Effect of positioning on the breathing pattern of preterm infants.

Respiration, as judged by gas exchange and pulmonary function, is improved in preterm infants kept in the prone rather than the supine position. The influence of position on the breathing pattern as documented by the pneumogram was studied in 14 stable preterm infants with recent clinical apnoea. Ten of the infants had oximetry and nasal flow studies simultaneously with the impedance pneumogram. Each infant had consecutive nocturnal pneumograms, one in the prone, one in the supine position. The infants were kept for more than six hours in the assigned position. A significant increase in apnoea density and in periodic breathing was found in the supine v the prone position (mean (SE) 4.5 (0.7)% v 2.5 (0.5)%, and 13.6 (3.2)% v 7.7 (2.2)%, respectively). There was no positional difference in the incidence of bradycardia and prolonged apnoea. The examination of obstructive apnoea, mixed apnoea, and cyanotic spells did not reveal a consistent disparity between the two positions. These findings indicate an increase in central apnoea in preterm infants kept predominantly in the supine position. Possible relations of positional changes to lung mechanics are discussed. When evaluating pneumograms, attention must be given to the position in which they were performed.     

Incidence and mechanism of bradycardia during apnoea in preterm infants.

Bradycardia occurred during 363 of 1520 apnoeas of 10 seconds'' duration recorded in 28 preterm infants. The incidence increased with increasing duration of apnoea (10% of 10-14 seconds, 34% of 15-20 seconds, and 75% of greater than 20 seconds, p less than 0.001). This was similar for each type of apnoea--central, mixed, and obstructive. During 133 apnoeas in five infants the time from the start of the apnoea to the onset in the fall in oxygen saturation (mean 6.9 seconds) was significantly related to the onset of the fall in heart rate (mean 9.3 seconds) (r = 0.67, p less than 0.001). Recovery in heart rate coincided with resumption of air flow rather than breathing efforts and preceded the recovery in oxygen saturation. These results suggest that bradycardia occurs during apnoea as a response to falling oxygen saturation, probably through a peripheral chemoreceptor reflex that is manifest when breathing efforts are absent or ineffective.     

Ontogeny of sleep and awake states in relation to breathing in preterm infants.

This review will focus on the development of behavioural states and breathing during early developmental stages prior to term gestation. Although these behavioural states are immature during early development, their cyclicity is clearly seen. Preterm infants characteristically have a large proportion of indeterminate sleep and small amount of wakefulness. Whereas oxygenation is relatively stable during active and quiet sleep in ventilated preterm infants, indeterminate sleep and arousals are associated with hypoxaemic episodes. Arousals have also been linked to apnoea in spontaneously breathing infants. Since well-defined sleep cycles are beneficial for the oxygenation of preterm infants, we should explore ways to promote their natural sleep while they are exposed to neonatal intensive care. Care practices such as clustering procedures, kangaroo care and optimal positioning have been shown to improve the integrity of sleep. Optimizing the sleep cycling might improve the long-term outcome of preterm infants. More studies in this area are clearly needed.     

Sleep apnoea profile in preterm infants recovering from respiratory distress syndrome.

Polygraphic recordings were made on 10 preterm infants recovering from respiratory distress syndrome and 12 healthy preterm control infants at 40, 52, and 64 weeks'' conceptual age to study the influence of respiratory distress syndrome on the development of the sleep apnoea profile. Two significant differences were found: infants with respiratory distress syndrome not only had a lower incidence of non-obstructive apnoea and periodic breathing at 40 weeks but also a persistently higher incidence of obstructive and mixed apnoea at 52 and 64 weeks'' conceptual age; the latter finding being related to non-rapid eye movement sleep only. While the lower incidence of both types of apnoea at 40 weeks suggests an advanced maturation of respiratory drive, the persistence of obstructive and mixed apnoea related to non-rapid eye movement sleep may reflect the impact of respiratory distress syndrome on airway structures.     

Current definitions for neonatal apnoea: Are they evidence based?

