What is the DART Protocol in the NICU?

The DART protocol is a specific low-dose dexamethasone regimen used in neonatal intensive care units to help wean very premature infants off mechanical ventilation. DART stands for “Dexamethasone: A Randomized Trial,” named after the landmark multicenter trial published in 2006 that tested whether a short, carefully dosed course of this steroid could get ventilator-dependent babies breathing more independently without the serious brain-related side effects that had made neonatologists afraid to use steroids at all. The protocol delivers a cumulative dose of 0.89 mg/kg over ten days, which is a fraction of the doses used in earlier eras of neonatal care, and that distinction matters enormously for both efficacy and safety.

The Problem DART Was Designed to Solve

Premature infants born before 28 weeks of gestation or weighing under 1,000 grams often develop chronic lung inflammation that keeps them dependent on a breathing machine for weeks or months. This inflammation is part of the pathway toward bronchopulmonary dysplasia, or BPD, one of the most common and consequential complications of extreme prematurity. Dexamethasone, a potent synthetic steroid, had been used since the early 1990s to reduce this lung inflammation, and it worked. The problem was that early protocols used high doses, sometimes 0.5 mg/kg per day or more, and follow-up studies revealed devastating consequences.

A pivotal study found that children who received early, high-dose dexamethasone had dramatically higher rates of cerebral palsy compared to those given placebo. The dexamethasone-treated group showed cerebral palsy in about half the children, versus roughly 15% in the placebo group. Developmental delay was also substantially more common in the treated group.¹ Those findings were alarming enough that many NICUs stopped using postnatal steroids almost entirely. But infants who genuinely could not come off the ventilator still needed something. Clinicians were stuck between a drug that helped the lungs but hurt the brain, and no drug at all. DART was the attempt to find a safe middle ground.

How the Dosing Schedule Works

The DART protocol enrolled very preterm or extremely low birth weight infants who remained ventilator-dependent after the first week of life. The regimen delivers intravenous dexamethasone in a tapering course over ten days, with a total cumulative dose of 0.89 mg/kg.² The dose starts higher and steps down over the course, giving the lungs an initial anti-inflammatory push and then gradually withdrawing the drug to minimize systemic exposure.

To put that cumulative dose in perspective, a more recent study compared the DART regimen to what researchers called an “enhanced low dose” protocol, which delivers 1.35 mg/kg over a similar period. Even that enhanced version is still considered low-dose by historical standards. For context, the AAP has stated that high-dose dexamethasone at 0.5 mg/kg per day does not appear to offer extra benefit over lower doses and should not be used.³ The DART dose represents a deliberate attempt to give the smallest effective steroid exposure, acknowledging that every milligram carries potential risk to a developing brain.

What the Steroid Does Inside the Lungs

The lungs of a chronically ventilated preterm infant are in a state of ongoing inflammation. White blood cells, particularly neutrophils, flood the airways. Inflammatory signaling molecules ramp up, and proteins leak from damaged tissue into the lung fluid. This inflammation stiffens the lungs, makes gas exchange harder, and keeps the baby dependent on the ventilator. Dexamethasone interrupts this cycle.

Studies measuring the contents of fluid washed from the airways of treated infants consistently show that dexamethasone reduces neutrophil counts, lowers levels of inflammatory signaling molecules, and decreases protein concentrations in the lungs.⁴ At a cellular level, the drug works by interacting with the machinery that cells use to turn inflammatory genes on and off. After treatment, the levels of immune-signaling chemicals in airway fluid drop, and inflammatory cells decrease.⁵

That reduction in inflammation translates directly into measurable improvements in lung mechanics. Treated infants show better lung compliance, meaning the lungs stretch more easily with each breath, and improved airflow. One study documented that dexamethasone-treated infants had roughly half the neutrophil burden in their airways compared to untreated infants, alongside measurable gains in lung function and reduced need for ventilator support.⁶

Short-Term Effectiveness at Getting Babies Off the Ventilator

The original DART trial was a multicenter, international, randomized controlled trial, and its primary question was practical: does this low-dose regimen help chronically ventilated preterm infants get extubated? The trial showed that infants receiving the DART protocol were more likely to come off the ventilator successfully than those receiving saline placebo.² For clinicians watching an infant struggle on a ventilator week after week, with all the complications prolonged mechanical ventilation brings, that result mattered.

