For years, surgeons have been trying to find ways of operating on babies in the womb, reasoning that medical abnormalities might be more easily fixed while a fetus is still developing. But with substantial risks to babies and mothers, and a mixed record of success, fetal surgery is mostly used when babies are likely to die otherwise.
Now, for the first time, a rigorous clinical trial shows fetal surgery can help babies with a condition that is not life-threatening. Babies with a form of spina bifida, a debilitating spinal abnormality, were more likely to walk and experience fewer neurological problems if operated on before being born rather than afterward.
The U.S.-government funded study, published this week in The New England Journal of Medicine, is likely to galvanize interest in trying to address problems before birth, including operating on serious heart defects and bladder blockages, and potentially using fetal bone marrow or stem cell transplants for sickle cell anemia and immune disorders.
“It’s a good start, a step in the right direction,” said Joe Leigh Simpson, at Florida International University, who wrote an editorial that accompanied the research. “It showed improvement and that there’s reason to continue looking for a better mousetrap.”
Still, he said, “the improvement that was hoped for, the home run or the holy grail” of eliminating all major problems “obviously did not occur.”
And as technology increasingly allows doctors to diagnose problems in a developing fetus, the study underscores the remaining risks and hurdles, including developing less-invasive techniques to avoid creating other problems for babies or mothers.
The spina bifida procedure was considered beneficial enough that an independent safety monitoring board stopped the study early so babies scheduled to receive surgery after birth could have access to prenatal surgery.
But there were medical downsides for the women and infants: greater likelihood of being born several weeks earlier than the postnatal group, related breathing problems and thinning or tearing at women’s surgical incisions, requiring Caesarean sections for later births.
“While this is a very promising and quite exciting result,” said a study author, Diana Farmerat the Benioff Children’s Hospital at the University of California, San Francisco, “not all the patients were helped here, and there are significant risks. This procedure is not for everyone.”
The spina bifida study involved the most severe form, myelomeningocele, in which the spine does not close properly and the spinal cord protrudes. Children may experience lower-body paralysis, fluid on the brain, bladder problems and learning disabilities.
Many babies now receive surgery to close the spinal opening after birth, but nerve damage from the spinal cord’s exposure to amniotic fluid remains. Also, the brainstem may be pulled into the spinal column. Excess fluid in the brain may require draining with implanted shunts, which can lead to infection or need repeated surgical replacement.
In the study, about 80 babies were randomly selected for surgery after birth; another 80 had the spinal opening surgically closed in utero, between 19 and 26 weeks of pregnancy. Two in each group died.
Before surgery, babies in the prenatal group had more severe spinal lesions than the postnatal group, but more in the prenatal group had better results, said a co-author, Scott Adzickat Children’s Hospital of Philadelphia.
Those who received prenatal surgery were half as likely to have a shunt, and eight times as likely to have a normally positioned brainstem. There was “much better motor function of the legs,” Dr. Adzick said, and at 30 months old, nearly twice as many walked without crutches or orthotics.
Dr. Adzick said prenatal surgery may “stop exposure of the developing spinal cord and perhaps avert further neurological damage” or stop the leak of spinal fluid that causes brainstem problems.