Spirometry, the familiar test in which a patient blows forcefully into a mouthpiece, measures how much air can be exhaled and how quickly. It is cheap, widely available and reproducible, which explains its dominance in both clinics and research studies. Yet it fundamentally measures airflow through large and medium airways. The injury pattern left by extreme preterm birth, often described as chronic lung disease of prematurity or bronchopulmonary dysplasia in its severe forms, is primarily one of disrupted alveolar and vascular development. The distal lung, where gas exchange actually happens, and the pulmonary circulation, which must carry the entire cardiac output through a finely branched vascular tree, are the structures most affected. Spirometry can remain deceptively normal in people whose gas transfer capacity and pulmonary vasculature are substantially impaired.

The evidence for this blind spot is accumulating rapidly. A study by Harris and colleagues, published in Pediatric Research, examined school-aged children born preterm and found that reduced diffusion of carbon monoxide across the lung, a marker of impaired gas exchange surface, was associated with elevated pulmonary artery pressures. This finding is significant because it links two silent abnormalities: a lung that cannot transfer oxygen efficiently and a heart that must pump against higher resistance in the pulmonary circulation. Neither abnormality would necessarily be flagged by a routine spirometry test, and both may progress quietly for decades before producing symptoms.

Longitudinal data reinforce the concern. Research published in the European Respiratory Journal followed individuals born extremely preterm into adulthood and documented persistent deficits in lung diffusion capacity that did not normalize with growth. A systematic review and meta-analysis by Gibbons and colleagues in the European Respiratory Review synthesized findings across lung volumes, gas transfer and oscillometry, a technique that measures airway resistance during quiet tidal breathing rather than forced expiration. Together, these studies sketch a consistent picture: preterm birth leaves a durable imprint on the distal lung and its mechanics that forced expiratory volumes capture only partially, if at all.

The clinical implications extend beyond the lungs. Survivors of extreme preterm birth appear to face elevated long-term risks of pulmonary vascular disease and cardiovascular complications, a concern articulated in a lifespan-oriented framework by Simpson and colleagues in The Lancet Respiratory Medicine. The developing lung and its vasculature are built in tandem during the canalicular and saccular stages of gestation, precisely the window that extreme preterm birth interrupts. When alveolarization is curtailed, the vascular tree that should accompany each new alveolus is curtailed with it. The result is a lung with fewer, larger airspaces and a reduced, remodeled vascular bed, a combination that increases the workload on the right ventricle and may set the stage for pulmonary hypertension and early cardiovascular decline in adult life.

What would a comprehensive assessment look like in practice? The commentary by Beaven and Finlay points toward a battery of complementary tests, each interrogating a different component of the cardiopulmonary system. Lung clearance index, derived from multiple-breath washout, quantifies ventilation inhomogeneity in the small airways and peripheral lung units, and has proven sensitive to early lung disease in other pediatric populations. Body plethysmography measures total lung volumes, revealing the restricted or hyperinflated patterns that spirometry alone can miss. The single-breath or rebreathing diffusing capacity for carbon monoxide directly probes the gas exchange surface. Oscillometry adds information about peripheral airway resistance without requiring maximal effort, an important advantage in young children who cannot reliably perform forced maneuvers.

Cardiovascular assessment deserves equal billing. Echocardiography can estimate pulmonary artery pressures and right ventricular function, while newer techniques such as cardiac magnetic resonance imaging offer precise quantification of right ventricular mass and ejection fraction. Exercise testing integrates the entire system, revealing whether oxygen delivery keeps pace with metabolic demand, and cardiopulmonary exercise testing can unmask limitations that are invisible at rest. Reduced exercise capacity has been documented in preterm-born cohorts, and the physiological basis, whether ventilatory limitation, gas exchange impairment, vascular limitation or deconditioning, can only be disentangled by measuring multiple variables simultaneously during exertion.

The concept of treatable traits offers a compelling rationale for this expanded toolkit. As Zanetto and colleagues argued recently in the American Journal of Respiratory and Critical Care Medicine, clinicians caring for preterm-born individuals with chronic lung disease of prematurity should identify and target specific, modifiable characteristics across the lifespan rather than relying on a single diagnostic label. A patient with preserved spirometry but reduced diffusion capacity and elevated pulmonary artery pressures needs a very different management plan from one with airflow obstruction and air trapping. Without comprehensive phenotyping, the first patient may be falsely reassured and the second may receive therapies that do not address their dominant abnormality. Treatable traits might include airway reactivity, ventilation inhomogeneity, impaired gas transfer, pulmonary vascular dysfunction, muscle weakness and physical deconditioning, each with its own therapeutic levers.