However, the DART protocol is not the last word. A 2025 study compared the standard DART regimen (0.89 mg/kg cumulative) against an enhanced low-dose protocol (1.35 mg/kg cumulative) and found that the higher dose outperformed DART on several respiratory measures. Infants on the enhanced regimen needed less time on both invasive and non-invasive ventilation, were more likely to be off supplemental oxygen by 36 weeks corrected age, and had a higher extubation success rate.⁷ This raises the question of whether DART’s dose, chosen conservatively to protect the brain, might sometimes be too conservative for the lungs. Some units have begun exploring whether a slightly higher but still low-dose course might offer a better balance.

The Critical Two-Year Safety Follow-Up

The most important question about any steroid given to a premature infant is not whether it helps the lungs in the short term but whether it harms the brain in the long run. The DART investigators followed their trial participants to age two and published the results separately. There was little evidence of a difference in the combined outcome of death or major disability between the dexamethasone group and the controls. Rates of cerebral palsy, mortality, and the combined outcome of death or cerebral palsy were not substantially different between groups, and there were no obvious effects on growth or hospital readmissions after discharge.⁸

That finding was reassuring, especially in contrast to the alarming cerebral palsy rates seen with high-dose regimens. But the trial was not large enough to definitively rule out smaller effects, and two years is a relatively short follow-up window for detecting subtle cognitive or behavioral differences that might emerge in school-age children. The evidence is encouraging, not conclusive. Clinicians who use the DART protocol are making a judgment that the benefits of getting a struggling infant off the ventilator outweigh the residual uncertainty about long-term brain effects, particularly when the infant is at high risk of dying or developing severe lung disease if left untreated.

When to Start Steroids

The DART trial specifically targeted infants who were still ventilator-dependent after the first week of life. That timing was deliberate. Starting steroids in the first few days after birth, before it is clear which infants truly need them, exposes babies to drug risks who might have improved on their own. Waiting too long means the inflammation has already done more damage and the infant has endured more time on the ventilator.

A large propensity-score analysis compared outcomes when postnatal dexamethasone was started earlier (around day two or three) versus later (day six or beyond). The later group was more likely to develop severe BPD or die before discharge, and they spent substantially longer on invasive ventilation, with a mean difference of about 17.5 extra days. They were also extubated at a later corrected age, on average about three weeks later than infants started on steroids earlier.⁹ An earlier pilot trial similarly found that starting dexamethasone sooner led to faster extubation, with a median of 14 days to extubation in the early group versus 24 in the late group.¹⁰

The practical takeaway is that once it becomes clear an infant is not going to wean from the ventilator without pharmacological help, waiting does not tend to improve outcomes and may make them worse. But starting too early, before the clinical need is evident, raises the risk of treating infants who did not need the drug.

Acute Side Effects During Treatment

Even at the DART protocol’s low dose, dexamethasone is not a benign medication. The steroid affects virtually every organ system, and several short-term side effects are well documented in premature infants. A trial studying early dexamethasone in extremely low birth weight infants found that treated infants were more likely to develop hypertension and more likely to need insulin for high blood sugar during the treatment period.¹¹ Both of these effects are dose-related and generally resolve after the course ends, but they require monitoring.

The heart is another area of concern. One study found that infants receiving dexamethasone developed thickening of the heart muscle wall, with the septal and left posterior wall becoming significantly larger during treatment and for a week after weaning. About one in five treated infants developed left ventricular hypertrophy that was clinically significant, with signs of reduced cardiac output.¹² This cardiac thickening is typically transient and reversible, but it underscores why NICU teams monitor echocardiograms and blood pressure closely during a steroid course. The DART protocol’s lower dose and shorter duration were designed in part to reduce the severity of these acute effects compared to older, more aggressive regimens.

Is Hydrocortisone a Safer Alternative?

