Sleep apnea in infants and the risk of SIDS

The examination of the respiratory function in 184 sleeping infants gave evidence of a significant difference in several parameters between the so-called SIDS risk group and the control group. The risk group (97 babies) consists of 60 infants with frequent prolonged apneas, 30 infants with postnarcotic apneas and 7 near miss infants. Polygraphic registration during sleep showed significantly more apneas in the risk group. These apneas often appeared more frequently during certain periods. The average respiratory deficit expressed as the MA-value (MA = average apnea duration) in the risk group was significantly higher than in control infants. Besides that we were able to prove a more frequent pathological gastroesophageal reflux in the risk infants than in control infants.     

The role of gastro-oesophageal reflux in the aetiology of SIDS

Gastro-oesophageal reflux (GOR) has been identified as a possible cause of SIDS. Several features of GOR unique to infants presenting with apparent life-threatening events (ALTEs) have led to its 'pathogenic' definition. One is that the life-threatening apnoea itself is initiated by GOR, another is that the ALTE relates to prolonged reflux during sleep, in a vulnerable sleep-state, and finally that the ALTE relates to excessive quantities of GOR. The presumption of GOR 'pathology' as a cause of SIDS however, is questionable in these susceptible infants for three reasons: firstly, GOR is physiological and occurs in most infants; secondly, there is no general consensus on what constitutes normal physiological reflux, and thirdly, variation in the recording technique and methods of data analysis and interpretation may account for the differences between study groups. It seems likely therefore if GOR is implicated in SIDS, additional factors are involved. Under certain circumstances, physiological GOR may trigger life-threatening apnoea in apparently healthy infants, that leads to SIDS. One mechanism that could explain such a death is reflex apnoea by stimulation of laryngeal chemoreceptors (LCR) during sleep. The conditions under which this could be fatal are the occurrence of gastric contents refluxed to the level of the pharynx during sleep, in the young infant who has depressed swallowing and arousal. That is, the occurrence of GOR to the level of the pharynx during sleep, an infrequent event that is usually innocuous, could be converted to a fatal event if swallowing is impaired and arousal depressed, by a variety of mediating factors such as prone sleeping, prematurity, sedatives, seizures or upper respiratory tract infections. The identification of LCR responses, particularly in prone sleeping and premature infants provide further evidence that this mechanism may be implicated in the aetiology of SIDS in apparently healthy infants.     

Gastric emptying and gastro-oesophageal reflux in preterm infants.

Gastro-oesophageal reflux is common in preterm infants, but the role of gastric emptying as a causal factor has not been studied before. Gastric emptying was therefore measured in 19 healthy preterm infants (median gestational age 32 weeks) while concurrently measuring 24 hour lower oesophageal pH, using an antimony pH electrode, positioned manometrically. Real time ultrasonic images of the gastric antrum were obtained, and measurements of antral cross-sectional area (ACSA) were made immediately before a nasogastric feed and then during subsequent gastric emptying until ACSA returned to its pre-feed value. Half emptying time (50% delta ACSA) was calculated as the time taken for the ACSA to fall to half the maximal postprandial increment. Mean (SEM) reflux index for the group was 11.9 (2.0)%; number of reflux episodes per 24 hours: 15.4 (1.7); and number of reflux episodes longer than five minutes 5.5 (0.8). Average half emptying times for an individual infant were: median (range) 46 (18-105) minutes. There was no association between gastric emptying rates and any of the indices of gastro-oesophageal reflux, either during the entire 24 hour period for which the lower oesophageal pH was recorded, or in the postprandial periods after the feeds which were studied ultrasonically. Gastro-oesophageal reflux was also unrelated to feed volume and feed type. Asymptomatic gastro-oesophageal reflux is common in preterm infants, but gastric emptying time is not a determinant of it. Inappropriate relaxation of the lower oesophageal sphincter or abnormal oesophageal motility offer more plausible explanations.     

Fundoplication in preterm infants with gastro-oesophageal reflux

Gastro-oesophageal reflux in preterm infants may result in recurrent pulmonary insult due to aspiration of gastric contents, and intractable obstructive apnoea. Fundoplication is effective in controlling reflux when medical management has failed. Our experience between 1981 and 1990 was reviewed to assess the efficacy of early surgery in the management of 11 such infants. The infants had a median gestational age of 29 weeks and a median birthweight of 1032 g. Nine infants had fundoplication for recurrent aspiration pneumonitis and two for intractable apnoea. The median age at the time of surgery was 100 days and the median weight of the infants was 2640 g. Nine infants were oxygen dependent and two were still ventilated at the time of surgery. The operative procedure was well tolerated by 10 of the 11 infants. Surgery failed to control reflux in two infants, although good control was obtained in the one who had subsequent surgery. Three infants required prolonged ventilation postoperatively; two of them died later from pulmonary failure. The median time to discharge was 24 days (8-113 days). All infants with intractable apnoea were cured by surgery. Fundoplication is an effective method of management when used early in the treatment of chronic gastro-oesophageal reflux in preterm infants. There is minimal morbidity from the surgical procedure.     

