Gastro-oesophageal Reflux In Preterm Infants Research Articles

Lack of efficacy of a starch-thickened preterm formula on gastro-oesophageal reflux in preterm infants: a pilot study

Background: Gastro-oesophageal reflux (GOR) is common in preterm infants; conservative interventions (i.e. dietary changes) should represent the first-line approach. Aim: To evaluate by combined pH and impedance monitoring (pH-MII) the effect of a new preterm formula thickened with amylopectin (TPF) on GOR features in symptomatic preterm infants. Methods: Twenty-eight symptomatic preterm newborns underwent a 24-hour pH-MII; each baby received eight meals (four of TPF and four of a preterm formula [PF]). GOR indexes (number, acidity, duration and height of GORs) after TPF and PF meals were compared by Wilcoxon Signed Ranks Test. Viscosity of PF and TPF was measured. Results: TPF significantly decreased the number of acid GORs detected by pH-monitoring (TPF vs. PF: median 20 vs. 24.5, p = 0.009), while it had no influence on Reflux Index (RIpH), nor on acid and non-acid GOR indexes detected by MII, GOR physical features, and GOR height. TPF’s viscosity was extremely higher than PF’s, and further increased at pH 3 after the addition of pepsin. Conclusions: The new formula was found to reduce the number of acid GORs detected by pH-monitoring; it did not reduce neither total oesophageal acid exposure nor non-acid GORs. At present its extended clinical use cannot be recommended.

Sodium Alginate (Gaviscon®) does not reduce apnoeas related to gastro-oesophageal reflux in preterm infants

BackgroundApnoea of prematurity (AOP) frequently recurs in preterm infants. We have previously shown that a significant but variable proportion of AOP is induced by gastro-oesophageal reflux (GOR). AimThe aim of this study is to evaluate the efficacy of sodium alginate in reducing the frequency of GOR-related AOP. SubjectsTwenty-eight preterm infants with AOP were studied by a six-hour recording of combined multichannel intraluminal impedance and pH monitoring and polysomnography, including two three-hour postprandial periods: sodium alginate was given after one single meal named as drug-given (DG) meal, while the other as drug-free (DF). ResultsDuring 165h of registration, 715 apnoeas were recorded, 368 after-DG and 347 after-DF (p=.99); furthermore, 851 GOR episodes were detected, 315 after-DG and 536 after-DF (p=.001). No differences in the number of AOP were found between DG and DF. A significant reduction in the number of acid GORs and in acid exposure was found during DG, while the administration of sodium alginate didn't influence non-acid GOR indexes. The frequency of GOR-related apnoeas didn't differ between DG and DF. DiscussionSodium alginate doesn't reduce the total number of AOP nor GOR-related apnoeas. On the other hand, it reduces acid GOR features, while it had no effect on non-acid GOR indexes.

The efficacy of sodium alginate (Gaviscon) for the treatment of gastro-oesophageal reflux in preterm infants

Gastro-oesophageal reflux is common in preterm newborns; at present, no studies have evaluated the efficacy of sodium alginate in this population. To evaluate the effect of sodium alginate on gastro-oesophageal reflux features in preterm newborns by combined pH and impedance monitoring (pH-MII). Thirty-two symptomatic preterm newborns underwent a 24 h pH-MII, during which each baby was fed eight times. Sodium alginate was given four times at alternate meals [drug-given (DG) vs. drug-free (DF) meals]. Gastro-oesophageal reflux features (i.e. number, acidity, duration and height of gastro-oesophageal reflux) after DG and DF meals were compared by Wilcoxon signed ranks test. Sodium alginate significantly decreased the number of acid gastro-oesophageal reflux detected either by pH monitoring (DG vs. DF: median 17.00 vs. 29.00, P = 0.002) and MII (DG vs. DF: 4.0 vs. 6.00, P = 0.050), and also acid oesophageal exposure (DG vs. DF: 4.0% vs. 7.6%, P = 0.030), without any influence on non-acid gastro-oesophageal reflux. Furthermore, it decreased the number of gastro-oesophageal reflux reaching proximal oesophagus (DG vs. DF: 5.50 vs. 7.50, P = 0.030). The use of sodium alginate in preterm infants seems to be promising, because this drug decreases gastro-oesophageal reflux acidity and height with the advantage of a nonsystemic way of action and a more favourable safety profile over H2 blockers and PPIs.

