Two Cheap Tablets, One Clear Winner: Helping Newborn Lungs Open Up

What a study of 36 babies in Pune, India, found when comparing sildenafil and bosentan for high blood pressure in a newborn's lungs

Some newborns cannot get enough oxygen because the blood vessels in their lungs stay tightly closed after birth — a condition called persistent pulmonary hypertension of the newborn. The best treatment, a gas called inhaled nitric oxide, is unavailable in most hospitals worldwide. A trial in Pune, India, compared two inexpensive tablets in 36 such babies and found that one of them, sildenafil, lowered the pressure in the lung arteries roughly three times faster than the other.

Why a Baby's First Breath Is So Different

Before birth, a baby's lungs are filled with fluid and do almost no work. Oxygen arrives through the placenta, and the blood vessels inside the lungs are deliberately squeezed narrow so that blood bypasses them. At birth, everything is supposed to reverse within minutes: the lungs fill with air, the vessels relax and open wide, and blood floods through them to collect oxygen for the first time.

In a small number of babies, that switch does not flip. The lung vessels stay narrow, the pressure inside them stays high, and blood takes the old shortcuts it used before birth instead of flowing through the lungs. The result is a baby who looks blue and whose oxygen levels swing alarmingly from one minute to the next, even on a ventilator. Doctors call this persistent pulmonary hypertension of the newborn, usually shortened to PPHN [1]. It affects babies born at or near full term far more often than very premature babies [2]. The commonest triggers are meconium aspiration — where a baby inhales its own first stool during a difficult birth — along with infection and pneumonia [3],[4].

The Problem Families and Doctors Faced Before This Research

For about thirty years, the recognised treatment for PPHN has been a gas called inhaled nitric oxide, breathed in alongside oxygen. It relaxes the lung's blood vessels specifically, without dropping blood pressure elsewhere in the body, and large studies have shown it improves oxygen levels and reduces the number of babies who die or need to be put on a heart–lung bypass machine [5],[6]. If your baby is born in a hospital that has it, this is what they will receive.

Most babies in the world are not born in such a hospital. Nitric oxide needs specialist equipment, a constant supply of medical gas, and a budget that many hospitals simply do not have. A 2023 survey of 118 newborn intensive care units across India found that only one in four had access to it [7]. In the other three-quarters, doctors have had to improvise with ordinary tablets — crushed, dissolved in water, and given down a feeding tube into the baby's stomach.

Two tablets are commonly used. Sildenafil is the same drug sold as Viagra for adults; in newborns it is used because it helps lung blood vessels relax and stay relaxed. It has been studied in several small trials, and a major review concluded it may improve oxygen levels and survival, particularly in hospitals without nitric oxide [8],[9]. Bosentan works differently: instead of encouraging vessels to open, it blocks a natural chemical signal that keeps them squeezed shut [10]. Its track record has been confusing. One trial found it helped a lot [11]; a bigger one, testing it alongside nitric oxide, found it added nothing [12]. A few hospital reviews suggested both drugs were safe and useful [13],[14], and one earlier trial in Iran even suggested bosentan might work faster [15] — though the babies in that study were much more premature and the two groups did not start out equally ill. So a doctor at three in the morning, holding two bottles of tablets, had no clear answer about which to reach for. That is the gap this study set out to fill.

How the Study Was Done

Researchers at a large teaching hospital in Pune, India — Bharati Vidyapeeth Medical College — ran the trial in their newborn intensive care unit between July 2022 and January 2024. The unit had no nitric oxide available during that time, so the question was not academic; it was exactly the choice their own team faced every week. The study received no funding from any drug company [1].

Babies were eligible if they were born at 34 weeks of pregnancy or later and if a heart ultrasound scan confirmed that the pressure in their lung arteries was high and they needed extra oxygen. Babies with heart defects, a hole in the diaphragm, or conditions that could not be survived were not included, and neither were babies already receiving another drug for the same problem. Of 63 babies found to have PPHN during that period, 36 met all the criteria and joined the study.

A computer then decided at random which babies received which tablet — 18 got sildenafil and 18 got bosentan. This coin-toss approach is what makes a study trustworthy: it means the two groups differed only in the drug, not in how sick they were or which doctor chose their treatment. And in fact the groups did start out remarkably similar, right down to the pressure in their lung arteries, which averaged about 46 on the scale doctors use in both groups.

Each baby then had a heart ultrasound every day to see how the pressure was changing. The main question was simple: how many hours did it take for the pressure to drop by a quarter?

What They Found

The difference was large and it appeared quickly. In the sildenafil group, the pressure had fallen by a quarter within 36 hours for the typical baby. In the bosentan group, the typical baby took 96 hours — four days instead of a day and a half. The scans showed sildenafil ahead at every check: one day in, two days in, and three days in [1].

The knock-on effects followed the same pattern. Doctors counted a baby as a "treatment failure" if the pressure had not come down enough within two days or if a second medicine had to be added. That happened to 3 of the 18 sildenafil babies, and to 12 of the 18 bosentan babies. Put plainly: two out of three babies on bosentan needed something else, compared with roughly one in six on sildenafil. Eleven bosentan babies needed a second drug added, against three in the sildenafil group.

Some things did not differ. Babies in both groups came off the ventilator at about the same time, reached full milk feeds at about the same time, and went home after a broadly similar stay — the sildenafil babies left sooner on average, but the difference was not large enough for the researchers to be confident it was real rather than chance. Oxygen requirements dropped faster with sildenafil on the first day, but by the second and third days the two groups looked alike.

Both medicines were well tolerated. One baby in each group had a drop in blood pressure. There was one death in the study, in the sildenafil group — a baby with a rare inflammatory condition affecting newborns who developed shock that did not respond to treatment. The researchers did not attribute the death to the medication.

What This Means for Families

If your baby has PPHN and is being treated in a hospital without nitric oxide, this study supports starting with sildenafil rather than bosentan. It is not that bosentan is dangerous — it was as well tolerated as sildenafil — but that it appears to work too slowly for a condition where hours matter. The likely reason is that bosentan is absorbed from a newborn's stomach only sluggishly over the first half-day, so it is still building up while the baby is still struggling.

It is worth being clear about what this study does not show. It does not show that either drug helps babies survive, or come home sooner, or grow up healthier — the study was too small to answer those questions, and it deliberately did not include the sickest babies, those whose hearts were already failing and who needed intravenous medicines from the start. If your baby is in that group, the calculation is different and your team will explain why. It is also normal for a second medicine to be added; that happened to a fifth of the babies even in the better-performing group, and it is a routine adjustment rather than a sign that something has gone wrong.

The honest expectation to carry into the next few days is that the pressure in your baby's lungs will come down gradually, over a day or two rather than in an afternoon, and that the daily ultrasound is how the team tracks that progress. Ask to be told the number each day if it helps you — many parents find the falling figure reassuring.

What Researchers Are Working On Next

The most useful next study would compare sildenafil with milrinone, the intravenous drug that was used as backup in both groups here, and with the two given together. Researchers also want to test whether giving sildenafil through a drip instead of a feeding tube works faster still, since the same Pune group has already compared those two routes [16]. Above all, the field needs a study large enough to follow babies past the newborn period, checking how they walk, talk and learn at 18 months to two years — because now that most babies with moderate PPHN survive, how they thrive is the question that matters most to families.

References

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