Gastroesophageal Reflux in Neonates and Infants · Gastroesophageal reflux disease in neonates and infants. PediatrDrugs 2013;15:19-27 • FunderburkA, NawabU et al Temporal association

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Gastroesophageal Reflux in

Neonates and Infants

Thomas N. George, MD FAAPSystem Director, Neonatology, Children’s Minnesota

Professor of Pediatrics, University of Minnesota

Minnesota Perinatal Organization

45th Annual Conference

September 19.2019

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Take home points

• Gastroesophageal reflux is a frequent occurrence in all newborns, especially preterm newborns

• Avoid the “pathologizing” of this normal developmental phenomenon

• There is no role for medications for GER in premature infants

• Manipulations of feedings has minimal impact, and can be detrimental

• Strive to have all infants on their back to sleep, with head of the bed flat starting at 32 weeks

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Objectives

• To identify signs of neonatal and infant

gastroesophageal reflux (GER)

• To describe the difference between GER and GER

disease

• To describe effective and ineffective therapies of

neonatal and infant GER

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Gastroesophageal Reflux (GER)

Definition:

• The involuntary passage of gastric contents into the

esophagus

• “Happy Barfers”!!!

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GER

Normal physiological process

• Transient lower esophageal sphincter relaxation

(TLESR)

• Unrelated to swallowing and of relatively longer

duration than the relaxation triggered by a swallow

Most common visible symptoms

• Regurgitation and spitting up

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GER

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GER Signs: Regurgitation/vomiting

Differential:

• Sepsis

• Sepsis

• Sepsis

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GER Signs: Regurgitation/vomitingDifferential:

• Bowel obstruction –

• bilious could be from volvulus

• non-bilious would be more distal obstruction

• NEC

• Medications eg caffeine

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GER Signs: Regurgitation/vomitingDifferential:

• Pyloric Stenosis

• Inborn errors of metabolism

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GER – Term infants

Term babies

• Some babies/infants throw up after almost every

feedings, and many times between feedings

• ~70-85% of infants have reflux in the first 2 months

of life

• GER peaks at ~ 4 months of age, resolves by 12 –

18 months

• In one study, 10% of babies in a well baby clinic had

signs of GER

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GER – Preterm infants

• Common diagnosis in the NICU

• Large variation in how it is diagnosed and treated

• Diagnosis is typically made by clinical/behavioral

signs

• Documented that preterm infants have dozens of

episodes of TLESR every day

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• NG/OG tube through the LES can increase the

frequency of GER

• GER is more common immediately after feeding, likely

due to gastric distention

GER – Preterm infants

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• Prone positioning decreases GER versus supine

positioning

• If reflux reaches the upper esophagus, the Upper

Esophageal Sphincter reflexively opens and allows

material to enter the pharynx

• Results in frequent spitting up/emesis

GER – Preterm infants

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Gastroesophageal Reflux Disease (GERD)

When there are clinical consequences of GER:

• Acidic contents of stomach reflux into esophagus

and create potential to irritate and damage

mucosal surfaces from acid

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Gastroesophageal Reflux Disease (GERD)

When there are clinical consequences of GER:

• Failure to thrive from excessive emesis

• Bleeding

• Respiratory problems with frequent

coughing/recurrent aspiration or pneumonia

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Gastroesophageal Reflux Disease (GERD)

Treatment options may involve

• H2 blockers eg ranitidine

• PPI eg omeprazole

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Less likely in preterm infants:

• GER is only weakly acidic because of lower gastric

acid and frequent milk feedings

Gastroesophageal Reflux Disease (GERD)

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GER - Diagnosis

Clinically

• Clinical and behavioral signs felt to be associated

with GER: feeding intolerance, apnea, bradycardia,

desaturation

• Nonspecific behavioral signs felt to be associated

with GER : arching, irritability, apparent discomfort

with feedings

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Contrast study

• Doesn’t differentiate

between clinically

significant GER

from insignificant

GER

• One moment in

time

GER - Diagnosis

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pH probe study

• Typically used in older children and adults

GER - Diagnosis

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Multichannel Intraesophageal Impedance (MII)

