Which Tiny Babies Need Help Closing a Heart Blood Vessel? A New Way of Choosing, Tested for the First Time

What a small trial of selective early treatment in babies born before 26 weeks (SMART-PDA, Mitra et al., 2026) and an expert review of how research on the open ductus should be designed (Battersby et al., 2026) mean for families

Many babies born extremely early have an open blood vessel near the heart, and doctors have long debated whether medicine to close it early helps. A small 2026 trial in babies born before 26 weeks used repeated heart scans to give medicine only to babies with a large blood flow; it showed a bigger trial is possible and gave hopeful early signs, but no proof yet. An expert review explains why earlier studies may have missed babies who could benefit.

A blood vessel that is supposed to close after birth

Before birth, a baby does not breathe air, so most of the blood leaving the heart bypasses the lungs through a short blood vessel called the ductus arteriosus. It normally closes soon after birth. In babies born very early it often stays open; doctors call this a patent ("open") ductus arteriosus, or PDA. An open duct lets extra blood flow into the lungs and away from other organs. When that extra flow is small, it may do little harm. When it is large, doctors worry it may stiffen the lungs, make breathing support harder to reduce, and reduce blood flow to the gut and kidneys. Medicines such as ibuprofen and acetaminophen (also called paracetamol) can help the duct close.

How doctors and families have faced this question until now

For many years, closing the duct with medicine seemed the obvious thing to do. Studies confirmed that the medicines work at closing it: a large analysis that pooled 68 trials, involving 4802 babies, found high closure rates, yet babies given the medicines did not clearly live longer or have fewer serious bowel or brain complications [1]. Over the past few years, several large trials tested early treatment against a "watchful waiting" approach. The BeNeDuctus trial (early treatment versus watchful waiting for the open duct), run in hospitals in the Netherlands, Belgium and Denmark, found that waiting was at least as good: problems counted in its main result occurred in 46 of every 100 babies managed by waiting, compared with 64 of every 100 given early ibuprofen [2]. In the United Kingdom, the Outcome after Selective early treatment for Closure of patent ductus ARteriosus (Baby-OSCAR) trial found that early ibuprofen did not help babies survive without long-term lung disease [3]. In the United States, the PDA Randomized Clinical Trial, run across 33 hospitals of the national Neonatal Research Network, gave medicine a little later, between the second day and the third week of life; it was stopped early because more babies died after medicine than after waiting (about 10 in 100 compared with 4 in 100) [4]. A major 2025 review of 19 trials found that early medicine made little or no difference to survival, and that very early ibuprofen might even increase deaths among the most premature babies [5]; an American Academy of Pediatrics report [6] concluded that routine early medicine to close the duct is not recommended. For families, this meant hearing "we'll wait and watch" far more often than before. You can read more about these trials at https://inneosight.org/en-US/articles/pdatreatment2026 and https://inneosight.org/en-US/articles/baby-oscar-ibuprofen.

Why the size of the duct may not be the whole story

Many doctors who care for the very smallest babies still felt something was missing. In 2026, six experts from the United Kingdom, the United States, Canada, Qatar and the Netherlands — including leaders of some of the trials they discuss — wrote a review explaining why [7]. Most earlier trials chose babies mainly by measuring how wide the duct looked on a heart ultrasound scan (an echocardiogram). But width alone is a poor guide to how much blood is actually flowing through it [8]. One hospital in Iowa looked back at 357 babies born before 27 weeks: of the 178 who had a "wide" duct, only 70 (about 4 in 10) had a large blood flow. Another 54 had only a small flow, and 54 had a heart condition in which the open duct may actually be helping, so closing it could do harm [9]. In other words, earlier trials may have mixed together babies who might benefit, babies who did not need medicine, and babies who could be harmed — making it almost impossible to see a benefit even if one existed for a smaller group. The experts point out that treating only babies with a large flow had never been properly tested in a randomised trial.

