Gastroesophageal reflux (GER) and gastroesophageal reflux disease (GERD)
Definition
Gastroesophageal reflux: The North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPHGAN) define gastroesophageal reflux as the process of gastric contents moving into the esophagus independent of regurgitation or vomiting.
Gastroesophageal reflux disease: The presence of gastroesophageal reflux associated with troublesome symptoms and/or complications.
Incidence
While the majority of infants spit at least daily in the first few months of life, the true incidence of GERD in preterm infants is unknown, in part due to the difficulty in confirming a diagnosis in this population. In a study of healthy term infants, half of all parents reported at least daily regurgitation at 0 to 3 months of age. The peak prevalence occurred at 4 months, with 67% reporting regurgitation, and declined rapidly thereafter. Nevertheless medications for GERD are among the most commonly used drugs in the NICU and at NICU discharge with approximately 25% of ELBW infants being discharged home on antireflux medications.
Pathophysiology
Normal and preterm infant esophageal function
Normal esophageal motor function limits the movement of fluid from the stomach to the esophagus and is well developed in infants as early as 26 weeks’ gestational age.
Swallowing triggers antegrade esophageal peristalsis and lower esophageal sphincter (LES) relaxation, with the speed of peristalsis being faster in term than preterm infants.
Incomplete or asynchronous waves unrelated to swallowing occur more frequently in preterm infants than in adults.
The LES comprises esophageal smooth muscle and diaphragmatic skeletal muscle. Good LES tone is present at birth in both term and preterm infants including those of extremely low birthweight.
Transient LES relaxations (TLESRs)
TLESRs unrelated to swallowing allow GER by dropping lower esophageal pressure below gastric pressure.
While TLESRs often occur several times per hour in preterm infants, most TLESR events are not associated with GER. In fact, preterm infants with and without GERD experience a similar frequency of TLESRs, but infants with GERD have a higher percentage of acid GER events during TLESRs.
Although LES relaxations also occur during normal swallowing, these are less often associated with GER events than isolated TLESR events, likely due to the accompanying antegrade peristaltic wave propelling the fluid bolus toward the stomach.
Gastric emptying
Compared to adults and older children, infants ingest a much higher volume per kilogram of bodyweight, approximately 180 mL/kg/d; therefore, gastric emptying plays an important role in the passage of fluids through the upper gastrointestinal tract.
Gastric emptying time is inversely correlated with gestational age at birth.
Simultaneously decreasing the osmolality and increasing the volume of feeds promotes gastric emptying.
Emptying also occurs faster with human milk feedings than with formula. Prebiotics, probiotics, and hydrolyzed formulas may speed gastric emptying in formula-fed infants.
Fortification of human milk may slow gastric emptying.
Thickeners may delay gastric emptying.
While it seems logical that slower gastric emptying would be associated with increased GER, a study of the relationship between gastric emptying and GER in preterm infants found no association.
Milk buffering
Because milk feeds act as a buffer of gastric acid, GER events prior to feeding are much more acidic than GER events after feeding, when nonacid GER predominates.
Risk factors
Feeding tubes
In the NICU population, preterm and term patients with nasogastric or orogastric feeding tubes may experience more reflux episodes due to mechanical impairment of the competence of the LES.
Respiratory disease
It is also hypothesized that conditions that increase abdominal pressure or decrease intrathoracic pressure, such as labored breathing, may promote GER during TLESRs.
Other NICU diagnoses
Conditions with abnormal smooth muscle function, or an abnormal esophagus or LES, such as repaired esophageal atresia or congenital diaphragmatic hernia, or abdominal wall defects, such as gastroschisis, also predispose to GER.
Multiple medications
High osmolality of multiple oral medications combined with feeds decreases gastric emptying time.
Muscle tone abnormality
Hypertonia or hypotonia may predispose an infant to GER symptoms.
Clinical presentation
Signs and symptoms
Symptoms thought to be associated with GER in infants include regurgitation, Sandifer posturing, feeding intolerance, fussiness, stridor, apnea, bradycardia, or worsening lung disease.
However, studies have shown that these symptoms are poor markers of the presence of GERD as symptoms such as regurgitation, irritability, and vomiting are similar symptoms caused by food allergy, colic, and other disorders.
Furthermore, causal relationships between GERD and a many of these symptoms, including apnea and worsening lung disease, have not been well established.
Of note, several studies show that GER is rarely associated with cardiorespiratory events (<3%) and has been shown to have no or minimal effect on cardiorespiratory event duration or severity.
Condition variability
The presence of intermittent GER is common in infants with an increased occurrence with feeds and right lateral positioning.