Apnoea is defined as cessation of breathing with implicit pathophysiology. This review considers definitions of neonatal apnoea currently available and explores the evidence to support their use. For preterm and term infants, apnoea definitions appear arbitrary, are not supported by guidelines and vary from study to study. Although most alarms on infant breathing monitors are set to alert after a respiratory pause >20 s duration is detected, this time period is the equivalent of 17 missed breaths in a preterm infant. Apnoea is likely to be better defined by associated consequence than by pause duration alone in this age group; however, the degree of change in heart rate or oxygen saturation that defines a respiratory pause as pathological is yet to be defined. Further research is required to determine the characteristics that differentiate respiratory events of clinical consequence from normal respiratory variability in term and preterm infants.     

Relation between apnoea duration and type and neurological status of preterm infants.

The incidence, duration, and type of apnoea were determined in 28 preterm infants born at 27 to 34 weeks'' gestation, using polygraphic records of abdominal breathing movements and nasal airflow. Of the 1520 episodes of apnoea of 10 or more seconds duration, 1002 (66%) lasted 10 to 14 seconds, 311 (20%) lasted 15 to 20 seconds, and 207 (14%) lasted more than 20 seconds. Overall, 69% were central in type, 20% were mixed, and 11% were purely obstructive. With increasing duration of apnoea, the proportion of episodes of central apnoea decreased (69 to 29%) while that of mixed apnoea increased (20 to 60%). Eight infants had obstructive apnoea of more than 20 seconds duration. When they were compared with the 10 infants of similar gestational age and birthweight who had central or mixed apnoea, they had a higher incidence of intraventricular haemorrhage, hydrocephalus, positive pressure ventilation via an endotracheal tube, and abnormal neurological development during the first year of life.     

Breathing patterns of preterm infants during bottle feeding: role of milk flow

Milk flow achieved during feeding may contribute to the ventilatory depression observed during nipple feeding. One of the important determinants of milk flow is the size of the feeding hole. In the first phase of the study, investigators compared the breathing patterns of 10 preterm infants during bottle feeding with two types of commercially available (Enfamil) single-hole nipples: one type designed for term infants and the other for preterm infants. Reductions in ventilation, tidal volume, and breathing frequency, compared with prefeeding control values, were observed with both nipple types during continuous and intermittent sucking phases; no significant differences were observed for any of the variables. Unlike the commercially available, mechanically drilled nipples, laser-cut nipple units showed a markedly lower coefficient of variation in milk flow. In the second phase of the study, two sizes of laser-cut nipple units, low and high flow, were used to feed nine preterm infants. Significantly lower sucking pressures were observed with high-flow nipples as compared with low-flow nipples. Decreases in minute ventilation and breathing frequency were also significantly greater with high-flow nipples. These results suggest that milk flow contributes to the observed reduction in ventilation during nipple feeding and that preterm infants have limited ability to self-regulate milk flow.     

Preterm birth contributes to increased vascular resistance and higher blood pressure in adolescent girls

Preterm birth might induce permanent changes in vascular structure and function as well as in blood pressure. To elucidate this hypothesis and underlying mechanisms in girls born before term, the authors correlated neonatal data, including estradiol levels, with vascular function and structure and with blood pressure after puberty. In a case-control study design, 34 girls born before term and 32 gender- and age-matched control infants born at term were included. Pulse wave analysis was used to determine aortic pressure profiles and overall arterial compliance. Stiffness of the carotid artery and abdominal aorta was measured with ultrasonography. Pulse wave velocity in the forearm was measured with photoplethysmography. A laser Doppler technique was used to determine skin perfusion before and after transdermal delivery of acetylcholine, an endothelium-dependent vasodilator. It was found that preterm girls had significantly higher brachial and aortic blood pressure, a narrower but less stiff abdominal aorta, and lower peripheral skin blood flow than did control infants. Augmentation index, carotid stiffness, pulse wave velocity, endothelium-dependent vasodilatation, and heart rate were similar in the two groups. In the preterm group, blood pressure and vascular functions showed no association with intrauterine growth retardation or neonatal estradiol levels. In conclusion, preterm girls have higher blood pressure and an increased resistance in the vascular tree after puberty. These findings may have implications for future cardiovascular risk in the growing adult population surviving preterm birth.     

