Umbilical artery histomorphometry: a link between the intrauterine environment and kidney development.

Prematurity is a risk factor for hypertension, vascular stiffness, nephron deficit and adult onset cardiorenal disease. The vascular tree and kidneys share morphogenic drivers that promote maturation in utero before 36 weeks of gestation. Vascular elastin accrual terminates after birth leaving collagen to promote vascular stiffness. Our objective was to determine if the histomorphometry of the umbilical artery, an extension of the aorta, parallels nephron mass across gestational age groups. From a cohort of 54 newborns, 32 umbilical cord specimens were adequate for evaluation. The umbilical cord was sectioned, stained with trichrome, and digitalized. Muscular and collagenous areas of the umbilical artery were measured in pixels using the Image J 1.48q software. Total kidney volume was measured by ultrasound and factored by body surface area (TKV/BSA). The umbilical artery total area was significantly greater in term v. preterm infants (9.3±1.3 v. 7.0±2.0 mm2; P<0.05) and increased with gestational age; while the percent muscular and collagen areas were independent of gestational age (R 2=0.04; P=ns). Percent muscular area correlated positively with TKV/BSA (r=0.53; P=0.002); while an increase in collagen correlated inversely with kidney mass (r=-0.53; P=0.002). In conclusion, an enhanced % muscular area and presumed vascular elasticity was associated with increased renal mass in all infants. Umbilical artery histomorphometry provides a link between the intrauterine environment, vascular and kidney development.

Association between early postnatal weight loss and death or BPD in small and appropriate for gestational age extremely low-birth-weight infants.

OBJECTIVE: To examine the association between weight loss during the first 10 days of life and the incidence of death or bronchopulmonary dysplasia (BPD) in small for gestational age (SGA) and appropriate for gestational age (AGA) extremely low-birth-weight infants. DESIGN/METHODS: This is a retrospective analysis of a cohort of ELBW (birth weight <1000 g) infants from the NICHD Neonatal Research Network's database. The cohort consisted of 9461 ELBW infants with gestational age of 24-29 weeks, admitted to Network's participating centers during calendar years 1994-2002 and surviving at least 72 h after birth. The cohort was divided into two groups, 1248 SGA (with birth weight below 10th percentile for gestational age) and 8213 AGA (with birth weight between 10th and 90th percentile) infants. We identified infants with or without weight loss during the first 10 days of life, which we termed as 'early postnatal weight loss' (EPWL). Univariate analyses were used to predict whether EPWL was related to the primary outcome, death or BPD, within each birth weight/gestation category (SGA or AGA). BPD and death were also analyzed separately in relation to EPWL. Logistic regression analysis was done to evaluate the risk of death or BPD in SGA and AGA groups, controlling for maternal and neonatal demographic and clinical factors found to be significant by univariate analysis. RESULTS: SGA ELBW infants had a lower prevalence of EPWL as compared with AGA ELBW infants (81.2 vs 93.7%, respectively, P<0.001). In AGA infants, univariate analysis showed that death or BPD rate was lower in the group of infants with EPWL compared with infants without EPWL (53.4 vs 74.3%, respectively, P<0.001). The BPD (47.2 vs 64%, P<0.001) and death (13.8 vs 32.9%, P<0.001) rate were similarly lower in the EPWL group. The risk-adjusted odds ratios (ORs) showed that EPWL was associated with lower rate of death or BPD (OR 0.47, 95% CI: 0.37-0.60). In SGA infants, on univariate analysis, a similar association between EPWL and outcomes was seen as shown in AGA infants: death or BPD (55.9 vs 75.2%, P<0.001), BPD rate (48.3 vs 62.1%, P=0.002) and rate death (19 vs 40.8%, P<0.001) for those with or without EPWL, respectively. Multiple logistic regression showed that as in AGA ELBW infants, EPWL was associated with lower risk for death or BPD (OR 0.60, 95% CI: 0.41-0.89) among SGA infants. CONCLUSIONS: SGA infants experienced less EPWL when compared with their AGA counterparts. EPWL was associated with a lower risk of death or BPD in both ELBW AGA and SGA infants. These data suggest that clinicians who consider the association between EPWL and risk of death or BPD should do so independent of gestation/birth weight status.

Changes in mortality and morbidities among infants born at less than 25 weeks during the post-surfactant era.

