Table 1.

Summary of 12 studies examining relationship between GOR and ALTE, in date order

First author, year [ref.]	Study population size and classification	Investigation	Study type	Outcome	Comments
Macchini, 2017 [16]	n=41 41 infants, mean age 6 weeks At least one ALTE, and typical GOR symptoms No controls	Cardiorespiratory monitoring and pH impedance studies	Prospective Observational Follow-up with monthly clinical and cardiorespiratory monitoring	GORD in 80% of enrolled patients (moderate in 54%, severe in 27%) Significantly longer time taken for cardiorespiratory monitoring to normalise in cases of moderate-to-severe reflux (p<0.0001 between mild and moderate-to-severe group and p<0.05 between moderate and severe group)	6 patients <30 weeks’ gestation 8 very low birth weight (<1500 g) Authors recommended investigating for GORD in ALTE and treating with anti-reflux therapy to prevent new episodes of ALTE
Blasco-Alonso, 2014 [17]	n=39 Infants admitted with ALTE No controls	MII and pH studies	Prospective, over 3 years	MII and pH studies combined: GOR found in 33 (84.6%) pH study alone: 14 (35.9%) diagnosed as GOR (8 mild, 4 moderate, 2 severe) pH monitoring: 2692 episodes of GOR identified MII: 3219 episodes of reflux identified	Addition of MII to pH-impedance study increases the diagnostic yield by detecting alkaline and weakly acidic reflux Study confirmed presence of GOR in patients admitted after ALTE; it did not evaluate any link between GOR episode and either apnoea or ALTE
Kader, 2014 [14]	n=40 Infants with GOR, mean age 125 days, mean gestation 28.5 weeks	MII–pH impedance study	Retrospective data review	9 out of 40 (22.5%) showed evidence of GOR but apnoea was only seen in one patient and ALTE was not seen	Authors concluded that GOR is less likely to be a cause of desaturation, apnoea or ALTE
Semmekrot, 2010 [15]	n=110 Infants diagnosed with ALTE at secondary and tertiary paediatric units No controls	Retrospective note review of clinical diagnosis	Retrospective survey over 1 year	Clinical diagnosis of GOR in 37.3% of cases	29.5% were pre-term and 8.2% were term Recurrent ALTE in 10% of patients Not able to suggest any temporal association of causality
Cohen Sabban, 2009 [18]	n=58 Infants with ALTE, median age 2 months No controls	3-min interval during 24-h pH impedance study to establish a temporal relationship between GOR episode and ALTE	Prospective, over 4 years	31 patients positive with 70 apnoeas/GOR events; apnoeas seen before GOR episode in 34.2% (70.8% non-acidic), during GOR in 32.8% (65.2% non-acidic) and after GOR in 32.8% (43.4% non-acidic) In 18 patients who experienced more than one episode of apnoea during monitoring, a different temporal relationship with GOR was observed at each episode	For infants in whom a temporal relationship between GOR and apnoea was observed, there was no definite pattern Authors concluded that ALTE and GOR are likely to be concurrent events and not cause-and-effect
Cendón, 2008 [19]	n=16 Infants with diagnosis of ALTE, median age 3.04 months No controls	MII and pH impedance studies	Prospective	Four episodes of apnoea were noted in one patient, related to GOR	Authors did not find greater rate of GOR in patients with diagnosis of ALTE compared to general population Only one patient had an association between GOR and apnoea
Semeniuk, 2007 [20]	n=264 Children aged 4–102 months (mean±sd 20.78±17.23 months) of both sexes, with symptoms suggestive of GOR Subgroup of 8 children aged up to 2 years (mean±sd 10.00±2.78 months) of both sexes, with symptoms suggestive of ALTE, were selected from the group	24-h oesophageal pH monitoring for acid GOR diagnosis Radiography of oesophagus with barium swallow to evaluate the height of GOR “Immunoallergologic” tests to differentiate acid GOR as primary or secondary to food allergy	Prospective	From among 264 examined children who underwent 24-h oesophageal pH monitoring, acid GOR was confirmed in 170 (64.4%), and ALTE in 8 (4.8%)	Primary and secondary GOR were defined as the causative factors of ALTE in 8 (4.8%) examined infants Older children were studied, up to the age of 2 years
Mousa, 2005 [21]	n=25 Children with apnoea or ALTE, age 1–19 months No controls	Simultaneous pneumography, oesophageal pH-monitoring and MII	Prospective	Of 527 total apnoeic episodes, only 80 (15.2%) were temporally linked to GOR: 37 (7.0%) with acid reflux and 43 (8.2%) with non-acid reflux	Authors did not find any significant correlation between apnoea and frequency or duration of reflux episode, either with total reflux, non-acid or acid reflux
McGovern, 2004 [3]	8 studies involving 643 infants who presented with ALTE, age 0–13 months No controls	Reviewed the most likely diagnosis in infants with ALTE	Systematic review	The most common diagnosis was GOR (n=227)	There is a wide range of diagnoses reported after ALTE; GOR was found to be the most common assigned diagnosis Clinical diagnoses attributed by admitting clinician
Wenzl, 2001 [13]	n=22 Infants with symptoms of recurrent regurgitation and apnoea No controls	Simultaneous pH studies, MII, oronasal airflow and chest wall movement measurement	Prospective	364 GOR episodes were recorded by MII 165 apnoeas were documented by visual validation of polygraph records 49 apnoeas (29.7%) were associated with GOR; 11 (22.4%) of these showed acid reflux (pH <4)	A significant correlation between the time spent apnoeic and GOR was found (p<0.001): there is marked association between apnoea and GOR in infants
Dabadie, 1993 [22]	n=147 Four groups of infants under 12 weeks of age:  1) 37 infants with ALTE  2) 45 with ALTE and vomiting  3) 33 with solely gastrointestinal symptoms  4) 32 SIDS siblings	pH-impedance studies including 12 nocturnal hours	Prospective	Mean duration of nocturnal episode of reflux was higher in group 1 compared to groups 2 and 3 but didn't appear to relate to a history of ALTE	Nocturnal pH data profile failed to show a relationship between GOR and ALTE
See, 1989 [23]	n=22 16 infants with ALTE 6 controls manifesting clinical GOR	Simultaneous prolonged pH-impedance studies, pulse oximetry and transthoracic impedance pneumocardiography	Prospective	Despite absence of vomiting in 90% of patients with ALTE, the incidence of GOR was similar in both groups Desaturation <90% for >3 min observed during 60 episodes in 90% patients with ALTE 54 out of 60 episodes occurred within 4 min of pH falling to <4.0	Authors concluded that unsuspected (occult) GOR is common in infants presenting with ALTE and, in these patients, GOR may be directly associated with hypoxaemic episodes