A Small Heart Vessel That Should Close: Comparing Two Common Medicines for Premature Babies

What a study of paracetamol and ibuprofen means for families of babies with a patent ductus arteriosus

Many premature babies are born with a tiny blood vessel near the heart that is supposed to close on its own in the first days of life but sometimes stays open. When it does, doctors often use one of two familiar medicines — paracetamol (also called acetaminophen) or ibuprofen — to help it close. A recent study compared these two medicines head-to-head in premature babies and found that more babies' vessels closed with paracetamol. This article explains what that vessel is, why it matters, and what the study does and does not tell families.

The vessel every baby has before birth

The study discussed here followed premature babies with this open vessel and compared two medicines commonly used to close it [1]. To make sense of what it found, it helps to start with what the vessel is and why it matters. Before a baby is born, the lungs are not yet used for breathing, so blood needs a shortcut that bypasses them. That shortcut is a small vessel called the ductus arteriosus, and every baby has one in the womb. Once a baby is born and takes those first breaths, the lungs open up, pressures inside the chest change, and the little vessel normally tightens and seals itself closed within a few days [2]. When it stays open, doctors call it a patent ductus arteriosus, or PDA — "patent" simply meaning "still open." The more premature a baby is, the more likely the vessel is to remain open, which is why PDA is so much more common in the smallest, earliest babies than in those born closer to term.

Why an open vessel sometimes needs attention

Here is a reassuring fact that shapes everything about how this condition is handled: in a great many babies, the vessel eventually closes on its own without any treatment at all, especially in babies who are a bit bigger and more mature [3]. Because of that, doctors do not automatically treat every open vessel. They watch, measure, and treat only when the opening is large enough to strain the baby's heart and lungs. When a significant opening does persist, it can make breathing harder and has been linked to problems such as lung disease, bleeding in the brain, and bowel injury, which is why an important, persistent PDA is taken seriously [4]. Doctors judge whether an opening is "significant" using an ultrasound of the heart, called an echocardiogram, which is painless and can be done right at the bedside.

How doctors came to have a choice of medicines

For decades, the medicines used to close a PDA were anti-inflammatory drugs — first one called indomethacin, then ibuprofen, the same drug family many adults use for aches and fevers. These work by lowering the natural chemical signals that keep the vessel open. Over the years, though, doctors learned two things that changed their approach. First, they recognized how often the vessel closes by itself, so they became more patient and selective about treating [3]. Second, they began looking for gentler options, because the older anti-inflammatory drugs can affect a fragile baby's kidneys and stomach. Paracetamol — the same medicine widely used for fever and pain — turned out to help the vessel close through a slightly different chemical route, and it was first used mainly when ibuprofen could not be given or had not worked [5]. A large review of all the available studies later confirmed that paracetamol, ibuprofen, and indomethacin all help close the vessel better than no medicine, which opened the door to using paracetamol as a first choice rather than a backup [6].

What this study did

The new study was carried out at a single hospital in Peshawar, Pakistan, over six months in 2024 [1]. The researchers included premature babies who were born at 30 to 37 weeks (a full-term pregnancy is about 40 weeks), weighed at least about 1250 grams, were two to four days old, and had an open vessel confirmed by heart ultrasound. They divided 256 babies into two equal groups by chance — a method called randomization, which helps make the groups fair to compare. One group of 128 babies received paracetamol by mouth, and the other group of 128 received ibuprofen by mouth, each for about three days. Afterward, the doctors repeated the heart ultrasound to see whether the vessel had closed.

What the study found

The vessel closed in about 84 out of every 100 babies given paracetamol, compared with about 70 out of every 100 babies given ibuprofen [1]. In plain terms, that is roughly one extra baby out of every eight whose vessel closed with paracetamol rather than ibuprofen. The difference was large enough that it was unlikely to be due to chance alone. The advantage for paracetamol showed up most clearly among the slightly bigger and more mature babies in the study. The two groups of babies were similar to begin with — about the same age, weight, and maturity — which makes the comparison more trustworthy.

It helps to know what "closing" actually means here. The medicines do not physically seal the vessel the way a stitch would; instead, they lower the natural chemical signals that keep it open, allowing the baby's own body to finish a job it would normally complete on its own. Doctors confirm success with a repeat heart ultrasound, and if the vessel is still open they can consider a second course or a different approach. Both paracetamol and ibuprofen are given as a short course — a few doses spread over about three days — either by mouth or through a small feeding tube, so the medicine itself does not require a needle. Families are sometimes surprised that a team may choose to watch and wait rather than treat right away; this is not neglect but a reflection of how often these vessels close by themselves, and a short period of careful observation can spare a baby medicine it does not need [3].

What it means for families, and what it does not

If your baby has a PDA, this study offers some genuine reassurance: both medicines work for many babies, and paracetamol — a drug with a long, familiar track record — closed the vessel a bit more often here. Earlier research had suggested the two medicines work about equally well [7], and reviews have described paracetamol as closing the vessel about as well as the older drugs while being gentler on the body [8], so this new result fits comfortably alongside what was already known and modestly strengthens the case for paracetamol.

