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Cerebral blood flow (CBF) volume can be measured quantitatively by colour duplex sonography. To test the reliability of CBF volume measurements in newborns, two "blinded" examiners performed a prospective test-retest study in 32 neonates (postmenstrual age 32 to 42 weeks). Measurements were done in the internal carotid and vertebral arteries. Intravascular flow volumes (FV) were calculated as the product of angle-corrected time-averaged flow velocity and the cross-sectional area of the vessel. The CBF volumes measured by the two examiners were very close (mean +/- SD, 62.6 +/- 20.6 vs. 62.1 +/- 21.2 mL/min, NS; coefficient of variation, 6.3%; intraclass correlation coefficient, 0.98). The 95% limits of agreement, according to Bland and Altman, ranged from -7.3 to +8.4 mL/min. In comparison with other test-retest studies, the reproducibility of quantitative CBF measurements reported here is among the best ever found. We conclude that CBF volume can be measured reliably even in preterm neonates.

Background: The aim of this study was to explore whether population-based data from a regional quality control program can be utilized to compare the neonatal outcome of small for gestational age (SGA) and appropriate size for gestational age (AGA) new-borns., Methods: The Center for Quality Management in Health Care maintains perinatal data for almost all births in Lower Saxony (Germany). Neonatal data are collected for all infants admitted to hospital within 10 postnatal days. We evaluated linked perinatal and neonatal datasets of 4126 very low birthweight infants (VLBW; < 1500 g), born in 1991 - 1996. After checking for completeness, representativeness, and validity, exclusion criteria were defined to minimize bias and to yield similar proportions of SGA- and AGA-neonates. Since inclusion of all multiple births would lead to an overestimation of maternal risk factors, one sibling was randomly selected from each set of multiples. Bias arising from not well defined study populations should be shown based on univariable mortality analyses (Kaplan-Meier survival curves)., Results: Application of exclusion criteria resulted in a final study population of 1623 independent (disjunctive) new-borns from 25 - 29 weeks gestation, 173 of whom were SGA, 1450 AGA. Kaplan-Meier curves from the initial study population and the well defined study base differed significantly. Trend analysis revealed a significant (p < 0.05) increase in proportions of both VLBW (from 0.95 % in 1991 to 1.11 % in 1996; + 17 %) and SGA infants (from 22.7 % to 27.4 %; + 21 %) within the observational period. A well defined data selection process is necessary if data collected for other purposes are to be used for epidemiological studies. Neglecting this labour-intensive work may be one reason for the varying results on the outcome of SGA and AGA infants.

Aim: This article reviews recent studies on the relationship between patient volume, level of care, and peri- or neonatal outcome for term and preterm infants., Methods: A PubMed search was performed using various combinations of keywords related to neonates, patient volume and outcome published since 2000., Results: Two studies on term infants showed that perinatal mortality in Norway and Germany was 2 - 3 times higher for term infants born in institutions with less than 500, and 40 - 80 % higher in those with < 1000 births/year compared to larger hospitals. For preterm infants, the mortality risk for those born in hospitals without a level III neonatal intensive care unit (NICU) was almost twice as high as for those born in hospitals with such an NICU. With regard to patient volume, studies from both the USA and Germany showed a significantly, up to 56 % higher mortality risk for infants admitted to units with less than 36 or 50 very low birth weight (VLBW) admissions per year compared to larger NICUs., Conclusions: Although patient volume or level of care are poor predictors of neonatal outcome, the above data provide arguments for a more rigorous perinatal centralisation, aiming to restrict term deliveries to hospitals with at least 1000 births per year and VLBW deliveries to perinatal centres with 24 h on-site availability of a neonatologist and at least 36 - 50 VLBW admissions per year. This may result in a significant reduction in perinatal mortality in Germany. In the interest of the families at risk of loosing their child, we must strive further to achieve this goal.

Preterm infants can be infected with human cytomegalovirus (HCMV) transmitted via breast milk of their HCMV-seropositive mothers, 96 % of whom reactivate the virus during lactation. 38 % of exposed VLBW infants become infected, with 48 % of these developing at least one symptom. Whether priority should be given to the multiple advantages of breast milk feeding or to the avoidance of a possible HCMV infection by exclusive formula feeding still cannot be decided due to insufficient data on the long-term outcome of infected infants. Inactivation of HCMV in breast milk can be achieved safely only via heat treatment, but the clinical consequences resulting from the use of pasteurized breast milk are unknown. Given the above situation, the authors decided to continue breast-feeding of VLBW and ELBW infants in their units after obtaining informed parenteral consent, until data for an evidence-based decision become available.

Surfactant composition and function differ between vertebrates, depending on pulmonary anatomy and respiratory physiology. Because pulmonary development in pigs is similar to that in humans, we investigated surface tension function, composition of phospholipid molecular species, and concentrations of surfactant protein (SP)-A to -D in term newborn pigs (NP) compared with adolescent pigs (AP), using the pulsating bubble surfactometer, mass spectrometry, high-performance liquid chromatography, and immunoblot techniques (IT). NP was more potent than AP surfactant in reaching minimal surface tension values near zero mN/m. Whereas SP-A and SP-D were comparable, SP-B and SP-C were increased 3- to 4-fold in NP surfactant. Moreover, fluidizing phospholipids such as palmitoylmyristoyl-PC (PC16:0/14:0) and palmitoylpalmitoleoyl-PC (PC16:0/16:1) were increased at the expense of PC16:0/16:0 (32.4 +/- 0.6 versus 44.5 +/- 3.2%, respectively). Whereas concentrations of total anionic phospholipids were similar in NP and AP surfactant (9.9 +/- 0.3 and 12.0 +/- 0.3%, respectively), phosphatidylinositol was the predominant anionic phospholipid in NP surfactant. We conclude that, compared with AP, NP surfactant displays better surface tension function under dynamic conditions, which is associated with increased concentrations of SP-B and SP-C, as well as fluidizing phospholipids at the expense of PC16:0/16:0.

Surfactant reduces surface tension at the air-liquid interface of lung alveoli. While dipalmitoylphosphatidylcholine (PC16:0/ 16:0) is its main component, proteins and other phospholipids contribute to the dynamic properties and homeostasis of alveolar surfactant. Among these components are significant amounts of palmitoylmyristoylphosphatidylcholine (PC16:0/ 14:0) and palmitoylpalmitoleoylphosphatidylcholine (PC16:0/ 16:1), whereas in surfactant from the rigid tubular bird lung, PC16:0/14:0 is absent and PC16:0/16:1 strongly diminished. We therefore hypothesized that the concentrations of PC16:0/14:0 and PC16:0/16:1 in surfactants correlate with differences in the respiratory physiology of mammalian species. In surfactants from newborn and adult mice, rats, and pigs, molar fractions of PC16:0/14:0 and PC16:0/16:1 correlated with respiratory rate. Labeling experiments with [methyl-(3)H]choline in mice and perfused rat lungs demonstrated identical alveolar proportions of total and newly synthesized PC16:0/14:0, PC16:0/16:1, and PC16:0/16:0, which were much higher than those of other phosphatidylcholine species. In surfactant from human term and preterm neonates, fractional concentrations not only of PC16:0/16:0 but also of PC16:0/14:0 and PC16:0/ 16:1 increased with maturation. Our data emphasize that PC16:0/14:0 and PC16:0/16:1 may be important surfactant components in alveolar lungs, and that their concentrations are adapted to respiratory physiology.