PA26 NO EFFECT OF SODIUM ALGINATE (GAVISCON®) ON APNOEA OF PREMATURITY INDUCED BY GASTRO-OESOPHAGEAL REFLUX

Background and aims: Apnoea of prematurity (AOP) is one of the most common and frequently recurring problem in preterm infants and its relationship with gastro-oesophageal reflux (GOR) is widely debated in literature. Our previous study highlights an increase of AOP in periods after GOR. The aim of this study is to evaluate the efficacy of sodium alginate (Gaviscon®) in reducing frequency of AOP related to GOR in preterm infants by a simultaneous and synchronized pH-Intraluminal Impedance Monitoring (pH-MII) and polysomnography in preterm infants. Materials and methods: Twenty-eight preterm infants (gestational age < 33 weeks; mean birth weight 1100 gr) were studied as they had recurrent apneas. Patients who were taking drugs influencing gastrointestinal motility or gastric acidity and infants with malformations, major gastrointestinal problems or sepsis were ruled out. They underwent a six-hour simultaneous and synchronized recording of polysomnography and pH-impedance monitoring (pH-MII). Polysomnography detects apneas by recording of breathing movement, nasal airflow, electrocardiogram and pulse oximeter saturation. To avoid possible artefacts a portable camera video registered the infants during all the recording. We considered as apnoeas each oral/nasal flow cessation lasting at least 5 seconds. Apnoeas were then classified as central (CA), obstructive (OA) and mixed (MA) depending on absence or presence of obstructed respiratory efforts. pH-MII is the state-of-the-art methodology for GOR detection in preterm newborns. By pH-MII monitoring we registered both acid and non acid GORs. A standard period of 30 seconds after the onset of GOR episodes was chosen in order to test the temporal relation between GOR and apnoea. Apnoeas detected within 30 seconds after the onset of a GOR episode were defined GOR-induced. Layouts involved 2 post-prandial periods lasting 3 hours each one, characterized by presence or absence of treatment with Gaviscon® (2cc/kg) after meal. The period after Gaviscon administration was called GAV, the other No-GAV. The meal after which Gaviscon® was administered was randomly assigned in order to avoid any possible carry-over effects. During the analysis of layouts the investigator was blind to the administration of Gaviscon. pH-MII and polysomnography data were independently analyzed by two different investigators and then compared. Data obtained during these two periods were finally compared. Results: Seven-hundred-fifteen apnoeas were recorded during 165 hours of registration and then divided according to the administration of Gaviscon®. Comparing data found after the treatment with those registered during freetreatment periods, we found no differences in number of total apnoeas (AOP during GAV vs NO-GAVwas 12.4±9.5 vs 13.1±12.0 apnoeas/period, p=0.99) and related events (see Table 1).

Combined oesophageal impedance‐pH monitoring in preterm newborn: comparison of two options for layout analysis

Gastro-oesophageal reflux (GOR) is common in preterm infants. Combined multichannel intraluminal impedance and pH monitoring (pH-MII) is emerging as an useful tool to study both acid and non-acid GOR in this population. We aimed to highlight main advantages and limits of pH-MII in preterm infants and to test whether the inclusion of GOR episodes detected only by pH monitoring details better the features of GOR. Fifty-two symptomatic preterm infants underwent a 24-hour, continuous and simultaneous measurement of pH-MII. Each layout was analyzed using two different options: option 1 included GOR episodes detected by MII and then classified as acid or non-acid according to the associated pH change; option 2 included GOR episodes detected by MII and also GOR episodes detected only by pH sensor. By adopting option 1, a total number of 2834 GOR episodes was detected by MII: 2162 of them were characterized as non-acid and 672 were characterized as acid. The median (range) number of acid MII-GOR episodes was 10 (1-52); the median (range) number of non-acid MII-GOR episodes was 36.5 (2-119). Median (range) acid MII-GOR-bolus exposure index was 0.28% (0.02-2.73%); median (range) non-acid MII-GOR-bolus exposure index was 1.03% (0.06-38.15%). By adopting option 2, an average of 53.2 acid GOR episodes and an average of 11% oesophageal exposure to acid GOR more than by option 1 was detected. An accurate and detailed description of GOR in preterm infants can be obtained only by including in the analysis all acid GOR episodes detected by pH sensor.

Diagnosis of Gastro-Oesophageal Reflux in Preterm Infants: Sonography vs. pH-Monitoring

Objectives: To compare the ultrasound examination with pH-metry in order to evaluate the diagnostic accuracy of sonography for diagnosis of gastro-oesophageal reflux (GOR) in preterm infants. Methods: A prospective study was conducted on 31 premature infants <34 weeks with clinically diagnosed GOR. First, they underwent 24-hour pH-monitoring; successively, the sonographic assessment was performed within 12 h after pH-monitoring. The two operators who performed the pH-monitoring and sonography respectively, were unaware of each other’s results. Results: Twenty-one patients (67.7%) had significant GOR with a reflux index >5 (GOR group). The median (range) reflux index in this group was 9.19% (6.04–20.1). Ten newborns (32.3%) did not have significant GOR with a reflux index <5. Sonography was positive for GOR in 8 patients (25.8%); all 8 infants with sonographic diagnosis of GOR had a reflux index >5. Therefore, sonographic diagnosis did not produce false positives. Sonography was negative in 23 newborns (74.2%); 13 of these were positive to pH-monitoring and may therefore be considered as false negatives. Respect to continuous 24-hour pH-monitoring, sonography showed a specificity of 100% but a very low sensitivity of 38% with a positive prediction value of 100% and a negative prediction value of 43%. Conclusions: Sonography should not replace 24-hour pH monitoring for detecting GOR in preterm infants. However, sonography has a very high specificity and a positive predictive value of 100%. When clinicians suspect GOR in preterm infants, it could be useful for selection of cases to refer for pH-metry.