At the same time, it is important to keep the study in perspective. It was done at one hospital, in babies who were mostly moderately premature rather than extremely premature — and the tiniest, earliest babies are exactly the ones for whom this decision is usually hardest and most important. Because so many vessels close on their own [9], and because this study did not include a "no-medicine" comparison group, some of the closures in both groups may have happened naturally rather than because of the drug. The study also did not report detailed information on side effects, so it cannot on its own prove that the two medicines are equally safe, even though other research has been reassuring on that point [10]. None of this means the finding is wrong — only that it is one helpful piece of a larger picture, and that your baby's team will weigh it alongside your baby's own gestational age, kidney function, and overall condition.

What families can expect and what researchers are working on next

If treatment is recommended, you can expect your baby's team to first confirm with a heart ultrasound that the opening is significant, then give a short course of one of these medicines by mouth or through a feeding tube, and afterward repeat the ultrasound to check whether it worked. If the vessel has not closed, doctors may give a second course, switch medicines, or, in a small number of cases, discuss other options. It is completely reasonable to ask your team why they chose a particular medicine, whether waiting is an option for your baby, and what the plan is if the first course does not work. Researchers, meanwhile, are studying how to make treatment even better — including whether combining paracetamol and ibuprofen might help close the most stubborn vessels [11] — and larger, more rigorous studies in the smallest babies are still needed to settle which medicine should truly come first. For now, the encouraging message is that families have effective, well-established options, and that this study adds to the confidence doctors can have in paracetamol as one of them.

References

  1. Shah SMA, Khan SA, Sadiq F, et al. Comparison of the Effectiveness of Paracetamol and Ibuprofen in the Management of Patent Ductus Arteriosus in Preterm Neonates: A Randomized Controlled Trial. Mol Cell Pediatr. 2025;12(1):2. doi:10.1186/s40348-025-00189-x ↩
  2. Van Vonderen JJ, te Pas AB, Kolster-Bijdevaate C, et al. Non-invasive measurements of ductus arteriosus flow directly after birth. Arch Dis Child Fetal Neonatal Ed. 2014;99:F408–F412. doi:10.1136/archdischild-2014-306033 ↩
  3. de Carvalho Nunes G, Wutthigate P, Simoneau J, et al. Natural evolution of the patent ductus arteriosus in the extremely premature newborn and respiratory outcomes. J Perinatol. 2022;42(5):642–648. doi:10.1038/s41372-021-01277-2 ↩
  4. Capozzi G, Santoro G. Patent ductus arteriosus: patho-physiology, hemodynamic effects and clinical complications. J Matern Fetal Neonatal Med. 2011;24(sup1):15–16. doi:10.3109/14767058.2011.607564 ↩
  5. Oncel MY, Yurttutan S, Uras N, et al. An alternative drug (paracetamol) in the management of patent ductus arteriosus in ibuprofen-resistant or contraindicated preterm infants. Arch Dis Child Fetal Neonatal Ed. 2013;98:F94. doi:10.1136/archdischild-2012-302044 ↩
  6. Mitra S, Florez ID, Tamayo ME, et al. Association of placebo, indomethacin, ibuprofen, and acetaminophen with closure of hemodynamically significant patent ductus arteriosus in preterm infants: a systematic review and meta-analysis. JAMA. 2018;319(12):1221–1238. doi:10.1001/jama.2018.1896 ↩
  7. Bagheri MM, Niknafs P, Sabsevari F, et al. Comparison of oral acetaminophen versus ibuprofen in premature infants with patent ductus arteriosus. Iran J Pediatr. 2016;26(4):e3975. doi:10.5812/ijp.3975 ↩
  8. Bardanzellu F, Neroni P, Dessì A, Fanos V. Paracetamol in patent ductus arteriosus treatment: efficacious and safe? Biomed Res Int. 2017;2017:1438038. doi:10.1155/2017/1438038 ↩
  9. Klerk J, Engbers A, Beek F, et al. Spontaneous closure of the ductus arteriosus in preterm infants: a systematic review. Front Pediatr. 2020;8:541. doi:10.3389/fped.2020.00541 ↩
  10. Allegaert K, Anderson B, Simons S, van Overmeire B. Paracetamol to induce ductus arteriosus closure: is it valid? Arch Dis Child. 2013;98(6):462–466. doi:10.1136/archdischild-2013-303688 ↩
  11. Shah SD, Makker K, Nandula P, et al. Effectiveness of dual medication therapy (oral acetaminophen and oral ibuprofen) for the management of patent ductus arteriosus in extremely premature infants: a feasibility trial. Am J Perinatol. 2022;39(12):1326–1333. doi:10.1055/s-0040-1722329 ↩