Effect of weight and age on respiratory complexity in premature neonates

Very low-birth-weight premature infants often suffer from a variety of respiratory problems, including respiratory distress syndrome (RDS), hypopnea and periodic breathing, and apnea. These conditions are likely related to immaturity of the respiratory centers; yet how respiratory rhythms originating from these centers, including their complexity, relate to demographic measures of prematurity remains largely unknown. In 39 neonates with mild RDS (22 males, 28 +/- 2 wk gestational age, 1,036 +/- 234 g body wt), we derived the univariate association between complexity of two respiratory rhythms [respiratory rate (RR) and tidal volume (Vt)] and postmenstrual age, gestational age, postnatal age, and weight at time of study. RR and Vt rhythm complexities were assessed using approximate entropy, sample entropy, base scale entropy, and forbidden words entropy estimated for 300 consecutive breaths determined from respiratory inductance plethysmography, irrespective of breathing effort rate or amplitude, collected during sleep while the neonates were exposed to nasal continuous positive airway pressure (4-6 cmH(2)O). RR and Vt exhibited increased complexity with increased maturity, but only in terms of base scale entropy and forbidden words entropy, which are based on pattern matching, rather than approximate entropy and sample entropy, which are based on conditional probabilities. Specifically, RR complexity as measured by forbidden word entropy increased with increasing weight (r = 0.502), postconceptional age (r = 0.423), and gestational age (r = 0.493). As measured by base scale entropy, RR complexity increased with increasing weight (r = 0.488) and postconceptional age (r = 0.390). Vt complexity, measured by base scale entropy, was greater with increased postnatal age (r = 0.428). Our results indicate that respiratory rhythms become more complex with increasing levels of maturity, as indicated by increased weight and several age parameters. This emphasizes the importance of the later weeks of gestation in the maturation of respiratory centers in the brain and suggests a promising use of entropy measures in exploring respiratory maturation in infants.