In this prospective cohort study, we aimed at determining the prevalence of GER and GERD in infants followed longitudinally from birth to 12 months of age. 157 infants were included of the 272 eligible. The rate of refusal to participate was 42%. This figure is comparable to other published population-based studies of pediatric GER. In 2002, Martin et al. approached 3200 mothers and 2000 agreed, wich suggested that 1200 mothers (37.5%) refused to participate [6]. Almost half of the infants aged less than 12 months experienced at least one daily episode of regurgitation, mainly in the first three months of life. The prevalence of physiological GER peaked at age 3 months, 60% of infants, while GERD peaked at age 1 month; almost 20%. The risk factors for GER and GERD were family history of GER, and exposure to passive smoking.
More than two-thirds of infants regurgitated daily at one month and this figure gradually declined until 12 months of age. Although the timeframes were somewhat different, the rates were similar to those published by Nelson et al. In a cross-sectional survey from pediatric practice, half of the 948 infants regurgitated at least once a day between 0 and 3 months, peaking at 67% at 4 months, and decreasing thereafter to 61% at 6 months and 21% at 7 months of age [5]. Thus, the prevalence of regurgitation remained unchanged over the years. Our results are also similar to those published elsewhere. In the first prospective longitudinal study including 4672 infants (2002), “visible” regurgitation (“spilling”) peaked at 3-4 months of age (41% of infants) and decreased to 5% at age 13-14 months [6]. In a survey of pediatricians in 2005, the regurgitations were the most common gastrointestinal “symptom” in infants aged 0- 6 months, affecting 23.1% of infants [16]. The average prevalence of regurgitation over the first 2 years of life was 12% and common before 5 months of age, according to Campanozzi’s evaluation using Rome II criteria and the validated I-GERQ score [7]. Using I-GERQ, Salvatore’s performed a cross-sectional study of 200 infants from 0.5 to 12 months of age and found an average of 45% of healthy infants regurgitating daily [17]. A prospective study in 2010 of 128 infants in Michigan, USA, using an I-GERQ-R score, determined the prevalence of regurgitations at least once a day to be 82%, 77%, 83%, 67% at 1, 2, 4, and 6 months, respectively, with GERD in 25.5%, 12.5%, 8.0%, and 2.9% of infants, respectively [8].
In 2012, a French study included 10 394 patients, aged 0-17 years, seen by the family physicians (general practitioners and paediatricians). For patients presenting with GER symptoms, a 24-item questionnaire was completed by the physician. Martigne et al. estimated that 24.4% of infants (ages 0-23 months) had symptoms of GER. Among infants, 81% had GER symptoms at least twice a day. The high prevalence of regurgitation may be explained by the enrollment of children who were seen in the physician’s office. In addition, the diagnosis was established by the physician and not on parental reports of their children’s symptoms [4].
In the present study, environmental tobacco smoke exposure was associated with an increased risk of GER and GERD at 1 month of age. The prevalence of passive smoking was high. Overall, 39.7% of infants were exposed to passive smoking. Paternal smoking was more frequent than maternal smoking. In comparison, in Lebanon, in 2015, 48.2% of children aged between 3 and 15 years (527) were exposed to smoke at home [19]. In Macao, Zheng et al, demonstrated that 41.3% of children aged 6-14 years old (875 children) were exposed to tobacco. Among 415 smokers, the father’s smoking represented a large majority (92%) [20].
Tobacco smoke is known to induce the relaxation of the lower esophageal sphincter [18]. Two studies had already identified tobacco exposure as a risk factor for GER [18] and GERD [14], although other studies did not report that association [6,7,17].
Gender was not associated with an increased risk of GER or GERD, similar to what was reported in previous pediatric studies in which the occurrence of pathological pH monitoring data was equally frequent in boys and girls [21]. Likewise, in a systematic review that included 31 studies on the risk factors associated with GERD (only one pediatric study) the authors showed that sex was not associated with GERD [22].