The SMART-PDA trial: choosing babies by blood flow, not just width

The SMART-PDA trial (selective early medical treatment of the patent ductus arteriosus) was designed to test that idea [10]. Its plan was published in advance, in 2024 [11]. It was a "pilot" trial — a smaller trial run first to find out whether a larger one is possible — carried out in seven specialist newborn intensive care units, four in Canada and three in the United States, between November 2021 and September 2024. It included babies born before 26 weeks of pregnancy who still had an open duct on a heart scan in the first three days. Of 185 babies who could have joined, 116 were enrolled, and 104 babies were then placed by chance into one of two groups.

In the "SMART" group (51 babies), doctors repeated the heart scan every three days during the first week. They gave medicine — usually ibuprofen — only if the scan showed a lot of blood flowing through the duct, judged by several measurements rather than width alone, and, unless the flow was very large, only if the baby was also showing signs of strain, such as needing more help with breathing. In the comparison group (53 babies), no further scans or duct medicine were given in the first week unless a baby became seriously unwell, for example with bleeding in the lungs.

What the researchers found

The trial's main aim was to show that a larger trial is possible, and it succeeded: 63 out of every 100 eligible babies were enrolled, and only 1 baby out of 53 in the comparison group received the medicine outside the rules. In the SMART group, about one baby in four (12 of 51) never needed the medicine at all, while those treated in the first week typically started at around two days old.

The researchers also looked at important health outcomes, while stressing that a trial this small cannot prove them. None of the 51 babies in the SMART group had bleeding into the lungs, compared with 6 of the 53 babies in the comparison group. A serious bowel illness called necrotising enterocolitis (NEC) occurred in 3 babies in the SMART group and 8 in the comparison group. The number of babies who died was the same — 9 in each group — and almost all babies in both groups (about 92 in every 100) still needed some breathing support at 36 weeks after the start of pregnancy, the point doctors use to check for long-term lung disease. When the researchers ranked the outcomes that matter most to families, starting with death and then lung bleeding, infection, bowel illness and the eye disease of prematurity (using a method called a "win ratio" that compares babies in pairs [12]), they estimated an 85% chance that the SMART approach was better. That is encouraging, but it also means a real chance that it is not. Among the very smallest babies, born at 24 weeks or earlier, the estimated chance of benefit was lower, at 60%.

What this means for your baby today

The researchers themselves say their results should not yet change how babies are cared for. This was a small trial, the doctors knew which group each baby was in, and the hospitals involved all had special expertise in heart scans that not every unit has. Many babies in the comparison group (34 of 53) were given the medicine at some point during their hospital stay anyway, typically at around 9 days old, and the overall number of babies who received the medicine at some point was not lower with the SMART approach. The trial also did not follow the children after they left hospital, so we do not know about longer-term development.

If your baby has an open duct, it is entirely reasonable to ask your team how they are assessing it: whether they are looking at how much blood is flowing, not just how wide the duct is, and whether they have checked the pressure in the lungs and how well the heart is pumping. Ask what signs would make them consider treatment, and whether your hospital is taking part in any research. Watchful waiting remains the recommended approach for most babies [6], and it is not the same as doing nothing — your baby is being closely monitored.

What researchers are working on next

The expert review lays out a plan for the next, larger trials [7]. They want to include only the babies at highest risk — those born before 28 weeks with a large blood flow confirmed by detailed heart scans, reviewed by a central team of experts. They suggest testing very early treatment, within the first day, to see whether it prevents bleeding in the brain or lungs, and later treatment, in the second week, to see whether it shortens the time babies need breathing machines. They also want parents to help choose which outcomes are measured, building on earlier work in which parents and former patients helped agree the outcomes that matter most in newborn research [13]. Interestingly, several hospitals in SMART-PDA were no longer willing to place their tiniest babies in the comparison group, which is one reason the researchers reported this small trial on its own [10]. Designing a fair trial that doctors and families can accept is now one of the biggest challenges.

