Introduction
The ability to diagnose, manage, and treat Gastroesophageal Reflux Disease (GERD) in NICU infants is not very straight forward. Gastroesophageal Reflux (GER) is a very common occurrence amongst all babies, but especially NICU infants. Reflux is also a contentious topic in the neonatology world regarding the most up-to-date way to manage and treat it.
For me personally and professionally, it is difficult to have one solid opinion about the diagnosis and management of GER and GERD. As a former NICU nurse, I saw so many infants experience reflux. As a NICU parent, my son, William, struggled with reflux once we brought him home and yes, at that time, it was managed with medication. And finally, now as a Neonatal Nurse Practitioner, I am more knowledgeable about what the evidence does and does not show regarding reflux and understand its complexity. So I can appreciate how nurses advocate for their patients, I completely acknowledge the internal battle parents endure as they helplessly watch their baby grapple with reflux and its associated symptoms, AND I also embrace what the research has shown and why providers do not hastily start infants on reflux medications.
For this podcast episode, we initially break down Gastroesophageal Reflux (GER) and Gastroesophageal Reflux Disease (GERD), including an explanation for how they are different. We discussed what some of the common symptoms are, how it is typically diagnosed, and concluded with the recommended management strategies and pharmacological and non-pharmacological treatment methods. I hope this provides you with some clarity and up-to-day knowledge!
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Episode 51
Gastroesophageal Reflux and Gastroesophageal Reflux Disease
What is the difference?
What is the difference between GER and GERD? GER is defined as the retrograde passage of gastric contents into the esophagus and possibly the oral cavity with or without regurgitation and/or vomiting. GERD is differentiated because it involves troublesome symptoms or complications that persist and affect daily functioning due to the events associated with GER.
How common is GER?
Gastroesophageal reflux is a common occurrence in all infants. On average, infants experience 30 episodes of gastric fluids refluxing into the esophagus per day. Regurgitation occurs in 40-60% of healthy 0-4 month-old infants. The frequent occurrence of reflux is related to the infants’ frequent feeding cycles as well as the large volumes of milk ingested at each feeding time. Additionally, reflux is more common due to the infants’ necessary supine position (lying on back) following feedings which places the gastroesophageal junction in a liquid environment. As you likely know, the supine position is the position that is most protective against sudden infant death syndrome (SIDS). So despite the increased risk of reflux in the supine position, it remains the recommended position for infants.
The most important mechanism thought to contribute to GER is the transient relaxation of the lower esophageal sphincter. (LES). The sphincter is made up of intrinsic smooth muscle. The LES is an autonomous contractile apparatus that becomes active or relaxes based on different activities. The LES relaxes during swallowing, pharyngeal stimulation, with distention in the esophagus, abdominal straining, and GER. In general, reflexes kick in when there is retrograde movement of contents which are abruptly halted with contraction of the upper esophageal sphincter (UES). This barrier function matures with development and age.
Transient LES relaxation (TLESR) is defined as an abrupt decrease in LES pressure at or below intragastric pressure, unrelated to swallowing. It is the most common mechanism of GER in infants. When this occurs, it allows regurgitation of stomach contents into the esophagus.
But, this is a part of normal developmental phenomenon that will resolve with age and maturation.
How does GERD impact hospital length of stay
Studies have shown that preterm infants diagnosed with GERD have a longer hospital stay and higher hospital costs when compared to infants not affected by GERD. It has been estimated that the diagnosis of GERD in a NICU infant increased the hospital cost by an average of $70,000. And unfortunately, many of these infants will continue to require additional treatment and healthcare costs post NICU discharge as well.
Contributing factors for preterm infants
Gastroesophageal reflux is an almost universal phenomenon in preterm infants and more common when compared to healthy term infants. Gastroesophageal Reflux Disease is also known to be prominent in children who have other underlying medical conditions other than prematurity including neurologic impairments, and pulmonary problems including cystic fibrosis.
