Proton Pump Inhibitor Efficacy In Infants With Gastroesophageal Reflux

Proton pump inhibitors are often used in the treatment of gastroesophageal reflux in infants. Gastroesophageal reflux is characterized by regurgitation of gastric contents into the esophagus. This condition is commonly found in practice, especially in infants less than 3 months old. [1,2]

 

Currently, therapy using gastric acid blockers, including proton pump inhibitors, is increasingly being used for gastroesophageal reflux and gastroesophageal reflux disease (GERD). The problem is, the use of these therapies is often based solely on symptoms, without investigation or objective clinical evidence. In fact, the use of proton pump inhibitors routinely and in the long term, is not without risks. [2,3]

 

Examples of proton pump inhibitors include omeprazole, lansoprazole, pantoprazole, and rabeprazole.

 

Use of Proton Pump Inhibitors in Infants with Gastroesophageal Reflux

Pharmacotherapy in cases of infant gastroesophageal reflux is symptomatic, not definitive therapy. Therefore, many experts consider that cases of gastroesophageal reflux in infants do not actually require pharmacotherapy. Management can be done by giving thicker milk, postural therapy, and lifestyle changes to reduce the possibility of regurgitation. Pharmacologic therapy may be considered if conservative therapy does not respond adequately. [4-6]

 

The use of gastric acid inhibitors, including proton pump inhibitors, continues to increase every year. In infants, this increase is reported to be 3-4-fold. [3] Proton pump inhibitors act by inactivating the H+/K+-ATPase transporter on parietal cells in the gastric mucosa. The effect is an increase in gastric pH and a decrease in the volume of gastric secretions which accelerates gastric emptying, so that gastroesophageal reflux symptoms are expected to improve. [2,3]

 

Efficacy and Risks of Using Proton Pump Inhibitors in Infants with Gastroesophageal Reflux

A study attempted to evaluate the efficacy of pantoprazole in 234 infants aged 1-11 months with symptoms of gastroesophageal reflux. In this study, the intervention given was pantoprazole 1.2 mg/kg/day. This study found that symptom improvement was not significantly different between the pantoprazole group and the placebo group. [7,8]

 

Another clinical trial evaluated the efficacy of rabeprazole 10 mg/day in 286 infants with symptoms of gastroesophageal reflux. The results of the study showed that there was no significant difference in symptom improvement between patients receiving rabeprazole and those receiving placebo. [7,9]

 

Similar results were demonstrated by a systematic review evaluating the efficacy of proton pump inhibitors in children aged 0-17 years with symptoms of gastroesophageal reflux. Of all the infant studies analyzed in this systematic review, 1 study showed it was more effective than hydrolysis formulas, 2 studies showed ineffectiveness, and 2 studies showed efficacy comparable to placebo. This systematic review concluded that proton pump inhibitors are not effective for gastroesophageal reflux in infants. [10]

 

A recent Cochrane review analyzed 24 studies with a total of 1201 participants. This study found that proton pump inhibitors can reduce the symptoms of gastroesophageal reflux in confirmed erosive esophagitis. Meanwhile, in analyzes for younger children (under 18 months of age), this drug did not show any improvement in symptoms. [2]

 

Potential Risk

The use of proton pump inhibitors has the potential to cause several side effects, such as an increased risk of gastrointestinal and respiratory infections, vitamin B12 deficiency, hypomagnesemia, fractures, and the risk of increased stomach acid after the drug is discontinued if used for a long time (> 8 weeks).

 

Suppression of gastric acid production during the use of proton pump inhibitors has been shown to increase the risk of necrotizing enterocolitis, sepsis, and meningitis in infants admitted to the intensive care unit. By decreasing the barrier in the stomach, nosocomial infections easily enter and form colonization in the gastrointestinal tract. Long-term use of proton pumps in children has also been shown to increase the risk of colonization with Campylobacter sp and Salmonella sp bacteria. [11]

 

Recommended Clinical Guidelines

Clinical guidelines by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) state that the available scientific evidence is inconclusive regarding the efficacy of proton pump inhibitors in reducing symptoms of crying, irritability. , vomiting, regurgitation, or other symptoms of gastroesophageal reflux when compared to placebo. The following is a summary of the recommendations from these guidelines:

1.     Proton pump inhibitors are recommended as first-line therapy in reflux-related erosive esophagitis for infants with GERD.

2.     Proton pump inhibitors are not recommended for the treatment of crying or irritability in otherwise healthy infants.