There are practical hurdles to overcome before comprehensive assessment becomes standard care. Many of the recommended tests require specialized equipment, trained personnel and cooperative patients, which limits their availability in ordinary clinical settings and in the low-resource environments where much of the world’s preterm births occur. Reference ranges for children and young adults born preterm are incomplete for several modalities, complicating interpretation. Radiation exposure argues against routine computed tomography, and the research community continues to seek safe, non-invasive imaging surrogates of alveolar and vascular structure. Standardizing protocols across centers and across the age spectrum, from infancy through adulthood, remains an unfinished project, and longitudinal cohorts that follow preterm-born individuals with repeated multi-modal assessments are still relatively rare.

Nevertheless, the direction of travel is clear. The generation born after the widespread adoption of surfactant therapy and gentle ventilation is now reaching adulthood in large numbers, and their long-term cardiopulmonary trajectory is becoming a matter of public health, not just neonatology. Detecting silent gas exchange impairment and early pulmonary vascular change during the school years, when interventions such as exercise programs, vaccination, smoking prevention and targeted follow-up can still alter the course, is far preferable to discovering these problems when symptomatic disease emerges in mid-life. The commentary by Beaven and Finlay makes the case that spirometry, whatever its virtues, cannot carry this burden alone. A comprehensive cardiopulmonary assessment, combining measures of lung volume, ventilation distribution, gas transfer, airway mechanics, pulmonary hemodynamics and exercise capacity, offers the best chance of understanding, monitoring and ultimately improving the lifelong health of the fastest-growing population of adult survivors of neonatal intensive care.

Subject of Research: Cardiopulmonary assessment of lung and cardiovascular outcomes in survivors of extreme preterm birth

Article Title: Beyond spirometry: towards comprehensive cardiopulmonary assessment after extreme preterm birth

Article References: Beaven, M. L., & Finlay, P. (2026). Beyond spirometry: towards comprehensive cardiopulmonary assessment after extreme preterm birth. Pediatric Research. https://doi.org/10.1038/s41390-026-05399-1

Image Credits: AI Generated

DOI: 10.1038/s41390-026-05399-1

Keywords: extreme preterm birth, bronchopulmonary dysplasia, spirometry, lung diffusion capacity, pulmonary hypertension, chronic lung disease of prematurity, lung clearance index, oscillometry, cardiopulmonary exercise testing, treatable traits, pediatric lung function, right ventricular function

The clinical stakes are considerable. Infants with bronchopulmonary dysplasia face elevated risks of motor delay, cerebral palsy, cognitive impairment, language difficulties, and behavioral challenges that can persist well into school age. Their prolonged hospitalizations, often stretching across many months, are characterized by exposure to invasive procedures, sedating and sometimes neurotoxic medications, extended mechanical ventilation, and the sensory environment of an intensive care unit that bears little resemblance to the womb. Yet the same extended stay also represents an extended opportunity, a window in which structured developmental care, physical therapy, occupational therapy, and family-centered interventions can be woven into daily management. The question the research addresses is whether neonatal units are systematically seizing that opportunity or leaving developmental support to happenstance and individual clinician initiative.

Neurodevelopmental therapy in the neonatal setting encompasses a broad spectrum of practices. At its most structured, it includes standardized developmental assessments performed at regular intervals, referrals to physical and occupational therapists with neonatal expertise, individually calibrated positioning and handling strategies, oral feeding support that respects the infant’s respiratory limitations, and structured programs that prepare families to continue stimulation and therapy after discharge. At its least structured, it amounts to informal bedside advice delivered when staffing allows. The literature has long suggested that early, intensive developmental intervention can improve trajectories for high-risk infants, but translating that evidence into routine practice across a heterogeneous network of intensive care units has proven difficult, and the new study illuminates precisely where the translation breaks down.

A central theme emerging from the work is the striking variability in how units that care for infants with BPD organize their developmental services. Some centers embed dedicated neurodevelopmental teams within the neonatal intensive care environment, with therapists rounding alongside neonatologists and nurses and contributing directly to individualized care plans. Others rely on consultation models in which therapists evaluate infants but remain peripheral to daily medical decision-making. Still others provide developmental programming only in fragments, dependent on the availability of personnel and the priorities of individual attending physicians. This patchwork means that two infants with comparable degrees of lung disease, admitted to different units, may receive profoundly different developmental care purely as a function of where they happen to be born.

The technical details of why this variability matters are grounded in the neurobiology of the preterm brain. The third trimester of pregnancy, which extremely preterm infants spend largely in the intensive care unit, is a period of extraordinary cerebral organization: cortical folding, myelination, synaptogenesis, and the pruning of neural circuits all proceed at a pace unmatched at any later stage of life. Sensory experience during this period literally shapes the architecture of the developing nervous system. Painful procedures, prolonged prone positioning, excessive light and noise, and handling practices that disrupt sleep can disrupt these processes, while calibrated positive sensory input, skin-to-skin contact, and supported early feeding experiences can support them. Neurodevelopmental therapy is, in this sense, not an adjunct to intensive care but an integral component of protecting the brain while the lungs are being treated.

