See “Noncompliance With NASPGHAN-ESPGHAN Practice Guidelines for GER in Europe: Is There a Point?” by Thaler on page 396.
Guidelines are systematically developed statements created to assist practitioners in making decisions about appropriate care for specific diseases based on the best available evidence (1). Although several guidelines have been developed for the management of gastroesophageal reflux disease (GERD) in children, no study has specifically assessed the effect of these guidelines on the general pediatrician's approach to the patient with possible GERD.
GERD is a common condition, defined by the passage of gastric contents into the esophagus causing troublesome symptoms and/or complications, affecting up to 3.3% of the pediatric population (2). In October 2009, the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) published new clinical practice guidelines for the diagnosis and management of reflux in the pediatric population, updating and unifying the previous ESPGHAN and NASPGHAN guidelines as a means of improving uniformity of practice and quality of patient care. Because the diagnosis of GERD was excessively made in healthy infants with bothersome but harmless symptoms of physiologic gastroesophageal reflux (GER) (3–6), the committee reevaluated the 2001 diagnostic and therapeutic algorithms and highlighted the need for efforts to distinguish physiologic GER events from GERD. The diagnosis of GERD is inferred by performing tests showing excessive frequency or duration of reflux events, esophagitis, or a clear association of symptoms and signs with reflux events in the absence of alternative diagnoses. According to the guidelines, only in older children and adolescents with typical reflux symptoms, a time-limited trial of acid-suppressive treatment may be useful as diagnostic test (7).
GERD management in children includes lifestyle changes, pharmacologic therapy, and surgery. Among the pharmacologic agents, proton pump inhibitors (PPIs) are confirmed superior to histamine-2 receptor antagonists (H2RAs) for healing erosive esophagitis and relieving symptoms; however, the dramatic increase in the patterns of prescribing PPIs during the past several years has raised concerns related to their appropriate use and associated cost (8). For instance, although irritable infants are frequently empirically treated with PPIs because reflux esophagitis is believed the cause of crying, to our knowledge there is no evidence supporting the usefulness of PPIs as a diagnostic test in this age group. Therefore, according to the new guidelines, PPI treatment is recommended for use in a much smaller number of pediatric patients than before.
The main objective of the study was to investigate the present approach of European general pediatricians to the management of infants, children, and adolescents with GER symptoms. Secondary objectives were to evaluate the implementation of the 2009 NASPGHAN-ESPGHAN clinical practice guidelines on the diagnosis and management of GER and to assess patterns of prescribing PPIs among pediatricians from different European countries.
This prospective, multicentre study was performed in 11 European countries: Belgium, Germany, Greece, Italy, Lithuania, Macedonia, the Netherlands, Portugal, Serbia, Slovenia, and Spain. For each country, a coordinator randomly identified a sample of general pediatricians, fairly distributed across the entire national territory, from a national database, using block number randomization tables. Selected pediatricians were contacted by e-mail and were asked to complete a questionnaire investigating their approach to children with suggestive reflux symptoms, such as regurgitation, vomiting, heartburn, chest pain, weight loss or poor weight gain, irritability in infants, ruminative behavior, hematemesis, dysphagia, odynophagia, wheezing, stridor, cough, and hoarseness (https://links.lww.com/MPG/A250). The questionnaire consisted of 12 multiple-choice case reports–like issues concerning clinical management, the use of diagnostic tools, and the treatment options for GER/GERD in infants, children, and adolescents. Eleven versions of the questionnaire, one for each language of the participating countries, were created. One-fifth of the involved pediatricians were asked to answer both the English and their native language versions to validate the translated versions of the questionnaire. The national data obtained from the questionnaires were collected and analyzed by the coordinators. The study period was December 1, 2011 to May 31, 2012. The present implementation of 2009 NASPGHAN-ESPGHAN reflux guidelines and the patterns of prescribing PPIs were evaluated based on pediatricians’ answers.
The study was approved by the independent ethics committee of the University of Naples Medical School and was conducted in accordance with the Declaration of Helsinki and guidelines for Good Clinical Practice. Data were entered into Excel (Microsoft, Redmond, WA) and analyzed with SPSS software, version 8.0 (SPSS Inc, Chicago, IL). Results are expressed as percentages. Comparisons were made among data from different countries. Statistical analyses included determination of means, t test, χ2 test, and Fisher exact test, with significance accepted at the 5% level. The majority of these comparative data are not shown because the study did not claim to detect statistically relevant differences in the management of reflux among pediatricians from the 11 participating countries. The sample size has been computed with the SPSS multivariate analysis of variance, considering an overall number of 167,444 European pediatricians (power 99%; α 0.05; first type error 0.05) (9).
A total of 1350 questionnaires were sent to pediatricians in 11 European countries. The number of responders was 567 (42%). To ensure that the English and native language of the questionnaires were comparable, 110 (19.4%) respondents agreed to answer both the English and their native language versions of the questionnaire. Among these respondents, the matching rate between the English and native language answers was close to 100% (1314/1320). Table 1 shows the number of questionnaires returned for each country.