The pathogenesis of GER in preterm infants is thought to be multifactorial and partially due to their immature or impaired anatomic and physiologic factors. As I just stated, the most important mechanism thought to contribute to GER in preterm infants, as well as older infants and adults is transient relaxation of the lower esophageal sphincter. Preterm infants have several episodes of transient lower esophageal sphincter relaxation or TLESR each day, that may or may not be associated with episodes of GER. But, infants with GERD are more likely to experience acid regurgitation during LES than those without GERD.
Although delayed gastric emptying is more common in preterm infants compared with mature newborns, it does not appear to play a contributory role in GER. Data has shown that infants with symptomatic GER do not have delayed gastric emptying compared with other asymptomatic infants. Yet, we do know that GER is more common immediately after a feeding but this is most likely due to gastric distention.
Another factor that places preterm infants at an increased risk for GER, is their indwelling ng or og tube that is utilized for feedings. With the tube in proper position, there is incomplete closure of the LES which allows gastric contents to rise up into the esophagus.
Additionally, GER may occur more frequently in infants who have respiratory disorders, like bronchopulmonary dysplasia (BPD). To learn more about BPD, listen to Episode 36 HERE. The contributing factor is thought to be due to the infant’s increased work of breathing which results in an increase of the intra abdominal pressure compared to the intrathoracic pressure. The mismatched pressure is due to coughing, airflow obstruction, or crying. Once this occurs, it causes the LES tone to decrease and contributes to TLESR. Additionally, these infants are often treated with Caffeine which may exacerbate GER due to an increase in secretion of gastric acid and a decrease in LES pressure.
Infants with Intraventricular Hemorrhage (IVH) or Hypoxic Ischemic Encephalopathy (HIE) are more likely to experience GERD due to an increased risk of problematic mechanisms that may contribute to reflux. The incidence of GERD is around 15 – 75% in children with neurologic impairment.
Clinical Manifestations
One of the problematic factors in the ability to diagnose GER or GERD is the nonspecific nature of the symptoms. One paper I reviewed classified the presenting symptoms nicely into 4 different groups.
- Gastrointestinal Symptoms: Regurgitation, vomiting/emesis, and/or abdominal distention.
- Cardiorespiratory : Episodes characterized with bradycardia, tachycardia, apnea, periodic breathing, tachypnea, increased respiratory effort, desaturations.
- Somatosensory: Irritability, back arching, crying, and grimace.
- Aerodigestive: swallowing and feeding difficulties, sneezing, coughing, choking, and breathing disturbances.
Oftentimes, infants can present with more than one category of symptoms or cues. And, assuming the troublesome symptoms are due to reflux events in the absence of evidence remains controversial. According to research, it is likely that in many cases GER is not the underlying cause of these symptoms. It is difficult to prove that reflux events are causing one or multiple symptoms. This is especially true when we attempt to define “troublesome” symptoms due to infants being nonverbal.
Relationship to Other Conditions
Before we dive into the Diagnostic Evaluation and Treatment of GER and GERD, let’s break down its relationship or lack thereof to apnea, respiratory disease, and failure to thrive.
GERD is often linked to apnea as a precursor for episodes of apnea, oxygen desaturations, and bradycardia episodes with assumptions that pharmacologic treatment or medications may decrease the incidence or severity of these events. But, researchers have closely examined the timing of reflux episodes in relation to apneic events and found that they are rarely temporally related AND that GER does not prolong or worsen apnea. The lack of a causal relationship was disputed in studies that utilized cardiorespiratory monitoring, including respiratory inductance plethysmography, heart rate monitoring, oxygen saturation, and esophageal pH testing to detect acidic GER. The Up-To-Date article touched on 3 different studies that illustrated the lack of association between apnea and reflux. They also stated that some studies suggest the opposite that apnea may actually precipitate GER. Additionally, there is no evidence that pharmacologic treatment of GER with medications that reduce gastric acidity and promote gastrointestinal motility decrease the risk of recurrent apnea or bradycardia in preterm infants.