The bottom line

For years, the question has been whether doctors should close the open duct with medicine. These two papers suggest a better question: which babies, chosen by how much blood is truly flowing, might benefit? The SMART-PDA trial shows that this approach can be tested fairly in babies born before 26 weeks, with hopeful early signs such as less lung bleeding, but no difference in survival and no proof yet. A larger, carefully designed trial is the next step.

References

  1. 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 ↩
  2. Hundscheid T, Onland W, Kooi EMW, et al. Expectant Management or Early Ibuprofen for Patent Ductus Arteriosus. N Engl J Med. 2023;388(11):980-990. doi:10.1056/NEJMoa2207418 ↩
  3. Gupta S, Subhedar NV, Bell JL, et al. Trial of Selective Early Treatment of Patent Ductus Arteriosus with Ibuprofen. N Engl J Med. 2024;390(4):314-325. doi:10.1056/NEJMoa2305582 ↩
  4. Laughon MM, Thomas SM, Watterberg KL, et al. Expectant Management vs Medication for Patent Ductus Arteriosus in Preterm Infants: The PDA Randomized Clinical Trial. JAMA. 2026;335(7):588-599. doi:10.1001/jama.2025.23330 ↩
  5. Mitra S, Scrivens A, Fiander M, Disher T, Weisz DE. Early treatment versus expectant management of hemodynamically significant patent ductus arteriosus for preterm infants. Cochrane Database Syst Rev. 2025;6(6):CD013278. doi:10.1002/14651858.CD013278.pub3 ↩
  6. Ambalavanan N, Aucott SW, Salavitabar A, Levy VY. Patent Ductus Arteriosus in Preterm Infants. Pediatrics. 2025;155(5):e2025071425. doi:10.1542/peds.2025-071425 ↩
  7. Battersby C, Levy PT, Gupta S, de Boode WP, Mitra S, McNamara PJ. Making sense of the evidence: designing randomised controlled trials for preterm infants with high-shunt volume patent ductus arteriosus. Arch Dis Child Fetal Neonatal Ed. 2026;111(5):F413-F424. doi:10.1136/archdischild-2025-330266 ↩
  8. de Freitas Martins F, Ibarra Rios D, F Resende MH, et al. Relationship of Patent Ductus Arteriosus Size to Echocardiographic Markers of Shunt Volume. J Pediatr. 2018;202:50-55.e3. doi:10.1016/j.jpeds.2018.06.045 ↩
  9. Bischoff AR, Dias Maia P, McNamara PJ. Beyond diameter: redefining echocardiography criteria in trials of early PDA therapy. J Perinatol. 2026;46(3):332-336. doi:10.1038/s41372-025-02523-7 ↩
  10. Mitra S, Hebert A, Castaldo MP, et al. Selective early medical treatment of the patent ductus arteriosus in extremely low gestational age infants: a pilot randomised controlled trial (SMART-PDA). Arch Dis Child Fetal Neonatal Ed. 2026;111(6):F547-F555. doi:10.1136/archdischild-2026-330462 ↩
  11. Mitra S, Hébert A, Castaldo M, et al. Selective early medical treatment of the patent ductus arteriosus in extremely low gestational age infants: a pilot randomised controlled trial protocol (SMART-PDA). BMJ Open. 2024;14(7):e087998. doi:10.1136/bmjopen-2024-087998 ↩
  12. Pocock SJ, Ariti CA, Collier TJ, Wang D. The win ratio: a new approach to the analysis of composite endpoints in clinical trials based on clinical priorities. Eur Heart J. 2012;33(2):176-182. doi:10.1093/eurheartj/ehr352 ↩
  13. Webbe JWH, Duffy JMN, Afonso E, et al. Core outcomes in neonatology: development of a core outcome set for neonatal research. Arch Dis Child Fetal Neonatal Ed. 2020;105(4):425-431. doi:10.1136/archdischild-2019-317501 ↩