OBJECTIVES: To compare mortality and death or major morbidity (DOMM) among infants <25 weeks estimated gestational age (EGA) born during two post-surfactant era time periods. STUDY DESIGN AND PATIENTS: Comparative cohort study of very low birthweight (501-1500 g) infants <25 weeks EGA in the NICHD Neonatal Research Network born during two post-surfactant era time periods (group I, 1991-1994, n=1408; group II, 1995-1998, n=1348). Perinatal and neonatal factors were compared, and group related mortality and DOMM risk were evaluated. RESULTS: Mortality was higher for group I (63.1% v 56.7%; p=0.0006). Antenatal steroids (ANS) and antenatal antibiotics (AABX), surfactant (p<0.0001), and bronchopulmonary dysplasia (p=0.0008) were more prevalent in group II. In a regression model that controlled for basic and delivery factors only, mortality risk was greater for group I than for group II (odds ratio (OR) 1.4, 95% confidence interval (CI) 1.2 to 1.7); the addition of AABX and surfactant, or ANS (OR 0.97, 95% CI 0.79 to 1.2) to the model appeared to account for this difference. There was no difference in DOMM (86.8% v 88.4%; p=0.2), but risk was lower for group I in regression models that included ANS (OR 0.70, 95% CI 0.52 to 0.94). CONCLUSION: Survival to discharge was more likely during the more recent period because of group differences in ANS, AABX, and surfactant. However, this treatment shift may reflect an overall more aggressive management approach. More consistent application of treatment has led to improving survival of <25 week EGA infants during the post-surfactant era, but possibly at the cost of greater risk of major in-hospital morbidities.

Effect of chestwall distortion on the measurement of pulmonary mechanics in preterm infants.

The purpose of this study was to determine the effect of chestwall distortion (CWD) on the measurement of pulmonary compliance (CL) and resistance (RL). Inductance plethysmography was used in 15 preterm infants to determine CWD as total compartmental displacement ratio (TCDR) and out of phase movement between ribcage and abdomen as phase shift (PS). Flow was measured by pneumotachography and esophageal pressure change (Pe) with a water-filled catheter. CL and RL were calculated by linear regression analysis. Seven infants (mean +/- SD: BW, 1,484 +/- 186 g, GA 32.4 +/- 2.2 weeks, age 8.7 +/- 4.7 days) had a breathing pattern characterized by episodes with a high degree of CWD, followed by periods with minimal CWD (distortion group). In this group lung function measurements were analyzed separately during periods with and without CWD. The remaining 8 infants (BW, 1,244 +/- 233 g, GA 30.4 +/- 2.4 weeks, age 7.4 +/- 3.1 days) always breathed with minimal CWD, and the measurements in this group (non-distortion group) were used as a reference for the values obtained in the distortion group. Measurements of TCDR, PS, CL, RL, and tidal volume (VT) obtained in the absence of CWD were not significantly different between distortion and non-distortion groups. The measurements obtained in the presence of CWD showed a significantly higher TCDR and PS, but CL and RL were not significantly different from the CL and RL measurements obtained in the distortion and non-distortion groups in the absence of CWD. The only significant effect of CWD was a reduction in VT.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of chest wall distortion and esophageal catheter position on esophageal manometry in preterm infants.

The purpose of this study was to determine the effect of chest wall distortion on esophageal manometry by measuring simultaneous esophageal pressure changes at two sites in preterm infants. Fourteen infants were studied (mean +/- SD; birth weight, 1340 +/- 260 g; age, 8.5 +/- 4 d). Esophageal pressure was measured through two water-filled catheters, one placed just above the cardia (Pes1) and the other at the level of the carina (Pes2). Chest wall distortion was measured by inductance plethysmography, and inspiratory and expiratory flow by pneumotachography. No significant differences were found between the peak to peak esophageal pressure changes measured through the lower and higher catheters during both airway occlusion (18.7 +/- 4.4 versus 18.3 +/- 2.6 cm H2O) and spontaneous breathing (9.4 +/- 1.8 versus 9.0 +/- 1.8 cm H2O), although half of the infants had significant chest wall distortion. Mean pulmonary compliance and resistance measures calculated from the two pressures for individual infants showed small differences consistent with the difference between Pes1 and Pes2. For the whole group of 14 infants, however, these differences were not significant. The pressure changes from the lower and higher measuring sites for each breath were analyzed using linear regression. The weighted average of the mean slopes of the 14 infants was significantly different from 1.0 (mean +/- SD: 0.92 +/- 0.10, range: 0.75-1.10; p < 0.05). In some of the infants, the slopes for different breaths were not consistent, but varied from breath to breath.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of respiratory muscles in upper airway narrowing induced by inspiratory loading in preterm infants.

