Balloon in Trachea Boosts Survival When Large Diaphragm Hernia Stunts Fetal Lung Development

By Gene Emery

June 09, 2021

NEW YORK (Reuters Health) - Temporarily inflating a balloon in the trachea of a fetus can significantly improve survival when the child has a severe congenital diaphragmatic hernia on the left side, but not if the condition is less severe, according to results from the international TOTAL trial.

"It's a new hope for a lot of patients," Dr. Jan Deprest, a professor of obstetrics and gynecology at University Hospitals Leuven, in Belgium, told Reuters Health in a video call.

"In the past, unfortunately, for one of two parents of babies with this condition, the prognosis was not good. In some countries, patients would decide to terminate pregnancy. The babies have a lot of morbidity," he said. "With this randomized trial, we can tell patients this really works. It's safe for the babies and we also know it's safe for the mother."

Dr. Deprest and his colleagues, whose study appears in the New England Journal of Medicine, used a balloon already sold to treat adult brain aneurysms and took advantage of the fact that fetal lungs are producing amniotic fluid. When the balloon is inflated in the trachea after the hernia has allowed the abdominal organs to encroach into the chest cavity, "there's a buildup of pressure that forces the lungs to grow," Dr. Deprest explained.

When the balloon is removed, usually after a few weeks, it sparks pulmonary maturity.

All of the newborns received conventional surgery to properly partition the organs and close the diaphragm.

When the in-utero problem was severe and balloon surgery was performed at 27 to 29 weeks of gestation, 40% of the infants survived to discharge versus only 15% of the babies where there was no in utero intervention (P=0.009).

Survival at six months of age was also 2.67 times higher among the infants who received the in-womb surgery, known as fetoscopic endoluminal tracheal occlusion or FETO.

When the hernia was judged to be of moderate severity, the rates of survival to discharge from the neonatal intensive-care unit were 63% with FETO versus 50% without, a non-significant increase of 27% (P=0.06).

At six months, 54% of the FETO babies were alive without oxygen supplementation versus 44% in the control group, respectively.

The problem was adverse events.

The odds of preterm, prelabor rupture of membranes was nearly four times higher with the fetal surgery, with rates of 44% among FETO recipients and 12% in the control group, a significant difference. The risk of preterm birth was nearly three times higher, which also represented a significant risk increase.

In cases where the herniation was severe, the risk of prelabor membrane rupture was even greater - 4.5-fold - with rates of 47% and 11% respectively. The chances of preterm birth were 2.6 times higher.

The results were also presented during the International Society for Prenatal Diagnosis' International Conference on Prenatal Diagnosis and Therapy.

Congenital diaphragmatic hernia occurs in about one in 4,000 births, with 85% of the defects on the left side. It is the most costly noncardiac birth defect, costing the U.S. healthcare system more than $250 million per year.

Postnatal survival rates are typically 20% in severe cases, 55% in moderate cases and 85% in mild. Death is usually caused by respiratory failure, pulmonary hypertension or both.

The team used lung-to-head ratios to rate severity. The portion of the trial testing FETO on severely affected fetuses was halted early for efficacy after an analysis of the first 80 cases. In the cases of moderately-affected fetuses, the intention-to-treat analysis included 196 women.

The two analyses are presented in separate reports.

In the moderate cases, the FETO procedure was done between 30 and 32 weeks gestation. The balloon was removed in the 34th week.

In 39% of the cases, the balloon had to be removed early, usually because the woman went into labor or she had a preterm, prelabor rupture of membranes.

In one case, doctors failed to puncture and remove the balloon in a timely manner after birth and the child died. In another, it took up to 3 minutes to remove the balloon after birth.

In one of the deaths, the woman had moved away from the hospital and the doctors in the hospital where she delivered were not prepared to deal with the balloon.

"There are things that can go wrong when you're technically not prepared," said Dr. Deprest. "This is something that can't translate to all hospitals," only those with experience in fetal surgery.

There were eight cases where the balloon spontaneously deflated.

Technological improvements might be able to enhance future outcomes. Today's endoscopes are 30% smaller and the researchers are planning to test balloons that have a magnetic valve, eliminating the need for a second operation.

If a balloon deflates in utero, the pressure behind it usually expels it from the trachea. Otherwise, the fetus spits it out or swallows it, eliminating it naturally, said Dr. Deprest.

He said the next step is to further analyze the data and find the sweet spot where the severity of the condition warrants the procedure and when it's better to wait until birth.

"We have to find out where the real cutoff is - when do we go with it and who will not benefit," Dr. Deprest said.

SOURCES: and The New England Journal of Medicine, online June 8, 2021.