Although infants with GER and GERD may experience frequent regurgitation, there is no evidence that this leads to suboptimal growth, nutritional difficulties, or failure to thrive. However, it has been shown in studies that infants with GER took longer to achieve full oral feedings.
In regards to bronchopulmonary dysplasia (BPD) there is no evidence that GER contributes to BPD, although it is suggested as I mentioned previously, that infants with BPD may be more susceptible to GER, but these infants do not have an increased incidence of symptomatic GER.
Guidelines
To help guide decision-making for the diagnosis, and management of GER with non-pharmacological and pharmacological treatments, the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) published guidelines in 2018 on the approach to children presenting with GER and GERD. Unfortunately, the guidelines are not entirely clear about in their applicability to infants in the NICU, especially premature infants, but we are going to review them here. The guidelines included some great tables and algorithms throughout the article that I found incredibly helpful and wanted to share them with you. Go and grab your free resource so you can follow along now!
Diagnosis
Due to infants presenting with a variety and wide range of non-specific symptoms that may be interpreted as GERD, the reliability is not always clear which leads to both over and under diagnosis and treatment. Unfortunately, there currently is not a crib-side “gold standard” test available that is highly sensitive or specific to diagnose GERD.
Several methods have been used in the past to diagnose GER in the preterm population including contrast fluoroscopy, pH monitoring, and multi-channel intraesophageal impedance (MII) monitoring. So we will breakdown each of these now.
With contrast fluoroscopy, it can be used to show episodes of reflux, but it does not help with proper management due to its inability to differentiate between clinically significant GER from insignificant GER.
pH monitoring with an esophageal probe has been the most widely used diagnostic test for GER in infants. This is what we commonly used when I was a NICU nurse back in the early 2000s to diagnose GER. Unfortunately, it has been found that the diagnostic value is limited due to the need for proper placement of the probe which is difficult because there is a wide spectrum of sizes of preterm infants. Additionally, the gastric pH in premature infants is >4 approximately 90% of the time, and an abnormal esophageal pH does not correlate well with symptom severity. Therefore, measurement of esophageal pH is not a reliable method to diagnose GER in preterm infants.
Currently, the most accurate method for detecting GER is the multi-channel intraesophageal impedance (MII) monitoring which is frequently combined with simultaneous pH measurement. It can be used to track the movement of fluids, solids, and air in the esophagus by measuring changes in electrical impedance. The MII can discern whether a fluid bolus is traveling antegrade (swallowing) or retrograde (reflux) in the esophagus as well as the height of the retrograde bolus. Combined with the pH sensor, it is thought to be a reliable technique to determine acidity and for diagnosing GER in preterm infants.
Despite these available diagnostic tools, the responsibility of whether or not to treat GERD empirically or wait, or to consider additional tests for troublesome symptoms ultimately rests with the physician.
Management and Treatment
A thorough physical exam of the infant combined with a focused history should be completed. The infant’s symptoms and clinical condition should be followed closely to monitor for worsening symptoms. The initial management needs to always consider optimal nutrition, feeding methods, and continuation of breastfeeding.
The initial management of GER is conservative and typically consists of dietary changes. There are also feeding modifications that may be recommended if there is a definitive relationship between symptoms and GER. For breastfed infants, a modification in the maternal diet free from all dairy, including casein, whey, and eggs should be followed for 2 to 4 weeks to help to rule out a protein allergy that may mimic GERD. For formula-fed infants, the same practice applies if trying to rule-out a cow’s milk protein sensitivity, consider trying a 2 to 4 week trial of an extensively hydrolyzed protein formula. The practice guidelines from 2018 recommend a trial at a minimum of 2 weeks to adequately assess symptom improvement.
It may be beneficial to consider a trial of decreased volume feedings with or without an increase in the frequency. The guidelines suggest to modify feeding volumes and frequency according to age and weight ensuring not to overfeed infants with GERD. But, this should be done in collaboration with a dietitian and/or provider to closely monitor the infant’s overall growth.