Developmental maturation of gastro-oesophageal reflux in preterm infants

The frequency and duration of gastro-oesophageal reflux were examined in 40 preterm infants and compared with a previously published healthy cohort of 74 term infants. Selection required that the infants were born between 24 and 32 weeks' gestation, had a normal head ultrasound and were studied at term post-menstrual age. Multi-channel pen recordings of sleep state, movement, breathing and acid reflux were made. In term and preterm infants the frequency and duration of reflux were greatest in active sleep, rare in quiet sleep and significantly less in preterm than term infants in wakefulness and active sleep ( p <0.05). The fewer and shorter episodes in preterm infants could not be explained by sleep state, movement, gestational or postnatal age, days intubated, days on oxygen or the lowest pH of reflux episodes.     

The diagnosis and management of gastro-oesophageal reflux in infants

Gastro-oesophageal reflux (GOR) and gastro-oesophageal reflux disease (GORD) occur frequently during the first months of life. Gastro-oesophageal reflux may be a primary gastro-intestinal motility disorder, but it may also be secondary to other conditions such as cow's milk protein allergy. Objective diagnosis can be difficult because there may be absence of correlation between history, results of pH monitoring and histology. Severe GORD may cause minor symptoms, and minor GOR may cause severe symptoms. Several different therapeutic interventions exist. Simply stated, thickened formula reduces regurgitation and alginates and proton pump inhibitors can be used to decrease acid GOR, depending on the severity of the GORD. Efficacy data of prokinetic drugs are either lacking or disappointing. Regarding side-effects, interest has been focused on cisapride, although other molecules have similar effects. Long-term side-effects such as the nutritional consequence of therapeutic management have been insufficiently studied, especially for the acid-reducing molecules.     

Prone and left lateral positioning reduce gastro-oesophageal reflux in preterm infants.

AIM: To examine the effect of body position on clinically significant gastro-oesophageal reflux (GOR) in preterm infants. METHODS: Eighteen preterm infants with clinically significant GOR were studied prospectively using 24 hour lower oesophageal pH monitoring. Infants were nursed in three positions (prone, left, and right lateral) for 8 hours in each position, with the order randomly assigned. Data were analysed using analysis of covariance. RESULTS: The median (range) reflux index (RI) for the group was 13.8% (5.8-40. 4). There was no significant difference in the mean time spent in each position. RI (mean % (SEM)) was significantly less in prone (6. 3 (1.7)) and left lateral positions (11.0 (2.2)), when compared with the right lateral position (29.4 (3.2)); p<0.001. The mean (SEM) longest episodes (mins) of GOR were reduced by prone and left positions (8.6 (2.2) and 10.0 (2.4), respectively) compared with the right position (26.0 (3.9)); p<0.001. The mean (SE) number of episodes was reduced by prone (15.4 (2.8)) and left (24.6 (3.5)) positions when compared with right (41.6 (4.6)) (p<0.001). CONCLUSIONS: Prone and left lateral positions significantly reduce the severity of GOR, by reducing the number of episodes and the duration of the longest episodes. Such positioning offers a useful adjunct to the treatment in hospital of preterm infants with gastro-oesophageal reflux.     

Postural drainage and gastro-oesophageal reflux in infants with cystic fibrosis

Gastro-oesophageal reflux is increased in cystic fibrosis and it is possible that postural drainage techniques may exacerbate reflux, potentially resulting in aspiration and further impairment of pulmonary function. AIM: To evaluate the effects of physiotherapy with head down tilt (standard physiotherapy, SPT) on gastroesophageal reflux and to compare this with physiotherapy without head down tilt (modified physiotherapy, MPT). METHOD: Twenty (mean age 2.1 months) infants with cystic fibrosis underwent 30 hour oesophageal pH monitoring during which SPT and MPT were carried out for two sessions each on consecutive days. RESULTS: The number of reflux episodes per hour, but not their duration, was significantly increased during SPT compared with MPT (SPT 2.5 (0.4) v MPT 1.6 (0.3), p = 0.007) and to background (1.1 (0.)1, p = 0.0005). Fractional reflux time was also increased during SPT (11.7 (2.6)%) compared with background (6.9 (1.3)%) p = 0.03) but not compared with MPT (10.7 (2.7)%). There was no significant difference between MPT and background for number of reflux episodes, their duration, or fractional reflux time. CONCLUSIONS: SPT, but not MPT, was associated with a significant increase in gastro-oesophageal reflux in infants with cystic fibrosis.     

