Dr. Shahal Rozenblatt, Clinical Neuropsychologist, New York

NYTimes- Success of Spina Bifida Study Opens Fetal Surgery Door

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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 tremendous 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 that fetal surgery can help babies with a condition that is not usually 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 $22.5 million study, long awaited by experts and published online Wednesday 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 Dr. Joe Leigh Simpson, an obstetrician and geneticist 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 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, Dr. Diana Farmer, surgeon in chief at 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.

Conducting the study was itself challenging. Prenatal spina bifida surgery gained attention in the late 1990s when some medical centers, like Vanderbilt University, began performing it. A photograph in which a fetus’s hand appeared to be gripping the finger of a surgeon who had lifted the hand out of the womb was circulated by opponents of abortion rights, further raising the profile.

Leading experts suggested a clinical trial to determine if prenatal surgery was better than postnatal. They insisted on an unusual agreement: that all but three hospitals, in Philadelphia, San Francisco and Nashville, stop doing the procedure.

There were lots of places that wanted to do it amid pressure from eager patients, said Dr. Michael Harrison, who pioneered fetal surgery at the University of California, San Francisco, and was a principal investigator for the spina bifida trial before retiring. But we wanted to make sure it wouldn’t become a freak show. And if you offer treatment outside the trial, you’ll never have a trial because no mother would agree to flip a coin.

Ultimately the other hospitals acceded.

One reason spina bifida researchers wanted a trial was the experience with prenatal surgery for a condition in which the diaphragm has life-threatening abnormalities.

After early efforts to repair the condition prenatally, we thought we were heroes, Dr. Harrison said, but realized it worked only for milder cases. Another prenatal approach, forcing the lungs to grow, worked, but caused significantly premature births, making it no better than postnatal treatment, he said. He added that prenatal techniques had improved, becoming less harmful.

The spina bifida study involved the most severe form, myelomeningocele (MY-ell-oh-men-NING-guh-seal), 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. About one in 3,000 children have that form, said Dr. Alan Guttmacher, director of the National Institute of Child Health and Human Development, which financed and helped conduct the study.

Many babies now receive surgery to close the spinal opening after birth, but nerve damage from the spinal cord 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, Dr. Scott Adzick, chief of pediatric surgery at 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.

Although they were born at 34 weeks of pregnancy on average, compared with 37 weeks for the postnatal group, there was no difference in cognitive development, said Dr. Catherine Spong, chief of pregnancy and perinatology at the child health institute.

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.

Results were dramatic for Tyson Thomas, of Stansbury Park, Utah, now 22 months old. His mother, Jessica Thomas, a study participant, said doctors had described his brain malformation as the worst they had ever seen and said it would be likely that he wouldn’t be able to breathe on his own.

Since birth at 35 weeks gestation, she said, Tyson breathes independently, shows no brainstem malformation and is starting to talk. Bladder nerve damage will require him to urinate through catheters all his life. He now uses a walker and a foot brace, but is getting really close to walking on his own, said Ms. Thomas, a nurse.

Researchers will follow the children from ages 6 to 9 to see if benefits continue.

Several experts said they would now mention prenatal surgery as one option for some women. But since many women were excluded from the study, including those who were severely obese or whose babies conditions did not fit certain specifications, many may be ineligible.

The study should not propel surgeons to run around and start doing this for other conditions, said Dr. Terry Buchmiller, a fetal medicine expert at Children’s Hospital Boston who was not involved in the research. I can go in utero right now and fix a cleft lip, but I don’t think anybody is saying we ought to do that, because of the risk.

But she called the study a wonderful, almost several-decade journey of trying to improve the outcomes of a debilitating condition, adding, This looks to be potentially life-changing.