There is no consensus on home oxygen therapy in infancy. We hypothesised that this might lead to considerable variability in the practice of prescribing home oxygen to infants. To assess this variability, a structured questionnaire was sent to all departments of Paediatrics in Germany (n = 380). Response rate was 92% (n = 349). Indications were mostly (86%) based on long-term recordings of pulse oximeter saturation (S(P)O(2)). There was, however, a wide range (85-94%, mean 90%) of S(P)O(2)-values below which oxygen therapy was considered indicated. Hospitals more experienced with this therapy tended to prescribe oxygen at S(P)O(2) values closer to the physiological range. Similarly, S(P)O(2) values aimed for during therapy ranged from 86 to 100%, with hospitals prescribing home oxygen more frequently aiming for higher values. These differences would argue for concentrating home oxygen therapy to centers with the largest experience.

Background: The International Child Care Practices Study (ICCPS) has collected descriptive data from 21 centres in 17 countries. In this report, data are presented on the infant sleeping environment with the main focus being sudden infant death syndrome (SIDS) risk factors (bedsharing and infant using a pillow) and protective factors (infant sharing a room with adult) that are not yet well established in the literature., Methods: Using a standardised protocol, parents of infants were surveyed at birth by interview and at 3 months of age mainly by postal questionnaire. Centres were grouped according to geographic location. Also indicated was the level of SIDS awareness in the community, i.e. whether any campaigns or messages to "reduce the risks of SIDS" were available at the time of the survey., Results: Birth interview data were available for 5488 individual families and 4656 (85%) returned questionnaires at 3 months. Rates of bedsharing varied considerably (2-88%) and it appeared to be more common in the samples with a lower awareness of SIDS, but not necessarily a high SIDS rate. Countries with higher rates of bedsharing appeared to have a greater proportion of infants bedsharing for a longer duration (>5 h). Rates of room sharing varied (58-100%) with some of the lowest rates noted in centres with a higher awareness of SIDS. Rates of pillow use ranged from 4% to 95%., Conclusions: It is likely that methods of bedsharing differ cross-culturally, and although further details were sought on different bedsharing practices, it was not possible to build up a composite picture of "typical" bedsharing practices in these different communities. These data highlight interesting patterns in child care in these diverse populations. Although these results should not be used to imply that any particular child care practice either increases or decreases the risk of SIDS, these findings should help to inject caution into the process of developing SIDS prevention campaigns for non-Western cultures.

Aim: To demonstrate that skin-to-skin care (SSC) has no detrimental effects on the frequency of episodes of bradycardia and/or hypoxemia., Methods: Twenty-two spontaneously breathing preterm infants (median gestational age at birth, 29 weeks [range, 24-31 weeks]; age at study, 26 days [range, 7-72 days]; weight at study, 1310 g [range, 725-1890 g]) had three 2-hour recordings of breathing movements, nasal airflow, heart rate, and oxygen saturation as measured by pulse oximetry (SpO(2)) before, during, and after SSC. Rectal temperature was obtained every 2 hours. Recordings were analyzed for baseline heart and respiratory rates, bradycardia (heart rate < two thirds of baseline), and hypoxemia (SpO(2) < or =80%), as well as for breathing pattern (regular vs non-regular)., Results: Baseline heart rate and respiratory rate increased during SSC (P <.01), as did the combined frequency of bradycardia and hypoxemia (from 1.5/h [0-8] before to 2.8/h [0-15] during SSC; P<.05). Rectal temperature increased from 36.9 degrees C (36.2 degrees -37.4 degrees C) to 37.3 degrees C (36.6 degrees -38.6 degrees C; P <.01). The proportion of regular breathing pattern decreased from 14% (2%-28%) to 7% (3%-26%) with SSC (P<.01)., Conclusion: SSC was associated with a significant increase in the combined frequency of bradycardia and hypoxemia and with less regular breathing. These changes were unexpected and may have been related to heat stress. Body temperature, heart rate, and oxygenation should be monitored during SSC.

Despite their broad clinical use, there is no standardized comparative study on the functional, biochemical, and morphologic differences of the various commercial surfactants in relation to native surfactant. We investigated these parameters in Alveofact, Curosurf, Exosurf, and Survanta, and compared them with native bovine (NBS) and porcine (NPS) surfactant. For Curosurf and Alveofact the concentrations necessary for minimal surface tensions < 5 mN/m were six to 12 times higher (1.5 and 3 mg/ml, respectively) than with NPS and NBS. Exosurf and Survanta only reached 22 and 8 mN/m, respectively. Increasing calcium to nonphysiologic concentrations artificially improved the function of Alveofact and Curosurf, but it had little effect on Exosurf and Survanta. Impaired surface activity of commercial versus native surfactants corresponded with their lack in surfactant protein SP-A and decreased SP-B/C. The higher surface activity of Curosurf compared with Alveofact corresponded with its higher concentration of dipalmitoylphosphatidylcholine (DPPC). Despite their enrichment in DPPC Survanta and Exosurf exhibited poor surface activity because of low or absent SP-B/C. Ultrastructurally, Curosurf and Alveofact consisted mainly of lamellar and vesicular structures, which were also present in NPS and NBS. Exosurf contained crystalline structures only, whereas the DPPC-enriched Survanta contained separate lamellar/vesicular and crystalline structures. We conclude that in vitro surface activity of commercial surfactants is impaired compared with native surfactants at physiologic calcium concentrations. In the presence of SP-B/C, surface activity corresponds to the concentration of DPPC. Our data underscore the importance of a standardized protocol at physiologic calcium concentrations for the in vitro assessment of commercial surfactants.

Considering the decreasing incidence of sudden infant death syndrome (SIDS) and the yet unproven efficacy of home monitoring, current indications for home monitoring should be reconsidered. Documented monitoring still appears to be necessary in infants with apparent life-threatening events (ALTE) and in siblings of two or more SIDS victims. Home monitoring is also indicated in infants on home oxygen/ventilation or with specific respiratory control disorders, but is usually not indicated in asymptomatic preterm infants or in those with a single SIDS sibling, a mother indulging in drug abuse, or increased parental anxiety. The risk of SIDS in these groups is lower than that in infants of mothers who are heavy smokers, who are nowhere regarded as candidates for home monitoring. If monitoring is considered necessary, new generation pulse oximeters with low false alarm rates are probably the safest technical option because they sound the alarm comparatively early, yet do not give too many false alarms. Home monitor recommendations should be revisited, taking the above issues into account.

