The causes of the most common permanently disabling birth defect in the United States, spina bifida, are not well understood. And, there is no cure.
The most recent studies indicate that in the United States, approximately 13 percent of individuals born with spina bifida die before their first birthday; 25 percent die before turning age 18. Persons with this condition also are subject to excess mortality throughout adulthood.
The good news is, thanks to the latest medical treatments and technology, most people with spina bifida live a normal life. They have careers, get married and have children.
Nonetheless, preventing spina bifida is the ultimate goal. And, that goal is the driving force for several researchers at the Texas A&M Health Science Center Institute of Biosciences and Technology at Houston.
“My research focuses on identifying genes that influence the risk of common birth defects in humans and determining how such genes interact with each other and with environmental factors to ultimately result in these conditions,” said Laura Mitchell, Ph.D. “Most of my research focuses on three groups of birth defects: neural tube defects - which include anencephaly and spina bifida - congenital heart defects and facial clefts - which include cleft lip and cleft palate.”
Dr. Mitchell is principal investigator for the Spina Bifida Research Resource (SBRR) at the HSC-Institute of Biosciences and Technology and a member of its Center for Environmental and Genetic Medicine.
The Spina Bifida Association of America reports about 70,000 people in the United States have spina bifida. This condition occurs in the first month of pregnancy, when the neural tube, the structure that develops into the spinal cord and brain, does not form properly.
Although a woman can reduce her risk of having a child with spina bifida or other types of neural tube defects by taking a multivitamin containing folic acid prior to and during pregnancy, approximately 3,000 pregnancies are affected by spina bifida each year in the United States.
“Individuals with spina bifida are at risk for lower extremity weakness and paralysis, sensory loss, bowel and bladder dysfunction, orthopedic abnormalities, associated malformations of the nervous system, and specific learning disabilities,” Dr. Mitchell said. “These individuals require life-long, specialized, multi-disciplinary health care.”
Dr. Mitchell and her SBRR colleagues at HSC-IBT and the University of Pennsylvania School of Medicine are analyzing data provided by more than 600 spina bifida families nationwide since the study opened in 1997. Funded for the last five years by two grants from the National Institutes of Health, their work focuses on genes that may influence development of spina bifida.
“We have conducted analyses of about a half-dozen genes and had some positive findings,” Dr. Mitchell said. “The study will continue for an additional five years with funds from a new NIH grant. This will allow us to recruit an additional 400 families and expand the number of genes that can be studied.”
However, the SBRR is just one of several research efforts to understand the causes of spina bifida that are underway at the HSC-Institute of Biosciences and Technology. Studies in other populations, and in animal models, are ongoing at the Institute.
Dr. Mitchell and her colleagues also are taking their spina bifida research across the ocean. In collaboration with Dr. Richard Finnell, Ph.D., director of HSC-IBT; Dr. Kirby Donnelly, Ph.D., professor in the Texas A&M Health Science Center School of Rural Public Health; and Dr. Stephen Safe, D.Phil., director of the HSC-IBT Center for Environmental and Genetic Medicine, she recently received funding from the NIH to study the causes of neural tube defects in the Shanxi region of northern China.
Spina bifida and related diseases are extremely common in that area, with as many as one in every 100 babies having a neural tube defect.
The China study concentrates on the role of environmental factors in determining neural tube defects and is being conducted in association with Dr. Li Zhu, a professor at the Peking University Institute for Reproductive and Child Health.
“The recent trip to China was my first visit to this country,” Dr. Mitchell said. “My goal was simply to meet with some of the people that we will be working with, such as hospital administrators and research staff, to get familiar with the study region. The latter is particularly important when developing the study questionnaire because it gives some perspective on living environment, potential exposures, etc.”
According to Dr. Finnell, researching the causes of birth defects such as neural tube defects requires both population studies and laboratory investigations. And, with work conducted simultaneously in the United States and China, multiple objectives can be achieved.
“We hope to identify environmental factors that influence the development of spina bifida and help to explain the very high prevalence of these conditions in Shanxi,” Dr. Finnell said. “In addition, we are looking for genes that may influence whether an embryo that is exposed to a particular environmental factor actually develops a neural tube defect. We hope that by identifying the factors that influence the risk of neural tube defects and understanding how these factors interact to result in these conditions, we will be able to devise more effective intervention strategies to prevent birth defects.”
Back in the United States, Phase I of the SBRR study is being completed, with the second phase expected to start this summer. All aspects can be conducted by phone and/or mail. No travel is required, and there are no study costs.
“We are happy to put people onto a list of potential subjects for the next phase,” Dr. Mitchell said. “Participation will include an interview, usually with the mother of the individual with spina bifida, collection of samples for DNA and permission to contact additional relatives of that individual, such as the mother, father, siblings and maternal grandparents.”
For more information on the Spina Bifida Research Resource, call (866) 521-7289 or visit http://www.sbrr.info.
Revision date: June 20, 2011
Last revised: by Andrew G. Epstein, M.D.