Preventing Pulmonary Hypertension in Premature Infants

Brian Hanna, MDCM, PhD


December 01, 2014

Editorial Collaboration

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Hello. My name is Brian Hanna. I am one of the pediatric cardiologists at The Children's Hospital of Philadelphia. I am the director of the pulmonary hypertension program. I am going to talk to you today about pulmonary hypertension associated with pediatric neonatal chronic lung disease.

This has become an epidemic, at least within our program and every other program that people talk to me about. Currently, of our 670 active patients on therapy, the reason for the pulmonary hypertension in over 300 of them is neonatal chronic lung disease. The problem is that this is not pulmonary hypertension the way that pediatric cardiologists have been treating pulmonary hypertension for the past 15 years. This is pulmonary hypertension that is associated with lung hypoplasia, developmental delays, and significant loss of capillary bed as a result of diseases that are associated with chronic lung disease.

For me, the issue is: What is causing the inflammation that destroys the capillary bed? And, as a dumb plumber, I have only come up with four:

Oxygen toxicity;

Ventilator shear forces;

Viral illnesses; and


We believe that we limit the amount of oxygen toxicity and free radical production by keeping oxygen saturations in the small babies between 88% and 92%. But if you walk the wards in the middle of the night, you will see that a lot of the nursing care is performed using 100% oxygen. That is something that we have been quite successful in eliminating, and it does make a big difference to the production of chronic lung disease–associated pulmonary hypertension. Ventilator shear forces—the use of high-frequency oscillating ventilators—have made a big difference, but it still is a problem. Viral illnesses, of course, [are always an issue]. And then we are stuck with number four: microaspiration. I think that this is the key.

In our institution, we have two to three children "landing on the roof" [admitted via helicopter] with severe pulmonary hypertension every month. They come with a history of 3 or 4 weeks of progressive worsening in their lung disease, associated with a cold or some other issue. They are all about 3.5 to 4 months of age. They are born between 25 and 26 weeks' gestation. They were doing exceptionally well until they fell off the curve.

What we do with those children is to put their feeding tube in the jejunum. Not in the duodenum, in the jejunum. And the reason why we do that is that pepsin, which is the proteolytic enzyme from the stomach, is produced when protein is found in the second stage of the duodenum. So, cholecystokinin from the duodenum causes production and release of pepsin. Pepsin, when it is microaspirated, especially in an infant who is breathing at 60, 70, or 100 times per minute and cannot guard their airway well, can lead to chronic lung disease that is rapidly progressive and loss of the vascular bed.

Virtually 100% of the time, 2 weeks of jejunal feeding, very gentle ventilation, and limitation of oxygen therapy has improved right heart failure, as seen by echocardiography-measured grade of tricuspid regurgitation and the B-type natriuretic peptide (BNP) levels. A normal BNP is less than 35 pg/mL for small babies.

When that result happens, we then have two problems: Can we go back to normal feeding in the stomach, or do we need to do a fundoplication and a gastrostomy tube? We have different strategies and it depends on the child. We will attempt refeeding sometimes. But if the pulmonary hypertension is that profound because the lung disease is that profound, then we will go to a fundoplication.

That is my treatment for that disease of pulmonary hypertension. It is not always necessary to start sildenafil, bosentan, or prostacyclin in this group of individual children. The fundamental thing that you need to do is to make the lung disease better.

My message to you today is that although pulmonary hypertension–specific therapy is possible and safe in small babies with chronic lung disease–associated pulmonary hypertension, it is not always necessary. It is necessary to treat the cause for the lack of a vascular bed. And for me, there are those four things: oxygen, ventilators, viruses, and microaspiration of pepsin.

Thank you.