For infants with bronchopulmonary dysplasia specifically, the developmental challenge is compounded by respiratory physiology. Many of these infants remain on oxygen support for months, and their limited respiratory reserve constrains the energy available for the motor demands of feeding, reaching, and exploratory movement. Oral feeding, one of the most complex motor tasks the newborn brain must coordinate, becomes a delicate negotiation between nutritional needs and respiratory stability. Therapists with neonatal expertise are trained to titrate intervention intensity to the infant’s physiologic tolerance, monitoring desaturation events, heart rate patterns, and behavioral stress cues to ensure that therapy strengthens rather than exhausts the child. That level of specialization is precisely what the study identifies as unevenly distributed across the units caring for this population.

The research also directs attention to the institutional and systemic factors that determine whether neurodevelopmental services flourish or falter. Adequate therapist staffing ratios, dedicated funding for developmental programs, formal training pathways in neonatal therapy, and leadership that treats brain development as a quality metric alongside survival and growth all emerge as decisive variables. Units that have made developmental care a strategic priority tend to show more consistent assessment schedules, earlier therapy initiation, and stronger family engagement. Where such infrastructure is absent, even clinicians who are personally committed to developmental principles struggle to deliver them reliably. The implication is that improving outcomes for infants with BPD is not primarily a matter of individual clinician goodwill but of building systems in which developmental care is the default rather than the exception.

Families occupy a central position in this framework, and the study’s findings carry important implications for parents navigating prolonged intensive care stays. Parents of infants with BPD frequently report anxiety about their child’s future, and they are often the first to notice subtle delays in movement, feeding, or social engagement. Structured neurodevelopmental programs that involve parents as partners, teaching positioning strategies, coaching on developmental play, and preparing families for the transition home, convert the prolonged hospitalization into a period of skill-building for caregivers as well as infants. Equally important, standardized developmental follow-up after discharge allows the early signs of cerebral palsy, cognitive delay, or language impairment to be detected and addressed during the windows in which intervention is most effective, rather than at the point of school-entry failure.

The broader significance of this work lies in its reframing of what constitutes high-quality care for bronchopulmonary dysplasia. For much of the modern neonatal era, success in managing the disease was measured in survival, oxygen weaning, and growth velocity. Those metrics remain essential, but a growing body of long-term outcome research demonstrates that pulmonary health and neurodevelopmental health are inseparable in this population: children who escape severe lung disease can still carry substantial developmental burden, and developmental interventions delivered during the intensive care stay may influence outcomes that were once assumed to be fixed. By mapping the current landscape of neurodevelopmental therapy across units that care for these infants, the study provides a baseline against which progress can be measured and a pointed reminder that the lungs and the brain of the preterm infant must be treated as one patient, not two.

Looking forward, the research suggests concrete priorities for the neonatal community: standardizing developmental assessment protocols for infants with BPD, expanding access to therapists with neonatal subspecialty training, embedding developmental outcomes into unit-level quality improvement, and ensuring equitable delivery of services so that an infant’s developmental trajectory is not determined by geography or institutional circumstance. As the cohort of BPD survivors continues to grow, the neonatal intensive care unit is increasingly being judged not only by whether its smallest patients survive, but by how fully they thrive. Neurodevelopmental therapy, integrated deliberately and systematically into the care of infants with bronchopulmonary dysplasia, may prove to be one of the most powerful tools available for shifting that balance.

Subject of Research: Neurodevelopmental therapy practices in neonatal intensive care units caring for infants with bronchopulmonary dysplasia.

Article Title: Neurodevelopmental therapy in NICUs that care for infants with bronchopulmonary dysplasia

Article References: DeMauro, S. B., Burkhardt, M., Hanin, M., Miller, A. N., House, M., Ransom, M., DuPont, T., Lagoski, M., Wood, A., Brei, B. K., Brinker, K., Wittwer, C., Gibbs, K., & on behalf of the BPD Collaborative Neurodevelopment Group (2026). Neurodevelopmental therapy in NICUs that care for infants with bronchopulmonary dysplasia. Journal of Perinatology. https://doi.org/10.1038/s41372-026-02891-8

Image Credits: AI Generated

DOI: 10.1038/s41372-026-02891-8

Keywords: bronchopulmonary dysplasia, neonatal intensive care, neurodevelopmental therapy, preterm infants, developmental care, neonatology, infant brain development, occupational therapy, physical therapy, family-centered care, chronic lung disease of prematurity, developmental outcomes