According to the given answers, only 10 of the 567 (1.8%) pediatricians managed children in full compliance with the guidelines recommendations, with regard to both the use of diagnostic tools and therapeutic prescriptions. Conversely, 557 of 567 (98.2%) pediatricians committed ≥1 violations of the guidelines in their clinical practice. Among these, 255 (45%) gave an overall rate of answers in accordance with the guidelines of ≤50%. The different rates of adherence to guidelines recommendations by European pediatricians are shown in Figure 1. No significant differences in the adherence were reported among pediatricians from the different involved countries (P > 0.05). The study questionnaire with the overall percentages of each answer given by pediatricians is attached as Appendix 1 (online only, https://links.lww.com/MPG/A250).
Two hundred sixty of 567 (45.8%) pediatricians diagnose GERD based on clinical symptoms and physical examination without specific testing, irrespective of the age of the child. Only 106 of 567 (18.7%) varied their approach to diagnose GERD depending on the age of the child, and 182 of 567 (32.1%) always require specific testing (upper gastrointestinal (GI) endoscopy, esophageal pH monitoring) for diagnosis.
Even though the guidelines conclude that symptom description is unreliable and nonspecific for diagnosis of GERD in children younger than 8 to 12 years, 272 of 567 (48%) pediatricians base diagnosis on these criteria. Fifty-five of 567 (9.7%) pediatricians use esophageal and gastric ultrasonography (US) to diagnose GERD, despite a specificity of only 11% for this test. Only 183 of 567 (32.2%) recommend specific testing such as upper GI endoscopy and/or esophageal pH monitoring to confirm the diagnosis of GERD, as recommended by the guidelines. Data from each European country are shown in Table 2.
In children older than 8 to 12 years, 264 of 567 (46.6%) pediatricians diagnose GERD based upon clinical history and symptom description, in accordance with the guidelines; however, 41 of 567 (7.2%) use US for confirming the diagnosis of GERD in this age group. One hundred eighty-seven of 567 (33%) diagnose GERD only after specific testing, such as upper GI endoscopy and esophageal pH monitoring.
Three hundred eighty of 567 (67%) involved pediatricians consider PPIs the mainstay for the treatment of GERD, but 94 of 567 (16.6%) pediatricians consider H2RAs superior to PPIs for healing erosive esophagitis and relief of reflux symptoms and 41 of 567 (7.3%) and 35 of 567 (6.3%) believe in the higher efficacy of gastric acid–buffering agents and prokinetics, respectively.
Of the pediatricians surveyed, 36.2% treat uncomplicated recurrent regurgitation and vomiting in infants younger than 1 year with PPIs. An even higher percentage (38.9%) prescribed PPIs to infants with unexplained crying and/or distressed behavior. Data from each European country are shown in Table 2.
A therapeutic trial with PPIs is recommended by the guidelines only for older children and adolescents with heartburn and/or chest pain (typical symptoms); however, 287 of 567 (50.6%) pediatricians use an empiric trial of PPI therapy in children of all ages and 56 of 567 (9.9%) empirically treat children with atypical reflux symptoms with PPIs. In older children and adolescents with typical reflux symptoms, 194 of 567 (34.2%) pediatricians appropriately prescribe PPIs for 2 to 4 weeks.
Three hundred fourteen of 567 (55.4%) pediatricians gradually reduce acid-suppressant therapy to prevent rebound symptoms. The remaining 44.6% discontinue PPIs abruptly. A majority of pediatricians (387/567; 68.3%) were unaware that lower respiratory tract infections are the most frequent adverse event of PPI therapy in infants (10).
Considering the overall answers given by pediatricians regarding the use of PPIs in children, a large majority of pediatricians (465/567; 82%) prescribe PPIs in situations that did not concur with the recommended use in the NASPGHAN-ESPGHAN guidelines. The rates of overuse of PPIs in the different countries are shown in Table 2.
In this study, we investigated the diagnostic and therapeutic approaches of general pediatricians from 11 different European countries to children with symptoms suggestive of GER/GERD. The overall results of our survey show that the majority of pediatricians are unaware of the 2009 NASPGHAN-ESPGHAN guidelines, whereas only a small minority follow the recommendations for evidence-based optimal management of GER/GERD in their clinical practice.
One of the most frequent deviations from the NASPGHAN-ESPGHAN recommendations concerned the use of diagnostic modalities. The majority of the involved pediatricians do not perform specific testing to diagnose GERD and rely on the clinical history even in young children and infants. In these age groups, evidence from the literature shows symptom description to be unreliable and nonspecific because these individuals are not able to accurately communicate the quality and quantity of their symptoms (7). Therefore, the diagnosis of GERD must be inferred with tests showing excessive frequency or duration of reflux events, esophagitis, or a clear association of symptoms and signs with reflux events in the absence of alternative diagnoses. A survey performed among French pediatricians in 2012 found that 59% of pediatricians diagnosed GERD without performing specific testing, irrespective of age (11). Similarly, in 2011, Diaz et al (12) surveyed North American pediatric health care providers and documented the same attitude, even if at a lower percentage (31%).