• Most accurate method, reliable and reproducible

GER - Diagnosis

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GER and Clinical events

MII-pH (Funderburk et al)

• Prevalence of significant detected GER was low

• Majority of suspected clinical reflux behaviors did

NOT correlate directly to actual reflux

• Temporal relationship between:

• Irritability and reflux: 19%

• Bradycardia and reflux: 5%

• Gagging and reflux: 57%

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• Frequency of apnea during reflux was the same as

periods that were reflux free

• GER does not prolong or worsen apnea

GER and Clinical events

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GER – Treatment

Body positioning

• Head up angle – commonly used therapy

• Ineffective in reducing acid reflux

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Body positioning

• LLR and prone positioning – reduces vomiting –

other signs did not change

• LLR/prone is not consistent with positioning for SIDS

prevention

• Babies should be on monitors continuously

GER – Treatment

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AAP and NASPGN – recommend supine sleep

position

• to reduce SIDS risk

• Model appropriate positioning for family

Recommend supine and flat sleeping at ~ 32 weeks

And if the baby is still spelling?

• Most “spells” are not related to feeding, reflect immaturity that

requires ongoing in-house monitoring

GER – Treatment

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Feeding strategies

• Longer feeding duration and lower milk flow rates

associated with fewer GER events (median rate still

25.6 minutes)

• However, this is at nutritional cost –

• IL and protein bind to tubing

• Recommend feeding target to be given over 30

minutes

GER – Treatment

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Thickened feedings with rice cereal

• RCT of thickened feedings in term infants reduced

episodes of regurgitation

In preterm infants, small trials have been done:

• 1 trial of starch-thickened formula, total number of

GER episodes were unchanged compared with

standard formula

GER – Treatment

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Elemental or hydrolyzed protein formulas

• Reduce GI transit time

• Reduce symptoms in term infants with symptomatic

GER

In preterm infants

• Fewer reflux episodes as measure by MII, but did not

reduce behavioral signs of GER (Logarajha et al)

GER – Treatment

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Pharmacologic Treatment

• H2 blockers

• Decease acid secretion

• Not studied in preterm infants to assess effect on clinical

symptoms

• Increased risk of NEC

• Impact on microbiome

• PPI

• Ineffective in reducing GER signs in infants

GER – Treatment

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Pharmacologic Treatment

• Prokinetic agents

• None have shown to decrease GER symptoms in preterm

infants

• All linked to higher risk for pyloric stenosis (erythromycin),

cardiac arrhythmia (erythromycin) or neurologic side effects

(metoclopramide)

GER – Treatment

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How to counsel families:

• If stomach is full or position changes quickly, that could

cause GER

• GER rarely causes distress and usually goes away as

digestive tract matures, usually by six months, but can take

about a year

• Does not require drug treatment

• Try to keep baby upright for 30-60 minutes after feedings

• Feeding smaller, more frequent amounts can be helpful

GER – Treatment in preterm infants

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Consistent message to family from all team members:

• “Non pathologizing” of a normal developmental process

GER – Treatment

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It’s messy – it’s not pathologic

GER – A challenge and nuiscance

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Conditions with higher prevalence of GER

• Cerebral palsy

• Developmental delay

• Esophageal atresia/TE fistula

• CDH

• Obesity

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Term infants

If GERD suspected:

• Have mother avoid milk and dairy products for 2-4

weeks if breastfeeding

• Formula – consider extensively hydrolyzed formula

• Thickened formula – with one tablespoon of rice

cereal per 1-2 ounces of formula

• Formulas designed for reflux

• Avoid overfeeding, don’t refeed after spitting up

• Hold upright after feedings

• Smaller volumes, more frequently

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Clinical Report, AAP, Committee on Fetus and Newborn

Diagnosis and Management of Gastroesophageal

Reflux in Preterm Infants. Pediatrics July, 2018

AAP Recommendations

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GER and Preterm Infants

Recognition and education of all NICU staff and parents that:

• 1. Gastroesophageal reflux (GER) is a normal occurrence in preterm infants associated with

frequent and developmentally appropriate Transient Lower Esophageal Sphincter Relaxation

(TLESR) events; it is almost always not pathologic.

