A Tiny Blood Vessel, a Big Question, and a Major Clinical Trial

Understanding Patent Ductus Arteriosus and the TREOCAPA Study — For Everyone

Starting From the Beginning: What Is the Ductus Arteriosus?

Before a baby is born, it doesn't use its lungs — it gets all the oxygen it needs from its mother through the placenta. Because the lungs aren't working yet, the fetal body has a clever shortcut: a small blood vessel called the ductus arteriosus that diverts blood away from the lungs and straight into the rest of the body.

When a baby is born and takes that first breath, the lungs suddenly open up and start working. The body reads the signals — rising oxygen, falling hormone levels — and closes off this shortcut, usually within a day or two. In healthy, full-term babies, this works like clockwork. But in babies born very early — particularly those born more than two months premature — this "closing" mechanism often fails. The little vessel stays open when it should have shut. Doctors call this a patent ductus arteriosus, or PDA. Patent simply means "open" or "unclosed" [1].

When PDA happens, blood flows the wrong direction — from the aorta (the body's main artery) back into the lungs, overloading them with fluid. It's like having a plumbing leak that floods the lungs while leaving the rest of the body short on blood supply. For a tiny premature baby already struggling to survive, this can make breathing much harder and damage organs including the gut, kidneys, and brain [2].

How Doctors Have Treated PDA Over the Decades

The Surgical Era (1938–1970s): Closing It With an Operation

For a long time, the only way to fix a PDA was surgery — physically tying off the blood vessel. The first successful surgery of this kind was performed in 1938 on a 7-year-old girl at Boston Children's Hospital, and it launched the era of heart surgery for children [3]. By the 1970s, surgeons were performing this operation on premature babies as small as 600 grams, sometimes right in the NICU. It worked, but surgery on a tiny, fragile preemie carries serious risks: infection, bleeding, anesthesia complications, and more [4].

The Drug Era Begins (1976): Indomethacin

A breakthrough happened in 1976 when researchers discovered that a common anti-inflammatory painkiller called indomethacin — the same class of drug as ibuprofen — could close the PDA without surgery. The way it works: the ductus stays open because of a hormone-like chemical called prostaglandin. Indomethacin blocks the production of prostaglandins, and without them, the vessel constricts and closes [5].

This was huge news. Instead of risky surgery, doctors could give a drug through an IV. For decades, indomethacin became the go-to treatment for PDA in premature infants. It was even given preventively (prophylactically) to the tiniest babies to stop the PDA from ever becoming a problem — and as a bonus, it also reduced dangerous brain bleeds (intraventricular hemorrhages) in very premature infants [6].

But indomethacin had a dark side. By blocking prostaglandins throughout the body — not just in the ductus — it reduced blood flow to the kidneys (causing decreased urine output), to the gut (raising the risk of a life-threatening condition called necrotizing enterocolitis), and to the brain. Doctors needed something that worked just as well with fewer side effects.

Ibuprofen Takes the Stage (1990s–2000s)

Researchers tested ibuprofen — a cousin of indomethacin in the same drug family — and found it worked just as well for closing the PDA, closing it about 75–80% of the time [7]. Most importantly, ibuprofen didn't reduce blood flow to the kidneys and gut as severely. A large scientific review (called a Cochrane systematic review) concluded that ibuprofen was safer than indomethacin and should be the preferred drug. Surgeries for PDA started to decline as pharmacological treatment improved.

Rethinking Everything: Do We Need to Treat PDA at All?

Here's where things get interesting — and controversial. By the 2010s, doctors started noticing something unexpected: in some NICUs, particularly in Scandinavian countries, teams had pulled back on routinely treating PDA. They just watched and waited, supporting the baby with careful ventilation and fluids. And the babies... did fine. Many PDAs closed on their own. Outcomes weren't worse than in hospitals that treated aggressively. This prompted a big debate in neonatology: Is the PDA really the enemy, or are we sometimes treating a blood vessel finding that would resolve on its own, while exposing babies to drug side effects for no real benefit? [8]

Enter Acetaminophen: A Familiar Name in an Unexpected Role

In 2011, a doctor in Israel made a surprising observation: several premature infants who happened to receive acetaminophen — the same Tylenol you might have at home — for pain relief after birth had their PDA close on its own, without any anti-prostaglandin drugs. Could regular Tylenol close the ductus arteriosus? [9]

It turned out, yes — at least sometimes. Acetaminophen works through a slightly different pathway than indomethacin or ibuprofen; rather than fully blocking the prostaglandin-making enzyme, it appears to partially dampen a related step in that process. The effect on the ductus was real. Over the following years, dozens of small studies and case reports accumulated showing that acetaminophen could close the PDA in many infants, with apparently fewer kidney and gut side effects. By 2020, many NICUs had begun routinely using acetaminophen as a first-line or backup treatment for PDA — even though the evidence from large, rigorous trials was still limited [10].

The TREOCAPA Trial: The Definitive Test

Given the growing use of acetaminophen for PDA without solid evidence, a team of European neonatologists decided to run the definitive trial. Called TREOCAPA — short for Prophylactic Treatment of the Ductus Arteriosus in Preterm Infants by Acetaminophen — it enrolled 778 extremely premature babies (born between 23 and 28 weeks of pregnancy) across 43 hospitals in 14 countries. Half received intravenous acetaminophen starting within 12 hours of birth for 5 days; the other half received a saltwater placebo (a harmless dummy treatment). Neither the parents, nurses, nor doctors knew which treatment each baby received — that's called a "double-blind" study, and it's the gold standard for fairness and reliability [11].

