Existing treatment in preterm infants is not always necessary – not treating the ductus is as safe as treating it

6 December 2022

Treatment of premature infants, in which the blood vessel that supplies the body with oxygen before birth does not immediately close on its own, is not routinely required. Waiting for this blood vessel, the ductus, to close on its own is just as safe, according to research coordinated by the Radboud University Medical Center. There is even preliminary evidence that drugs that close the ductus increase the risk of chronic lung damage.

In premature infants, the ductus (or ductus Botalli), the blood vessel that supplies a fetus’s body with oxygen during pregnancy, often does not immediately close on its own. Worldwide, these children are often given the drug ibuprofen after birth, so that the vessel closes. For years, this was the prevailing thought, preventing complications such as a brain hemorrhage or chronic lung disease. But there has long been uncertainty as to whether patent ductus should be treated by administering drugs, or whether a wait-and-see policy is better.

Therefore, a study started in December 2016, led by Professor of Neonatology Willem de Boode, at the Radboud University Medical Center. This included 273 babies born at a gestational age of up to 28 weeks. In one group the ductus was closed with the help of ibuprofen, in the other group they waited for the ductus to close by itself. The results have now been published in the scientific journal New England Journal of Medicine, in an article in which PhD student Tim Hundscheid is the first author.

In this picture on the left the heart without an open ductus, on the right with an open ductus.

This shows that a wait-and-see policy where the ductus closes naturally over time is as safe as a policy where treatment is given. The starting point was the chance of a child surviving without serious complications in the lungs or intestines. De Boode, attached to the Department of Neonatology at the Radboudumc Amalia Children’s Hospital: ‘This means a huge revolution in our thinking about the ductus. Our dogma is changing.’

Is the cure worse than the disease?

This is not the only result. The researchers found evidence that ibuprofen may increase the risk of chronic lung disease. De Boode and colleagues are surprised by this result. ‘We expected to show that not treating would be as good as treating. But the results even tentatively indicate that the use of ibuprofen may have negative consequences. It seems that the drug, ibuprofen, is worse than the disease, patent ductus.’ The complications that we attributed to patent ductus are side effects that we also know from ibuprofen. ‘We want to find out exactly how it works with follow-up research,’ says the neonatologist.

According to De Boode, we cannot yet establish that no treatment is better than treatment. “There is definitely a select group for whom treatment is necessary. We now want to find out which children are involved, and also which treatment is best.’ A possible alternative to medication is an operation where a plug is inserted via a catheter through the groin, closing the ductus.

Parental involvement

Willem de Boode emphasizes the importance of scientific research in premature babies. “We still have a lot to learn about these children. That’s why this kind of research is so important, it increases our knowledge.’ He is especially grateful to parents of children who have cooperated. ‘Most parents were completely overwhelmed by the premature birth of their child and the admission to intensive care. Within the first three days after birth, we asked them if they would cooperate . I am very grateful that so many of them wanted to contribute to this research and gave us their trust. Without them we would never have gained this knowledge.’

About the publication

This article was published in the New England Journal of Medicine: Expectant Management or Early Ibuprofen for Patent Ductus Arteriosus – T. Hundscheid, W. Onland, EMW Kooi, DC Vijlbrief, WB de Vries, KP Dijkman, AH van Kaam, E. Villamor, AA Kroon, R. Visser, SM Mulder-de Tollenaer, B. De Bisschop, P. Dijk, D. Avino, C. Hocq, A. Zecic, M. Meeus, T. de Baat, F. Derriks, T. Brink Henriksen, K. Jacobsen Kyng, R. Donders, DHGM Nuytemans, B. van Overmeire, AL Mulder and WP de Boode for the BeNeDuctus Trial Investigators. DOI: 10.1056/NEJMoa2207418.

About the survey

The BeNeDuctus trial was conducted within the Neonatology Network in the Netherlands, the N3 Research Network. The aim is to combine knowledge and collaboration within research, development of guidelines and quality to improve diagnosis, treatment and outcome of sick newborns. This study, in which hospitals from Belgium and Denmark participated in addition to the nine Dutch centers with a neonatal intensive care unit, was funded by ZonMw (Netherlands) and KCE (Belgium). There has been close cooperation with Care4Neo, the association that looks after the interests of parents whose child is hospitalized immediately after birth.

In the picture: Professor of neonatology Willem de Boode.

Read the story of Rogier and Rosa about their son Jurre here.

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