Extrathoracic airway (ETA) narrowing is induced in preterm infants by inspiratory flow-resistive loading (IRL), which reduces intraluminal pressure within the region. Neuromuscular load compensation was evaluated over time in 10 infants [body wt 1.5 +/- 0.17 (SD) kg, gestational age 33 +/- 2.3 wk, age 12 +/- 5.2 days] during quiet sleep. Baseline (BL) studies were followed by IRL (125 cmH2O.l-1.s at 1 l/min). Minute ventilation, changes in esophageal pressure (Pes) and proximal airway pressure, and moving time averages of posterior cricoarytenoid (PCA), submental genioglossus (SM), and diaphragm (DIA) electromyograms were obtained during BL and 1 and 5 min of IRL. Total respiratory resistance was calculated from pressure and flow changes and was used to estimate ETA narrowing: there was an increase in total respiratory resistance from 90 +/- 15 to 120 +/- 34 and 151 +/- 86 cmH2O.l-1.s after 1 and 5 min of IRL, respectively (P < 0.05, 1-min IRL vs. BL), in association with a sustained decline in minute ventilation (P < 0.05) and increases in Pes and proximal airway pressure (P < 0.05). Phasic PCA activity was always present, but its duration was only transiently prolonged with IRL (P < 0.05, 1-min IRL vs. BL). SM activity was present in only one infant during BL and was recruited in two additional infants during IRL. The decline in Pes from 1 to 5 min of IRL occurred despite continuing increases in peak and average activities of the DIA moving time average, which may reflect an onset of DIA fatigue. The transient prolongation of phasic PCA activity and occasional recruitment of SM activity with sustained loading explain, in part, the ETA instability detectable by moderate IRL in sleeping preterm infants.

Upper airway stability and respiratory muscle activity during inspiratory loading in full-term neonates.

To investigate the role of genioglossus and posterior cricoarytenoid (PCA) activity in stabilizing the extrathoracic airway (ETA) of full-term infants during inspiratory flow-resistive loading (IRL), 10 unsedated full-term infants were evaluated in quiet sleep. IRLs were randomly imposed (L2, 125 cmH2O.l-1.s; L3, 250 cmH2O.l-1.s). Ventilation, total respiratory resistance (a correlate of ETA resistance), and moving time averages of PCA, submental activity of the genioglossus (SM), and diaphragm electromyogram were obtained. Results revealed no phasic activity in the SM during baseline breathing or with either IRL. Phasic PCA activity was always observed; burst duration increased with L2 and L3 (P < 0.01) and commenced earlier in relation to the onset of inspiratory airflow with both loads (P < 0.05). PCA activity always preceded that of the diaphragm and invariably outlasted it other than with L3. The upper airway negative pressure changes induced by IRL were insufficient to recruit SM activity; other potential stimuli such as transcutaneous PO2, transcutaneous PCO2, and pulmonary stretch receptor activation (increase in tidal volume) remained unchanged. Ventilation decreased with both loads (L3: P < 0.01), esophageal and mouth pressures increased (P < 0.01), and inspiratory time and inspiratory time divided by total time were both prolonged (P < 0.01). Total respiratory resistance remained unchanged with L2 but increased with L3 (P < 0.01). We concluded that ETA narrowing may be induced in full-term infants during quiet sleep with moderately large-sized IRL and that it is not entirely ameliorated by activation of the SM or PCA or by arousal.

Changes in ventilation and oxygen consumption during acute hypoxia in sedated newborn piglets.

