Key result
Cardiorespiratory phase synchronization increases with gestational age but is unrelated to infant clinical outcomes.
Why the study?
Cardiorespiratory coupling is a marker of autonomic nervous system maturation, and it was hypothesized that differences in autonomic maturation relate to disparate outcomes in premature infants.
Does the maturational trajectory of cardiorespiratory phase synchronization (CRPS) differ based on gestational age, discharge status, or clinical outcomes in extremely preterm infants?
Observational (n=191)
No
Does the maturational trajectory of cardiorespiratory phase synchronization (CRPS) differ based on gestational age, discharge status, or clinical outcomes in extremely preterm infants?
Autonomic maturation following preterm birth follows a fixed, predictable pattern of initial decline and subsequent increase in cardiorespiratory phase synchronization that is independent of clinical outcomes.
CRPS trajectory should not guide preterm infant management; leaves open its value as a research marker of autonomic maturation.
Background Cardiorespiratory coupling (cardiovascular-respiratory interactions) is a marker of autonomic nervous system function and maturation. We hypothesize that differences in autonomic maturation are associated with disparate outcomes of premature infants. Methods We collected continuous bedside cardiorespiratory data from birth to 40 weeks post-menstrual age (PMA) for 191 preterm infants born between 23–0/7 weeks to 28–6/7 weeks of gestation. Using the respiratory and ECG wave forms, we calculated cardiorespiratory phase synchronization (CRPS) as a measure of cardiorespiratory coupling. Using linear mixed effects modeling, we studied the trajectory of CRPS as a function of PMA and chronological age (CA) and any difference between groups separated by discharge status, respiratory outcome and neurological outcomes at the 40th week PMA, and different gestational ages. Results CRPS showed a decline reaching a nadir at approximately 3 weeks of age followed by a gradual increase toward term. The infants born at later GA showed higher values and steeper increases than infants of lower GA. Contrary to our hypothesis, the trajectory of the increase was similar regardless of outcome assessed. Conclusion Autonomic maturation following preterm birth shows a fixed predictable pattern that appears to be independent of respiratory or neurologic outcomes or clinicians’ assessment of readiness for discharge. Impact Cardiorespiratory phase synchronization (CRPS) trajectories, a marker of autonomic nervous system functio is provided for 175 extremely preterm infants across post-menstrual age (PMA) and chronological age (CA). CRPS initially declines but subsequently increases with advancing PMA and CA, irrespective of discharge status and respiratory and neurological outcomes at 40 weeks PMA. At all CAs after the initial decrease, CRPS was higher for infants born at 27–28 weeks compared to those born earlier.
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Krishnamurthi et al. (2026) conducted an observational in Extremely preterm infants born between 23+0/7 and 28+6/7 weeks gestation monitored from birth to NICU discharge or 40 weeks postmenstrual age (n=191). Monitoring cardiorespiratory phase synchronization (CRPS) as biomarker of autonomic nervous system development vs. Comparison by gestational age, discharge status, respiratory and neurologic outcomes was evaluated on Trajectory of cardiorespiratory phase synchronization (CRPS) over chronological and postmenstrual age. Cardiorespiratory phase synchronization declined in the first 3 weeks after birth and then increased with advancing gestational age and postmenstrual age, with later gestational age infants showing higher and steeper increases, but the maturational trajectory was independent of respiratory outcomes, neurological injury, or discharge status.
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