An interesting finding of our study concerns the use of US, which is still being used for diagnosing GERD in infants and children by 10% of the involved pediatricians, as well as in adolescents by 7.6% of them. According to the guidelines, US is not recommended as a test for GERD but can provide information not available through any other technology, allowing the exclusion of non-GER causes of symptoms, such as hypertrophic pyloric stenosis, hiatus hernia, and abdominal mass. When compared with the results of 24-hour esophageal pH testing, the sensitivity of color Doppler ultrasound, performed for 15 minutes postprandially, is approximately 95% with a specificity of only 11%, and there is no correlation between reflux frequency detected by US and reflux index detected by pH monitoring (13,14). To date, this is the first study to have assessed the use of US for GERD diagnosis in such an international setting. A previous study in a more limited national setting reported a lower percentage of children with suspected GERD undergoing diagnostic US (2%) (11).
The other major violation of the guidelines concerns the therapeutic approach to GER. Data from our survey confirm the overuse of PPIs, recently highlighted by several studies (3,8). For infants with uncomplicated GER, the NASPGHAN-ESPGHAN guidelines recommend only parental education, anticipatory guidance, and modification of feeding composition, frequency, and volume; however, when respondents were given a hypothetical “happy spitter” clinical situation, more than one-third of them ordered PPI treatment. Moreover, an even higher percentage of them were shown to overtreat infants with unexplained crying and/or distressed behavior with PPIs.
As already reported, the present clinical guidelines discourage the diagnosis and treatment of GERD based on clinical history and physical examination in young children. Contrary to this recommendation, approximately half of the responding pediatricians were managing these patients similar to adult patients, by treating symptoms suggestive of GERD with PPIs, regardless of a correct diagnosis.
The prescription of unnecessary acid-suppressive medications is, in our opinion, the most relevant source of concern arising from this study. PPI use in infants and children with GER/GERD has increased enormously during the last decade, as further confirmed by the present survey (3,12,15). PPIs are generally well tolerated (16) but have some shortcomings and may increase susceptibility to acute gastroenteritis and community-acquired pneumonia (17,18), respiratory infections (19), gastric polyps (20), and bacterial overgrowth (19,21). Although PPIs are widely considered the most effective acid-suppressive therapy for adults with GERD (22,23), the effectiveness and safety of PPIs in infants and children with GERD are less clear (24). Longitudinal long-term tolerability studies in the pediatric population are still needed because the few studies performed to date are mostly open-label and uncontrolled. Further considering the increasing evidence that PPIs offer little benefit for some of the symptoms for which they are commonly prescribed, a serious effort to curtail their empiric use in children is strictly required (24). As a matter of fact, following the present guidelines, PPI treatment should be prescribed in a much smaller number of pediatric patients than before.
The authors of this study are well aware of its methodologic imperfections. A relatively low return rate is commonly seen in this type of investigation (11,12,25). Although only 42% of the targeted pediatricians completed our questionnaire, we believe the sample represents a reasonable cross-section of pediatric health care providers. Because the targeted clinicians were free to respond to the survey, it is possible that those with more interest in GERD would have been more likely to complete the study questionnaire. A bias could have been, therefore, introduced by the inclusion of better-informed pediatricians. Nevertheless, in view of the findings of our study, this limit can only strengthen the relevance of our results. An important drawback is that the survey documented only the physicians’ proposed treatment of 1 type of patient. Unfortunately, for practical reasons, we could not investigate what is really practiced in the countries involved. Furthermore, the analysis of the questionnaires does not allow us to comment on the reasons for the European pediatricians’ failure to comply with recommendations, and therefore does not suggest specific interventions; however, the findings of this multicenter pan-European survey may suggest that more educational efforts are required in most European countries to increase the awareness and the adherence to international guidelines on GER as well as other conditions.
Finally, a main shortcoming of our study is that although several European countries took part in the survey, we were not able to draw a comprehensive picture of all of Europe based on this study because of the nonhomogeneous participation of countries and the small number of questionnaires returned in some of them.
Physiologic GER and GERD are frequent conditions in childhood and carry a correspondingly high burden of problems and costs for both families and national health systems, mainly because of inadequate testing and inappropriate medication prescription. Understanding the spectrum of management styles used in the care of children with reflux is paramount for improving quality of care, having a positive effect on a child's quality of life, achieving better health outcomes, and reducing overall health costs.
To date, this is the first study to have examined the knowledge and application of the 2009 NASPGHAN-ESPGHAN guidelines on GER and the only recent European survey of the management of reflux by general pediatricians. In conclusion, the results of our survey show that the present NASPGHAN-ESPGHAN guidelines for GER/GERD management, as well as other guidelines, are poorly adhered to by European general pediatricians (25,26). Educational efforts to ensure the appropriate use of health care resources and to avoid overtreatment of healthy infants and children are required. Moreover, if ESPGHAN and NASPGHAN continue to publish evidence-based guidelines, strategies need to be developed that assess knowledge acquisition, practice style changes, and, most important, improved outcomes in the patients with a specific disease.
A warm thanks to the European pediatricians who voluntarily and freely participated in the survey.
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