The purpose of this study was to evaluate the relationship between changes in minute ventilation (VE) and oxygen consumption (VO2) in response to acute hypoxia in the newborn piglet. Twenty-five (mean +/- SD; age, 4.7 +/- 1.1 d; weight, 1451 +/- 320 g) sedated, spontaneously breathing newborn piglets were studied. VE was measured by pneumotachography, and VO2 was measured by the open-circuit technique. Measurements were performed while the animals breathed room air and repeated after 10 min of hypoxia, which was induced by breathing 10% oxygen. Although the mean VE values during hypoxia displayed a typical biphasic ventilatory response, the individual pattern of this ventilatory response to hypoxia was variable. Thirteen animals sustained VE above baseline after 10 min of hypoxia, whereas the 12 remaining animals decreased VE after 10 min of hypoxia to values below their room air baseline. The VO2 values did not differ between groups during normoxia, and a similar decrease in VO2 occurred in both groups after 10 min of hypoxia. Furthermore, no correlation was observed between changes in VE and VO2 during hypoxia either in absolute values or in the percent change from room air baseline. Arterial PO2 decreased similarly in both groups, but PACO2 decreased significantly only in the group that sustained VE above baseline after 10 min of hypoxia. These data demonstrate that in this animal model the hypoxic ventilatory depression is not determined by the decrease in VO2 that occurs during hypoxia.

Comparison of the effects of acetazolamide and aminophylline on apnea incidence and on ventilatory response to CO2 in preterm infants.

Acetazolamide (ACTZ) reduces sleep apnea in adults exposed to high altitude and augments the ventilatory response to CO2. In order to determine the effect of ACTZ on the ventilatory response to CO2 and the incidence of apnea in preterm infants, 7 infants (BW, 1070 +/- 191 g; postnatal age, 9 +/- 7 days) were randomized to receive ACTZ (5 mg/kg/dose Q6h for 36 hr) and 7 infants (BW, 1092 +/- 292 g; post-natal age, 5 +/- 2 days) received aminophylline (AMINO; 8 mg/kg bolus then 2.5 mg/kg Q12h for 36 hr). Minute ventilation (VE), end-tidal CO2 (PETCO2), ventilatory response to CO2, number of apneic episodes (> or = 15 sec duration), and arterial blood gases were measured before and 24-36 hr after starting therapy. In the AMINO group there was a significant decrease in apnea frequency from 6 +/- 1 to 2 +/- 2 episodes over an 8 hr epoch (P < 0.05), while no significant change was observed in the ACTZ group. The end-tidal CO2 decreased significantly from 44 +/- 7 to 38 +/- 6 mmHg in the AMINO group and from 47 +/- 5 to 36 +/- 5 mmHg in the ACTZ (P < 0.05), which lead to a shift to the left of the CO2-response curve in both groups. The slope of the CO2 response curve did not change significantly in the AMINO group and decreased in the ACTZ group. There was a significant decrease of pH from 7.43 to 7.26 in the ACTZ group, whereas in the AMINO group pH increased from 7.38 to 7.44.(ABSTRACT TRUNCATED AT 250 WORDS)

Validation of cardiac output measurements with noninvasive Doppler echocardiography by thermodilution and Fick methods in newborn piglets.

Since cardiac output measured by the noninvasive pulsed Doppler technique has not been well correlated to results from the invasive thermodilution or Fick methods in neonates, the three methods were evaluated in 6 sedated newborn piglets (age < or = 7 days, weight 1.5 +/- 0.7 kg) in room air and after 10 min of hypoxia. Doppler velocities were measured in the ascending aorta, and the aortic root diameter was measured in early diastole. A Swan-Ganz catheter in the left pulmonary artery sampled mixed venous blood for central venous O2 content and measured cardiac output by thermodilution. Oxygen consumption was measured by the open-circuit technique and used to determine cardiac output by the Fick method. In room air, values obtained by pulsed Doppler, thermodilution and Fick methods (0.270 +/- 0.05, 0.246 +/- 0.05 and 0.241 +/- 0.05 liters/kg/min, respectively) were similar, with a correlation coefficient (r) between Doppler and thermodilution values of 0.89, Doppler and Fick values of 0.82 and thermodilution and Fick values of 0.88. Although hypoxia sometimes produced larger differences between paired values, correlation coefficients remained high (Doppler echocardiography vs. thermodilution, r = 0.96; Doppler vs. Fick methods, r = 0.92; thermodilution vs. Fick method, r = 0.95). The mean +/- SD of the percent difference between values obtained by Doppler echocardiography and thermodilution was 4.2 +/- 14.4% in room air and 12.8 +/- 14.4% in hypoxia, whereas differences in values obtained by Doppler and Fick methods was 6 +/- 14.9% in room air and 14.7 +/- 8.5% with hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic, hemodynamic, and ventilatory responses to respiratory load in sedated neonatal piglets.

