Gastroesophageal reflux increases the number of apneas in very preterm infants

Aim. Apnoea of prematurity (AOP) is a perplexing disorder of respiratory control that is very common in preterm infants and requires therapeutic intervention to avoid potential morbidity. The existence of a relationship between gastroesophageal reflux (GER) and AOP in preterm infants is still controversial. We aimed to evaluate the relationship between GER and apnoeas in preterm newborns, by the simultaneous and synchronized use of combined Multichannel Intraluminal Impedance and pH-monitoring (pH-MII), and polysomnography (PSG). Methods. Twenty-six preterm infants were studied as they had recurrent apnoeas. They underwent a 6-h simultaneous and synchronized recording of polysomnography and pH-MII. Each registration involved 2 post-prandial periods lasting 3 h each. Polysomnography detects and characterizes apnoeas, desaturations and bradycardia, by recording of breathing movement, nasal airflow, electrocardiogram, pulse oximeter saturation. All apnoeas lasting more than 5 s were considered, and classified as central (CA), obstructive (OA) and mixed apnoeas (MA). By pH-MII we registered acid/non acid GER. The temporal association between GER and apnoea was analysed by the frequency of apnoea in the 30 s preceding and following the onset of GER episodes. Apnoeas detected within thirty seconds after GER were defined GER-triggered. Results. One-hundred-fifty-four apnoeas out of 1136 were detected within 30 second before and/or after the onset of a GER episode. The frequency of apnoea during the 1-min time around the onset of a GER episode (mean 0.17/min; range [0–0.84/min]) was significantly different (p = 0.03) from the one detected during the GER-free period (0.12/min [0–0.43/min]), which is defined as the time difference between the total recording time and the time around all GER episodes. The frequency of apnoea before the onset of GER (0.10/min [0–0.69/min]) did not differ from the one detected during GER-free period (p = 0.17). The frequency of apnoea occurring after the onset of GER (0.25/min [0–1/min]) was higher than the one detected in the GER-free period (p = 0.02), and also than the one detected before the onset of GER (p = 0.01). A great inter-individual variability was documented in the ratio of GER-triggered apnoeas to the total number of apnoeas (median 10.34%, range: 0–20%), as well as in the ratio of GER-triggered apnoeas to the total number of GERs (median 5.77%, range: 0–50%). The increase of apnoeas after GER, defined as the difference between the number of apnoeas detected in the 30 s after GER and the one detected 30 s before GER, was calculated (median 2; range: −2/+8). A significant correlation was found between this difference and the total number of apnoeas (ρ = 0.425, p = 0.034); on the other hand, no correlation was documented between total number of GERs and GER-triggered apnoeas (ρ = 0.019; p = 0.930). Conclusion.We found that, in preterm infants with recurrent apnoeas, these events occur more frequently soon after GER than in the period immediately before GER or GERfree. This suggests that the relationship between GER and AOP is not simply by chance. The ratio of GER-triggered apnoeas to the total number of apnoeas is widely variable. Furthermore, the wide variability in the ratio of GERtriggered apnoeas to the total number of GERs documents that in some newborns a GER episode more likely evokes an apnoea. Patients who had the most significant increase of apnoeas after GER also had the highest number of total apnoeas: in other words, in the most unstable infants also GER episodes can easily act as a trigger event for apnoeas.Onthe other hand, the lack of correlation between GER-triggered apnoeas and total number of GERs highlights that the severity of GER is not predictive by itself of the risk of reflex apnoeas.