Vomiting and gastro-oesophageal reflux.

During radionuclide scans in 82 infants and children gastro-oesophageal reflux extending to the upper oesophageal/laryngeal level was detected in 636 one minute frames. Only 61 (9.6%) of these frames were associated with vomiting, defined as the appearance of milk at the mouth. Thus the absence of vomiting does not preclude appreciable gastro-oesophageal reflux.     

Management of gastro-oesophageal reflux.

Parental reassurance and thickened feeds are the only requirements in the management of infants with reflux when this is the sole detectable gastro-oesophageal abnormality. In view of the strong propensity for spontaneous clinical resolution and the excellent results achieved by conservative management, infants with reflux due to a partial thoracic stomach (hiatal hernia) uncomplicated by a stricture should be treated in the first instance by postural therapy, with or without thickened feeds and supplements of antacids, domperidone, and cimetidine. Those showing no response after an adequate period of conservative treatment should have an antireflux operation. The Belsey MK IV type of fundoplication is preferred. Only an exceptional patient will require to be treated surgically before 12 months of age. The same surgical antireflux procedure, combined with oesophageal dilatations as necessary, is the treatment of choice for patients with a partial thoracic stomach complicated by a reflux oesophageal stricture. A similar treatment regimen should be followed for patients with reflux after repair of an oesophageal atresia. Surgical correction is mandatory for all infants with reflux due to a large combined hiatal hernia.     

Acid oro-pharyngeal secretions can predict gastro-oesophageal reflux in preterm infants

Acid gastro-oesophageal reflux (GOR) is common in preterm infants but there is a lack of a non-invasive technique to establish the diagnosis. The aim of this study was to identify whether the presence of acid in oro-pharyngeal secretions (OPS) was a valid indicator of clinically significant acid GOR in preterm infants. A total of 23 infants with suspected GOR were studied with 24 h lower-oesophageal pH monitoring and during this period the OPS were tested for acid with litmus paper at 6 hourly intervals. Median (range) gestation was 28 weeks (24–31), birth weight 1023 g (480–1750) and age at study 34 days (11–76). Significant GOR was defined as a reflux index >5%. Of the investigated infants, 18 subjects (78%) had significant GOR. Of this group, 16 infants had acid in the OPS on at least one occasion. Five infants did not demonstrate significant GOR and in four of these acid was not detected in the OPS. Our data indicate that as a predictor for significant GOR, litmus-testing OPS for acid has a sensitivity of 89%, specificity of 80%, positive predictive value of 94% and a negative predictive value of 67%. The difference in the incidence of acid OPS between the GOR and the No GOR group was significant (P < 0.03). Conclusion The presence of acid in the oropharyngeal secretions may help in the prediction of acid gastro-oesophageal reflux in preterm infants. The method is simple, inexpensive cheap and involves minimal disturbance. We suggest that it could aid clinical diagnosis and indicate a need for further investigation of gastro-oesophageal reflux. Received: 30 June 1998 / Accepted in revised form: 18 November 1998     

Chest physiotherapy, gastro-oesophageal reflux, and arousal in infants with cystic fibrosis.

BACKGROUND: Postural drainage chest physiotherapy in infants with cystic fibrosis (CF) exacerbates gastro-oesophageal reflux (GOR) and may contribute to a more rapid deterioration in lung function. AIMS: To compare standard postural drainage chest physiotherapy (SPT) and a modified physiotherapy regimen (MPT) without head-down tilt, with regard to GOR, arousal state, and cardiorespiratory function. METHODS: Twenty infants with CF underwent 30 hour oesophageal pH monitoring, during which four chest physiotherapy sessions were administered (day 1: MPT-SPT; day 2: SPT-MPT). Arousal state, heart rate, and oxygen saturation were documented for each of the physiotherapy positions (supine, prone, right lateral, and left lateral with (SPT) or without (MPT) 30 degrees head-down tilt). RESULTS: Significantly more reflux episodes occurred during SPT than during MPT, but there were no significant differences in median episode duration or fractional reflux time. During SPT, left lateral positioning was associated with fewer reflux episodes compared to other positions. During supine and prone positioning, more reflux episodes occurred during SPT than during MPT. Infants were significantly more likely to be awake or cry during SPT. There was a significant association between crying and reflux episodes for SPT. Non-nutritive sucking was associated with a significant reduction in reflux episodes during SPT. Oxygen saturation during SPT was significantly lower during crying and other waking, and non-nutritive sucking during SPT was associated with a significant increase in oxygen saturation. CONCLUSIONS: SPT is associated with GOR, distressed behaviour, and lower oxygen saturation.     

