Respiratory trajectories of infants born before 26 weeks of gestation from birth to discharge: an exploratory analysis of the PLUSS-RCT

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Respiratory Trajectories of the Most Preterm Infants: What Happens After Birth? 👶🫁

Understanding the respiratory journey of extremely premature infants is essential for improving care, guiding research, and helping families prepare for the challenges ahead. A newly published exploratory analysis from the international PLUSS Trial provides one of the most detailed descriptions to date of respiratory support from birth until discharge in infants born before 26 weeks’ gestation.

Why is this important?

Infants born at the limits of viability face enormous respiratory challenges. Their lungs are structurally immature, surfactant deficient, and often require immediate respiratory support after birth.

While neonatal networks routinely report outcomes such as survival and bronchopulmonary dysplasia (BPD), relatively little is known about the day-to-day respiratory trajectory of these infants during their prolonged NICU stay.

This study sought to answer a simple but important question:

What does the respiratory journey look like for infants born before 26 weeks' gestation?

The Study

Researchers analyzed data from the international PLUSS Trial, which enrolled infants from 21 NICUs across Australia, New Zealand, Canada, and Singapore.

This analysis included:

• 601 infants born before 26 weeks’ gestation

• Infants born at:

  • 22–23 weeks (n=135)

  • 24 weeks (n=220)

  • 25 weeks (n=246)

All infants received surfactant therapy during their NICU admission.

What did they find?

Delivery room respiratory support

The need for intubation at birth was strongly related to gestational age:

• 97% of infants born at 22–23 weeks were intubated in the delivery room

• 74% of infants born at 24 weeks

• 64% of infants born at 25 weeks

Extubation remains challenging

The more immature the infant, the longer clinicians waited before attempting extubation:

Gestational Age	Median Age at First Extubation
22–23 weeks	15 days
24 weeks	6 days
25 weeks	3 days

However, extubation failure remained common:

• 66% of infants born at 22–23 weeks required reintubation

• 51% of infants born at 24 weeks

• 38% of infants born at 25 weeks

Prolonged mechanical ventilation

Among survivors to 36 weeks' postmenstrual age:

• 22–23 weeks: 36 days median mechanical ventilation

• 24 weeks: 26 days

• 25 weeks: 12 days

A striking finding was that for every week decrease in gestational age, infants required approximately two additional weeks of respiratory support and hospitalization.

Oxygen needs increase during the first two weeks

Contrary to what many might expect, oxygen requirements did not immediately improve after birth.

Instead, infants experienced a gradual increase in oxygen needs during the first 14 days of life, particularly those born at 22–24 weeks and those requiring ongoing mechanical ventilation.

This likely reflects the evolving nature of lung disease and ongoing pulmonary inflammation during the early neonatal period.

Respiratory support continues well beyond term age

At 40 weeks postmenstrual age:

• Only 11% of surviving infants born at 22–23 weeks had been discharged home

• 85% of those still hospitalized continued to require oxygen or respiratory support

Even among infants born at 25 weeks:

• More than half of hospitalized infants still required respiratory support at 40 weeks' postmenstrual age.

Bronchopulmonary dysplasia remains common

Survival without BPD was rare:

• Only 10% of infants born at 22–23 weeks survived without BPD

• 10% of infants born at 24 weeks

• 20% of infants born at 25 weeks

These findings highlight the ongoing burden of chronic lung disease among the most immature infants.

Why does this matter?

This study provides one of the clearest pictures yet of the respiratory course experienced by infants born before 26 weeks’ gestation.

The findings can help:

✅ Clinicians counsel families more accurately

✅ Set realistic expectations regarding respiratory support and NICU stay

✅ Identify opportunities to improve ventilation and extubation strategies

✅ Guide future clinical trials aimed at reducing lung injury and improving outcomes

Most importantly, these data remind us that survival at the margins of viability is increasingly achievable—but often requires months of intensive respiratory support and multidisciplinary care.

Looking Ahead

As neonatal care continues to improve, understanding respiratory trajectories becomes increasingly important. Studies such as this provide a foundation for developing better respiratory support strategies, improving extubation success, reducing chronic lung disease, and ultimately helping the smallest and most vulnerable infants thrive.

Congratulations to the PLUSS investigators and participating NICUs for providing this important insight into the respiratory journey of extremely premature infants. 👏🫁👶

Reference: Alarcon Martinez T, Francis KL, Kamlin O, Shalish W, Sant'Anna G, Hodgson KA, Dargaville PA, Lui K, Resnick SM, Schmölzer GM, et al. Respiratory trajectories of infants born before 26 weeks of gestation from birth to discharge: an exploratory analysis of a randomised controlled trial. Lancet Child & Adolescent Health, 2026.