Diagnosis and management of gastro‐oesophageal reflux in preterm infants in neonatal intensive care units

There is relatively little published information regarding gastro-oesophageal reflux (GOR) in preterm infants, therefore the aim of this study was to elucidate the incidence of GOR and management regimes employed for this condition in major neonatal intensive care units (NICUs). A standard questionnaire was sent to consultants in 77 level II (or secondary) and III (or tertiary) NICUs. Seventy-eight percent of consultants responded. Of babies born in these units, 40% were less than 34 wk gestational age and the estimated incidence of GOR in this group was 22%. GOR was diagnosed on a clinical basis alone in 42% of units, 8% used clinical features and/or investigations, and 50% used clinical features plus investigations and/or therapeutic trials. Intra-oesophageal pH monitoring was available in 93% of units but used regularly in only 32% of suspected cases. Common treatment strategies for diagnosed GOR included non-drug options--body positioning (98%) and placement on a slope (96%); and drugs--H2-receptor antagonists (100%), feed thickeners (98%), antacids (96%), prokinetic agents (79%), proton-pump inhibitors (65%) and dopamine-receptor antagonists (53%). However, the frequency with which all of these treatments were used varied widely between units. Surgery was required in only 1% of cases. GOR is perceived to be a common condition in preterm infants but the lack of published evidence relating to the management of GOR in preterm infants is reflected in the wide variation in diagnostic and treatment strategies used in major NICUs. It is clear that randomized, controlled trials to evaluate appropriate and effective treatments are needed.

Diagnosis and management of gastro-oesophageal reflux in preterm infants in neonatal intensive care units

Diagnosis and management of gastro-oesophageal reflux in preterm infants in neonatal intensive care units

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). 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.

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.

Does mechanical ventilation precipitate gastro-oesophageal reflux during enteral feeding?

The influence of intermittent positive pressure ventilation on gastro-oesophageal reflux in preterm infants is not known. In many neonatal units, however, concern that ventilation may increase gastro-oesophageal reflux (and therefore aspiration) leads to avoidance of enteral feeding during ventilation. We have therefore performed a crossover study of gastrooesophageal reflux by monitoring lower oesophageal pH in a group of nine enterally fed, very low birthweight infants both during assisted ventilation and normal breathing. All infants had less reflux during intermittent positive pressure ventilation (mean (SEM) reflux index 2.3 (0.6%)) than during normal breathing (mean (SEM) reflux index 6.1 (1.1%)). Assisted ventilation was associated with a significant reduction in the gastro-oesophageal pressure gradient, an effect which may be related to the use of positive and end expiratory pressure during ventilation. These data show that fear of gastro-oesophageal reflux should not preclude the use of enteral feeding in preterm infants receiving ventilation.

Gastro-oesophageal reflux in preterm infants.

Gastro-oesophageal reflux in very low birthweight infants was studied using a new 1 mm monocrystalline antimony oesophageal pH electrode. Gastro-oesophageal reflux was detected in 30 (85%) subjects. The mean (SEM) number of episodes of reflux in 24 hours was 12.1 (2.1), and 3.2 (0.6) lasted over five minutes. The mean reflux index was 4.5 (1.0)%, and the longest episode 17.1 (4.6) 17.1. Reflux was unrelated to postconceptional age or to resting lower oesophageal sphincter pressure. The mean reflux index was low at rest before feeds, being 1.8 (0.6)%, and increased slightly after feeds (3.8 (1.0)%), but was significantly increased after nursing care to 16.4 (3.0)%, and while xanthines were being given (5.9 (1.6)%. A subgroup of seven infants with xanthine resistant apnoea had severe gastro-oesophageal reflux that was not clinically apparent (reflux index 27.4 (3.6)%). Successful treatment of the reflux (reflux index: 3.6 (1.2)%) was associated with cessation of the apnoea. We conclude that gastro-oesophageal reflux is common, and is usually not clinically apparent, even when severe. It is important to consider gastro-oesophageal reflux in the differential diagnosis of xanthine resistant apnoea in preterm infants.

MATURATION OF THE LOWE OESOPHAGEAL SPHINCTER IN THE PRE-TERM NEONATE

Gastro-oesophageal reflux (GOR) is a common problem in pre-term neonates, yet little is known about the maturation of the lower oesophageal sphincter (LOS). We have studied the development of the LOS using a manometric technique in non-ventilated neonates; post conceptional age (PCA) 26-40 wk, weighing 0.7-4.4 kg. Immediately before a feed an end opening 1.5mm external diameter catheter was passed per nasally into the oesophagus and the pressure measured as it was advanced through the LOS. “Effective sphincter pressure” (ESP) was calculated as LOS pressure minus gastric fundal pressure: In contrast to previous studies, there was a close correlation between ESP and PCA (p<<0.001). The correlation of ESP with post natal age and weight was less marked though still significant (p<0.01). These findings offer a rational explanation for the high incidence of GOR in pre-term infants.