Another option to consider is thickened feedings. Thickened feedings are thought to decrease the incidence of GER, but it does not decrease the acidity of the reflux. Per the recommendations by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition, the use of thickeners may slightly improve the occurrence of overt regurgitation/vomiting, but it is uncertain if thickening feedings improves other signs and symptoms of GER and if their use leads to side effects in infants. For term infants with GER and GERD, it is recommended to use 1 TBSP of dry rice cereal per 1 oz. of formula. The US Food and Drug Administration and the American Academy of Pediatrics (AAP), issued a warning about the use of thickened feedings and its association with necrotizing enterocolitis (NEC) in premature infants.
Continuous or transpyloric feedings may reduce the incidence of apnea/bradycardia in preterm infants with GER. Despite this, there is no evidence in research to support the use of continuous or transpyloric feedings to help reduce GER.
Although a common initial approach to management of reflux is to raise the infant’s head of the bed, but it has been shown to be ineffective in reducing acid reflux in older infants. Additionally, car seat placement was found to elicit worse acid GER in term infants. The AAP and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition have stated that all infants, even those with GER, should be placed to sleep in the supine position or on their back with the exception of the rare infants for whom the risk of death from GER is greater than the risk of SIDS. They do not recommend positional therapy with either head elevation or lateral and prone positioning to treat symptoms of GERD in sleeping infants.
Pharmacologic Options for GERD
Pharmacologic therapy or the use of medications has a limited role in infants with GER. The AAP’s “Choosing Wisely in Newborn Medicine” initiative targeted decreasing the frequency antireflux medications are used in infants. Therefore, pharmacologic therapy is reserved for infants who fail conservative management and for those who have symptoms or diagnostic test results that are strongly suspicious for GERD. Additionally, the routine use of antireflux medications for treatment of symptomatic GERD or for the treatment of apnea and desaturations in preterm infants should also be avoided. If you recall as I stated before, there is not supportive evidence that treatment of GER with medications that decrease gastric acidity or increase gastrointestinal motility actually decrease the risk of recurrent apnea or bradycardia in preterm infants.
Prokinetic agents like Metoclopramide (Reglan , domperidone, and erythromycin have been used in older infants to reduce the symptoms of GER, but they have not been shown to reduce the occurrence of lower esophageal relaxations or symptoms in preterm infants. Additionally, they all have the potential for significant adverse effects. The 2018 guidelines suggest not to use any of the mentioned prokinetic agents in the treatment of GERD in infants and children.
Another medication used at times is Sodium Alginate combined with sodium bicarbonate. In the presence of gastric acid, alginate formulations precipitate into a low-density viscous gel and act as a physical barrier protecting the esophagus from acidification. Once they are combined with sodium bicarbonate, a carbon dioxide foam forms and protects the lower esophagus from acidification. Use of Sodium Alginate with sodium bicarbonate may decrease the signs of GER in older infants and in preterm infants with a decrease in the frequency of regurgitation, a decrease in the number of acidic GER episodes, and a decrease the amount of total esophageal acid exposure. Unfortunately, the long-term safety has not been evaluated in preterm infants.
Proton pump inhibitors (PPIs) or medications like omeprazole and lansoprazole otherwise known as Prilosec and Prevacid block the proton pump in the gastric parietal cell which is the last step in the acid secretory pathway. They ultimately decrease acid secretion and will maintain the stomach pH > 4, but they have not been shown to relieve the clinical signs of GER in clinical trials. Additionally, they are also associated with adverse reactions and events. The guidelines do recommend the use of PPIs as a first-line treatment of reflux-related erosive esophagitis in infants and children with GERD.
Histamine (H2) receptor blockers (H2RA) like ranitidine and famotidine or otherwise known as Zantac and Pepcid decrease hydrochloric acid secretion and increase the intragastric pH. Unfortunately, there have not been studies done in preterm infants and there are adverse side effects associated with their use including an increased incidence of NEC. The guidelines suggest to use H2 receptor blockers in the treatment of reflux related erosive esophagitis in infants and children if PPIs are not available or contraindicated.