Aim: To study the effect of doxapram on the frequency of apnoea, bradycardia and hypoxaemia., Methods: Fifteen infants, median gestational age at birth 27 weeks (range 24-30), age at study 27 days (12-60), with >/=6 episodes of bradycardia or hypoxaemia/6 h despite serum caffeine levels in the therapeutic range, received doxapram either intravenously (0.5-2 mg/kg/h) or orally (2-8 mg/kg every 2 h). Six-hour recordings of pulse oximeter saturation (S(P)O(2)), pulse waveforms, ECG, breathing movements and nasal airflow were performed immediately before as well as 1, 3 and 6 days after onset of treatment. Recordings were analysed for apnoea (>/=4 s), bradycardia (heart rate < 2/3 of baseline) and hypoxaemia (S(P)O(2)

The authors investigated whether there was a decline in infants sleeping prone and other modifiable risk factors for sudden infant death syndrome (SIDS) in Germany, where, as in some other countries, no nationwide intervention campaign against the prone sleeping position had been initiated. Data were obtained from parents by mailed questionnaires in two cross-sectional studies in 1991 (n = 3,330) and 1995 (n = 3,124). Prevalence of prone sleeping decreased from 37.6% to 8.7% (p < 0.05) in the German population and from 44.1% to 32.0% (p < 0.05) in the Turkish immigrant population. Parents who laid their infants prone in 1995 were less likely to follow advice from physicians, public media, and other parents (relative risks < 0.5, p < 0.05) and were more likely to have a low educational level, to be <20 years old, to be single parents, to have two or more children, to be raised in West Germany, or to be of Turkish ethnicity. Although the information on prone sleeping being a risk factor for SIDS became known among the population, these data suggest that subgroup-specific public intervention campaigns may be needed to reduce the prevalence of prone sleeping even further in those countries where no nationwide campaign has been initiated.

To gain information on the cardiorespiratory changes occurring immediately before sudden infant death (SID), recordings of heart rate and chest wall impedance were analyzed in nine infants who had died at a median age of 4.8 mo (range 1-6 mo) while attached to a memory monitor. Postmortem diagnoses were sudden infant death syndrome in seven infants and mild bronchopulmonary dysplasia in two infants. Primary cause of the monitor alarm was bradycardia in all but two infants. Heart rate fell to < or = 15 bpm 7.5 min (range 1.4-25.2 min) after the first alarm; there was no indication of heart block or ventricular tachycardia. Apnea (> 20 s) began 0.3 to 13.7 min (median 2.7 min) after this alarm in five infants and 7 to 20 s before it in three infants; in the remaining infant, stimulation occurred before any apnea. Gasping was already present at the time of the first monitor alarm in three infants and occurred within 2.7 min after it in a further four infants. One infant only began to gasp 13 min after the first monitor alarm. The duration of gasping ranged from 3 s to 11 min in those five infants in whom it was not interrupted by resuscitation. The latter was given to three infants 4, 21, and 228 s after the monitor alarm but had no effect on the ongoing decrease in heart rate. Since gasping only occurs if PaO2 is < 5-15 mm Hg, it is most likely that the seven infants who gasped at or shortly after the first monitor alarm were already severely hypoxemic at that time. This hypoxemia developed in the absence of prolonged central apnea. The role of other mechanisms potentially resulting in severe hypoxemia, such as upper airway obstruction or rebreathing, remains to be determined.

There is considerable uncertainty regarding the oxygen saturation threshold below which additional inspired oxygen should be given to infants with acute or chronic lung disease. In the absence of data from controlled studies, recommendations can only be based on reference values for healthy infants and on observational studies regarding the pathophysiological effects of acute and chronic hypoxia. Reference values for pulse oximeter saturations (SpO2) in term and preterm infants show that during normal breathing 95% of infants maintain SpO2 at or above 93-97%, depending on age. Studies of infants with chronic lung disease (CLD) show that (1) when SpO2 was kept at > or =93% by administration of home oxygen, rates of sudden infant death were reduced; (2) weight gain was significantly better when SpO2 was maintained at > or =93-95%, (3) increasing SpO2 from 82 to 93% by delivering low-flow oxygen resulted in a 50% reduction in pulmonary artery pressure, (4) O2 administration to mildly hypoxemic infants (SPO2 89%) caused a 50% decrease in airway resistance, and (5) low-flow oxygen reduced the frequency of intermittent hypoxemic episodes, even in infants who had values of > or =90% at rest. Based on these data, it is recommended that oxygen therapy should be considered in infants whose baseline SpO2 is <93%, and that SpO2 should be maintained at > or =95% when infants are managed at home.

In 1990 the Innocenti Declaration on promoting breastfeeding was proclaimed in Florence/Italy. It became the subject of resolution 45.34 of the World Health Assembly in 1992. In the Federal Republic of Germany there was no wide-scale mass-media campaign to promote breastfeeding as in other countries. But mother-to-mother support groups, medical services and the newly founded National Breastfeeding Committee supported prolonged breastfeeding in public. The effects of the joint effort could be estimated by comparing the results of two postal surveys in 1991 and 1995. The surveys were conducted in Lower Saxony, North-Rhine-Westphalia and Berlin. A tendency could be shown toward more exclusive breastfeeding. Breastfeeding with supplementary food increased by a factor of 1.3 after adjusting for the variables mother's age, sleeping in parents' room or bed and no-smoking household. In Lower Saxony the increase was by a factor of 1.5 starting from a lower base value. The baby sleeping in the parents' room or in their bed furthered breastfeeding by a factor of 1.5 to 4. Non smoking mothers are 4 times more willing to breastfeed their infants than smoking mothers. German mothers breastfeed their infants two to three times more often than turkish mothers.

Systemic fungal infection occurs in 2 to 4.5% of very low birth-weight (VLBW) infants (< 1,500 g) and may be fatal in 25 to 54%. Candida sp. is the major pathogen and amphotericin B the treatment of choice. To reduce side effects and optimize drug action, a formulation of amphotericin B encapsulated in liposomes (AmBisome) has been introduced. Data on 21 VLBW infants who received a full course of AmBisome was collected and its toxic effects with emphasis on nephrotoxicity and hypokalemia assessed. The median gestational age was 25 weeks (range 23-31) with a median birth-weight of 730 g (range 450-1,370). Antifungal therapy was started at a median age of 13 days (range 1-49). The median dose given was 2.6 mg/kg/day (range 1-5), and the median duration of therapy was 28 days (range 11-79), corresponding to a median cumulative dose of 71 mg/kg (range 12-271). Hypokalemia (< 3.0 mmol/l) was observed in 30% before, and 15% during AmBisome treatment. Twenty-one days after the termination of therapy, hypokalemia was not present in any patient. Median maximum daily potassium supplementation did not exceed doses usually recommended for VLBW infants. The median of the maximum creatinine levels before treatment was 121 mumol/l (range 71-221) and fell to 68 mumol/l (range 31-171) during treatment and 46 mumol/l (range 26-62) 21 days after the termination of therapy. All patients treated with AmBisome eradicated fungi and recovered clinically. AmBisome showed no certain nephrotoxicity in VLBW infants in this study.