Because of dexamethasone’s reputation for neurodevelopmental harm, some clinicians have wondered whether hydrocortisone might be a gentler option for treating or preventing BPD. Hydrocortisone is a less potent steroid with a shorter duration of action and different effects on developing brain tissue. One study comparing the two drugs found that while general movement quality was similar between hydrocortisone-treated and dexamethasone-treated infants up to term age, hydrocortisone-treated infants scored higher on motor assessments at three months.¹³

That sounds promising, but the overall evidence has not supported a clean swap. A Canadian position statement concluded that there is no evidence hydrocortisone is an effective or safe alternative to dexamethasone for treating evolving or established BPD.¹⁴ The issue is that hydrocortisone, while possibly gentler on the brain, has not been shown to achieve the same degree of lung improvement that dexamethasone provides. Some NICUs use hydrocortisone for early prevention of BPD and reserve dexamethasone, via the DART protocol, for infants who are already stuck on the ventilator and need more aggressive lung anti-inflammatory treatment. The two drugs may serve different roles rather than being interchangeable.

Matching the Risk to the Intervention

One of the more nuanced discussions in modern neonatology is about who should receive postnatal steroids at all. The thinking has shifted from a blanket approach to a risk-stratified one. Data from a large European cohort illustrate why this matters. In that study, about 28% of infants in the highest BPD risk group received postnatal steroids, compared to roughly 13% of moderate-risk infants and only about 4% of those at low risk. After statistical adjustment, steroid treatment was associated with increased gross motor impairment in the highest-risk group specifically, while no significant difference in cognitive development was found in the overall population after adjustment.¹⁵

The interpretation is complicated. The sickest babies are the ones most likely to receive steroids, and they are also the ones most likely to have poor outcomes regardless of treatment. Disentangling the drug effect from the underlying illness severity is one of the hardest problems in neonatal research. What the data suggest is that the benefit-to-risk ratio of steroids shifts depending on how sick the infant is. For a baby who has a reasonable chance of coming off the ventilator without steroids, the DART protocol’s risks, however small, may not be worth taking. For a baby who is deteriorating and has a high probability of dying or developing severe BPD without intervention, the calculus tilts toward treatment. Most clinical guidelines now reflect this, recommending that steroid use be reserved for infants at the highest risk of severe lung disease.

Inhaled Steroids and Emerging Approaches

Delivering steroids directly to the lungs rather than through the bloodstream is an appealing concept because it could reduce systemic exposure and protect the brain. Inhaled budesonide and intratracheal budesonide mixed with surfactant are the main candidates in this space. In one case report, a preterm infant with severe pulmonary hemorrhage received intratracheal budesonide combined with surfactant, and the oxygenation index dropped substantially within hours, with respiratory conditions improving and the need for supplemental oxygen falling within 24 hours.¹⁶

Case reports are the weakest form of evidence, though, and the field is still working through larger trials to understand whether intratracheal budesonide can reliably prevent or treat BPD with fewer side effects than systemic dexamethasone. The AAP has acknowledged that evidence remains insufficient to make recommendations about alternative steroid preparations and routes beyond dexamethasone.³ For now, the DART protocol remains the most evidence-backed approach for systemic steroid treatment of ventilator-dependent preterm infants, but the landscape is evolving.

Ventilation Strategies That Work Alongside Steroids

The DART protocol does not exist in a vacuum. How an infant is supported after extubation matters just as much as getting them off the ventilator in the first place. A failed extubation, where the baby has to be reintubated, is a significant setback that carries its own risks. One study comparing two modes of non-invasive respiratory support after extubation found that neurally adjusted ventilatory assistance, a mode that synchronizes the ventilator to the baby’s own breathing signals, reduced the reintubation rate from 50% to about 12% compared to standard nasal continuous positive airway pressure.¹⁷

Pairing the DART protocol with optimized post-extubation support is a practical reality in most NICUs. The steroid course reduces lung inflammation enough to attempt extubation, and the post-extubation ventilation mode helps the infant succeed once the breathing tube comes out. Neither piece alone solves the problem for many of these chronically ventilated babies. Caffeine therapy, careful fluid management, and nutritional optimization also play supporting roles, though the DART protocol addresses the specific barrier of airway inflammation that keeps the infant ventilator-dependent.