3.     Proton pump inhibitors are not recommended for the treatment of regurgitation in healthy infants

4.     Proton pump inhibitors can be used for 4-8 weeks to treat typical symptoms (eg heartburn and epigastric or retrosternal pain) in children with GERD.

5.     Proton pump inhibitors are not recommended for extraesophageal symptoms (eg cough and wheezing), unless typical symptoms or investigations indicate GERD[7]

In Indonesia, the Ikatan Dokter Anak Indonesia (IDAI) still recommends the use of proton pump inhibitors. for the purpose of reducing symptoms and supporting mucosal healing. However, IDAI stated that in principle, gastroesophageal reflux does not need to be treated. If symptoms worsen or do not improve by 12-18 months of age or if there are danger signs, the patient should be referred to a pediatric gastrohepatologist. [12]

 

Conclusion

The available scientific evidence and clinical guidelines do not recommend the use of proton pump inhibitors in infants with gastroesophageal reflux as routine therapy. Proton pump inhibitors have many side effects, including an increased risk of gastrointestinal and respiratory infections, especially if given over a long period of time.

 

References:

1.     Mattos AZd, Marchese GM, Fonseca BB, Kupski C, Machado MB. Antisecretory treatment for pediatric gastroesophageal reflux disease – a systematic review. Arq Gastroenterol. 2017;54:271-80.

2.     Tighe M, Afzal NA, Hayen A, Munro A, Beattie RM. Pharmacological treatment of children with gastro-oesophageal reflux (Review). Cochrane Database of Systematic Reviews. 2016(11):1-82.

3.     Safe M, Chan WH, Leach ST, Sutton L, Lui K, Krishnan U. Widespread use of gastric acid inhibitors in infants: Are they needed? Are they safe?. World J Gastrointest Pharmacol Ther. 2016;7(4):531-539. doi:10.4292/wjgpt.v7.i4.531

4.     Leung AK, Hon KL. Gastroesophageal reflux in children: an updated review. Drugs in context. 2019;8:1-12.

5.     Poddar U. Gastroesophageal reflux disease (GERD) in children. Paed Int Child Health. 2018:1-7.

6.     Baird DC, Harker DJ, Karmes AS. Diagnosis and Treatment of Gastroesophageal Reflux in Infants and Children. Am Fam Physician. 2015;92(8):705-14.

7.     Rosen R, Vandenplas Y, Singendonk M, Cabana M, Lorenzo CD, Gottrand F, et al. Pediatric Gastroesophageal Reflux Clinical Practice Guidelines: Joint Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). J Pediatr Gastroenterol Nutr. 2018;66(3):516-54.

8.     Winter H, Kum-Nji P, Mahomedy SH, Kierkus J, Hinz M, Li H, Maguire MK, Comer GM. Efficacy and safety of pantoprazole delayed-release granules for oral suspension in a plasebo-controlled treatment-withdrawal study in infants 1-11 months old with symptomatic GERD. J Pediatr Gastroenterol Nutr. 2010 Jun;50(6):609-18. doi: 10.1097/MPG.0b013e3181c2bf41. PMID: 20400912.

9.     Hussain S, Kierkus J, Hu P, Hoffman D, Lekich R, Sloan S, Treem W. Safety and efficacy of delayed release rabeprazole in 1- to 11-month-old infants with symptomatic GERD. J Pediatr Gastroenterol Nutr. 2014 Feb;58(2):226-36. doi: 10.1097/MPG.0000000000000195. PMID: 24121146.

10. Van der Pol RJ, Smits MJ, van Wijk MP, Omari TI, Tabbers MM, Benninga MA. Efficacy of proton-pump inhibitors in children with gastroesophageal reflux disease: a systematic review. Pediatrics. 2011 May;127(5):925-35. doi: 10.1542/peds.2010-2719. Epub 2011 Apr 4. PMID: 21464183.

11. Bruyne PD, Ito S. Toxicity of long-term use of proton pump inhibitors in children. Arch Dis Child. 2017;103:78-82.

12. Ikatan Dokter Anak Indonesia. Rekomendasi Diagnosis dan Tata Laksana Penyakit Refluks Gastroesofageal. 2016. http://spesialis1.ika.fk.unair.ac.id/wp-content/uploads/2017/03/Rekomendasi-Diagnosis-dan-Tata-Laksana-Penyakit-Refluks-Gastroesofagus.pdf