Based on the known properties of ambroxol and dexamethasone to inhibit inflammation and increase endogenous surfactant levels, the potential advantage of donor pretreatment with either drug was investigated in an acute rat double-lung transplant model. Donor animals were randomly assigned to one of three treatment groups: an ambroxol group (AMB; 0.4 mg/kg), a dexamethasone group (DX; 2 mg/kg); or an untreated control group (CN). Drugs were given intraperitoneally 6 h prior to harvest. Following standard preservation and 16 h of cold ischemia, the donor double lung block was implanted into syngeneic recipients using custom-designed stents for the vascular anastomosis. During reperfusion, serial measurements of graft pulmonary vascular resistance and alveolar-arterial oxygen difference were obtained. Separate graft ventilation allowed determination of graft dynamic lung compliance. Final assessment included weight gain and histology. For phospholipid analysis, lung lavages were performed in the three study groups at the end of reperfusion and compared to levels before graft harvest. Donor pretreatment did not significantly affect preharvest phospholipid levels. Survival following graft ischemia and reperfusion was shortest after AMB (92 +/- 5 min) and longest after DX (110 +/- 5 min; DX vs AMB P < 0.03) and CN (116 +/- 4 min; CN vs AMB P < 0.02). DX pretreatment provided better compliance (P < 0.02) and lower vascular resistance (P < 0.0001) than AMB treatment. Airway resistance was lower in the AMB and DX groups than in controls (P < 0.04 and P < 0.02, respectively). The alveolar-arterial oxygen difference was markedly similar in all groups. Graft weight gain amounted to 114% +/- 10% in AMB, 88% +/- 12% in DX, and 98% +/- 13% in CN (P = NS). Thus, in this rat lung transplantation model, donor pretreatment with dexamethasone did not improve graft function compared to untreated controls and donor pretreatment with ambroxol was found to be potentially detrimental to graft function during reperfusion.

Alveolar surfactant is well known for its ability to reduce minimal surface tension at the alveolar air-liquid interface to values below 5 mN/m. In addition, it has been suggested that an analogous conductive airway surfactant is also present in the airways. To elucidate the composition, possible origin, and surface activity of conductive airway phospholipids (PL), we compared in adult porcine lungs the PL classes and phosphatidylcholine (PC) molecular species of nonpurified tracheal aspirate samples with those of bronchoalveolar lavage fluid (BAL), tracheobronchial epithelium, and lung parenchyma. We also analyzed PL and PC composition, protein content, and surface activity of surfactant isolated from tracheal aspirates (SurfTrachAsp), BAL (SurfBAL), and the 27,000 x g pellet of BAL (SurfP27000) by density-gradient centrifugation. Although PL composition revealed contributions of the airways to tracheal aspirates, the composition of PC molecular species of tracheal aspirates was similar to that of BAL and lung parenchyma, but differed considerably from that of airway epithelium. SurfTrachAsp had the same PL and PC composition as SurfBAL and SurfP27000, indicating that this fraction of tracheal aspirates may have originated from the alveoli. Nevertheless, minimal and maximal surface tensions were higher in SurfTrachAsp than in SurfBAL and SurfP27000. Analysis of surfactant proteins A, B, and C (SP-A, SP-B, and SP-C) revealed that SP-A was decreased and SP-B and SP-C were absent, whereas total protein was increased in SurfTrachAsp. We conclude that as compared with alveolar surfactant, PL of SurfTrachAsp show the same composition, but that surface-tension function is impaired and the concentration of surfactant proteins is decreased in SurfTrachAsp.

Treatment of chronic lung disease of prematurity requires effective aerosol delivery of different therapeutic agents. Aerosols can be generated by a metered dose inhaler (MDI) or a jet nebulizer. An MDI combined with a spacer device is easier to use and avoids undesirable effects noted in conjunction with jet nebulization. We compared the clinical effectiveness of 200 micrograms (2 puffs) salbutamol delivered from an MDI in conjunction with a valved spacer device (Aerochamber), and 600 micrograms given via jet nebulizer (PariBaby) on 2 consecutive days, the order being randomized. Thirteen spontaneously breathing very preterm infants [mean (SD) gestational age 27.2 (1.8) weeks; birth weight 0.90 (0.34) kg] were studied at a corrected age of 37 (2.3) weeks. Mean (SD) study weight was 1.83 (0.38) kg. Dynamic lung compliance and resistance were determined from measurements of flows, volumes, and transpulmonary pressures, using a pneumotachometer and a small esophageal microtransducer catheter before and 20 min after salbutamol application. Baseline values before salbutamol administration were similar on both occasions: the mean (SD) compliance was 7.7 (3.0) mL.kPa-1.kg-1 pre-MDI plus-spacer and 8.4 (3.1) pre-jet nebulizer; the resistance was 10.4 (4.0) kPa.L-1.s pre-MDI plus-spacer and 9.7 (3.4) pre-jet nebulizer. Following salbutamol, compliance did not change significantly with either MDI plus spacer or jet nebulizer. Resistance fall significantly with MDI plus spacer (mean -2.2; 99.9% CI -0.35, -4.35) and jet nebulizer (-2.4; 99% CI -0.39, -4.42). We conclude that even in small preterm infants 200 micrograms salbutamol via MDI plus spacer improves dynamic resistance as effectively as 600 micrograms via jet nebulizer and may therefore be a preferable mode of aarosol administration.

Damage to the respiratory system caused by inhalation of toxic products of combustion and the subsequent development of adult respiratory distress syndrome (ARDS) are the main lethal factors in burns patients. Treatment with exogenous surfactant is one of the therapeutic options. However, no clinical reports have yet been published about this therapy. We report on two patients with burn injuries of second to third degree affecting 42% and 48% respectively of the total body surface plus inhalation injury complicated by ARDS. Both patients were treated with bovine surfactant (Alveofact). The therapeutic effects on oxygenation and pulmonary function were monitored. Intrabronchial application of surfactant by bronchoscopy during exhaustive conventional mechanical ventilation resulted in improved gas exchange with an increase in arterial O2 pressure (paO2); inspired O2 concentration (FiO2) was lowered and there was an improvement in lung compliance. Both patients survived this critical situation. We conclude that treatment with exogenous surfactant in postburn victims with ARDS is a promising therapeutic approach to improve the survival rate of these high-risk patients.