Some neonatal species fail to develop the expected degree of hypercapnia during hypoventilation with mechanical loads. We studied 13 spontaneously breathing, sedated piglets (1-9 days old), grouped by age as young (< or = 3 day old) or old (> 3 day old). Baseline measurements of minute ventilation, arterial blood pressure (BP), cardiac output, and O2 consumption were repeated after continuous (inspiratory and expiratory) flow-resistive loading of 330 cmH2O.l-1 x s for 10 min. Older animals [n = 6, age 6.6 +/- 1.9 (SD) days, wt 1.99 +/- 0.5 kg] increased metabolic rate (9.8 +/- 1.4 to 10.5 +/- 1.3 ml.min-1 x kg-1, P < 0.01), whereas younger animals (n = 7, 2.6 +/- 0.6 days, 1.37 +2- 0.3 kg) invariably decreased metabolic rate with loading (9.7 +/- 1.6 to 7.9 +/- 2.6 ml.min-1 x kg-1); changes were different between groups (P < 0.02). Although ventilation decreased with loading in both groups (P < 0.01), younger animals showed a relatively greater fall from baseline values (38 vs. 27%). Despite differences in the degree of hypoventilation, arterial CO2 tension increased similarly in both groups (21%). BP increased (P < 0.01) with loading in older but not younger animals. We conclude that the decreased metabolic rate and limited hemodynamic response in younger piglets reflect an accomodative response to hypoventilation in contrast to that of older animals, which display an adult pattern of increased metabolic rate and BP with loaded breathing.

Effect of maturation on the extrathoracic airway stability of infants.

The influence of maturation on extrathoracic airway (ETA) stability during quiet sleep was determined in 13 normal preterm infants of 1.41 +/- 0.14 (SD) kg birth weight and 32 +/- 2 wk estimated gestational age. Studies began in the first week of life and were performed three times at weekly intervals. A drop in intraluminal pressure within the ETA was produced by external inspiratory flow-resistive loading (60 cmH2O.l-1 x s at 1 l/min); an increase in intrinsic resistance, indicating airway narrowing, was sought as a measure of ETA instability. Baseline total pulmonary resistance was not significantly different between weeks 1, 2, and 3 (88 +/- 35, 65 +/- 24, and 61 +/- 17 cmH2O.l-1 x s, respectively) but increased markedly above baseline with loading to 144 +/- 45 cmH2O.l-1.s during week 1 (P < 0.001), 89 +/- 28 cmH2O.l-1 x s at week 2 (P < 0.01), and 74 +/- 25 cmH2O.l-1 x s at week 3 (n = 10). The increment with loading was significantly greater during week 1 than during weeks 2 or 3 (P < 0.02). Similar studies were also done in seven full-term infants in the first week of life to evaluate the influence of gestational maturity on ETA stability. Despite a relatively greater drop in intraluminal pressure within the ETA of term vs. preterm infants with loading (P < 0.001), total pulmonary resistance failed to increase (68 +/- 21 to 71 +/- 32 cmH2O.l-1.s). These data reveal that ETA instability is present in preterm infants at birth and decreases with increasing postnatal age. Full-term neonates, by comparison, display markedly greater ETA stability in the immediate neonatal period.

The effects of respiratory training with inspiratory flow resistive loads in premature infants.

Respiratory training of premature infants was performed to determine whether improved respiratory muscle strength and/or endurance would result. Twenty-two premature infants were randomized into control and training groups for 2 wk, using inspiratory flow-resistive loads for training (75 cm H2O.L-1.s in wk 1 and 90 cm H2O.L-1.s in wk 2). Respiratory endurance was assessed by the time interval required for the development of a 5-torr rise in transcutaneous CO2 tension during the hypoventilation induced by loaded breathing, using a moderately severe resistive load (250 cm H2O.L-1.s at 1 L.min-1). Respiratory strength was assessed by the maximum negative airway pressure generated during occluded breaths, a pressure-time integral, and an effort index. Results revealed that respiratory muscle endurance, which was not initially different between control and trained groups, increased significantly after 2 wk in the trained group by 137% (median value, p less than 0.05), whereas it remained unchanged in the control group (-24%). The trained group of infants also showed a significant decrease in baseline breathing frequency between the initial and final measurements taken 2 wk apart when compared with controls (p less than 0.05) and a lesser increase in inspiratory time with loading in the final measurement as compared with the initial value (p less than 0.05). There was no significant difference between the control and trained groups in initial or subsequent measures of respiratory muscle strength. Inspiratory flow-resistive load training appears to improve the respiratory endurance of premature infants in whom respiratory muscle fatigue has been described to play a role in the development of respiratory failure.