The guidelines reiterate to not use H2RAs or PPIs for the treatment of crying/distress or visible regurgitation in otherwise healthy infants. They recommend a 4 to 8 week course of treatment with regular evaluation of the efficacy and need of long-term acid suppression therapy in infants and children with GERD.
For some infants, surgical intervention with fundoplication may be used. The surgery is typically reserved for infants with severe GERD who have failed maximum medical management.
So there you have it! Unfortunately, as you just heard, there is not a clear cut diagnostic tool or management plan for NICU infants with GER and GERD. I know that many infants in the NICU struggle with reflux, there is no doubt about it, but in the absence of a single “gold standard” diagnostic tool and/or management plan, especially for preterm infants, it makes it so difficult to properly educate you, my listeners on the topic. Additionally, I must point out that the guidelines I referred to and some of the resources I used are from 2018 and 2019 because that is all that is currently available. Even the “Up-to-Date” article that I reviewed did not cite more recent studies. Hopefully, there are current studies occurring right now that will help provide more clear cut recommendations for diagnostic tools and management plans for GER and GERD as it applies to infants in the NICU.
Additionally, I must add that all infants are different, so what may work for one infant may not work for another. Also, each NICU will manage and treat reflux differently, so I encourage parents to be an advocate for your child, ask questions, and be involved in their daily plan of care. Although you may want to rush to treat your child’s reflux, just know that the medications available do not come without the potential for adverse side effects. And, as you just heard there is not a clear cut treatment plan or optimal medication to use right now. So be patient, support your infant, and continue to work alongside their care team to find the right management and treatment plan for your individual infant, which may often be the tincture of time.
Closing
Although the recommendations are not crystal clear for how to manage reflux, I hope you found the information I provided throughout the episode helpful. At the very least, I hope you have a much better understanding of the difference between GER and GERD and realize now – if you didn’t already – that the diagnosis and management of reflux, especially amongst our NICU population is not very straight forward. For parents or even professionals that work in the NICU, you can appreciate why reflux is such a controversial topic in the neonatology world. I hope the information I provided today did not muddy the waters for you more, but provide you with the most up-to-date, evidence-based information available on GER and GERD.
For parents and NICU clinicians, please continue to advocate for your children or patients. Monitor their symptoms and pass the information along, but do not become frustrated if you feel like the providers are not moving forward or it appears they are not doing anything. I promise, they are very closely monitoring the infant and their symptoms. As you heard me say, it is not recommended to immediately start infants on reflux medications, especially premature infants. Also, despite what you may have heard elsewhere, all infants needs to be placed on their backs to sleep. They should not be on their abdomens or have the head of their bed elevated at home.
Remember, if you have not already, grab your free resource with the tables and algorithms from the guidelines specific to GER and GERD that I referred to throughout the episode.
Resources
Eichenwald, E. (2018). Diagnosis and management of gastroesophageal reflux in preterm infants. Pediatrics, 142(1). https://doi.org/10.1542/peds.2018-1061
Gomella, T., Eyal, F., & Bany-Mohammed, F. (2020). Gomella’s Neonatology: Management, Procedures, On-Call Problems, Diseases, and Drugs, 8th Edition. McGraw-Hill.
Gulati, I. & Jadcheria, R. (2018). GERD in the NICU infant: Who needs to be treated and what approach is beneficial? Pediatrics Clinics of North America, 66(2), 461-473.
Martin, R. & Hibbs, A. (2021). Gastroesophageal reflux in premature infants. UpToDate. Retrieved on August 2023 from https://www.uptodate.com/contents/gastroesophageal-reflux-in-premature-infants#H6
Rosen, R., Vandenplas, Y., Singendonk, M., Cabana, M., DiLorenzo, C., Gottrand, F., Gupta, S., Langendam, M., Staiano, A., Thapar, N., Tipnis, N., & Tabberd, M. (2018). Pediatric Gastroesophageal reflux clinical practice guidelines: Joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition, and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. Journal of Pediatric Gastroenterol Nutrition, 66(3), 516-554.
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