To study the effects of apneic pauses, sighs, and breathing patterns on functional residual capacity (FRC), we measured FRC repeatedly in 48 healthy preterm infants (weight at study 2,042 +/- 316 g [mean +/- SD], postconceptional age 36.6 +/- 2.0 wk), during unsedated sleep using a modified heliox/nitrogen washout technique. Breathing movements and pulse oximeter saturation (SpO2) were recorded throughout and recordings analyzed for the presence of regular and nonregular breathing pattern, apneic pauses, sighs, and desaturations (SpO2 < 90%) during the last 2 min prior to each FRC measurement. FRC was lower during nonregular than during regular breathing pattern (23.3 +/- 7.2 ml/kg versus 26.9 +/- 7.8 ml/kg, p < 0.02); however, this apparent effect of breathing pattern disappeared after controlling the data for apneic pauses. Apneic pauses resulted in a significant decrease in FRC: mean FRC was 20.0 +/- 6.8 ml/kg if measured within 2 min of an apneic pause, 26.0 +/- 6.9 ml/kg if measured after a sigh (p < 0.001), and 24.0 +/- 7.7 ml/kg if there had been neither a sigh nor an apneic pause (p < 0.05). The interval between the apneic pause and the FRC measurement had no effect on FRC. There was an inverse correlation between FRC and the speed with which SpO2 fell during desaturation (r = -O.5, p < 0.03). Apneic pauses resulted in a persistent reduction in FRC in these preterm infants. Sighs appeared to restore FRC. The significant relationship between FRC and the speed of desaturation found in this study underscores the importance of endogenous or exogenous strategies that help to increase FRC, such as sighs or the application of continuous positive airway pressure, for the stability of oxygenation in preterm infants who have difficulty maintaining their oxygenation.

To determine the importance of static lung inflation during storage, graft performance was evaluated at different levels of intratracheal pressure and varying ischemic intervals. Lewis rat lungs were perfused with low-potassium Euro-Collins and stored for 4 or 8 hr either in atelectasis (4 hr: group I; 8 hr: group IV, respectively) or 13 (group II; V) or 26 cmH2O of airway pressure (groups III, VI). Following implantation continuous measurement of alveolar-arterial oxygen difference (AaDO2*) and pulmonary vascular resistance (PVR) were performed. Separate ventilation allowed assessment of mechanical lung function of the graft. At the end of reperfusion (120 min) weight gain, histology, and phospholipid and protein content in the pulmonary lavage were compared between the groups. Despite significant differences in survival at 4 hr of ischemia graft function did not differ in groups I to III. In contrast, static inflation had a significant impact after 8 hr of ischemia. Lungs stored in atelectasis (group IV) could not be reperfused and failed immediately. Survival in group V was 83+/-11 versus 107+/-7 min in group VI (P<0.05). Compliance at 80 min was 27+/-3 in group V and 52+/-6 ml/cmH2O in group VI (P<0.02). Corresponding values for PVR were 232+/-92 and 112+/-16 mmHg/ml/min, respectively (P<0.05). Less inflation and longer ischemia resulted in a reduction of the large to small phospholipid aggregate ratio and deterioration of surfactant function in the bubble surfactometer. In conclusion, while the amount of static lung inflation may not be critical following short ischemia, the performance of the graft improves significantly with full inflation (26 cmH2O) following extended ischemia (8 hr).

Objective: There have been indications of a recent decrease in intubation rates of very low birth weight (VLBW) infants in Germany. We wanted to quantify this decrease and analyze its effect on clinical outcome., Methods: Population-based data on the treatment and outcome at hospital discharge from a statewide quality assurance program were analyzed for 2001 VLBW infants (500 to 1499 g) born from 1992 to 1994 in Lower Saxony, North Germany., Results: The proportion of patients not intubated and mechanically ventilated increased from 7% to 14% in infants less than 1000 g and from 28% to 44% in those greater than or equal to 1000 g (P < .02 and < .01, respectively). This increase was not associated with any significant increase in adverse outcome such as death, intraventricular hemorrhage, periventricular leucomalacia, or bronchopulmonary dysplasia (BPD). Instead, there was an increase in the proportion of infants less than 1000 g who survived without BPD (from 38% in 1992 to 48% in 1994; P < .05) and a decrease in the proportion of infants greater than or equal to 1000 g in whom BPD developed (from 14% to 9%; P < .05)., Conclusions: The data from a statewide quality assurance program show a significant reduction in the aggressiveness of the treatment of VLBW infants, which was not associated with an increased mortality or morbidity. This observational study, however, cannot define whether a more selective approach to the intubation of VLBW infants will ultimately result in a better outcome. A randomized, controlled trial would be required to answer this clinically important question.

The nitrogen washout technique usually involves exposure of the patient to 100% oxygen for several minutes. This may be dangerous in preterm infants who are at risk of retinopathy of prematurity (ROP). We wanted to know whether heliox (79% He, 21% O2) can be used instead of oxygen when determining functional residual capacity (FRC). FRC measurements were made in 14 preterm infants [median (range) gestational age at birth 34 wk (27-37 wk), and at time of study 36 wk (33-40 wk)] who were breathing room air. FRC was measured using a computerized infant pulmonary function system, beginning in random order with either 100% O2 followed by heliox or vice versa. There was no systematic difference between the two methods with regard to lung volume measurements: mean (SD) FRC values, corrected for body weight, were 22.9 (7.1) mL/kg for O2 and 23.4 (7.0) mL/kg for heliox. We did not observe a systematic influence of the type of washing gas used (heliox or oxygen) on FRC in these infants. Our results suggest that the use of heliox instead of pure oxygen may be a suitable and safer alternative for FRC measurements with the nitrogen washout technique in preterm infants who are breathing low concentrations of inspired oxygen and are still at risk of ROP.