Nonlinear pressure/volume relationship and measurements of lung mechanics in infants.

We examined the effects of within-breath changes in compliance (C) upon the accuracy of measurements of compliance and resistance (R) by linear regression analysis and by Mead and Wittenberger's method. These effects were illustrated by a computer model and by lung models with linear and nonlinear pressure/volume relationships, and were also studied in 14 normal spontaneously breathing premature infants (mean +/- SD, BW 1,290 +/- 200 g, GA 29.9 +/- 2.7 weeks, age 7.4 +/- 2.1 days). Flow was measured by pneumotachography and tidal volume was derived as digitally integrated flow, and transpulmonary pressure as airway minus esophageal pressure. We found that C and R calculated from the equation of motion is accurate only if C and R remain constant throughout the respiratory cycle. Calculated compliance depends more on C at the end than at the beginning of inspiration. A decreasing C leads to underestimation or R, while an increasing C leads to an overestimation of inspiratory R. Calculated total R may be accurate, but with low r values for measurement points. Mead and Wittenberger's method and the regression method are similarly affected by changing C; however, since the regression method is based on many more measurement points and therefore allows the detection and analysis of within-breath changes of C and R, it is less prone to erroneous results secondary to signal artifacts than Mead and Wittenberger's method.

Assessment of airway resistance in preterm infants during incremental inspiratory flow-resistive loading.

Extrathoracic airway (ETA) stability was tested by inspiratory flow-resistive loading in 10 preterm infants to determine whether ETA collapsibility was directly related to the size of the added load. A fall in intraluminal pressure was produced by applying two inspiratory flow-resistive loads of lower (L1) and higher (L2) magnitudes. An increase in intrinsic resistance was used as an index of upper airway collapsibility. Total pulmonary resistance did not change from baseline with L1 (73 +/- 26 to 71 +/- 25 cmH2O.l-1.s) but increased significantly with L2 (72 +/- 21 to 99 +/- 34 cmH2O.l-1.s, P less than 0.02) secondary to a rise in inspiratory resistance (55 +/- 21 to 109 +/- 55 cmH2O.l-1.s, P less than 0.05). Expiratory resistance did not change significantly with either load. Proximal airway pressure was more negative with L2 than with L1 in every infant (mean -4.5 +/- 0.6 vs. -3.6 +/- 0.9 cmH2O, P less than 0.05). This study shows that the ETA of preterm infants is pressure passive at high but not at low collapsing pressures, and possible explanations include limited "active" compensation by upper airway dilator muscles and an overwhelming of the "passive" defense offered by the intrinsic rigidity of the ETA to large changes in transmural pressure.

Metabolic and respiratory effects of flow-resistive loading in preterm infants.

Oxygen consumption (VO2) was measured during hypoventilation induced by moderate-sized flow-resistive loading in 12 preterm infants, and the results were compared with those obtained under basal conditions immediately before and after the loaded run, each of which lasted for 7-10 min. Loading was performed with a continuous flow-resistive load (inspiratory and expiratory), which was approximately threefold greater in magnitude than the intrinsic resistance of preterm infants. VO2, minute ventilation (VE), transcutaneous oxygen tension (PtCO2), and transcutaneous carbon dioxide tension (PtcCO2) were continuously monitored. Results revealed that VE decreased significantly with loading, from 336 +/- 103 to 231 +/- 58 (SD) ml.min-1.kg-1 (P less than 0.001), while returning to basal levels of 342 +/- 59 ml.min-1.kg-1 after discontinuation of the load. VO2 decreased from 7.2 +/- 1.2 to 5.9 +/- 0.9 ml.min-1.kg-1 with loading (P less than 0.001) and returned to 7.2 +/- 1.2 ml.min-1.kg-1 at the second basal measurement. PtcCO2 remained unchanged with loading, and PtcCO2 only increased from 39 +/- 8 to 41 +/- 9 Torr (P less than 0.05) with loading, while returning to 40 +/- 9 Torr at the second basal measurement. Results indicate a decrease in the metabolic rate and ventilation with loading, with relatively little increase in PtcCO2. These data can explain prior observations that minimal disturbances in oxygen and carbon dioxide tensions occur with hypoventilation during flow-resistive loading in neonates, although the precise mechanism for this reduction remains to be determined.

