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Preterm Bronchopulmonary Consequences Endure : Expert hypothesizes that persistent low blood flow in adults is an adaptive mechanism learned in utero.


 

MONTREAL — The first long-term follow-up of infants with bronchopulmonary dysplasia suggests that the consequences of preterm birth lessen over time, but are enduring.

“The consequences of preterm birth clearly seem to lessen over time going from the newborn period into early adult life; but being small for gestational age and preterm, the effects are much more long-lasting, both in terms of airflow obstruction and cardiovascular reprogramming,” Dr. Andrew Bush said at the International Congress on Pediatric Pulmonology.

The analysis included 60 adults, aged 20–22 years, from an original cohort of 300 babies with chronic lung disease of prematurity, and 50 new, age-matched term controls. The preterm group included 23 adults who were defined as small for gestational age (less than 1,500 g) and 37 defined as appropriate for gestational age (1,500–2,000 g). Evaluations included spirometry, exhaled nitric oxide testing, skin-prick tests, and exercise tests.

Forced expiratory volume in 1 second (FEV1) z scores were not significantly different among the three groups. But when those scores were plotted by birth weight, birth weight was found to be a significant determinant of FEV1 outcomes for preterm small-for-gestational-age (SGA) babies even after 20 years of environmental influences and self-abuse, said Dr. Bush, professor, National Heart and Lung Institute, Royal Brompton Hospital, London.

Birth weight also was a determinant of FEV25–75 scores in this group. No association between birth weight and lung function was found in preterm appropriate-for-size survivors or controls, he said.

Using respiratory mass spectrometry, the investigators, led by Indra Narang, also of Royal Brompton Hospital, measured cardiac output and carbon monoxide transfer (DLCO). During exercise in healthy subjects, there can be a fivefold rise in cardiac output as a result of increases in both heart rate and stroke volume. DLCO can increase by up to 50% because of recruitment and distention of the pulmonary capillaries, particularly in the upper airways.

Both cardiac output and DLCO were reduced at rest, but normalized on exercise in preterm SGA survivors. Here, too, these findings were not present in the other groups.

Dr. Bush hypothesized that an adaptive mechanism may be at work.

“Is it possible that being SGA in utero you're programmed to protect your brain and kidneys at times of starvation, at times of low oxygen supply, and that this effect is persisting into adult life; so that at rest you have persistent low blood flow as an adaptive mechanism that's been programmed into you before birth?” he suggested. “I emphasize this is tentative and hypothesis generating.”

Dr. Bush acknowledged that the follow-up numbers are small, but called the findings intriguing. Questions for the future include how to monitor this aging preterm population; will their lung function deteriorate faster as they age, putting them at higher risk for chronic obstructive pulmonary disease; and how to address new bronchopulmonary consequences that will arise as neonatologists become more skilled at salvaging even more immature babies.

Cardiac output was reduced at rest, but normalized on exercise in preterm SGA survivors. DR. BUSH

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