Testing the association between gastroesophageal reflux and apnea in infants

There is controversy regarding the association between gastroesophageal reflux and apnea. The controversy is further confused by the variety of ways reflux is detected, the varying methods of data analysis and the heterogeneity of subjects studied.

To determine if apnea is associated with reflux and to determine whether the association differs with acid or non acid reflux.

We prospectively evaluated infants with apparent life-threatening events or apnea by simultaneous pneumography, esophageal pH and multichannel intraluminal impedance monitoring. Apneic events and reflux frequency, duration, acidity and height were recorded. Apneic events were considered to be temporally linked to gastroesophageal reflux when they occurred during a gastroesophageal reflux episode or within 5 minutes after clearance of the refluxate. Data described with frequency tables, scatterplots and time series graphs were analyzed by regression analysis and chi testing.

Twenty-five infants (10 males) aged 1 to 19 months were studied for up to 24 hours. Of 527 total apneic episodes, only 80 (15.2%) were temporally linked with gastroesophageal reflux: 37 (7.0%) with acid reflux and 43 (8.2%) with non-acid reflux. Scatterplots revealed no significant correlation between apnea and frequency or duration of reflux episodes. Individual chi analyses within subjects found limited associations between reflux and apnea. Regression analyses showed a significant association between apnea and reflux in 4 of 25 subjects.

We found little evidence for an association between apnea and total reflux, acid reflux or non-acid reflux. There was no difference between acid gastroesophageal reflux and non-acid gastroesophageal reflux in the frequency association with apnea. Either a chi statistic for each subject or R value computed from a lagged regression model for each subject can be used as an index of association in patient evaluation.