Ventilatory control and carbon dioxide response in preterm infants with idiopathic apnea

Idiopathic apnea in preterm infants, more than 30 weeks of gestation, after the first week of life is uncommon and poorly understood. To study ventilatory control in these infants we measured minute ventilation, respiratory frequency, tidal volume, end-tidal oxygen pressure and carbon dioxide pressure, and transcutaneous oxygen pressure before and during the fifth minute of breathing 4% carbon dioxide in air. Nine healthy preterm infants and eight infants with three or more episodes of apnea (greater than or equal to 20 s) in 24 hours were studied during active sleep. We found that infants with apnea had a significantly increased alveolar carbon dioxide pressure while respiratory frequency, minute ventilation, and slope were significantly decreased. Alveolar-transcutaneous oxygen gradients were essentially unchanged. These preterm infants with apnea have a decreased carbon dioxide sensitivity. They have a decreased minute ventilation primarily as a result of decreased respiratory frequency and their alveolar-transcutaneous oxygen gradient is normal. Our findings suggest that the major deficit in these infants is a central disturbance in the regulation of breathing.     

Non-invasive ventilation of the preterm infant

Non-invasive ventilation (NIV) is increasingly being used in preterm infants with the purpose of reducing the risk of adverse pulmonary outcome associated with invasive mechanical ventilation. This review analyzes the evidence from physiologic and clinical studies on the use of NIV in the preterm infant. Physiologic data indicate advantages of NIV with regard to ventilation, gas exchange, breathing effort and thoraco-abdominal distortion. Data from clinical trials have consistently shown facilitation of weaning from mechanical ventilation and potential benefits in infants with RDS and apnoea. Long term improvements in respiratory outcome have also been reported but need to be confirmed in larger trials.     

Blood pressure or blood flow: Which is important in the preterm infant? A case report of twins

There is a poor association between systemic blood flow and blood pressure in preterm infants in the first days of life. Very preterm babies can have early low systemic blood flow with poor myocardial contractility but normal blood pressure. Superior vena cava flow measured by echocardiography can be used to determine systemic blood flow. Low superior vena cava flow is a risk factor for mortality and morbidity in preterm infants. We report the case of preterm twins with contrasting relationships among systemic blood flow, myocardial contractility and blood pressure. The first twin with normal blood pressure, but low superior vena cava flow and poor myocardial contractility in the first hours of life developed a severe intraventricular haemorrhage and died, despite cardiovascular support. The second twin with low blood pressure but normal superior vena cava flow did not develop adverse outcomes in the first days of life. These cases underline the usefulness of neonatal functional echocardiography in early understanding and management of the preterm infant, and the inaccuracy of other clinical parameters used to assess cardiovascular function.     

Cardiovascular effects of carbon dioxide in ventilated preterm infants

Sick preterm infants may, under certain conditions, demonstrate blood pressure passive cerebral blood flow in response to changes in arterial carbon dioxide tension. Blood pressure in turn depends on cardiac output and peripheral resistance. A Doppler technique for assessing cardiac output compared favourably in terms of reproducibility to a thermodilution technique in a group of infants undergoing cardiac catheterization for congenital heart disease. Doppler was subsequently used to monitor changes in cardiac output following an increase in arterial carbon dioxide tension of 1 kPa in 25 ventilated preterm infants. Blood pressure increased significantly (p = 0.006). However, heart rate did not change significantly (p = 0.16) and, in addition, both stroke and minute volume decreased (p = 0.023, p = 0.02, respectively). This suggests that accompanying changes in components of peripheral resistance exert important effects on blood pressure in the preterm neonate in response to changes in arterial carbon dioxide tension.     

Autonomic reflexes in preterm infants

Some autonomic nervous reflexes often tested in adult medicine have been studied in 21 preterm infants (25-37 gestational weeks). The aim was to develop such tests for preterm infants and see if there were any differences in babies with recurrent apnea and bradycardia and babies who had been exposed to sympathicolytic drugs before birth. To test sympathetic nervous activity the peripheral vascular resistance was measured before and during 45 degrees of head-up tilting. To test parasympathetic nervous activity the degree of bradycardia was measured in response to cold face test (application of an ice-cube on the fore-head) and laryngeal stimulation with saline. Finally the heart rate changes after a sudden noise (85 dB) were studied as an indicator of both sympathetic and vagal activity. The peripheral resistance was found to be relatively low in these preterm infants, particularly in some infants tested at the postnatal age of about two months. Heart rate and mean blood pressure did not change during tilting, while the peripheral resistance increased significantly mainly due to lowered limb blood flow. The median decrease of the heart rate during the cold face test was 20.0% and during laryngeal receptor stimulation 23.7%. The sudden noise usually caused a biphasic heart rate response. An autonomic nervous reflex score was calculated and found to be negative (parasympathetic) in infants with recurrent prolonged apnea and bradycardia and positive in infants with clinical signs of increased sympathetic nervous activity.     