N-acetylneuraminic acid (sialic acid) storage disease is a rare autosomal recessive lysosomal disorder. Clinically two major forms exist, an infantile type with severe progression leading to early death, and a milder form (Salla disease) with a protracted course. Intermediate forms may also exist. Diagnosis rests on the determination of an excessive excretion of sialic acid in urine and concomitant storage in fibroblasts, the severe forms exhibiting the highest excretion and storage. We present clinical, morphological, and biochemical data on three non-Finnish patients with sialic acid storage disease. Patient 1 was a preterm infant with neonatal ascites, coarse face, hepatosplenomegaly, pale skin, and wispy hair. Vacuolated lymphocytes were abundant in a peripheral blood smear and he excreted large amounts of free sialic acid. High levels of free sialic acid were also found in cultured skin fibroblasts. He died at age 6 months from progressive respiratory insufficiency. Patient 2 was an 11-month-old Egyptian girl with coarse face, frequent upper respiratory tract infections, hepatosplenomegaly, and severe psycho-motor retardation. Sialic acid excretion was elevated, likewise the storage in fibroblasts. Histological investigations documented vacuolar storage in a skin biopsy and in iliac crest tissue. Patient 3 was a 16-year-old girl with slightly coarse face, severe generalized muscular hypotonia, ataxia, and kyphoscoliosis originally diagnosed as having post-partum asphyxia. She suffered progressive motor function loss and had dysarthria. Urinary sialic acid was elevated and a skin biopsy demonstrated vacuolization. The clinical variability of sialic acid storage disease is exemplified by these three cases. Simple urinary screening for free sialic acid facilitates the diagnosis. The degree of urinary excretion may indeed correlate with clinical presentation and progression.

Objective: To determine whether episodes of prolonged hypoxemia occur without prolonged apneic pauses (> or = 20 seconds) and without bradycardia (pulse rate, < or = 100 beats per minute) in apparently well preterm infants., Methods: Long-term recordings of arterial oxygen saturation as measured by pulse oximetry (SpO2), photoplethysmographic (pulse) waveforms from the oximeter, and breathing movements were performed in 96 preterm infants (median gestational age at birth, 34 weeks; range, 28 to 36 weeks) who were breathing room air. Recordings started at a median age of 4 days (range, 1 to 60 days)., Results: During a median duration of recording of 25 hours, 88 episodes in which SpO2 fell to 80% or less and remained there for 20 seconds or longer were identified in 15 infants. The median duration of these prolonged desaturations was 27 seconds (range, 20 to 81 seconds). In 73 episodes (83%), SpO2 continued to fall to 60% or less. Twenty-three desaturations were associated with prolonged apneic pauses and 54 with bradycardia; 19 of these were associated with both apnea and bradycardia. Thirty desaturations (34%; 10 infants) occurred without bradycardia and without prolonged apnea., Conclusions: These results indicate that a proportion of apparently well preterm infants exhibit episodes of severe prolonged hypoxemia unaccompanied by prolonged apneic pauses or bradycardia. Such episodes, therefore, would be difficult to detect if only breathing movements and heart rate are monitored. Indications for the use of oxygenation monitors in preterm infants should be reconsidered.

This study aimed to determine whether preterm infants who have a history of apparent life-threatening events (ALTE) have abnormalities in oxygenation and, if so, whether the ALTE would stop with oxygen therapy. We assessed 92 patients (median gestational age at birth, 32 weeks (range, 24 to 36 weeks); median birth weight, 1840 gm (650 to 3500 gm)) who had had a single (n = 20) or recurrent ALTE. Median postnatal age at referral was 3.2 months (0.5 to 44.7 months). All had been considered otherwise free of symptoms and adequately oxygenated in air at the time of discharge from their neonatal unit, before the ALTE. Fifty-two patients had received mouth-to-mouth resuscitation, and 40 vigorous stimulation. Ninety-one patients underwent 8- to 12-hour recordings of arterial oxygen saturation, the plethysmographic waveforms from the oximeter, breathing movements, and electrocardiograms. These recordings were compared with previously published data from 110 "healthy" preterm infants made at around 6 weeks after discharge from hospital. Compared with these data, 49 recordings (54%) were normal, 19 showed abnormal hypoxemic episodes, 6 had abnormally low baseline arterial oxygen saturation (< 95%), and 17 had both. In 31 of 33 patients, ALTE stopped or were reduced in frequency or severity after additional inspired oxygen (0.1 to 1.0 L/min via nasal cannulas) was given. Oxygen was given for a median duration of 3.9 months (range, 0.8 to 17.2 months). Persistent events in the remaining two patients were subsequently found to be due to intentional suffocation in one and epileptic seizures in the other. Monitoring of transcutaneous oxygen tension at home was undertaken in 84 patients. To date, this has been discontinued in 81 after a median duration of 7.3 months (0.3 to 18.9 months). We conclude that recognition and treatment of abnormalities in episodic or baseline hypoxemia may reduce the risk of further ALTE in previously preterm infants.

Objective: To describe the physiologic changes that occur during epileptic seizure (ES)-induced apparent life-threatening events (ALTE) and to provide an explanation for the mechanism whereby the hypoxemia characterizing these events occurred., Patients and Design: Six infants were retrospectively selected from a group of 17 because they had ALTE documented on physiologic recordings where the first change in signals was in the electroencephalogram (EEG). The 17 infants had clinical features suggestive of partial seizures (but normal standard EEGs) and were from a sample of 172 infants with recurrent ALTE. All 17 infants underwent continuous recordings of breathing, electrocardiogram (ECG), oxygenation, and EEG, but only in 6 was an ES-induced ALTE recorded and the physiologic changes described., Results: Twenty-three ALTE were documented in six infants. Events commenced with an abnormality in the EEG, followed by a decrease in SaO2 after a median interval of 27 seconds (range 2 to 147). Despite resuscitation, the median duration of severe hypoxemia (SaO2 < or = 60%) was 40 seconds (range 8 to 74). In 18 events (five infants) there was a median of four apneic pauses (range 1 to 9) preceding the decrease in SaO2 by a median duration of 24 seconds (range 3 to 48). The longest apneic pause per event lasted a median of 19 seconds (range 8 to 47). Breathing movements continued in five events (four infants), and expiratory airflow in one. Sinus tachycardia was found in 19 of the 23 events (six infants), but there were no cardiac arrhythmias., Conclusions: ES in infants can manifest as ALTE and be accompanied by potentially life-threatening episodes of severe hypoxemia and apnea, despite a normal EEG between events.

Objective: To review the technical principles of transcutaneous PO2 (tcPO2) monitors and pulse oximeters and to discuss methodological and practical issues related to the use of these devices in infants and children., Design: Literature review and summary of personal experience., Results: tcPO2 measurements are influenced by skin thickness, sensor temperature, amount of contact gel used, and state of peripheral perfusion. The average in vivo response time to a rapid decrease in PaO2 is approximately 16 seconds. Sensitivity to both hypoxemia (PaO2 < 50 mm Hg) and hyperoxemia (PaO2 > 80 to 100 mm Hg) is approximately 85%. Pulse oximeters require careful sensor placement (to avoid optical shunts) and adequate pulse pressures (> 20 mm Hg). They are prone to movement artifact. There are considerable differences in bias and precision between different brands, resulting, for example, in quite different upper alarm limits required to detect hyperoxemia reliably. The normal range of oxygen saturation measured by pulse oximetry, measured with one brand of pulse oximeter (Nellcor) during regular breathing, is 95% to 100% in preterm infants and 97% to 100% in full-term infants and children., Conclusions: Because both devices have their specific shortfalls, they should ideally be used in combination, particularly in critically ill preterm neonates. Where this is not feasible or necessary, clinicians must be aware of the limitations of the device they are using.

