GERD: Does it hurt?

Prof E De Greef

Kidz’HEALTH Castle

Colloque de douleur néonatale ‘au creux de mon ventre’ 6/2/20

WHAT IS GERD?

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GER: the passage of gastric contents into the esophagus with or without regurgitation and vomiting. GERD: when GER leads to troublesome symptoms and/or complications. Refractory GERD: GERD, not responding to optimal treatment after eight weeks.

Statement 1

Pediatric GER Clinical Practice Guidelines: Joint Recommendations of NASPGHAN & ESPGHAN

Rosen R (NASPGHAN) - Vandenplas Y (ESPGHAN) - JPGN 2018;66:516-554

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Nelson 1997

Regurgitation in infants

15 %

20 %

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Natural evolution of regurgitation in infants

Age (months)

% infants

Natural evolution of regurgitation in healthy infants Hegar B, Vandenplas Y. Acta Paediatr 2009;;98:1189-93

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Pediatric GER Clinical Practice Guidelines: Joint Recommendations of NASPGHAN & ESPGHAN

Rosen R (NASPGHAN) - Vandenplas Y (ESPGHAN) - JPGN 2018;66:516-554

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Pediatric GER Clinical Practice Guidelines: Joint Recommendations of NASPGHAN & ESPGHAN

Rosen R (NASPGHAN) - Vandenplas Y (ESPGHAN) - JPGN 2018;66:516-554

8 17-2-2020

Pediatric GER Clinical Practice Guidelines: Joint Recommendations of NASPGHAN & ESPGHAN

Rosen R (NASPGHAN) - Vandenplas Y (ESPGHAN) - JPGN 2018;66:516-554

GERD DIAGNOSIS?: DIAGNOSIS

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Barium swallows • The WG suggests NOT to use barium contrast studies for the diagnosis of GERD in infants and children Voting: 8,8,9,9,9,9,9,9,9,9 (88) • Based on expert opinion, the WG suggests to use barium contrast studies for excluding anatomical abnormalities. Voting: 8,8,8,9,9,9,9,9,9,9 (87)

Statement 2

Pediatric GER Clinical Practice Guidelines: Joint Recommendations of NASPGHAN & ESPGHAN

Rosen R (NASPGHAN) - Vandenplas Y (ESPGHAN) - JPGN 2018;66:516-554

11 2/17/2020

Ultrasonography • Based on expert opinion, the WG suggests NOT to use ultrasonography for the diagnosis of GERD in infants and children. VOTING: 8, 8, 8, 9, 9, 9, 9, 9, 9, 9 (87) • Based on expert opinion, the WG suggests to use ultrasonography for

excluding anatomical abnormalities. VOTING: 8, 8, 8, 9, 9, 9, 9, 9, 9, 9 (87)

Statement 3

Pediatric GER Clinical Practice Guidelines: Joint Recommendations of NASPGHAN & ESPGHAN

Rosen R (NASPGHAN) - Vandenplas Y (ESPGHAN) - JPGN 2018;66:516-554

12 2/17/2020

Esophago-Gastro-Duodenoscopy : The working group suggests not to use EGD for diagnosing GERD in infants and children. VOTING: 7, 8, 8, 8, 9, 9, 9, 9, 9, 9 (84) Based on expert opinion, the working group suggests to use EGD with biopsies to assess complications of GERD, in case an underlying mucosal disease is suspected and prior to escalation of therapy. VOTING: 6, 8, 8, 9, 9, 9, 9, 9, 9, 9 (85)

Statement 4

Pediatric GER Clinical Practice Guidelines: Joint Recommendations of NASPGHAN & ESPGHAN

Rosen R (NASPGHAN) - Vandenplas Y (ESPGHAN) - JPGN 2018;66:516-554

13 2/17/2020

Scintigraphy: The working group recommends not to use scintigraphy for the diagnosis of GERD in infants and children. VOTING: 8, 8, 8, 9, 9, 9, 9, 9, 9, 9 (87)