Circulatory effects of ventilator rate and end-expiratory pressure in unparalysed preterm infants

Impairment of cerebrovascular autoregulation may be important in the pathogenesis of ischaemic brain injury in preterm infants. A previous study in ventilated preterm infants paralysed with pancuronium showed that changes in cerebral blood flow velocity (CBFV) were related to concomitant changes in arterial blood pressure. In a similar study in unparalysed infants, changes in CBFV in response to changes in ventilator rate or end-expiratory pressure were independent of associated changes in the arterial blood pressure. These results emphasize the importance of avoiding large swings in blood pressure in paralysed infants. Whether alternative paralysing agents have similar effects warrants further study.     

Maturation of peripheral arterial chemoreceptors in relation to neonatal apnoea.

Apnoea and periodic breathing are the hallmarks of breathing for the infant who is born prematurely. Sustained respiration is obtained through modulation of respiratory-related neurons with inputs from the periphery. The peripheral arterial chemoreceptors, uniquely and reflexly change ventilation in response to changes in oxygen tension. The chemoreflex in response to hypoxia is hyperventilation, bradycardia and vasoconstriction. The fast response time of the peripheral arterial chemoreceptors to changes in oxygen and carbon dioxide tension increases the risk of more periodicity in the breathing pattern. As a result of baseline hypoxaemia, peripheral arterial chemoreceptors contribute more to baseline breathing in premature than in term infants. While premature infants may have an augmented chemoreflex, infants who develop bronchopulmonary dysplasia have a blunted chemoreflex at term gestation. The development of chemosensitivity of the peripheral arterial chemoreceptors and environmental factors that might cause maldevelopment of chemosensitivity with continued maturation are reviewed in an attempt to help explain the physiology of apnoea of prematurity and the increased incidence of sudden infant death syndrome (SIDS) in infants born prematurely and those who are exposed to tobacco smoke.     

RELATIONSHIP BETWEEN APNOEA AND BRADYCARDIA IN PRETERM INFANTS

Abstract. Vyas, H., Milner, A. D. and Hopkin. I. E. (Department of Child Health, Department of Neonatal Medicine and Surgery, City Hospital, Nottingham, England). Relationship between apnoea and bradycardia in preterm infants. Acta Paediatr Scand, 70: 785, 1981.-Nine studies were carried out on seven babies who were having repeated episodes of bradycardias without any clinically obvious apnoea. Their mean gestational age was 31.7 weeks (range 29 to 36 weeks) and the mean birth weight was 1.56 kg (range 1.08 kg to 2.16 kg). Investigations were carried out in a total body plethysmograph. Face mask with a pneumotachograph attached to it measured flow. Tidal volume was obtained by integrating these signals. An oesophageal balloon measured intrathoracic pressure changes and the heart rate was measured from ECG chest electrodes. A total of 172 episodes of apnoea were observed. In 50 % of these apnoeas, the airway was closed as determined by the absence of cardiac artefact on the flow signals. Apnoea was associated with bradycardia in just over 25 % of all apnoea. It tended to occur early (11 to 14 sec). Whether the apnoea was central or obstructive had no effect on the pattern provided the baby did not make any inspiratory efforts. Inspiration against a closed airway produced bradycardia in over 50 % of obstructive apnoea, the heart rate falling precipitously within 1 to 2 sec. These findings indicate that often bradycardias occur too early-in apnoea to be due to central hypoxia and must be due to a peripheral mechanism.     

Upper airways obstruction and apnoea in preterm babies.