In the current study, a family history of GER in the first or second-degree relatives was a strong risk factor for physiological GER and GERD in the first 3 months of age. Four studies reported an association between having GERD symptoms and having a genetically related family member with gastrointestinal symptoms [23-26].
We did not find a statistically significant relationship between breastfeeding and the risk of GER nor GERD, consistent with other studies showing no protective benefit of breastfeeding on GER/GERD [6,8,14]. Nonetheless, Heacock et al. suggested that episodes of reflux were shorter in breastfed infants [27]. In Campanozzi’s cohort, breastfeeding reduced the frequency of regurgitations as compared to formula feeding [7].
Management options for physiological GER include lifestyle changes [7] (feeding and positional modifications), parental education, reassurance and anticipatory guidance [2]. Providing parental education and support as part of the treatment of GERD in association with pharmacologic treatment [3]. The use of alginates may slightly improve visible regurgitation/vomiting as signs and symptoms of GER [3]. Severe GERD may be treated with acid suppressors especially in older infants [2,28]. The use of PPIs as the first-line treatment of reflux-related erosive esophagitis in infants is recommended [3]. The use of histamine receptor antagonists is recommended if PPIs are contra-indicated or not available [3].
Approximately 5 % of the cohort received PPIs at any time-point. In recent decades, the prescription of PPIs has expanded in the pediatric population [9,11]. De Bruyne et al. demonstrated an increase in acid-suppressant prescriptions among Belgian pediatricians including PPIs between 1997 and 2009 [10]. In a retrospective analysis of PPI prescribing patterns for newborns and infants, the authors estimated that prescriptions had more than doubled from 2004 to 2008 in the United States [12]. Although PPIs are generally highly effective for treating erosive disease [29], they are not effective in reducing GERD symptoms in infants as demonstrated in a systematic review [30]. Moreover, the gastric contents of the milk-fed infants are non-acidic during a large part of the day, obviating the need for suppression of gastric acid secretion. The use of PPIs may increase the risk of adverse events such as necrotizing enterocolitis, pneumonia, upper respiratory tract infection, urinary tract infection, or Clostridium difficile infections [3]. In addition,PPI may increase the risk of bone fracture, dementia, myocardial infarction, renal disease [3], vitamin B12 deficiency, and hypomagnesaemia [11]. However, these adverse events are controversial in studies[3]. Of notice, in our cohort, the symptoms of GER and GERD largely resolved over time. The use of PPIs in this population is therefore questionable. Several randomized controlled trials in infants with GERD showed no difference between PPI and placebo [3].
A major strength of our study was its prospective design. Furthermore, we included a relatively long follow-up (one year), as opposed to some studies that ended after 6 months. The population was based on infants born at term and healthy, remaining without serious complications for the first 3 months of life. With an almost 90% rate of return, our study results can, therefore be generalized to any well-baby visit. In addition, comparing our results to those from an academic rural population in the USA showed little difference to our experience in a small urban community in France, thus rendering our findings extrapolative to other populations [8].
Nonetheless, there are several limitations to this study. First, we used the I-GERQ-R questionnaire as a surrogate for accurate gastroesophageal reflux diagnosis. This score was validated in many languages including French and was developed to distinguish GER from GERD on clinical criteria. However, items such as the frequency of crying and other infant behaviors can be influenced by underlying diseases and falsely increase the total score. Van Howe and Storms suggested that a high score in the first months of life may reflect colic-associated symptoms and that GERD should not be considered a likely diagnosis until 3 months of age [8]. While sensitive as a screening tool, the I-GERQ-R score should probably be complemented by other, albeit more invasive, tests to exclude other potential diseases (e.g. Eosinophilic esophagitis) in severe or persistent cases despite pharmacological treatment [3, 31]. The second limitation of our study was that participating mothers were somewhat younger than non-participants mothers. Nonetheless, the number of older children was the same between the two groups. Third, we did not ask questions to evaluate the socioeconomic status. This potential selection bias may have affected risk factors like environmental tobacco smoke exposure. Lastly, the sample size was insufficient to investigate factors associated with the persistence of GERD at older ages where the prevalence of GERD was low.