Statement 7

Pediatric GER Clinical Practice Guidelines: Joint Recommendations of NASPGHAN & ESPGHAN

Rosen R (NASPGHAN) - Vandenplas Y (ESPGHAN) - JPGN 2018;66:516-54

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PPI-trials • Based on expert opinion, the WG suggests a trial up to 8 weeks of PPIs for typical symptoms (heartburn, retrosternal or epigastric pain) in children as a diagnostic test for GERD. VOTING: 3, 7, 7, 7, 8, 8, 8, 9, 9, 9 (75)

Statement 9

Pediatric GER Clinical Practice Guidelines: Joint Recommendations of NASPGHAN & ESPGHAN

Rosen R (NASPGHAN) - Vandenplas Y (ESPGHAN) - JPGN 2018;66:516-54

15 2/17/2020

PPI trial • Based on expert opinion, the WG suggests not to use a trial of PPIs as a diagnostic test for GERD in patients presenting with extra-intestinal symptoms. VOTING: 7, 8, 8, 8, 8, 8, 8, 9, 9, 9 (82) • Based on expert opinion, the WG suggests not to use a trial of PPIs as a diagnostic test for GERD in infants. VOTING: 5, 6, 7, 7, 7, 8, 8, 9, 9, 9 (75)

Statement 9

Pediatric GER Clinical Practice Guidelines: Joint Recommendations of NASPGHAN & ESPGHAN

Rosen R (NASPGHAN) - Vandenplas Y (ESPGHAN) - JPGN 2018;66:516-54

16 2/17/2020

pH-metry • Based on expert opinion, in places were pH-MII is not available, the WG suggests to use pH-metry only - to correlate persistent troublesome symptoms with acid GER events VOTING: 6, 7, 7, 7, 7, 8, 8, 9, 9 (77) - to clarify the role of acid reflux in the etiology of esophagitis and other signs and symptoms suggestive for GERD. VOTING: 6, 7, 7, 7, 7, 8, 8, 9, 9 (77) - to determine the efficacy of acid suppression therapy. VOTING: 6, 7, 7, 7, 7, 8, 8, 9, 9 (77)

Statement 10

Pediatric GER Clinical Practice Guidelines: Joint Recommendations of NASPGHAN & ESPGHAN

Rosen R (NASPGHAN) - Vandenplas Y (ESPGHAN) - JPGN 2018;66:516-54

17 2/17/2020

Impedance (pH-MII) Based on expert opinion, the WG suggests to consider pH-MII testing only to • correlate persistent troublesome symptoms with acid and non-acid GER events VOTING: 6, 7, 7, 7, 8, 8, 8, 9, 9 (78) • clarify the role of acid and non-acid reflux in the etiology of esophagitis and other signs and symptoms suggestive for GERD. VOTING: 6, 7, 7, 7, 8, 8, 8, 9, 9 (78) • determine the efficacy of acid suppression therapy. VOTING: 6, 6, 7, 7, 7, 8, 8, 9, 9 (76). • differentiate patients with NERD, hypersensitive esophagus and functional heartburn in patients with normal endoscopy. VOTING: 6, 6, 6, 7, 7, 7, 8, 9, 9 (74)

Statement 11

Pediatric GER Clinical Practice Guidelines: Joint Recommendations of NASPGHAN & ESPGHAN

Rosen R (NASPGHAN) - Vandenplas Y (ESPGHAN) - JPGN 2018;66:516-54

NEONATAL PAINOR DIAGNOSIS

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In children unable to talk, pain reporting is reliant on parents and/or caregivers. Parents usually know their child’s typical behavioural response to pain and this can be included in the pain assessment. Observation of behaviour in relation to pain is a valid approach for pain assessment in children below three years old, and in children with limited verbal and cognitive skills.

