A chance for more effective treatment of transient breathing disorders in newborns

Your clinic is implementing the REFSAL project financed by the Medical Research Agency (ABM). This is the first non-commercial project in Polish neonatology for years. What group of newborns does it cover?

We qualify newborns who have transient breathing disorders, including the transient tachypnea of the newborn (abbreviated as TTN), shortly after birth. These include both babies born ahead of time, who are 8 or less weeks short from the normal end of the gestation period, and those born on time. However, the project does not cover premature babies born under 32 weeks of gestation because in this group we usually deal with another type of breathing disorder called respiratory distress syndrome (RDS). We had to separate these two groups of newborns from each other. Of course, in children born on the verge of indications for our study, that is at 32-33 week of pregnancy, we have to find out which disorder we are dealing with, which is not easy.

How common are transient breathing disorders?

The occurrence of this type of disorder depends on which month of pregnancy these newborns are born. When it comes to the range of 32-34 weeks of gestational age, transient breathing disorders develop in up to 10% of newborns. It follows that immature newborns are more likely to develop the TTN. The second group is the so-called “late premature babies”, that is babies born during a period ranging from 34 weeks to 36 weeks and 6 days of pregnancy; here the incidence of TTN is 5%. In contrast, about 1% in full-term newborns.

What are the symptoms of these disorders?

The newborn begins to breathe quickly, pull in the intercostal space and move the nose wings, and the sternum collapses. These are typical symptoms of not only the TTN but also other types of respiratory disorders.

Is the cause of the TTN known?

Breathing disorders of the nature of TTN are caused by impaired absorption of pulmonary fluid. In intrauterine life the lungs of the fetus are filled with fluid. It is both pulmonary fluid produced by the endothelium of the alveoli pulmonis and, in some part, amniotic fluid. However, when a newborn is born, the fluid should be absorbed. Childbirth by the forces of nature promotes the absorption of pulmonary fluid. If this does not happen, and the fluid remains in the lungs, temporary breathing disorders appear.

Is it true that the risk of the TTN increases when a baby is born by cesarean section?

It is true. The percentage of cesarean sections is increasing in Poland. Why is this happening? It seems that this has to do with the increasing number of so-called c-sections “on request”, but probably an obstetrician would answer this question more competently. The percentage of c-sections in the Mazovian province is currently 47%. In our center it is as much as 60% but this is because we deal with infants born from highly endangered pregnancies in the case of which delivery by c-section is a necessity.

Why do infants born by c-section develop transient breathing disorders?

In order for the pulmonary fluid to be efficiently absorbed, and not to remain in the lungs, adrenaline, i.e. the stress hormone, is needed. The c-section is stress-free for the fetus, unlike the natural childbirth. There is no stress, so the pulmonary fluid cannot be absorbed properly. It is interesting that a human being needs stress from the very beginning in order to adapt well to the extrauterine environment, to the outside world.

We are talking about transient disorders. Does this mean that they do not require treatment?

Indeed, these disorders, as the name suggests, are transient. However, this does not mean that we leave them only for observation. It is always necessary to treat, that is, to give the newborn respiratory support. After providing this support the disorders pass for good after some time in a large group of our small patients. But we also have newborns in whom transient breathing disorders have malignant, or severe, forms. We provide respiratory support in each of these cases. For example, we can use non-invasive methods, such as continuous positive airway pressure (CPAP). Some newborns require intubation and invasive ventilation. A case of malignant TTN can be also associated with pulmonary hypertension. This is due to the fact that the pulmonary circulation of the fetal type has not fully transformed into the pulmonary circulation of the adult type. Pulmonary circulation in the fetus encounters high resistance, so blood practically does not flow through the lungs. This must change after the birth. This is a huge hemodynamic change. The blood flow rate in the lungs is now about 20 times higher than before the birth. Unfortunately, if there is a transient breathing disorder, especially malignant one, the pulmonary hypertension syndrome, that is, persistent fetal circulation, can develop. Then the stay of the newborn in the hospital is definitely longer. Sometimes, if the pulmonary hypertension is very severe, we need to use more advanced treatments including the administration of drugs to increase arterial blood pressure. These drugs are called catecholamines. Sometimes it is even necessary to use nitric oxide inhalation to counter the resistance of the pulmonary vessels.

What is investigated by the REFSAL project?

We investigate the effect of salbutamol, a drug used to treat asthma in both children and adults, on the absorption of the pulmonary fluid. Salbutamol belongs to the group of beta-mimetics and acts on beta-adrenergic receptors in the endothelium of pulmonary vessels. And the synergistic effect of this drug on these receptors can promote increased resorption of the pulmonary fluid. We have found three studies in the literature on the effectiveness of salbutamol in the treatment of transient respiratory disorders. We have decided to continue this research, but on a much larger group of newborns. We want to check the effect of salbutamol on the absorption of the pulmonary fluid to see whether it shortens the duration of transient breathing disorders and the time of mechanical and non-invasive ventilation. We also want to see if salbutamol prevents the occurrence of pulmonary hypertension. For this purpose, for each newborn qualified for the project, we conduct an echocardiographic assessment twice, i.e. we check whether there are any features of pulmonary hypertension. We also included an ultrasound examination of the lungs in the project. It enables both the assessment of transient breathing disorders and the diagnosis of other lung diseases including pneumonia. The gold standard in Poland is to perform radiological examinations in such cases. However, we have also included ultrasonography to be able to compare the results of the both diagnostic methods.

Is the project implemented only by the Neonatology and Neonatal Intensive Care Clinic of the Medical University of Warsaw, or also by other centers?

Eight centers participate in our study and the Medical University of Warsaw plays the role of the project leader. This means that we, as a university, are the initiator of the project, we have developed its protocol, we have taken care of its preparation, we are responsible for the logistics of the study and we watch over its course. We are responsible for the entire project. Of course, it should be emphasized that whole teams of people in each center are involved in the implementation of the study. These are not only doctors but also nurses who prepare the drug, consultants (radiologists and cardiologists) who evaluate radiological and echocardiographic examination results, and the administrative team. There is a really huge staff working on it.

Let's look at this project from the perspective of mothers and their newborn children. What benefits will it bring to them?

We hope that salbutamol will prove effective and safe in the treatment of transient breathing disorders. We hope that, thanks to this therapy, if our hypotheses are confirmed, our small patients will require ventilation for a shorter time and they will be able to avoid the occurrence of pulmonary hypertension. If the treatment with salbutamol is successful, the time of hospitalization of a newborn with a transient breathing disorder will be shorter. Faster recovery in the neonatal period also means a lower risk that the child will develop asthma or other respiratory diseases in the future. These are also lower medical costs.

Interwieved by Iwona Kołakowska
Photos Artur Dusza
Biuro Komunikacji i Promocji Uczelni