Promoting fetal survival and lung development for severe congenital diaphragmatic hernia

Dec. 17, 2020

Congenital diaphragmatic hernia (CDH), diagnosed via anatomic scan in the second trimester of pregnancy, can put a fetus at risk of incomplete lung development. This leads to a NICU stay for the newborn with extracorporeal membrane oxygenation support — potentially for an extended period — or even death. The diaphragmatic hole, most often observed on the left side, can envelop the liver, stomach and bowel and compress the heart and lungs, leading to underdeveloped lungs, or pulmonary hypoplasia.

FETO offers prenatal option for CDH

Fetoscopic endotracheal occlusion (FETO) offers a prebirth intervention that allows fetuses with CDH a better opportunity for survival and for expansion of their expected lung area and lung area to head circumference ratios. Around 20 weeks' gestation, the maternal-fetal medicine specialist occludes the fetal trachea with a detachable balloon, inflating and filling the lungs with fluid, thereby promoting prenatal lung growth and potentially lowering pulmonary hypoplasia postnatally.

The actual FETO procedure takes only 20 to 30 minutes. However, the preparation time far surpasses the actual procedural interval, including determining fetal position and needle trajectory. Usually patients are admitted for one day.

During the intervening weeks following balloon placement, the expectant mother is required to live locally — within a 10- to 15-minute drive — so the on-call team is able to remove the balloon quickly in case of any emergency.

"If you establish a program for fetal intervention, the most important thing is to plan for emergent situations," says Rodrigo Ruano, M.D., Ph.D., an obstetrician and maternal-fetal medicine specialist at Mayo Clinic in Rochester, Minnesota, who has completed more than 90 fetal endoscopic tracheal occlusions for severe congenital diaphragmatic hernia. "We did this safely when I practiced in Brazil, and then Houston, and now at Mayo Clinic."

After the six weeks of balloon placement, the balloon is removed at 34 weeks' gestation in a second procedure, after which the mother is free to return home. A fetus with CDH needs to be born in a specialty center equipped to care for the newborn, says Mauro H. Schenone, M.D., an obstetrician-gynecologist and maternal-fetal medicine specialist at Mayo Clinic's campus in Rochester, Minnesota, who works alongside Dr. Ruano on fetal intervention.

FETO can transform the lung to head ratio from 20% to 30% to 80% or higher, and reduce the rate of extracorporeal membrane oxygenation use from 70% to 30% postnatally, indicates Dr. Ruano. After the infant's respiratory status has proved stable, surgery can be undertaken for hernia repair.

Need for fetal anatomy exam and prompt referral for intervention with CDH

CDH is present in 1 out of every 2,000-3000 births, explains Dr. Ruano, who emphasizes that such defects make an 18- to 22-week fetal anatomy exam crucial. He also emphasizes the importance of immediate referral upon CDH diagnosis to a specialist fetal surgical center to begin prenatal work-up, as he and colleagues describe in the Oct. 30, 2020, issue of Prenatal Diagnosis. Mayo Clinic's campus in Minnesota is one of only six or seven medical centers where FETO for CDH is offered. Alternatively, the physician may elect to continue watching fetal development. However, if the CDH is severe enough, the chance of fetal survival is low without intervention, according to Dr. Schenone.

FETO risks and survival rates

Preterm delivery is one of the potential risks of FETO. On average, an expectant mother whose fetus is diagnosed with CDH delivers at 34 to 35 weeks' gestation, and some deliver at full term. Less than 5% of expectant mothers who've undergone FETO for CDH will deliver before 30 weeks' gestation. Premature membrane rupture is also a potential risk of the procedure. If this occurs at 35 to 37 weeks, the fetus can be delivered safely.

Dr. Ruano acknowledges that CDH presents a challenging situation for expectant parents and providers alike. He notes that mothers expecting babies diagnosed with CDH often feel scared. He attempts to provide hope for them and yet also be realistic. Because FETO can greatly increase the survival of a fetus with severe CDH, FETO can also change the direction of an expectant mother who is considering termination options, he says.

The survival rate for fetuses undergoing the FETO procedure for CDH is 70% to 80%. For the 20% of fetuses who do not survive, the lungs are too diseased and grow very little during balloon placement.

Clinical trials for FETO for CDH intervention

Dr. Ruano has conducted previous clinical trials demonstrating the benefit of FETO for lung development and is currently accruing patients to a phase I safety trial of FETO for CDH, observing maternal complications, safety in balloon placement, and overall program and fetal outcomes. The study will include 10 patients total, and the investigators need to accrue three additional patients.

"We are here to help and to give patients hope," says Dr. Ruano. "This procedure can help babies and provide better lungs. We are carefully following all guidelines to conduct this program safely."

FETO for CDH was first performed at Mayo Clinic's campus in Rochester, Minnesota, in January 2017, as noted in the June 2018 issue of Mayo Clinic Proceedings. It is not yet offered at Mayo Clinic's campuses in Arizona and Florida.

For more information

Perronne, EE. Prenatal assessment of congenital diaphragmatic hernia at North American Fetal Therapy Network (NAFTNet) centers: A continued plea for standardization. Prenatal Diagnosis. In press.

Ruano, R, et al. Fetoscopic therapy for severe pulmonary hypoplasia in congenital diaphragmatic hernia: A first in prenatal regenerative medicine at Mayo Clinic. Mayo Clinic Proceedings. 2018;93:693.