Summer 2011

Fetal Treatment — New Devices and Procedures

As the birthplace of fetal surgery, the UCSF Fetal Treatment Center is an international leader in treating diseases in utero. Professor Emeritus Michael Harrison, M.D., the center's founder, performed the world's first open fetal surgery at UCSF in 1981.

Now under the direction of Associate Professor Hanmin Lee, M.D., the center has a team of experts who provide the full range of fetal interventions, tailoring treatment to each specific family and problem. "For many families, we are the end of the road," Lee said. "A lot of families tell us, 'Before we got to you, we didn't have hope.'" Lee is an expert in minimally invasive neonatal surgery, and has pioneered the application of these techniques to fetal surgery.

At Least Two Patients

Every fetal surgery has at least two patients — the mother and the fetus — and sometimes more, in the case of twins. When presenting different options to families, the most important consideration is the safety of the mother and her reproductive potential. Minimally invasive approaches can reduce the potential harm to the mother, and may also result in less preterm labor, the major complication of fetal intervention.

The Fetal Treatment Center receives about 350 referrals annually. Jody Farrell, R.N., M.S., P.N.P., the center's clinical coordinator, obtains the history from the referring physician and has the obstetric records sent to UCSF for review.

About 250 families come to UCSF for a multidisciplinary counseling session with geneticists, obstetricians, pediatric and fetal surgeons, ultrasonographers, neonatologists, social workers and other specialists. Pregnant families meet with up to eight specialists in one day. Then, the following week, the patient is presented before the Fetal Treatment Center team, and recommendations are forwarded to the patient and referring physician. This multidisciplinary conference is attended by about 50 specialists.

The team works together to develop a complete, accurate diagnosis, made possible in part by UCSF’s outstanding radiology and cardiology departments. Professor Diana Farmer, M.D., a fetal surgeon, surgeon in chief of UCSF Benioff Children's Hospital and chief of the Division of Pediatric Surgery, said, "We have a lot of experience in watching these disorders over time, and being able to predict which ones get better on their own, and which ones are going to get worse and put the fetus at risk." In many cases, fetuses do not require intervention, or can be treated after birth. "We partner extensively with patients’ referring doctors, because often the best recommendation is for patients to go back and deliver at home," Farmer said.

Another strength of the Fetal Treatment Center is that surgeons conduct laboratory research, helping to bring the latest innovations to patients as soon as possible. "Our trademark is judicious and ethical application of novel and emerging technologies and procedures," Lee said. "We accomplish this by having robust animal data, conducting novel interventions in the context of trials, when appropriate, and bringing all the different experts together in one room to discuss new enterprises."

New Devices and Treatments

The Fetal Treatment Center provides interventions for the most severe fetal conditions. The most common anomaly seen by the center is Twin-Twin Transfusion Syndrome (TTTS), in which identical twins sharing a placenta and blood vessel connections develop an imbalance in blood circulation. There may be significant transfer of blood from one twin to the other, causing dehydration for the twin with insufficient blood, and cardiac failure for the twin receiving too much blood. Neither will survive without intervention.

Lee led a clinical trial to determine optimal treatment for TTTS. Fetal surgeons insert a straw-sized scope and use a thin laser fiber to photocoagulate the blood vessels connecting the twins, separating the blood supplies and often saving one or both fetuses.

Lee was also a leader in discovering improved treatment for some forms of congenital cystic adenomatoid malformation (CCAM), also known as congenital pulmonary airway malformation (CPAM). CCAMs occur when a cystic piece of abnormal lung tissue replaces one lobe of the lung. Although many CCAMs can be treated postnatally, fetuses with CCAM that also develop hydrops experience almost 100 percent mortality.

About a decade ago, the Fetal Treatment Center team observed several pregnant women who had fetuses with microcystic CCAMs and hydrops, and received preoperative steroids before fetal surgery, but then declined surgery at the last moment. Nevertheless, their fetuses survived. Lee is currently leading a trial to determine if administering steroids prenatally in such cases provides a better treatment alternative.

"The hypothesis is that steroids drive lung maturation in the CCAMs to become more normal lung tissue," Lee said. Preliminary data to indicate that fetuses with microcystic CCAMs and hydrops that are treated with steroids have an 80 percent survival rate, compared with about 50 percent for open fetal surgery, and less than 10 percent with no treatment.