The following self-report pain scales (Faces Pain Scale-Revised, Poker Chip Tool, the Visual Analogue Scale (VAS), and the Oucher Photographic and Numerical Rating Scale (NRS) have been recommended to measure pain intensity in children with acute and persisting pain by both the Ped-IMMPACT and SPP-ATF reviews.

GERD, DOES IT HURT?

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Background: • The relation between gastroesophagel reflux (GER) and

distressed behavior, expressed as crying in infants is still unclear.

• Parents are often very anxious and concerned when their infant is crying and distressed, and these episodes are often interpreted as pain.

• Acid inhibitors are often empirically started in distressed infants despite not supported by literature and guidelines

Gastroesophageal reflux disease in infants: how much is predictable with questionnaires, pH-metry, endoscopy and histology?

Salvatore S1, Hauser B, Vandemaele K, Novario R, Vandenplas Y. J Pediatr Gastroenterol Nutr. 2005 Feb;40(2):210-5

Clinical symptoms, histology and pH study show poor correlation in infants.

Clinical symptoms such as regurgitation and crying are less frequent in unselected infants than in infants suspected of gastroesophageal reflux disease.

Questionnaires are poorly predictive for the severity of gastroesophageal reflux disease

They do not correlate with esophageal acid exposure (pH-metry) and with esophagitis (histology)

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Effect of antireflux medication, placebo and infant mental health intervention on persistent crying: a randomized clinical trial.

Jordan B1, Heine RG, Meehan M, Catto-Smith AG, Lubitz L. Paediatr Child Health. 2006 Jan-Feb;42(1-2):49-58

Antireflux medications and IMHC were not superior to placebo in treating infants with persistent crying.

Although the reduction in maternal distress was similar in all treatment groups, the individualized IMHC reduced the need for subsequent admission to a mother-infant unit.

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“In infants and toddlers there are no symptoms or group of symptoms that can reliably diagnose GERD or predict treatment response” (evidence B)

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Pediatric GERD and acid-related conditions (ARC): trends in incidence of diagnosis and acid suppression therapy. Nelson SP. J Med Eco 2009;12:348-55.

• Between 2000 and 2005, annual incidence of GERD/ARC diagnosis among infants (age ≤1 year) more than tripled (from 3.4 to 12.3%) and increased by 30% to 50% in other age groups • Patients diagnosed by GI specialists (9.2%) were more likely to be treated with PPIs compared to patients diagnosed by primary care physician • PPI-initiated patients doubled: 1999: 31.5% - 2005: 62.6% • When compared with H²RA-initiated patients: associated with 30% less discontinuation 90% less therapy switching in 1st month higher comorbidity burden higher pre-treatment total HCU and costs 29

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Changes in prescription patterns of acid-suppressant medications by Belgian pediatricians: analysis of the national database [1997-2009]. De Bruyne P. J Pediatr Gastroenterol Nutr. 2014;58:222-5.

• Increase 7-fold from 20,782 daily defined doses (DDDs) in January 1997 to 142,912 DDDs in June 2009 per month • During this study period, reimbursed volume increased of: H2-RAs from 2575 to 38,996 DDDs per month PPIs from 3472 to 103,926 DDDs per month

20 infants: 584 total reflux episodes, 36% positive for “stress” (16% acid and 84% weakly acidic reflux episodes). Significant association between reflux (both acid and weakly acid GER) and disconfort (> skin conductance) in all infants

5 (DB)RCT

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DISTRESSED BEHAVIOR AND GER IN INFANTS: NEW INSIGHTS

• Objectives and study: The relation between gastroesophagel reflux (GER) and distressed behavior, expressed as crying in infants is still unclear.

• The "Face, Legs, Activity, Cry, Consolability (FLACC)" scale

is a validated measurement used to assess pain for infants and young children*.

• The objective of this study was to assess the relation between GER and the FLACC score.

