Research Ethics Blog

Spina bifida is a serious developmental birth defect in which the spinal cord and backbone fail to develop completely and infants may be born with some of the spinal cord protruding out of their middle or lower back. Treatment typically involves surgery as soon as possible to repair the birth defect. There are different forms of the defect and depending on the presenting form and the treatment, children born with spina bifida may have varying levels of disability.

Surgery on the spina bifida deformation can occur prenatally, i.e., while the fetus is still in the womb, or it can occur soon after birth. A recent story in The New York Times notes that there is now clinical evidence that surgery done while the fetus is still in the womb results in better outcomes and far less disability for children compared to children who have the defect repaired surgically after birth.

The story highlights a seven-year study (that recently ended) in which mothers of fetuses who had been diagnosed with spina bifida were randomized into one of two treatment arms: to either have reparative surgery prenatally or to have surgery soon after birth to repair the spina bifida defect. The study was stopped after it was found that the outcomes in the prenatal surgery arm were simply better — children were less disabled, were more likely to walk and had less neurological complications.

Here is the story from The New York Times: Risk and Reward In Utero

“It was one of the hardest decisions I had to make to be in the study,” said Ms. Shapiro [a pregnant woman who enrolled in the study], who knew how disabling spina bifida was because her sister-in-law has it. “It was a big disappointment that we didn’t get the prenatal surgery because I knew that that was the surgery that was most likely going to help him the most, because otherwise why would they be doing the study? But at the same time, he could have died or been born prematurely from prenatal surgery. When they explained everything to us, I wanted to be in it regardless.”

This is a fascinating study. The potential for the future is pretty amazing. But, as the story notes, the study raised some interesting ethical issues.

First, the study was stopped by the local monitoring board as clinical equipoise was disturbed when the prenatal surgery was found to be so much better, in terms of outcomes, than surgery done after birth. Prenatal surgery was seen as a potential panacea, in the 1990s and early 2000s, for repair of the spina bifida defect (see the link to the 2003 story below) but while outcomes were generally good, the surgery did (and still does) involve significant risk to both mom and fetus — and there wasn’t enough good data on outcomes, the safety risks and health complications. Thus the obvious need for a clinical trial. Did the trial start out with clinical equipoise though? We’ve written about clinical equipoise here before, i.e. the genuine uncertainty about what the preferred treatment might be at the outset of a clinical trial. Physicians and parents, as the story demonstrates, clearly believed that the prenatal surgery option resulted in better outcomes and was worth the risk. In fact, many pregnant women who enrolled in the trial did so just to have a chance at accessing prenatal surgery.

The physicians who were involved in the study knew that pregnant women would not enroll in the study if the prenatal surgery was offered elsewhere (as it was up until the study), so they persuaded other hospitals not included in the study to stop offering the prenatal surgery. Thus, pregnant women were essentially forced to enroll in the trial for a chance to be randomized into the treatment arm that provided the prenatal surgery. However, as a result of randomization, many of these women who enrolled were randomized into the other treatment arm and received surgery after the birth of their infant.

It’s interesting (from both a practical and an ethical perspective) that a procedure, albeit one with risks involved, that was offered before the start of the trial to pregnant women carrying fetuses with diagnosed spina bifida, was, for all intents and purposes, no longer offered except (possibly) through enrollment in a clinical trial. Physicians who, before the trial, could offer this treatment to their patients (with all the potential risks and benefits involved), were no longer free to do this if they were providing care in a hospital that was not part of the clinical trial. While some bioethicists quoted in the story feel that the move to limit access to the prenatal surgery was a bold, collaborative step, others state that it was ethically problematic to take away any notion of choice for pregnant women by severely limiting access to an option many already felt to be superior, that was desired by many even with the risks.

While many clinical trial participants enroll with altruistic objectives, others enroll in order to access treatments and procedures that might only be available through a trial. This is seen, often, with drugs that are not yet freely available on the market until clinical testing is complete. In this case, clearly, pregnant women would be interested and motivated to enroll, out of genuine concern for the future of the child they are carrying. Altruism might well be part of the motivation — as the story notes, one gracious woman who was randomized into the after-birth surgery felt that while her son did not benefit from the surgery as much as he might have from prenatal surgery (he has some significant disabilities), participation in the trial contributed to knowledge about his disease. Needless to say, it’s a good thing that the trial was done and also a good thing that it has been stopped in order to make what has been shown to be a superior treatment available, once again, to all.

If you’re interested in this really fascinating topic, here are two related stories. The first is a recent story from The New York Times on the possibilities related to the outcomes of this trial: Success of Spina Bifida Study Opens Fetal Surgery Door.

The second is a much older story from The National Review in 2003, on the emerging possibilities of fetal surgery for spina bifida. (I remember this story when it was published for the unforgettable image, shown above, called “The Hand of Hope”): Miracles of Life: The Beltway goes inside the womb

~ by Nancy Walton on February 15, 2011.

Posted in by Nancy Walton, children, clinical trials, consent, ethics committees, neurological, recruitment