Gastroesophageal reflux (GER) is a common disorder in infancy [1
]. The rate of GER diagnosis has increased more than 20 fold in hospitalized infants under a year of age over the past few decades [12
]. Whether this increase in diagnosis is due to a true increase in pathologic reflux or an increased awareness of diagnosis remains undetermined.
EPM is considered a reliable method of measuring acid reflux [13
]. It establishes the presence of abnormal acid reflux, determines if there is a temporal association between acid reflux and frequently occurring symptoms, and assesses the adequacy of therapy in patients who do not respond to treatment with acid suppressants [13
]. Although considered the gold standard of diagnosing GERD previously [14
], EPM currently should be viewed with limitations [1
]. EPM may be of normal range in some patients, but brief episodes of GER may cause complications such as ALTE, cough, or aspiration pneumonia [13
The prevalence of an abnormal GER documented by distal esophageal pH monitoring is estimated to be 8% in an unselected, asymptomatic sample of infants [4
]. In our current study, which included only symptomatic infants who qualified for a 24-hour EPM study, 31.8% of patients had pathologic reflux. Reference values for age-related normal values from EPM in asymptomatic infants have been published from Europe [3
]. Control data in asymptomatic infants is not available from the US as it would be difficult to perform such studies in North America due to ethical reasons.
In our definition of the GERD group, we used a reflux index of 5% as a cut off value similar to our previous studies [15
]. Despite it being a different cutoff value as compared to the NASPGHN cutoff of 12% in the 1st
year of life, we feel that a 5% cutoff is more applicable to our patient population and our diagnostic equipment. This different cutoff percentage may result in a higher incidence of GERD in our study as compared to other studies; however previous studies were performed on asymptomatic kids in contrast to our symptomatic population [4
]. The currently recommended normal values for EPM parameters are thought to be based on limited data from studies done on healthy infants with parameters not normally distributed [4
], or studies with controls older than our study group [16
]. There is a need for more normal data before EPM results can be confidently interpreted [17
]. Data also depend on technical hardware such as recording devices and electrodes together with such patient characteristics as age, position, activity, and medication [18
]. We recommend that even a lower cutoff value of reflux index for diagnosing GERD in infancy is needed to improve its sensitivity and specificity as a criteria of diagnosis [18
Gender has been reported to play a role in reflux in healthy and symptomatic adults [5
]. However, gender related values in infancy have not been evaluated previously. Richter et al [5
] have shown that men tend to have more physiologic reflux than women in all EPM parameters from data on 110 healthy adults from three different centers. Fass [6
] and associates reported that normal males had more variability and higher parameters in comparison to females for all values on pH monitoring. Ter [7
] and coworkers assessed the same pH monitoring criteria in 353 symptomatic adults. Men had significantly more reflux and significantly higher values for all reflux parameters. In contrast, Shoenut et al [19
] reported that the severity of reflux was not significantly different in adults between the two genders in referred symptomatic patients. It has been proposed that gender differences in parietal cell mass may account for this observation in adults [20
]. Stomachs of men have more parietal cells and thus secrete more acid than women [20
]. Based on these observations, it has been suggested that different gender-specific criteria be used in evaluating pH-monitoring results in adults. However, such size related differences between genders are unlikely to manifest in infancy.
There have been very limited data on gender differences in EPM parameters in infancy regarding both severity and prevalence in physiologic or pathologic reflux groups. A slight male preponderance for GER has been observed in pediatric studies. In asymptomatic infants it was 1.27:1 [21
] and in a study of symptomatic infants and children it was 1.3:1 [22
]. These figures are similar to our incidence of 1.3:1 for male: female. This incidence was present in both control and GERD groups as well as by ethnicity. Although our population is different from European infant data in that totally asymptomatic infants were screened for sudden infant death syndrome by pH monitoring and polysomnography by them [21
]. Our patients are similar to data from Shepherd et al [22
] in being symptomatic but their patients were older than our cohort.
Several studies in adults have shown that Caucasians have a higher frequency of symptoms, incidence, and complications of GERD (ulcers, strictures, or Barrett's esophagus) as compared to African Americans and Asians [23
]. Caucasian ethnicity was also shown to be positively related to treatment satisfaction in adults with GERD [27
]. A recent study in Thai infants also suggested that these infants had earlier resolution of regurgitation in comparison to their Western cohort [28
]. Our present study showed a higher proportion of Caucasian infants having abnormal EPM parameters i.e. with GERD compared to AA infants. This suggests that racial differences in the incidence of GERD as previously reported in adults may also be present in infants [23
]. This is a particularly valid observation as overall, majority of infants in our referral population are AA. We have observed this higher prevalence of GERD in Caucasians in another study as well [29
]. Our data makes a strong case for racially associated genetic predisposition for GERD.
Dietary factors have been incriminated as one of the possible etiologies for increased incidence of GERD. However, most infants are usually on similar feedings regardless of ethnicity. Ostakul et al also did not observe any association of the prevalence of reflux regurgitation with the type of feeding i.e. breast milk vs. formula among Thai infants [28
A lower concentration of gastric juice hydrogen ion concentration was reported in basal state and after pentagastrin stimulation in adult AA as compared to Caucasians [30
] which may explain ethnic predisposition for Caucasians in the etiology of GERD. Although unlikely in infancy, the role of these factors in the etiology of racial differences in infants remains to be determined. The higher trend of EPM parameters in Caucasian females in comparison to all other groups is another interesting observation in our study. This finding has not been previously reported in adults or in the pediatric population. A significant association between the body mass and symptoms of reflux has been reported in postmenopausal women with estrogens being implicated as etiology of GERD, however, we cannot speculate on such a hormonal factor in infancy [31
]. Our Caucasian females were significantly older (5 months versus 3.5 months) as compared to the Caucasian males (p = 0.03) in the GERD group. Although GER symptoms peak at 4 months [32
], such a disposition for higher reflux parameters has not been previously reported. Since the etiology of such racial differences in unclear, it is important to conduct further studies to better understand the racial differences and to overcome any racial disparities that may result from overlooking such differences [33
The main limitation of our study is that it was a retrospective study which made it difficult to quantify the severity of symptoms on referral. It should also be noted that our study was conducted in an urban tertiary care center setting with the majority of patients being of African American origin. The ethnic distribution of patients and time of referral to such a center may play a role in determining the incidence of GERD.