Liliane Sacré

Continuous long-term esophageal pH monitoring has become the preferred test to quantify acid gastroesophageal reflux. Because reflux to a limited extent is physiologic, the determination of optimal thresholds to separate normal from abnormal reflux is mandatory. Esophageal pH was measured during 24 hours in 509 healthy thriving infants, aged 3 days to 1 year, using a glass microelectrode with an external reference electrode connected to a portable recorder. Percentiles of the four parameters studied (reflux index or percent of the investigation time with a pH less than 4, number of episodes with a pH less than 4 during 24 hours, number of episodes lasting greater than 5 minutes, the duration of the longest episode (in minutes) are presented. A percentile curve of the reflux index regarding the age distribution shows that the normal range for the reflux index during the first 12 months of life is about 10% (95 percentile), decreasing from 13% at birth to 8% at 12 months. Application of an age-related percentile curve offers a close-to-reality possibility of data interpretation and illustrates that there is inevitably an overlap of data between normal and abnormal populations, because reflux is a phenomenon occurring to some extent in every human being.

The incidence of atopic manifestations was analyzed in infants "at risk" because of histories of atopy in first degree relatives. The incidence of atopic manifestations was significantly reduced (P = .0011) during the first 6 months of life when only the whey hydrolysate was administered (2/32 infants, 6.3%) compared with the incidence when an adapted formula was given (14/35 infants, 40%). This beneficial effect continued during the 6 to 12-month period, after diversification of the diet at 6 months. At the age of 1 year, 7/32 (21.8%) of the infants in the whey hydrolysate group had presented with manifestations of probable atopic disease compared with 17/35 (48.6%) infants in the adapted formula group (P = .021). The incidence of cow milk protein sensitivity was evaluated at 5/32 (15.6%) in the hydrolysate group and 15/35 (42.8%) in the adapted formula group (P = .014). Other foods such as egg and fish may be responsible for manifestations in three infants in hydrolysate group and in five infants of the adapted group (9.4% and 14.3%, respectively NS). These preliminary data show that the administration of a whey hydrolysate during the first 6 months of life to babies "at risk" decreased the incidence of atopic disease up to the age of 12 months. The incidence of cow milk protein sensitivity appeared to be decreased, whereas the incidence of sensitivities to other food proteins was comparable in both groups.

Milk thickening agents are believed to reduce episodes of gastroesophageal reflux, but their use has not been evaluated thoroughly. We studied the effect of these agents in 30 bottle-fed babies, 6-8 weeks old, with clinical gastroesophageal reflux pathology. Continuous 24-hour esophageal pH monitoring revealed gastroesophageal reflux pathology for all parameters studied: reflux index (18.4%), duration of the longest reflux episode (23.3 min), number of reflux episodes in 24 h (34.5), number of reflux episodes greater than 5 min (6.8). All investigations were performed in prone-anti-Trendelenburg position. The infants were treated with milk thickening agents (1 g to 115 ml, as recommended by Carre). Most (n = 25) showed clinical improvement of their symptoms. A second pH monitoring was performed under treatment conditions after 7-14 days, and showed in 24 infants a decrease of the number of reflux episodes (15.1 in 24 h) (p less than 0.001), but a comparable reflux index (17.8%) (NS) and number of long lasting (greater than 5 min) reflux episodes (7.8) (NS). The duration of the longest reflux episode, however, increased significantly (56.6 min) (p less than 0.001). In six infants all parameters were within normal ranges at follow-up. Milk thickening agents seem clinically effective as a treatment for gastroesophageal reflux in individual cases, but can lead to occult gastroesophageal reflux episodes of long duration, possibly increasing the risk for esophagitis or respiratory dysfunction.

Summary: To determine whether gastroesophageal reflux (GER) might be a factor in the pathogenesis of apnea in certain infants, we analyzed the frequency of prolonged central apnea (>15 s) and of numerous irregularly repeated short apneas (5-15 s) (“respiratory dysfunction”) in infants with an apparent life-threatening event (ALTE) (group 1, n = 62), in control infants (group 2, n = 387), and in infants with GER pathologic findings (group 3, n = 60). Finally, the incidence of GER was analyzed in 76 infants with a respiratory dysfunction during sleep (group 4). Gastroesophageal reflux was investigated using 24-h esophageal pH monitoring; respiration during sleep was investigated by polysomnography. The pH monitoring data and results of sleep investigation were analyzed in a double-blind study. A great number of infants who had an ALTE appeared to suffer from GER (42%, 26 of 62 infants), especially if the ALTE occurred while the infant was awake (52%, 14 of 27 infants). In the control infants, pH monitoring data were abnormal in 8.5%; respiratory dysfunction was observed in 5%. In those with a respiratory dysfunction, GER was detected in 75% (15 of 20 infants). In those with GER, respiratory dysfunction was observed in 45% (15 of 33 infants). In groups 3 and 4, respiratory dysfunction was associated with abnormal pH data in 40-43%. If, in the infants with a respiratory dysfunction, the GER pathologic symptoms were treated efficiently (normalization of pH data), respiratory dysfunction disappeared in 92%. If GER was resistant to therapy, respiratory dysfunction persisted in 81% (13 of 16 infants). Results failed to show any causal relationship between prolonged apnea and GER. We conclude that GER in infancy is often associated with a typical breathing pattern during sleep characterized by multiple irregularly repeated short apneas. The recognition of this breathing pattern in (control) infants screened for risk of sudden infant death syndrome should result in GER investigations. We recommend studying GER in all infants with an ALTE.

Theophylline and caffeine are two drugs frequently administered to infants at risk for sudden infant death syndrome, because of their stimulatory effects on the respiratory system. These drugs are known to increase gastric acid secretion and to decrease lower esophageal sphincter pressure that, in turn, possibly increases gastroesophageal reflux (GER). Thirty babies were tested for GER before and during caffeine treatment. Eighteen were studied under the same conditions while undergoing theophylline treatment. All results of pH monitoring before treatment were within normal ranges. Episodes of GER increased significantly (P less than .001) in about 50% of the group treated with caffeine and in 66% of the group treated with theophylline. These results were independent of plasma xanthine concentrations (within or below therapeutic ranges) and of the efficacy of the drug. In addition, an increase was noted for the number of episodes of GER in 24 hours (from 5.3 to 17.1 in the caffeine group and from 5.3 to 24.3 in the theophylline group) and for the time pH was less than 4 (from 0.87% to 6% in the caffeine group and up to 13% in the theophylline group). Because GER is another known risk factor for sudden infant death syndrome, the administration of xanthine derivatives in babies at risk for sudden infant death syndrome should be carefully considered in each case.