Myelomeningocele Clinical Trial

Farmer led the MOMS (Management of Myelomeningocele Study) clinical trial, comparing whether patients with spina bifida benefit from fetal surgery compared to postnatal surgery. She was the senior author of a paper published in February 2011 in the New England Journal of Medicine, demonstrating that prenatal surgery for myelomeningocele reduced the need for shunting and improved motor outcomes at 30 months. Prenatal surgery had been associated with maternal and fetal risks, particularly an increased risk of preterm delivery. The eight-year trial was stopped early because results were positive.

"Up until spina bifida, we would only consider fetal surgery in cases of life or death for the newborn," Farmer said. "Now, after three decades of no maternal deaths in this country from open fetal surgery, we're asking if the risks are justified to consider just making fetuses better. Based on our findings, it appears that fetal surgery can provide a better option for these patients than waiting to treat them after birth."

Another common condition is congenital diaphragmatic hernia (CDH), in which a hole in the fetus's diaphragm allows the abdominal organs to migrate into the chest, compressing the lungs. Harrison developed an intervention to occlude the fetal trachea, stimulating lung development by blocking the exit of fetal lung fluid. This fluid forces the lungs to expand, and can then displace the abdominal organs out of the chest. Assistant Professor Doug Miniati, M.D., is developing a new device that intermittently occludes the trachea, which may support more normal lung development.

Harrison is now developing a new way to seal the uterine membrane during fetal surgery. "The limiting factor in all fetal intervention is premature rupture of the membranes," he said. "Whether we use a needle, laser or knife, we have to open the membranes to access the fetus. When those membranes come off the uterine wall, they cause preterm labor and delivery."


Building on 30 years of experience — he had to invent many of the tools and devices used in fetal surgery himself — Harrison was recently awarded an FDA stimulus grant to fund the Pediatric Device Consortium. This group of physicians, scientists, engineers, designers and students collaborates on developing devices specifically designed for children. Harrison is working with chemists and engineers to develop a gel-like adhesive that can be delivered to the space between the muscle of the uterine wall and the membrane, preventing spread of amniotic fluid into this space after fetal intervention. "A lot of the chemistry of this adhesive will derive from the science of how ocean creatures like mollusks stick to rocks," Harrison said.

Other Fetal Treatment Center innovators include Assistant Professor Shinjiro Hirose, M.D., and Assistant Professor Tippi MacKenzie, M.D.. Hirose, an expert in minimally invasive fetal surgery, is currently investigating improved treatments for gastroschisis, a congenital defect in which the anterior abdomen does not close properly, allowing the intestines to protrude outside the fetus.

MacKenzie, a fetal surgeon, investigates mechanisms of tolerance induction following in utero stem cell transplantation. This could eventually lead to novel fetal treatments for metabolic problems such as sickle cell anemia, immune deficiencies and diabetes.

Now, almost all diseases are identified and diagnosed before birth," Farmer said. "We want to correct defects before birth, so there are no more birth defects. There are just fetuses that got treatment. I want the spina bifida kids to be able to walk when they're born. (If we were successful), no child would ever get diabetes, and sickle cell anemia would be eliminated. I think it's doable. The latest frontier is correcting the fetal origins of adult disease."

LIFE Clinic

In addition to diagnosing fetal disease, counseling families and performing fetal intervention when appropriate, the Fetal Treatment Center provides long-term follow-up care to patients through its LIFE Clinic, the Long-term Infant-to-adult Follow-up and Evaluation Program.

The clinic started in 2002, and now serves almost 200 children who received either prenatal or postnatal treatment for congenital anomalies, including congenital diaphragmatic hernia, esophageal atresia, pulmonary sequestration, CCAM/CPAM, sacrococcygeal teratoma, choledochal cysts, imperforate anus, Hirschsprung's disease and other conditions. Children are followed into adulthood.

In addition to assessing fetal surgery patients' long-term outcomes and screening for related comorbidities, the clinic helps provide resources on how to best manage these diseases. Barbara Bratton, R.N., M.S., P.N.P., clinical coordinator for the LIFE Clinic, said, "We try to pull together what the standards are for caring for each patient, given their different conditions, and put that in a letter to their primary care provider."

Farmer said, "It's like a cancer survivors' clinic. Before, the fetuses died. Now that patients are living with these different deformities and birth defects, we support them into adolescence and adulthood as they learn to live with these conditions."

Consultations and Referrals

For more information, please contact the Fetal Treatment Center at or (800) RX-FETUS.

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