In preterm infants, reliance on the detection of apnoeic pauses and/or bradycardia results in significant amounts of hypoxaemia remaining undetected. In addition, recordings of breathing movements and ECG do not have predictive value for subsequent sudden infant death. In recent years, the ability to continuously monitor and record arterial oxygen saturation (SaO2) has produced important information regarding the mechanisms for respiratory events in the preterm population. Normal data on SaO2 (Nellcor N-200) and breathing movements have been collected in 160 preterm infants. Median baseline SaO2 during regular breathing was 99.5% (range 88.7-100) at the time of discharge from SCBU and 100% (95.3-100) at follow-up 6 weeks later. Episodic desaturations (SaO2 < or = 80% for > or = 4 s) ranged between 0 and 355 episodes per 12-hour recording. In a study of a separate group of 16 preterm infants with recurrent cyanotic episodes of unknown cause, the total number of abnormal hypoxaemic episodes was markedly increased. These hypoxaemic episodes were associated with three breathing pattern: (i) absent breathing movements; (ii) continued breathing movements, but absent airflow, and (iii) continuous airflow and breathing movements. Thus, preterm infants with cyanotic episodes have an increased number of clinically unapparent hypoxaemic episodes, some of which occur with continued breathing and airflow. In another study of 79 patients who had been born preterm and had a history of an apparent life-threatening event, 43 (54%) had abnormal oxygenation on multichannel recordings, including 23% with clinically undetected baseline hypoxaemia.(ABSTRACT TRUNCATED AT 250 WORDS)

To obtain normal data on arterial oxygen saturation as measured by pulse oximetry (SpO2; Nellcor N200), we obtained 12-hour tape recordings of SpO2, photoplethysmographic waveforms, instantaneous pulse rate, and observations of breathing movements on 55 preterm neonates (25 girls) who had been admitted to one of four special care baby units but had no signs of respiratory distress and were breathing room air at 24 hours of age. Their median gestational age at birth was 35 weeks (range, 30 to 36), and their median age at the time of study 1 day (range, 1 to 7). Median baseline SpO2, measured only during regular breathing, was 99.4% (range, 90.7 to 100; 5th percentile, 95.5). Ten recordings (18%) contained a total of 83 episodes of desaturation (defined as a fall in SpO2 to < or = 80% for > or = 4 seconds). The 95th percentile for desaturation frequency was eight per recording. One infant had 55 episodes of desaturation and thus accounted for two thirds of all episodes observed. Only one of the episodes of desaturation in this infant, and none of those in the other nine infants, had been noted clinically, nor had the abnormally low baseline SpO2 (90.7%) in one infant. Baseline SpO2 in these nondistressed preterm neonates was higher than might be expected, given the SpO2 levels currently recommended for preterm infants with respiratory failure. A minority of infants, however, had a low baseline SpO2 or a high frequency of episodes of desaturation, the potential effects of which remain to be determined.

Objective: To obtain information on breathing patterns and oxygenation in children., Design: Overnight tape recordings of arterial oxygen saturation (SaO2; Nellcor N200 in beat-to-beat mode), photoplethysmographic waveforms, and breathing movements in 70 healthy children (mean age 8.0 years, range 2 through 16). Analysis of recordings for pauses in breathing movements of > or = 4 seconds (apneic pauses), for episodes in which SaO2 fell to < or = 90% (desaturations) and, only during the state of regular breathing, for baseline SaO2, heart rate, and respiratory rate., Results: Both baseline heart rate and respiratory rate decreased with increasing age (r = -.7 and -.3, respectively, P < .01). Baseline SaO2 was similar to that previously observed in infants (median 99.5%, range 95.8 to 100, 5th centile 96.6%). Every recording showed apneic pauses, with a frequency that did not vary consistently with age (median 7.7/h, range 0.6 to 25.5). One hundred nineteen apneic pauses in 43 recordings lasted for 15 to 19.9 seconds, and 23 lasted for > or = 20 seconds (longest 28.8 seconds). The number of episodic falls in SaO2 to < or = 90% decreased with age (r = -.3, P < .01); such episodes were found in 47% of children aged 2 through 6 years, but in only 13% of those aged 12 through 16 years. The 95th centile for desaturation frequency in the total group was 0.6/h. In six episodes in four patients, SaO2 fell to < or = 80%., Conclusions: Apneic pauses, some of which can last for more than 20 seconds, are a normal phenomenon in healthy children and adolescents, but only a small minority of apneic pauses affect blood gas homeostasis. Information concerning oxygenation may be more relevant to our understanding of the maturation of respiratory control than the recording of breathing signals alone.

The pathogenesis of bradycardias in preterm infants is poorly understood. Because their pathogenesis may involve both apnea and hypoxemia, we set out to analyze the proportion of bradycardias that were associated with an apneic pause and/or a fall in arterial oxygen saturation (SaO2), and the temporal sequence of the three phenomena, in overnight tape recordings of SaO2 (Nellcor N100 in beat-to-beat mode), breathing movements, nasal airflow, and ECG in 80 preterm infants at the time of discharge from hospital. A bradycardia was defined as a fall in heart rate of > or = 33% from baseline for > or = 4 s, an apneic pause as a cessation of breathing movements and/or airflow for > or = 4 s, and a desaturation as a fall in SaO2 to < or = 80%. A total of 193 bradycardias were found in 46 (58%) of the recordings (median, three per recording; range 1-18). There was a close relationship between bradycardias, apneic pauses, and desaturations: 83% of bradycardias were associated with apneic pauses and 86% with desaturations. Where all three phenomena occurred in combination, the time from the onset of apnea to the onset of the fall in SaO2 was shorter (median interval, 0.8 s; range -4.9-+ 11.5 s) than that from the onset of apnea to the onset of bradycardia (median, 4.8 s; range -4.0-+ 14.0 s). Hence, most bradycardias (86%) commenced after the onset of the fall in SaO2. We conclude that bradycardia, apnea, and hypoxemia are closely linked phenomena in preterm infants.

The pathogenesis of apnoea in preterm infants is poorly understood. Thus, it is yet unknown (1) whether the descriptive distinction between "central", "obstructive" and "mixed" apnoeas is also reflected by differences in their respective pathogenesis, (2) how and where the airway closure occurs during the so-called "obstructive" apnoeas, (3) whether "central" apnoeas do indeed result from a disturbance in the central nervous control of breathing, as implied by their name, or whether they constitute a reflex response to a disturbance in the periphery of the lung, and (4) whether non-apnoeic mechanisms contribute to the hypoxaemia so frequently observed during these episodes. This paper summarises the present knowledge regarding the above issues. It also reviews the current definitions for apnoea, bradycardia and hypoxaemia in preterm infants, describes indications for intervention, and discusses some strategies aimed at preventing these episodes.