Measurements of tidal flow, volume, and oesophageal pressure were recorded on a group of 8 severely preterm infants with periodic respiration. Analysis of the flow trace for evidence of cardiac artefact, and the tidal volume trace to identify at what point of the tidal cycle apnoea starts, indicated that upper airways obstruction was associated with about half these attacks. It is surmised that this is produced by glottic closure.     

Clinical signs and CRP values associated with blood culture results in neonates evaluated for suspected sepsis

Aim: To identify which clinical signs at presentation are most predictive of sepsis subsequently confirmed by blood culture and to investigate whether the predictive power of the clinical signs varies by gestational age. Methods: Among 401 newborn infants <28 days of age with suspected sepsis, nine signs of sepsis and C‐reactive protein (CRP) values were prospectively recorded. Logistic regression assessed the association of these signs and laboratory values with a subsequently confirmed diagnosis of sepsis by positive blood culture. The analysis was stratified by gestational age with mutual simultaneous adjustment for the signs and sex. Results: Five of the nine clinical signs (feeding intolerance, distended abdomen, blood pressure, bradycardia and apnoea), along with CRP were statistically significantly associated with a positive blood culture. After simultaneous adjustment for all of the signs, apnoea, hypotension and CRP were independently predictive of positive blood culture. When the material was stratified by gestational age, differences in the association with positive blood culture were found for bradycardia, tachypnea and irritability/seizures. Conclusion: In this selected population of infants with suspected sepsis, apnoea and hypotension are independently predictive of a confirmed diagnosis, while bradycardia is more predictive among preterm infants and tachypnea among term infants.     

Effect of blood transfusion on apnoea, bradycardia and hypoxaemia in preterm infants

We studied the effect of blood transfusion on the frequency of apnoea, bradycardia and hypoxaemia in 21 spontaneously breathing preterm infants with a median gestational age at birth of 28 (range 23–31) weeks. Age at time of study was 22 days (3–84), weight 925 g (640–2120). The patients exhibited frequent episodes of bradycardia and/or hypoxaemia and were anaemic (median haemoglobin level 109 (82–120) g/l). One infant received two transfusions and was thus studied twice. Four-hour recordings of pulse oximeter saturation (SpO₂), pulse waveforms, transcutaneous oxygen pressure, electrocardiogram, breathing movements and nasal airflow were performed immediately before and after transfusion, and again after a further interval of 12 h. Recordings were analysed for isolated and periodic apnoeas (> 4 s), bradycardias (heart rate < 2/3 of baseline), and episodic desaturation (SpO₂≤ 80%). There were no significant changes in the frequency, severity and/or duration of apnoea, bradycardia or desaturation following transfusion. The average SpO₂ nadir reached during each desaturation, however, increased by 3% following transfusion (P < 0.05), and there was a trend towards shorter desaturations. Conclusion The occurrence of frequent episodes of apnoea, bradycardia and/or hypoxaemia does not, on its own, justify a blood transfusion in moderately anaemic preterm infants. Received: 25 July 1996 / Accepted: 24 September 1996     

Autonomic Reflexes in Preterm Infants

ABSTRACT. Some autonomic nervous reflexes often tested in adult medicine have been studied in 21 preterm infants (25-37 gestational weeks). The aim was to develop such tests for preterm infants and see if there were any differences in babies with recurrent apnea and bradycardia and babies who had been exposed to sympathicolytic drugs before birth. To test sympathetic nervous activity the peripheral vascular resistance was measured before and during 45° of head-up tilting. To test parasympathetic nervous activity the degree of bradycardia was measured in response to cold face test (application of an ice-cube on the fore-head) and laryngeal stimulation with saline. Finally the heart rate changes after a sudden noise (85 dB) were studied as an indicator of both sympathetic and vagal activity. The peripheral resistance was found to be relatively low in these preterm infants, particularly in some infants tested at the postnatal age of about two months. Heart rate and mean blood pressure did not change during tilting, while the peripheral resistance increased significantly mainly due to lowered limb blood flow. The median decrease of the heart rate during the cold face test was 20.0% and during laryngcal receptor stimulation 23.7%. The sudden noise usually caused a biphasic heart rate response. An autonomic nervous reflex score was calculated and found to be negative (parasympathetic) in infants with recurrent prolonged apnea and bradycardia and positive in infants with clinical signs of increased sympathetic nervous activity.