDH
The NICHD’s interest in understanding the causes of and contributing factors to CDH is in line with its overall efforts to understand and prevent a wide range of birth defects. Within the NICHD’s Division of Extramural Research, the Developmental Biology and Structural Variations Branch (DBSVB) supports some of the Institute’s research on CDH, much of it with a specific focus on possible genetic causes or mechanisms of the condition.
In one project, the Branch supports a unique collaboration between basic scientists who study CDH and clinicians who work with CDH patients and their families. Combining the investigative power of Massachusetts General Hospital and the Children’s Hospital of Boston, this project takes a more multidisciplinary approach. First, the clinicians conduct comprehensive interviews, and study staff collect specific biological samples from CDH infants and children and their families. Then the basic scientists subject the samples to sequencing and other genetic investigations to identify the most likely candidate genes. They then study the most promising gene candidates in animal models to confirm the genes’ involvement in diaphragm development.
Relying on the combined expertise and knowledge of clinicians, bench researchers, and families affected by CDH offers a fresh way to study complex conditions such as CDH. In addition, these areas of research could provide a way to screen for CDH risk and a foundation for improved management and care for CDH patients. Learn more about this project at Gene Mutation and Rescue in Human Diaphragmatic Hernia.
Other DBSVB-supported studies that focus on the genetics of CDH include: Retinoid-Related Genes In Diaphragm And Cardiac Development, Molecular Genetic Analysis of Congenital Diaphragmatic Hernia, and Identification Of Novel Genes For Congenital Diaphragmatic Hernia. The Branch also supports studies of CDH as part of other conditions, such as CdLS.
A study supported by the Pregnancy and Perinatology Branch (PPB) is looking at how pulmonary blood flow in the developing embryo of a mouse affects normal lung development, as a way to shed light on defects in lung development, including CDH. Understanding the mechanisms that underlie the lung defects in CDH could lead to more effective treatment options directed specifically at disrupting those mechanisms. Read more at Pulmonary Blood Flow in Lung Development and Congenital Diaphragmatic Hernia.
Even though CDH is a relatively common and serious birth defect with life-long consequences, little is known about the condition. Through its research, the NICHD aims to understand the causes and mechanisms of CDH as a critical first step in improving survival and outcomes for infants and families affected by CDH.
For more information on CDH, select one of the following links:
- NICHD Resources
- Organizational Units
- Supported Projects:
- Gene Mutation and Rescue in Human Diaphragmatic Hernia
- Retinoid-Related Genes In Diaphragm And Cardiac Development
- Molecular Genetic Analysis of Congenital Diaphragmatic Hernia
- Identification Of Novel Genes For Congenital Diaphragmatic Hernia
- NIPBL, Cohesin and Related Structural Birth Defects
- Pulmonary Blood Flow in Lung Development and Congenital Diaphragmatic Hernia
- Related A to Z Topics
- Previous NICHD Spotlights on birth defects
- Centers for Disease Control and Prevention: Data & Statistics on Birth Defects
- National Library of Medicine
Originally Posted: July 17, 2013
- Centers for Disease Control and Prevention. (2013). Data & Statistics: In the United States. Retrieved from http://www.cdc.gov/ncbddd/birthdefects/data.html.
- National Library of Medicine, Genetics Home Reference. (2011). Congenital diaphragmatic hernia.
- Haroon, J. & Chamberlain, R.S. (2013). An Evidence-Based Review of the Current Treatment of Congenital Diaphragmatic Hernia. Clinical Pediatrics, 52(2), 115–124. PMID: 23378478