*Kabes A et al. Further validation of the nonverbal pain scale in intensive care patients Crit Care Nurse 2009;29: 59-66 Voepel-Levis T et al. Merkel S Reliability and validity of the Face, Legs, Activity, Cry, Consolability behavioral tool in assessing acute pain in critically patients Am J Crit Care 2010;19: 55-61

FLACC 0 1 2

FACE No particular expression or smile

Occasional grimace or frown, withdrawn, disinterested

Frequent to constant quivering chin, clenched jaw

LEGS Normal position or relaxed

Uneasy, restless, tense

Kicking or legs drawn up

ACTIVITY Lying quietly, normal position, moves easily

Squirming, shifting back and forth, tense

Arched, rigid, or jerking

CRY No cry Moans or whimpers, occasional complaints

Crying steadily, screams or sobs

CONSOLABILITY

Content, relaxed Reassured by touching, hugging, voice, distraction

Difficult to console or comfort

The scale was scored in a range of 0–10 with 0 representing no pain and 2 the maximum pain expression for any of the five categories (Merkel S. 2002)

• Prospective study (Jan - Nov 2015) consecutively including infants submitted to MII/pH-monitoring for suspected GER-disease (GERD) with episodes of crying during the investigation.

• Symptoms considered as temporally associated with GER if within a 2-minutes period of time. All MII-pH tracings analyzed by a single author (SS) blind to the result of the FLACC score.

• Parents were instructed to fill in a symptom diary and the FLACC scale during episodes of crying.

• The medians of the total FLACC score were analysed according to the presence/absence, duration, kind and extension of GER events.

• Statistical analysis was performed using Kruskal-Wallis (test H) and t test when appropriate.

DISTRESSED BEHAVIOR AND GER IN INFANTS: NEW INSIGHTS

Methods

• 62 subjects (age 15 days -23 months, mean age 3.5 months – 36 males)

• 452 episodes of crying with the FLACC completed: •235 (52%) episodes of crying not associated with GER. •217 (48%) of crying associated with GER

DISTRESSED BEHAVIOR AND GER IN INFANTS: NEW INSIGHTS

Results

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Figure 1. Comparison of FLACC scores according to temporal association between distress and GER episodes assessed by MII-pH monitoring

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FLACC scores in acid GER vs NON-acid GER

The median values of FLACC were not significantly different between

• EXTENSION: •Proximal (FLACC 5.5) or only distal (FLACC 4.8) GER,

• DURATION: •Subjects with (median FLACC 2) or without (median FLACC 5) abnormal acid exposure.

• AGE: •Neither younger age or duration of GER were significantly correlated with high values of FLACC (P=0.15).

DISTRESSED BEHAVIOR AND GER IN INFANTS: NEW INSIGHTS

Results

BUT

• Weakly acidic reflux presented a significant higher value of FLACC compared to acid reflux events (FLACC 6 vs 4, Test H di Kruskal-Wallis: P=0.0002).

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• In infants, most episodes of crying (and pain) were not associated with GER.

• The presence, kind, temporal sequence, duration, extension of concomitant GER could not be predicted by the FLACC scale.

• In infants, weakly acidic reflux was perceived more painful compared to acid reflux episodes, suggesting that volume may be more painful than acid.

DISTRESSED BEHAVIOR AND GER IN INFANTS: NEW INSIGHTS

Conclusions

GERD, DOES IT HURT? WHAT’S YOUR OPINION?

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At what age, regurgitations are experienced as most troublesome by the parents? 0-3 months

4-6 months

6-12 months

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Which of the following statements is correct in a crying infant suspected of having GERD: I suspect the crying to be related to GERD. I do

an Rx follow through to exclude GERD

I suspect the crying to be related to GERD. I perform a gastroscopy to exclude GERD before treatment

I suspect the crying to be related to GERD. I do a pH-monitoring or Impedance as an objective measurement

I suspect the crying to be related to GERD. I do a trial with PPI to assess the effect on GERD.

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