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. 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% 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-third 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 . 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 . In a survey of pediatricians in 2005, the regurgitations were the most common gastrointestinal “symptom” in infants aged 0–6 months, affecting 23.1% infants . 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 . 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 . 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 .
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 infant (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 .
In the present study, environmental tobacco smoke exposure was associated with an increased risk of GER and GERD at 1 month of age. Tobacco smoke is known to induce the relaxation of the lower esophageal sphincter . Two studies had already identified tobacco exposure as a risk factor for GER  and GERD , although other studies did not report that association [6, 7, 17]. The fact that paternal smoking was significantly more frequent than maternal smoking may be related to a sociocultural context wherein more men than women smoked, mothers may be more sensitive than father to avoid smoking in the baby’s environment.
Gender was not correlated with an increased risk of GER or GERD, such as found in previous pediatric study in which the occurrence of pathological pH monitoring data was equally frequent in boys and girls . A systematic review that included 31 studies of risk factors associated with GERD (only one pediatric study) published in 2014, showed that male sex was not associated with GERD .
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 [21–23].
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 . In Campanozzi’s cohort, breastfeeding reduced the frequency of regurgitations as compared to formula feeding .
Management options for physiological GER include lifestyle changes  (feeding and positional modifications), parental education, reassurance and anticipatory guidance . Providing parental education and support as part of the treatment of GERD in association with pharmacologic treatment . The use of alginates may slightly improve visible regurgitation/vomiting as signs and symptoms of GER . Severe GERD may be treated with acid suppressors especially in older infants [2, 26]. The use of PPIs as first-line treatment of reflux-related erosive esophagitis in infants is recommended . The use of histamine receptor antagonists is recommended if PPIs are contra-indicated or not available .
In our cohort, family physicians prescribed dietary manipulation (addition of a thickening agent to formula) to 22% of infant at 3 months of age. The prescription of pharmacological consisted mainly of antacids, prokinetics, and PPI peaking at 10%, 6% and 3% respectively, at 3 months of age. We found an overprescribing of pharmacological treatments in infants with GER: nearly 80% of the prescriptions were unjustified, approximately 1% of the cohort received PPIs at any time point. 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 . 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 United States . Although PPIs are generally highly effective for treating erosive disease , they are not effective in reducing GERD symptoms in infants as demonstrated in a systematic review . 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. Adverse effects of PPIs are known such as an increase risk of infections: necrostizing enterocolitis, pneumonia, upper respiratory tract infection, urinary tract infection, and Clostridium difficile infections . PPI increase the risk of bone fracture, dementia, myocardial infarction, renal disease , vitamin B12 deficiency and hypomagnesaemia . 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.
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 .
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 . While sensitive as a screening tool, the I-GERQ-R score should probably be complemented by other, albeit more invasive, testing to ensure a proper diagnosis of GERD before prescribing pharmacologic therapy . The second limitation to our study was that participating mothers were somewhat younger than the non-participants mothers. Nonetheless, the number of previous children was the same between the two groups. Third, we did not ask sufficient 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 GER at older ages where the prevalence of GERD was low.