Diagnosis of GER and GERD
Clinical observation
Although the association between most physical symptoms and GER is unproven, clinical assessment continues to be the most widely used method of diagnosing GERD. These assessments are not diagnostic of GER or GERD or predictive of response to therapy and should be used in combination with quantitative investigational tools such as pH-metry, multiple intraluminal impedance, GI contrast study, and scintigraphy whenever possible. While quantitative tools can document the amount of GER, a diagnosis of GERD cannot be made without clinical symptoms or complications.
pH-metry
Esophageal pH monitoring is the conventional modality for quantifying GER and is generally accepted as the gold standard.
Events are traditionally defined as a drop in pH of <4, based on data in adults showing heartburn induced by GER occurs at this pH level.
Occasional brief episodes of acid reflux are normal in infants and can be captured with short-term continuous monitoring; however, longer monitoring over a 24-hour period has been shown to be more reliable for obtaining reproducible results.
Limitations: pH monitoring is limited by its ability to only detect acid-based reflux and, with frequent feeds in preterm infants, may miss many bolus events as milk buffers the gastric contents. It is not clear which characteristic of the refluxate is most likely to trigger symptoms: the acidity, volume, or height. While extrapolation from esophagitis in older populations has tended to focus diagnostic and therapeutic efforts on acidity, there is a paucity of data demonstrating acidity to be the cause of morbidity in infants.
Reference values: Acid reflux can vary widely in healthy asymptomatic infants. In a small study of asymptomatic preterm infants, monitored at a median postmenstrual age of 32 weeks, the median acid reflux index was 5.6%, (range 0.0% to 20.7%). In a larger study of asymptomatic term infants (age 3 to 365 days), there were 24ŷ31 events/24-hour study with a median acid reflux index of 4% (95th percentile 10, range 1 to 23). Although there are no current standards for treatment, an acid reflux index of 10% accompanied by clinical symptoms is often considered the threshold for an abnormal study.
Multiple intraluminal impedance monitoring (MII)
The MII system can detect the presence and location of a fluid or air bolus and is the only method of recording GER that can detect both acid and nonacid GER. With multiple electrodes placed along the catheter, the direction of the bolus can be detected as it moves antegrade, from the proximal to the distal tip of the catheter as occurs during a swallow, or retrograde, from the distal tip to more proximal channels as occurs during reflux. The MII GER definition requires a retrograde drop in at least two consecutive impedance channels to less than or equal to 50% of the baseline preceding the event. The MII-based GER event is defined as acidic if it is accompanied by a drop in pH of <4. MII events occurring without a drop in pH <4 are generally considered nonacid GER.
Limitations: The MII catheter should be placed between T7 and T9 and verified by chest radiograph. Placement too high may result in missed GER events, while too low may result in constant low impedance due to continuous monitoring of stomach contents. Although MII represents a step forward in the quantification of GER, in symptomatic infants 9% to 59% of pH events may be missed by MII, with improvement with increasing age. The larger catheter diameter (7 Fr MII versus 5 Fr pH catheters) limits its use in smaller infants and increases the theoretical risk of esophageal trauma during catheter placement.
Reference values: Currently MII remains a research tool with limited use in the clinical setting due to minimal baseline data on which to base threshold values for interventional therapy. One small study of asymptomatic preterm infants reported a median acid-based MII exposure of 1.7% (range 0% to 6.4%) and a median nonacid-based MII exposure of 0.7% (range 0.3% to 1.2%). With the ability to detect both acid and nonacid reflux, this system may become a valuable diagnostic tool for GER in infants in the future.
Upper gastrointestinal (GI) series
An upper GI series can identify anatomic abnormalities of the upper GI tract that may mimic GERD; however, it should not be used to diagnose GERD. While GER may be noted on the study, the assessment occurs over such a brief period of time that the overall frequency of GER cannot be determined. Consider an upper GI on infants with severe GER in order to rule out anatomic cause, especially if the emesis is ever bilious.
Scintigraphy study
Also known as a milk scan or gastric emptying study, this nuclear medicine study documents postprandial GER over a longer time frame than the upper GI series, but does not record repeated pre- and postprandial windows like esophageal monitoring. The scintigraphy study can also detect delayed gastric emptying, which may mimic GERD, and if delayed images of the lungs are obtained, can document microaspiration of the refluxate if this is a clinical concern. However, nuclear scintigraphy is not recommended for the routine evaluation of pediatric patients with suspected GERD.
Management (see Figure 14-1)
Medical
Because the difference between pathologic GERD and physiologic GER hinges on the presence of complications and symptoms, the efficacy of GERD therapies must be judged on their impact on clinical parameters, and not physiologic measures.
Nonpharmacologic medical management
Small frequent meals
Positioning
While positioning has not been shown to be effective in improving GERD symptoms in systematic review, left-sidelying position has been shown to reduce postprandial reflux episodes and right-sidelying position improves gastric emptying.
Changes in formula or maternal dietary restrictions if bovine protein intolerance is suspected.
Thickened feeds
Thickening feeds has been shown to decrease clinical regurgitation in infants, although not specifically in acutely ill neonates or preterm infants.