Clinical predictors of pathological gastro-oesophageal reflux in infants with persistent distress

BACKGROUND: Gastro-oesophageal reflux (GOR) is common in infants with persistent crying. Empirical treatment with antireflux medications is common practice, although on clinical grounds it may be difficult to determine whether GOR is abnormal. AIMS: To examine the diagnostic accuracy of clinical predictors of pathological GOR in infants with persistent crying. METHODS: One hundred and fifty-one infants (82 male; median age 2.5 months, range 0.5-8.2 months) with persistent crying were prospectively studied. Crying and fussing were charted for 24 h, and parents completed a validated questionnaire on reflux symptoms. All infants underwent oesophageal 24-h pH monitoring. RESULTS: Twenty-seven (17.9%) infants had pathological GOR with a fractional reflux time (FRT) >10%. There was no significant association between total crying duration per 24 and FRT (P = 0.84) or the number of reflux episodes (P = 0.68). Pathological GOR was more common in infants under 3 months, compared to older infants (P = 0.04). Feeding difficulties were significantly associated with pathological GOR (P = 0.02). Backarching was not increased in infants with GOR (P = 0.30). Pathological GOR was significantly associated with the frequency of regurgitation (P = 0.04), but not with vomitus volume (P = 0.62). Regurgitation more than 5 times daily was the most specific reflux symptom (specificity 70.9%), but was a poor predictor of pathological GOR (positive predictive value 22.2%). In the absence of frequent regurgitation or feeding difficulties, pathological GOR was unlikely (negative predictive value 87-90%). CONCLUSIONS: Investigation and treatment of GOR in infants with persistent crying should be primarily directed at infants presenting with frequent regurgitation or feeding difficulties.     

Observations on gastro-oesophageal reflux,central apnoea and heart rate in infants

Respiratory movements and heart rate were monitored continuously during the course of 2 h radionuclide studies to detect gastro-oesophageal reflux (GOR) in 22 infants following a milk feed. Twenty infants had GOR, to upper oesophageal/pharyngeal level in 19, and 17 had central apnoea between 3 and 15s. Prolonged central apnoea (greater than 20s) was not observed. Bradycardia, defined as a heart rate less than 80 beats/min for 10s or more, was observed in only 1 infant who did not have GOR. No correlation was found between the number or duration of reflux episodes and the frequency of respiratory pauses between 3 and 17s. When data from individual infants were examined a possible temporal relation between the occurrence of GOR and central apnoea was seen in only two infants; in each case, detailed examination suggested that apnoea was more closely associated with sleep than with GOR. Although the respiratory monitoring system did not include airflow sensors, the almost complete absence of bradycardia suggested that prolonged obstructive apnoeas did not occur. We conclude that any relation between GOR and central apnoeas less than 15 s is not of a direct cause/effect nature.     

Postural drainage and gastro-oesophageal reflux in infants with cystic fibrosis

Accepted 8 November 1996
Gastro-oesophageal reflux is increased in cystic fibrosis and it is possible that postural drainage techniques may exacerbate reflux, potentially resulting in aspiration and further impairment of pulmonary function.
AIM—To evaluate the effects of physiotherapy with head down tilt (standard physiotherapy, SPT) on gastro-oesophageal reflux and to compare this with physiotherapy without head down tilt (modified physiotherapy, MPT).
METHOD—Twenty (mean age 2.1 months) infants with cystic fibrosis underwent 30 hour oesophageal pH monitoring during which SPT and MPT were carried out for two sessions each on consecutive days.
RESULTS—The number of reflux episodes per hour, but not their duration, was significantly increased during SPT compared with MPT (SPT 2.5 (0.4) v MPT 1.6 (0.3), p = 0.007) and to background (1.1 (0.)1, p = 0.0005). Fractional reflux time was also increased during SPT (11.7 (2.6)%) compared with background (6.9 (1.3)%, p = 0.03) but not compared with MPT (10.7 (2.7)%). There was no significant difference between MPT and background for number of reflux episodes, their duration, or fractional reflux time.
CONCLUSION—SPT, but not MPT, was associated with a significant increase in gastro-oesophageal reflux in infants with cystic fibrosis.