Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Survival improves in clinical trial for severe birth defect, with or without fetal surgery

14.11.2003


Endoscopic fetal treatment increases survival to 73 percent for a severe defect that hampers lung growth -- comparison group in a randomized trial increases survival to 77 percent with standard care in an expert neonatal intensive care unit



Newborns with a severe birth defect that hampers lung growth have an equal chance of survival whether they are treated with maternal/fetal surgery or receive their first operation after birth -- if the infant receives life support from the moment of birth from a highly experienced neonatal intensive care team.

Both treatments achieved far better survival rates than earlier standard therapy, according to an NIH-sponsored randomized clinical trial. Results are reported in the November 13, 2003 New England Journal of Medicine.


Pediatric surgeon Michael Harrison, MD, and his colleagues at the Fetal Treatment Center at UCSF Children’s Hospital called an early halt to the trial, which evaluated treatment for congenital diaphragmatic hernia (CDH). The trial compared patients who received maternal/fetal surgery with a control group of patients given an advanced form of standard postnatal care. In both groups, fetuses were diagnosed with a severe form of CDH that causes fetal lungs to be dangerously undersized at birth. The control subjects fared surprisingly well -- and that result underscores the need for randomized studies of surgical innovations, the researchers say.

The CDH fetal treatment technique in the trial was developed by UCSF pediatric surgeons. They used a small endoscopic tube, dubbed a fetoscope, to inflate a balloon inside the trachea of a fetus floating in its mother’s womb, and stimulate growth of the fetal lungs. At delivery, the newborn’s trachea was unblocked and the lungs cleared before the umbilical cord was cut. In this fetal treatment group, 73 percent of infants with severe CDH survived. The control group of newborns with comparably severe CDH were delivered at UCSF and treated from the moment of birth. UCSF neonatologists employed advances in life support for all infants in both groups. In the group given this advanced form of standard postnatal care, the survival rate was 77 percent.

Both results are a dramatic change from previous research that showed survival rates of less than 40 percent for newborns treated after birth for this severity of CDH.

Mothers and babies from both groups received care from the same group of experts in prenatal diagnosis, high-risk pregnancy care, surgery, and neonatal intensive care. Mothers in the fetal treatment group did not suffer lasting health problems, and those hoping for more children have been able to carry subsequent pregnancies to term. Newborns in the fetal treatment group were born on average six weeks younger in gestational age, yet survival and preliminary health outcomes were similar in both groups. The strongest predictor was the size of the fetus’ lungs at diagnosis - those with the smallest lungs were least likely to survive.

"This study shows how far we’ve come in trying to save babies affected with congenital diaphragmatic hernia - and how far we have to go," said Harrison, who is the study’s lead author. He is director and co-founder of the UCSF Fetal Treatment Center at UCSF Children’s Hospital, part of UCSF Medical Center, and professor of surgery, pediatrics, and obstetrics/gynecology at UCSF.

"We stopped the trial as soon as an interim data review showed that advanced neonatal care from the moment of birth will give fetuses with one type of severe CDH a similar chance of survival as fetal intervention, without the need for surgery to the mother," Harrison said. "Although survival in both groups is encouraging, long-term follow-up of survivors shows that, as they grow up, some children from both treatment groups continue to have significant health problems."

Although very intensive treatment either before or after birth allowed most babies to survive, half the babies needed supplemental oxygen as they left the hospital; most babies went home with gastrointestinal difficulties and trouble with feeding. The study continues, following the long-term outcome for the survivors.

Harrison said that both treatment approaches present dilemmas for physicians and patients. Intervention before birth helps increase lung size, but so far, fetal intervention also causes prematurity, which can cause problems of its own. Improved intensive care for newborns now has improved survival, but for the most at-risk CDH patients, it also has long-term side effects.

The study shows the importance and feasibility of randomized clinical trials to test the value of promising surgical procedures against advances in standard care, according to Sam Hawgood, MD, chief of neonatology at UCSF Children’s Hospital and interim chair of the department of pediatrics at UCSF.

"When a patient’s condition is very complex, as in the case of congenital diaphragmatic hernia, care at every level improves over time," Hawgood said. "This study was designed to compare the best available current care for each group, and to minimize confounding variables by treating the patients at the same institution for most stages of care." In other research - including a 1994 NIH study at UCSF - fetal surgery mothers and infants got all their care from one highly-experienced medical team, while comparable standard-care infants received this expertise only after they were transported to a number of different tertiary care hospitals.

Hawgood said that the study shows that to improve the chances of survival for fetuses with severe CDH, it may be important for the mother to deliver her baby at the same hospital where neonatal intensive care experts will care for the newborn, to ensure experienced care from the moment of birth.

Harrison said that one very positive result was that the trial could be done at all. "We found that a very novel intervention for a life-threatening fetal disease in the highly charged circumstances of pregnancy could be put to the test of a sound randomized clinical trial, " he said. Many physicians believe that such trials cannot be done because patients are not willing to accept a randomization that may assign them to standard care rather than an innovative new treatment. In this trial, with cooperation from other U.S. fetal treatment centers, UCSF was the only center offering this treatment for CDH, and offered it only within the context of the trial.

He credits the courage of mothers and families who came to UCSF seeking fetal surgery. "Our patients learned that we had developed a promising new therapy, but we did not know whether fetal intervention, which includes risks to the healthy mother, would be the right choice for them. If the CDH proved severe enough to warrant fetal intervention, the family then had to choose whether to accept randomization. Surprisingly, almost all chose to join the study. Each of these mothers offered a gift of knowledge to CDH mothers in the future," he said.

During the clinical trial, UCSF offered randomization to either maternal/fetal surgery or postnatal care for 28 mothers. Four decided not to participate.

The standard treatment for all babies with CDH at UCSF (whether treated before birth or not) is for neonatologists to put the baby on breathing support from the moment of birth. Both standard-care and fetal-surgery babies need advanced breathing support to allow their underdeveloped lungs to grow; neonatologists use a wide range of techniques including surfactant, nitrous oxide, high-frequency ventilation and ECMO (extra-corporeal membrane oxygenation). Later, pediatric surgeons repair the hole in the baby’s diaphragm and return the organs to their proper places.

Co-authors with Harrison and Hawgood in the NEJM study are: Roberta L. Keller, MD, Joseph A. Kitterman, MD, Per L. Sandberg, MD, Diana L. Farmer, MD, Hanmin Lee, MD, Roy A. Filly, MD, Jody A. Farrell, MSN, PNP and Craig T. Albanese, MD.

Janet Basu | EurekAlert!
Further information:
http://www.ucsf.edu/

More articles from Health and Medicine:

nachricht Millions through license revenues
27.04.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht New High-Performance Center Translational Medical Engineering
26.04.2017 | Fraunhofer ITEM

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

Bare bones: Making bones transparent

27.04.2017 | Life Sciences

Study offers new theoretical approach to describing non-equilibrium phase transitions

27.04.2017 | Physics and Astronomy

From volcano's slope, NASA instrument looks sky high and to the future

27.04.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>