Follow-up to landmark spina bifida study could influence future treatment

1/30/2013

HOUSTON — Almost 10 years ago, the Management of Myelomeningocele (MOMS) study began comparing two approaches to treatment for a serious form of spina bifida: prenatal surgery versus the standard postnatal repair.

This breakthrough study, funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and published by the New England Journal of Medicine in 2011, found that children whose spina bifida defects were repaired surgically before birth were more likely to walk without the assistance of orthotics or devices.  NICHD is one of the Institutes of the National Institutes of Health.

Now, a follow-up study, also funded by NICHD and informally known as MOMS2, is being conducted to determine whether prenatal repair done in the original study influenced the adaptive behavior of these children, now 5 to 9 years of age, compared with those who underwent postnatal repair.

One of the effects in question is the brain development of these children. Jenifer Juranek, Ph.D., a neuroimaging expert with the Texas Fetal Center and the Children’s Learning Institute at The University of Texas Health Science Center at Houston (UTHealth), is performing high-resolution magnetic resonance imaging (MRI) brain sequences on 177 of the children from the original study to investigate if those who underwent prenatal surgery experienced greater structural modification in their brains than those infants who underwent postnatal surgery.

The follow-up brain imaging protocol was set up by Juranek at each of the three original MOMS study sites: Vanderbilt University in Nashville, Tenn., The Children's Hospital of Philadelphia, and the University of California at San Francisco. Each follow-up image will be analyzed and quantified by Juranek for such key development indicators as brain volume, matter integrity, synaptic pruning (i.e., when excess connections between cells are eliminated) and myelination, which enables nerve cells to transmit information faster and allows for more complex brain processes.

“Researchers have demonstrated that many neurodevelopmental disorders like spina bifida may be linked to poorly-timed cellular events during brain development. These events lead to specific structural and functional brain development,” said Juranek. “With this follow-up study, researchers can evaluate the impact different intervention strategies have on brain structure, function and behavior.”

The results of the MOMS2 study could influence future surgical procedures for babies diagnosed with myelomeningocele, says KuoJen Tsao, M.D., associate professor of pediatric surgery at UTHealth Medical School and a co-director of the Texas Fetal Center.

“The MOMS study gave us data that goes two or three years out from surgery, but we know there is a lot of development beyond that,” said Tsao. “We know there are certain short-term outcomes, but there may be some long-term neurological effects we don’t know about. What’s most exciting about the MOMS2 study is they are going to follow these patients at school age.”

One common risk associated with myelomeningocele is the buildup of fluid inside the skull that leads to brain swelling. This swelling is repaired with shunts inserted into the brain to relieve pressure. The original MOMS study found that prenatal surgery reduced the need for shunts, which may improve long-term brain development.

“Once you put in a shunt you have risks,” said Juranek. “Getting into the center of brain isn’t easy. If you put in a shunt, you are likely to cut through gray and white matter, both of which are responsible for certain brain functions.”

Tsao added, “The important thing about the MOMS2 study is it will answer questions that we are asking now. That’s where Dr. Juranek’s work is very important.”

Other follow-up testing will look at other development factors such as attention, executive function and fine and gross motor skills.