Correlation properties of tidal volume and end-tidal O2 and CO2 concentrations in healthy infants.

We investigated whether breath-to-breath fluctuations in tidal volume (VT) and end-tidal O2 and CO2 exhibit long-range correlations and whether parameters describing the correlations can be used as noninvasive descriptors of control of breathing. We measured VT and end-tidal O2 and CO2 over n = 352 +/- 104 breaths in 26 term, healthy, unsedated infants (mean age +/- SD: 36 +/- 6 days) and calculated the detrended fluctuation function [F(n)]. The F(n) of the breath-to-breath time series of VT, O2, and CO2 revealed a linear increase with a breath number on log-log plots with a slope that was significantly different from 0.5 (random) and thus consistent with scale-invariant behavior. Long-range correlations were stronger for O2 than for VT and CO2. The F(n) of many individual signals exhibited a crossover behavior indicating that control mechanisms regulating fluctuations of VT, O2, and CO2 may be different on different time scales. Thus breathing has a memory up to at least 400 breaths that can be characterized by the simple indicator alpha.

Long-range correlations in rectal temperature fluctuations of healthy infants during maturation.

BACKGROUND: Control of breathing, heart rate, and body temperature are interdependent in infants, where instabilities in thermoregulation can contribute to apneas or even life-threatening events. Identifying abnormalities in thermoregulation is particularly important in the first 6 months of life, where autonomic regulation undergoes critical development. Fluctuations in body temperature have been shown to be sensitive to maturational stage as well as system failure in critically ill patients. We thus aimed to investigate the existence of fractal-like long-range correlations, indicative of temperature control, in night time rectal temperature (T(rec)) patterns in maturing infants. METHODOLOGY/PRINCIPAL FINDINGS: We measured T(rec) fluctuations in infants every 4 weeks from 4 to 20 weeks of age and before and after immunization. Long-range correlations in the temperature series were quantified by the correlation exponent, alpha using detrended fluctuation analysis. The effects of maturation, room temperature, and immunization on the strength of correlation were investigated. We found that T(rec) fluctuations exhibit fractal long-range correlations with a mean (SD) alpha of 1.51 (0.11), indicating that T(rec) is regulated in a highly correlated and hence deterministic manner. A significant increase in alpha with age from 1.42 (0.07) at 4 weeks to 1.58 (0.04) at 20 weeks reflects a change in long-range correlation behavior with maturation towards a smoother and more deterministic temperature regulation, potentially due to the decrease in surface area to body weight ratio in the maturing infant. alpha was not associated with mean room temperature or influenced by immunization CONCLUSIONS: This study shows that the quantification of long-range correlations using alpha derived from detrended fluctuation analysis is an observer-independent tool which can distinguish developmental stages of night time T(rec) pattern in young infants, reflective of maturation of the autonomic system. Detrended fluctuation analysis may prove useful for characterizing thermoregulation in premature and other infants at risk for life-threatening events.

Maternal atopic disease modifies effects of prenatal risk factors on exhaled nitric oxide in infants.

In a prospective healthy birth cohort, we determined whether levels of exhaled nitric oxide (eNO) in healthy unselected infants at the age of 1 month were associated with maternal atopic disease and prenatal and early postnatal environmental exposures. Tidal eNO was measured in 98 healthy, unsedated infants (35 from mothers with atopy) (mean age +/- SD, 36.0 +/- 6.2 days) and was compared with histories taken in standardized interviews. eNO was higher in males compared with females (17.7 vs. 14.6 ppb, p = 0.042) and infants exposed to postnatal maternal smoking (+4.4 ppb, p = 0.027), adjusting for weight and tidal breathing parameters. Prenatal tobacco exposure was associated with higher eNO (+12.0 ppb, p = 0.01) in infants of mothers with asthma and lower eNO (-5.7 ppb) in infants of mothers without asthma (p for interaction < 0.0001). Coffee consumption in pregnancy decreased eNO (-6.0 ppb, p = 0.008) only in children of mothers with atopy (p for interaction = 0.015). Paternal atopy had no influence. In the early phase of immunologic development, before the onset of infections and allergic disease, the effect of prenatal or early postnatal environmental factors on eNO was modified by the presence of maternal atopic disease. This underlines the complex interaction of maternal and environmental factors in the development of airway disease.