Comparison of dynamic and static measurements of respiratory mechanics in infants.

The objective of this study was to compare the conventional method of measuring respiratory mechanics, which requires the passage of an esophageal tube, with the occlusion technique, which is less invasive. Thirty-nine preterm infants who received mechanical ventilation on the first day were studied before discharge (mean +/- SD: postnatal age 67 +/- 23 days; weight 1790 +/- 300 gm), and 27 of them again at 1 year (weight 8.1 +/- 1.4 kg). Flows were measured through a nosepiece by pneumotachometry, tidal volume by integration of flow, esophageal pressure through a water-filled tube, and airway pressure directly at the nasal piece. Airway occlusion was performed at the end of inspiration, and the following relaxed exhalation was analyzed to give compliance (Crs) and resistance (Rrs) of the respiratory system. These values were compared with dynamic lung compliance (Cdyn) and expiratory resistance (Re) of the previous unoccluded breath. In the younger infants, dynamic and static measurements did not differ significantly and were well correlated (Cdyn/Crs, r = 0.91; Re/Rrs, r = 0.95). In the older infants, Crs was 80% of Cdyn (p less than 0.001), and Rrs was 24% higher than Re (p less than 0.001). The measurements were well correlated (Cdyn/Crs, r = 0.94; Re/Rrs, r = 0.91). The regression line Cdyn versus Crs had a slope (0.77) significantly less than 1; the regression Re versus Rrs had an intercept (13.8) significantly greater than zero. The lower Crs and higher Rrs values can be expected because the static determinations include the chest wall. In the more immature infants, the very compliant chest wall, in combination with an underestimation of Cdyn because of the higher breathing frequency of these infants, may obscure this difference. We conclude that the occlusion technique gives accurate and reproducible results, is easily applied, does not need the passage of an esophageal tube, and is well tolerated by the infants.

Oral feeding containers and their influence on intake and ventilation in preterm infants.

In order to determine whether changes in feeding container properties could expedite oral feeding without compromising ventilation, the rate of feeding and respiration were studied in 10 healthy preterm infants while using a collapsible feeding container, and the findings were compared to those obtained with the standard rigid bottle. Equal volumes of formula were offered from both containers. With the collapsible container, the total duration of feeding was significantly shorter, and the rate of ingestion of formula was significantly faster (p less than 0.01), while minute ventilation remained equally reduced from control levels during both feeds (p less than 0.05). The fall in ventilation was secondary to a reduction in tidal volume (p less than 0.001). Breathing frequency and transcutaneous oxygen tension did not change significantly with either trial. During feeding activity in both trials, airflow interruption occurred in both phases of the breathing cycle, but the total duration of interrupted airflow was greater with the collapsible container feed (p less than 0.001). Similar amounts of intra-oral negative pressure changes developed with sucking during both feeds. Results show that decreasing the rigidity of the feeding container shortened feeding time significantly without significantly affecting ventilation. Despite the greater duration of airflow interruption with the collapsible container, minute ventilation was sufficiently maintained to prevent compromised oxygenation.

Extrathoracic airway stability during resistive loading in preterm infants.

Extrathoracic airway (ETA) stability was tested in 10 preterm infants during sleep with a drop in intraluminal pressure produced by the application of an external inspiratory flow-resistive load (IRL, 125 cmH2O.1-1.s at 1 l/min). An increase in total pulmonary resistance was sought as the measure of airway narrowing. The role of the ETA in the increased pulmonary resistance with loading was examined by testing the same infants while endotracheally intubated and after extubation. Total pulmonary resistance decreased with loading during the intubated studies (102.5 +/- 41.2 to 82.4 +/- 33.3 cmH2O.1-1.s, P less than 0.05), whereas a significant increase in pulmonary resistance was seen with loading in the extubated studies (101 +/- 58.1 to 128 +/- 68.6 cmH2O.1-1.s, P less than 0.01). Intraluminal pressure in the ETA, measured by the lowest proximal airway pressure, fell significantly with loading in both conditions, with values changing from -0.7 +/- 0.3 to -4.7 +/- 2.7 cmH2O in the intubated infants and from -0.9 +/- 0.3 to -4.6 +/- 0.9 cmH2O) in the extubated infants (P less than 0.01). The results suggest ETA narrowing with loading in extubated infants despite the absence of overt obstructive apnea. Measurements of total pulmonary resistance with IRL can be used as a simple test of ETA stability.