Cases of severe congenital diaphragmatic hernia (hereinafter CDH) considered appropriate in line with the “Protocol for Clinical Trial” are treated by the implementation of fetoscopic endoluminal tracheal occlusion (hereinafter FETO) using a balloon, and subsequent progress is monitored. FETO and the balloon removal procedure are carried out at the National Center for Child Health and Development (hereinafter NCCHD).

CDH is a congenital condition in which a deficit develops in the diaphragm, through which the abdominal organs – the stomach, spleen, small intestine, large intestine and liver – herniate into the chest cavity, putting pressure on regular lung development. It is thought to occur in 1 in 2,500 live births. The greatest problem posed by this condition occurs as a result of the continual pressure placed on ordinary lung development during the fetal stage, which leads to hypoplasia of the lung. Depending on the size of the deficit, some cases may experience almost no symptoms or disorders; however, cases with the deficit in the rear outside of the diaphragm can lead to severe symptoms after birth, such as pulmonary hypertension or respiratory failure, etc.

Recently, progress has been achieved in diagnosis before birth, and treatment has been concentrated into major hospitals offering pre-birth care in perinatal centers, etc. Neonatal management has also improved, but the death rate remains high, at between 20−30% of cases.

The diaphragm is formed at around the 10^th week of pregnancy, and if there is a deficit in the diaphragm, the stomach, intestines, spleen and, in some cases, the liver, etc. may herniate into the chest cavity via this deficit. If multiple abdominal organs invade the chest cavity, the development of the lungs may be restricted, causing pulmonary hypertension and/or respiratory disorders during the neonatal period.

CDH can occur alone, but is also sometimes complicated by chromosomal abnormalities and/or other congenital anomalies.

Diagnosis is reached via an ultrasound examination. MRI is also used in order to evaluate the healthy lungs and the herniated organs in greater detail. Since prognosis is significantly affected by the presence or otherwise of complications, amniotic fluid is tapped for chromosomal examination, and ultrasound is also used in screening other organs. Concomitant hypoplasia of the lung is evaluated from the elevation or otherwise of the liver, the position of gastric bubbles herniated into the chest cavity, and O/E LHR (observed-expected Lung-to-Head Ratio). O/E LHR is calculated by measuring the surface area of the largest lung using a four-chamber cross-section of the heart, along with the trace method (see www.total.eu).

1)    Patients between 27 weeks 0 days and 31 weeks 6 days of pregnancy

2)    The mother is between 16 and 45 years old

3)    The fetus is a single pregnancy, diagnosed with left side CDH prior to birth

4)    The fetus has liver herniation (Liver up) CDH, wherein half or more of gastric bubbles in the chest crossing the midline are deflected into the right side  (Grade3)

The position of gastric bubbles is established from the observation of horizontal cross-section ultrasound images of the fetal chest area, where gastric bubbles have crossed a midline linking the spine and the sternum, and are deflected into the right side. Evaluation is conducted based on four stages – Gastric bubbles remaining inside the abdominal cavity (Grade 0) / Gastric bubbles in the chest have not crossed the midline at all (Grade 1) / Half or fewer than half of gastric bubbles in the chest have crossed the midline (Grade 2) / Half or more of gastric bubbles in the chest crossing the midline are deflected into the contra-lateral side  (Grade3).

5)    The patient has no other severe fetal malformations (chromosomal abnormalities or fatal cardiac disorders)

6)    The patient has no pregnancy-induced hypertension (PIH)

7)    No genital bleeding

8)    Premature Rupture of Membranes has not occurred

9)    Cervical length is a minimum of 20 mm

10)   The patient and the patient’s spouse have provided their consent

Severe CDH cases considered appropriate undergo FETO, in line with the Protocol approved by the ethical committee at NCCDH, and subsequent progress is monitored. FETO and balloon removal procedures are carried out at the NCCDH.

The purpose of FETO is to obstruct the fetal trachea, so that alveolar fluid accumulates and induces positive pressure in the lungs, with the result that the lungs expand, promoting their development, and allowing improvement in the infant’s respiratory condition after delivery.

The specific procedure is as follows.

1) Patients with O/E LHR under 25% undergo FETO between 27 weeks 0 days and 29 weeks 6 days’ gestation, while those with O/E LHR of 25% to 45% undergo FETO between 30 weeks 0 days and 31 weeks 6 days

2) Balloon removal takes place between 34 weeks 0 days and 34 weeks 6 days’ gestation

3) After delivery, the infant is proactively treated using standardized neonatal cares.

Period of research: Three years from October 2013

Target number of cases: 10 cases of early-phase safety trial

As of January 31^st, 2013 (Listed in order of registration)

According to reports from the Eurofetus group, in 210 cases of severe CDH to which FETO was applied, there was a 47.1% incidence of early premature rupture if the membranes (under 37 weeks’ gestation) within 30 days of FETO, and a 16.7% incidence within three weeks of FETO. The average delivery was at 35.3 weeks, with 30.9% preterm deliveries before 34 weeks, and 12.6% preterm deliveries before 32 weeks. 97.1% of deliveries were live births, while 48.0% of cases were reported to have survived and left hospital. When compared to an electively managed group for comparison, left side CDH cases with severe complications showed an improvement in survival rate from 24.1% to 49.1%.

(Primary Investigator)
Haruhiko Sago, M.D.
Head, Center of Maternal-Fetal, Neonatal and Reproductive Medicine Deputy Director, National Medical Center for Children and others National Center for Child Health and Development

2-10-1 Okura, Setagaya-ku, Tokyo 157-8535 Japan

(Administration Office)
Seiji Wada, M.D.
Center for Maternal-Fetal and Neonatal Medicine Division of Fetal Medicine National Center for Child Health and Development

2-10-1 Okura Setagaya-ku Tokyo 157-8535 Japan
Tel: 03-3416-0181
FAX：03-3416-2222