Certain brands of commercial thickeners (containing xanthan gum, based as a gel product), however, have been associated with late-onset NEC and should not be used in preterm or term infants.
Transpyloric feedings may reduce apneic events thought to be caused by severe reflux events; however, it may increase morbidity.
Pharmacologic therapy
Because of the risks of GERD medications and the lack of proven benefit in the NICU population, they should not be routinely prescribed. In an infant with severe complications of GERD in which the risk-benefit ratio warrants a trial of pharmacotherapy, the drug should be stopped if there is no clear benefit. Therapies include
Acid reducers
These agents (histamine-2 receptor blockers and proton pump inhibitors) are intended to decrease gastric acidity based on the theory that acidity is the characteristic of the refluxate that triggers unwanted symptoms.
Theoretically, acid reducers could decrease discomfort associated with acid reflux.
In observational studies, acid blockade has been associated with increased late-onset sepsis and NEC in premature infants.
Cimetidine use in VLBW infants has been associated with increased death or IVH.
A randomized trial of extubated preterm infants with apnea and bradycardia, combined therapy with ranitidine and metoclopramide was actually associated with increased bradycardia.
Prokinetic agents
The agents (metoclopramide and erythromycin) are used to encourage the antegrade movement of ingested milk. Cisapride is no longer available in the United States due to associated arrhythmias in children.
Erythromicin has been studied in feeding intolerance in preterm infants, but has not been shown to improve GERD. In addition, erythromycin stimulates the gut migratory motor complex, which is not fully developed until 32 weeks, and, therefore, is not recommended in less mature infants.
Surgical
Gastric fundoplication is usually not feasible in a critically ill or very small neonate. In general, infants need to be at least 2.5 kg before consideration.
Medical management is the mainstay of therapy until the infant becomes a suitable surgical candidate and has demonstrated that GERD symptoms will not improve over time, as they do in the majority of infants.
Fundoplication should be reserved for only those infants with serious consequences resulting from severe GERD (acute life-threatening events, recurrent aspiration pneumonia, oral aversion, failure to thrive, etc).
Complications resulting from fundoplication are not uncommon.
Post-Nissen dumping syndrome
This should be assessed in all infants upon resuming full feeds following fundoplication.
Check a bedside glucose 30 and 60 minutes after a feed and just before (ac) the next feed. If blood glucose levels are outside the range of 50 to 200, this is abnormal.
Treat dumping syndrome by slowing gastric emptying time with a feeding pump or adding corn starch (GT feed) or crushed baby cereal (oral feed) to the milk.
Gagging/retching
This can be very difficult to treat.
Feedings via a pump may help.
Venting the G-tube or continuous venting bags may help.
Baclofen or antiemetics may help.
Early developmental/therapeutic interventions
Positioning
Infants with chronic GER may develop a strong right-sided rotational head preference.
In order to prevent asymmetry in tone, torticollis, and/or plagiocephaly, aggressive attention to midline positioning should be taken.
Extensor bias
Infants with chronic GER may develop a strong extensor bias, with increased neck and back extensor tone.
Attention to strengthening neck/trunk flexor muscle groups may improve this bias.
Prognosis
Time is the primary factor in improving GER symptoms. Even among infants with established GERD, approximately half will improve over several weeks. Thus, watchful waiting is a prudent initial approach. Furthermore, when an infant appears to respond to a therapeutic intervention, it could be due to either the intervention or the natural history of the disease (resolution over time). For those infants started on antireflux medications, a trial off the medication prior to discharge, while still being observed in the transitional nursery, should be considered.
Discharge
Teaching
Parents should be instructed on supportive measures that may improve GER symptoms in the home environment.
Maintaining upright positioning after feeds
Limiting activity after feeds
Left-sided positioning after feeds (until placing the infant back to sleep)
Smaller, more frequent feeds
Parents should be instructed that GER symptoms will likely worsen after discharge, with an increase in feeding volumes, but that it will improve with time.
Parents should be taught how and when to give medications, if being discharged home on antireflux meds.
Caregivers should be instructed on the use of a bulb syringe in the event of nasal regurgitation, as well as infant CPR.
Monitoring
Prior to discharging an infant home on cardiorespiratory monitoring due to a history of reflux events, a thorough evaluation of the cause of apnea is warranted as apnea and bradycardia episodes are rarely caused by GER.
Consider home apnea monitoring in an infant with a history of ALTEs in the nursery thought to be due to reflux.
If utilized, home monitors should be equipped with an event recorder, have 24-hour service available, and parents should be instructed in infant CPR.
Safety
Parents should be advised that infants, even with a history of GER, should be positioned on their back for sleep. It is not safe to put them in a swing or bouncy seat in order to keep them upright during sleep in hopes to reduce GER symptoms.
Parents should be advised that cobedding infants, with adults or other children, is strongly discouraged.
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