• 2. In studies measuring true occurrence of GER, signs attributed to GER including feeding

intolerance, apnea, bradycardia, desaturation, feeding-associated arching, irritability and

recurrent emesis have not been shown to be associated with documented reflux.

• 3. Positioning (e.g. elevation of the head of bed) has not been shown to be effective in

decreasing signs attributed to reflux; if infants have had the head of the bed elevated, the

head of bed should be made flat by 32 weeks corrected gestational age and babies should

be supine to promote safe sleep practices in preparation for going home. Babies admitted at

32 weeks corrected gestational age or greater should not have the head of bed elevated

without a provider order.

• 4. Altering of feedings (e.g. infusion of feedings over extended periods of time) can reduce

the nutritional value of breastmilk from significant fat loss due to increased time in contact

with tubing; by 32 weeks corrected gestational age, it is recommended that all feedings be

given over no longer than 30 minutes (refer to feeding guidelines).

• 5. There is no role for medications for treatment of suspected GER in premature infants.

Memo to all team members

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Summary

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• Spit happens

Summary

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Take home points

• Gastroesophageal reflux is a frequent occurrence in all newborns, especially preterm newborns

• Avoid the “pathologizing” of this normal developmental phenomenon

• There is no role for medications for GER in premature infants

• Manipulations of feedings has minimal impact, and can be detrimental

• Strive to have all infants on their back to sleep, with head of the bed flat starting at 32 weeks

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Reference list

• Eichenwald EC and AAP Committee on Fetus and Newborn. Diagnosis and management of gastroesophageal reflux in preterm infants. Pediatrics 2018;142:e20181061

• Czinn SJ and S. Blanchard. Gastroesophageal reflux disease in neonates and infants. Pediatr Drugs 2013;15:19-27

• Funderburk A, Nawab U et al Temporal association between reflux-like behaviors and gastroesophageal reflux in preterm and term infants. J Pediatr Gastroenterol Nutri 2016: 62: 556-561

• Peter CS, Sprodowski N et al Gastroesophageal reflux and apnea of prematurity: no temporal relationship Pediatrics 2002, 109:8-11

• DiFiore JM Arko et al Apnea is not prolonged by acid gastroesophageal reflux in preterm infants. Pediatrics 2005;116:1059-1963

• Loots C Kritas et al Body positioning and medical therapy for infantile gastroesophageal reflux symptoms J Pediatr GastroenterolNutri 2014;59:237-43

• Jadcherla SR Chan CY et al. Impact of feeding strategies on the frequency and clearance of acid and nonacid gastroesophageal reflux events in dysphagic neonates J Parenter Enteral Nutri 2012: 36: 449-455

• Garzi A, Messina M et al An extensively hydrolysed cow’s milk formula improves clinical symptoms of gastroesophageal reflux and reduces the gastric emptying time in infants. Allergol Immunopathol (Madr) 2002;30:36-41

• Logarajaha V, Onga C et al PP-15 the effect of extensively hydrolyzed protein formula in preterm infants with symptomatic gastroesophageal reflux J Pediatr Gastroenterol Nutr 2015;61:526

• Guillet R Stoll BJ et al NICHD NRN Association of H2-blocker therapy and higher incidence of NEC in VLBW infants Pediatrics 2006;117:

• Orenstein SR, Hassall E et al. Multicenter, double-blind, randomized, placebo-controlled trial assessing the efficacy and safety of proton pump inhibitor lansoprazole in infants with symptoms of gastroesophageal reflux disease J Pediatr 2009;154:514-520

• Ho, T, Dukhovny D et al. Choosing wisely in newborn medicine: five opportunities to increase value Pediatrics 2015: 136. Available at www.pediatrics.org.cgi/content/full/136/2/e482

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• Comments welcome!

Thank you!