The trial was led by Dr. Jean-Christophe Rozé from Nantes University Hospital in France and published in JAMA Pediatrics on February 16, 2026.

What did they find?

The acetaminophen worked at closing the ductus: 71% of treated babies had their PDA closed by day 7 compared to 52% in the placebo group. So the drug clearly did something to the blood vessel. But here's the critical finding — it didn't actually help the babies survive better or have fewer serious complications. The rates of survival without major health problems (like severe lung disease, brain bleeds, or gut damage) were nearly the same in both groups: 66% in the acetaminophen group versus 64% in the placebo group. That small difference could easily be due to random chance [1].

And there was a worrying surprise: babies who received acetaminophen had a higher rate of cholestasis — a liver condition where bile doesn't flow properly — at 6.4% compared to 2.6% in the placebo group. This is a real safety concern. The conclusion: closing the ductus faster with acetaminophen didn't actually improve outcomes, and it introduced a new risk.

How Did the Medical World and the Public Respond?

Medical and Scientific Community

The neonatal community responded with significant interest. The podcast The Incubator, widely followed by neonatologists and NICU nurses, devoted a journal club episode to TREOCAPA in March 2026, noting that the results challenged the increasingly common practice of using acetaminophen for PDA and reinforced the message that "closing the ductus" and "helping the baby" are not the same thing [12]. A review published in the journal Biomedicines in early 2026 called the TREOCAPA results part of a broader "paradigm shift," arguing that the field needs to move away from ductus-closing strategies toward understanding which babies truly need intervention and which will do fine without it [13].

Medical news outlets including Medical Dialogues reported on the findings in April 2026, highlighting that early preventive acetaminophen "should not be routinely recommended" based on the trial results — language that carries real weight for NICU protocols globally [14].

The TREOCAPA Research Group

The trial's own website noted that families who participated in the study expressed hope that the results would be communicated clearly to parents and that information would be provided about what the findings mean for future care of preterm infants. The inclusion of family voices and perspectives in the trial's public communications represented a thoughtful approach to patient engagement [11].

What Does This Mean for Families?

For parents of premature babies, the TREOCAPA results carry a reassuring message wrapped in a sobering one. The reassuring part: even without this preventive treatment, more than 63% of babies born that prematurely survived without severe complications — a remarkable outcome for infants born months before their due date. The sobering part: there is still no proven pharmacological treatment that meaningfully improves outcomes beyond what careful supportive NICU care can achieve. Research is ongoing, and the next generation of clinical trials will likely focus on identifying which specific babies benefit from treatment and which do not, rather than treating all premature babies prophylactically.

The TREOCAPA trial is a reminder that in medicine, good intentions must always be tested with rigorous science. Closing a blood vessel is not the same as healing a baby.

References

  1. Rozé J-C, Cambonie G, Flamant C, et al. Prophylactic Treatment of Patent Ductus Arteriosus With Acetaminophen: A Randomized Clinical Trial. JAMA Pediatr. 2026;180(4):374–383. doi:10.1001/jamapediatrics.2025.6150
  2. Jain A, Shah PS. Diagnosis, Evaluation, and Management of Patent Ductus Arteriosus in Preterm Neonates. JAMA Pediatr. 2015;169(9):863–872.
  3. The pharmacological treatment of patent ductus arteriosus: a review of the evidence. Drugs. 1989. PMID: 2670518
  4. Oxnard SC et al. Ligation of the patent ductus arteriosus in the newborn intensive care unit. Ann Thorac Surg. 1977;23:564–567.
  5. Friedman WF, et al. Pharmacological closure of patent ductus arteriosus in the premature infant. N Engl J Med. 1976;295:526–529.
  6. Bandstra ES, et al. Prophylactic indomethacin for prevention of intraventricular hemorrhage in premature infants. Pediatrics. 1988;82:533–542.
  7. Ohlsson A, Walia R, Shah SS. Ibuprofen for the treatment of patent ductus arteriosus in preterm infants. Cochrane Database Syst Rev. 2013;(4):CD003481. doi:10.1002/14651858.CD003481.pub5
  8. Laughon MM, Simmons MA, Bose CL. Patency of the Ductus Arteriosus in the Premature Infant: Is It Pathologic? Pediatrics. 2004;113:e159–e167.
  9. Hammerman C, et al. Ductal Closure With Paracetamol: A Surprising New Approach to Patent Ductus Arteriosus Treatment. Pediatrics. 2011;128:e1618–e1621.
  10. Allegaert K, et al. Acetaminophen for the patent ductus arteriosus: has safety been adequately demonstrated? J Perinatol. 2023. PMID: 37169914
  11. TREOCAPA: prophylactic treatment of the ductus arteriosus in preterm infants by acetaminophen—statistical analysis plan. Trials. 2025. doi:10.1186/s13063-025-08751-8. Also: GFCNI TREOCAPA project overview. https://www.gfcni.org/research/treocapa
  12. The Incubator Podcast, Episode #410 – Journal Club, March 14, 2026. https://www.the-incubator.org/post/410-journal-club
  13. Kalikkot Thekkeveedu R, et al. PDA in Prematurity: Rethinking a Decades-Old Debate in 2026. Biomedicines. 2026;14(3):576. doi:10.3390/biomedicines14030576
  14. Baranwal M. Early Paracetamol for PDA Shows No Survival Benefit in Very Preterm Babies. Medical Dialogues. April 15, 2026. https://medicaldialogues.in/pediatrics-neonatology/news/early-paracetamol-for-pda-shows-no-survival-benefit-in-very-preterm-babies-research-reveals-168253