Comparative validation studies of pulse oximeters from different manufacturers have predominantly been performed in adult patients. However, due to differences in the patient-sensor interface, the results from those studies may not be transferable to the paediatric population. We therefore performed 123 simultaneous measurements (37 patients) of transcutaneous O2-saturation (StcO2) from 3 pulse oximeters and compared these with the arterial O2-saturation (SaO2) from a co-oximeter (Radiometer OSM 3). The median age of the 37 patients at the time of study was 2.0 months (range 1 day-5 years), their weight 4.7 kg (0.8-15.0 kg). The mean difference between StcO2 and SaO2 was -0.6% (SD 5.2%) for the Kontron 7840 pulse oximeter, -0.9% (SD 2.3%) for the Nellcor N200, and -1.2% (SD 3.5%) for the Radiometer OXI3 pulse oximeter. The corresponding 95% intervals were -7.4(-) + 9.6%, -5.7(-) + 4.3% and -7.0(-) + 6.3% for the Kontron, Nellcor and Radiometer instrument, respectively. These results demonstrate that neither of the 3 instruments systematically under- or overestimated SaO2. However, there were differences in precision, particularly in the low range of SaO2.

To evaluate the reliability of the Nellcor N200 pulse oximeter in the detection of hyperoxemia (oxygen tension > 80 mm Hg), we obtained 213 simultaneous recordings and measurements of transcutaneous oxygen saturation (SO2) and arterial oxygen tension (PaO2) in 50 patients. During 95% of measurements with PaO2 > 80 mm Hg, SO2 was > or = 96%; SO2 was also > or = 96% in 20% of measurements with PaO2 < or = 80 mm Hg (false-positive results for hyperoxemia). With the upper alarm limit set at 95%, the pulse oximeter identified 95% of hyperoxemic instances while allowing PaO2 to be kept to > 60 mm Hg.

A number of physiologic phenomena during some apneic/cyanotic episodes in infants and young children cannot be explained sufficiently on the basis of a cessation or reduction in alveolar ventilation alone. These include (1) the extremely rapid development of hypoxemia during some episodes, (2) the occurrence of hypoxemic episodes despite continuous ventilation, (3) differences in the speed of desaturation between different forms of apneic episodes, (4) the presence of continued breathing efforts and yet absent airflow despite bypass of the upper airway, and (5) evidence that apnea and hypoxemia may begin simultaneously. Potential mechanisms to explain these phenomena include the sudden development of an unevenness in the matching between ventilation and lung perfusion, the flow of blood through unventilated areas of lung, and a sudden impairment in gas diffusion. Evidence from physiological and morphological studies suggests that all of these mechanisms, although to a different extent, may be involved in apneic/cyanotic episodes. The recognition that nonapneic mechanisms can cause sudden profound hypoxemia may alter our approach to the identification, treatment, and prevention of these episodes.

Nineteen infants who were graduates from special care baby units underwent two overnight tape recordings of oxygen saturation (SaO2) and breathing movements; one during an upper (n = 12) or lower (n = 7) respiratory tract infection and the other when free of infection. Baseline SaO2 was lower during infection (median 99.6 vs 100%, p less than 0.01), with four patients having values (84.3-95.5%) below the normal lower limit for full-term infants (97%). The median number of apnoeic pauses was also lower during respiratory tract infection (4.7 vs 15.7/h, p less than 0.02). The median number of episodic desaturations (SaO2 less than or equal to 80%) did not change significantly (1.3 vs 1.9/h, p greater than 0.05), with the exception of one patient who had extremely increased values during infection for both apnoeic pauses (63/h) and desaturations (112/h). No infant, however, was considered clinically hypoxaemic. Clinically unsuspected hypoxaemia may thus occur during respiratory tract infection in a proportion of infants graduating from special care baby units. Such hypoxaemia may have potentially deleterious effects.

Forty-two randomly selected, full-term, healthy infants underwent 24-hour electrocardiographic recordings and breathing movements at about ages 6 weeks (median age, 43 days; range, 34 to 61 days) and 2 years (median age, 26 months; range, 21 to 35 months). The number and duration of apneic pauses of 3.6 seconds or longer were analyzed. Periodic apnea was defined as a sequence of three or more apneic pauses, each separated by fewer than 20 breaths. All other apneic pauses were defined as isolated. Median heart rates and respiratory rates, which were measured during regular breathing, decreased from 137/min and 35/min to 98/min and 21/min, respectively. The total duration of periodic apnea remained unchanged (median, 0.06 min/h vs 0.05 min/h). Although the median frequency of all isolated apneic pauses decreased from 3.6/h to 2.5/h, the number of those that were longer than 6 seconds increased from 0.37/h to 0.80/h, leading to an increase in the proportion of these pauses, among all isolated apneic pauses, from 10% at age 6 weeks to 32% at age 2 years. Only one apneic pause in one infant at age 6 weeks, but eight pauses in six children at age 2 years, were longer than 15 seconds. A knowledge of such normal variability in the duration of apneic pauses in older infants and young children is essential for the interpretation of pneumograms and alarms while monitoring breathing movements.

The characteristics of the arterial oxygen saturation (SaO2) signal during episodes of hypoxaemia (SaO2 less than or equal to 80% for greater than or equal to 4 s) associated with periodic and non-periodic apnoeic pauses were studied in 16 preterm infants with cyanotic episodes (patients). and 15 asymptomatic preterm infants (controls), matched on birthweight and gestational age. The patients showed a significantly higher percentage of apnoeic pauses followed by a hypoxaemic episode (25 vs. 6%, P less than 0.01), and a two-fold increase in the slope of the desaturation curve (8.4 vs. 4.3% per s, P less than 0.005) in periodic compared with non-periodic breathing. All other characteristic of oxygenation (baseline SaO2 before episodes of hypoxaemia, delay between onset of apnoeic pause and onset of desaturation, lowest SaO2 during episodes of hypoxaemia) were similar for periodic and non-periodic breathing patterns. Similar, but not significant, differences between isolated and periodic apnoeic pauses were also present in the controls. An analysis of episodes of bradycardia (less than or equal to 100 beats per minute (bpm] showed that out of 121 episodes in the patients 118 were accompanied by a fall in SaO2 to less than or equal to 80%, and in the remaining three SaO2 fell to 82%, 85% and 86%, respectively. Thus all episodes of bradycardia (less than or equal to 100 bpm) were associated with a fall in SaO2 detected by beat-to-beat pulse oximetry. Examination of hypoxaemic episodes and their relationship with bradycardia and with apnoeic pauses, periodic and non-periodic, may help the further understanding of the control of arterial oxygenation in preterm infants with cyanotic episodes.