GORD in infants and children

Dr Rajini Sarvananthan

. 2015 Jul 24;2015:0310.

GORD in infants and children

Rajini Sarvananthan ¹

PMCID: PMC4515879

Abstract

Introduction

Gastro-oesophageal reflux disease (GORD) is reflux which is associated with troublesome symptoms or complications, such as unexplained crying, feeding refusal, choking or gagging, sleep disturbance, abdominal pain, poor weight gain, and respiratory symptoms.

Methods and outcomes

We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of treatment for symptomatic gastro-oesophageal reflux in infants and children? We searched: Medline, Embase, The Cochrane Library, and other important databases up to October 2013 (BMJ Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview).

Results

At this update, searching of electronic databases retrieved 228 studies. After deduplication and removal of conference abstracts, 124 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 93 studies and the further review of 31 full publications. Of the 31 full articles evaluated, three systematic reviews and two RCTs were added at this update. In addition, one systematic review that was published after our search date was discussed in the Comments section. We performed a GRADE for nine PICO combinations.

Conclusions

In this systematic overview, we categorised the efficacy for 10 interventions, based on information relating to the effectiveness and safety of domperidone, feed thickeners in infants, H₂ antagonists, head elevated sleep positioning, hydrolysed formula, left lateral or prone sleep positioning, metoclopramide, proton pump inhibitors, sodium alginate, and weight loss.

Key Points

Reflux of gastric contents into the oesophagus in infants and children may cause recurrent vomiting (usually before 6 weeks of age), epigastric and abdominal pain, feeding difficulties, failure to thrive, and irritability.

At least half of infants regurgitate feeds at least once a day, but this only causes other problems in about 20% of infants, and most cases resolve spontaneously by 12 to 18 months of age. The majority of infants with regurgitation do not present with further symptoms or complications seen in GORD. Reassurance and simple feed changes (small frequent feeds) are often all that is needed, and these infants do not need further investigations or treatment.
Risk factors include infants born prematurely, lower oesophageal sphincter disorders, hiatus hernia, gastric distension, raised intra-abdominal pressure, and neurodevelopmental problems.

We searched for evidence of effectiveness from RCTs and systematic reviews of RCTs.

We extracted data from RCTs in our analysis of the selected interventions. We have focused on infants, including preterm infants, and children up to 12 years. Most of the evidence we found was in infants and very young children.

Thickened feeds (with rice cereal, carob-bean gum, carob-seed flour, sodium carboxymethylcellulose, pre-thickened milk formula) may reduce the severity and frequency of regurgitation and vomiting in the short term compared with no thickeners/standard milk formula in infants and children younger than 2 years.

We don’t know if hydrolysed formula reduces symptoms of GORD in infants and young children compared with placebo or no treatment as we found no RCTs.

Sodium alginate may be more effective in infants and children younger than 2 years at reducing the number of episodes of vomiting at 14 days, but we don't know whether it is more effective at reducing the number of regurgitation episodes.

The high sodium content of sodium alginate makes it unsuitable for use in preterm babies as this may result in complications of hypernatraemia.

Sleeping in the left lateral or prone position may improve oesophageal pH and number of episodes of reflux compared with sleeping supine or on the right side, but these positions increase the risk of sudden infant death syndrome (SIDS) compared with supine sleeping, and cannot be recommended in infants for that reason.

We don't know whether sleeping in the head elevated position reduces symptoms of GORD compared with sleeping in the horizontal position. Due to the increased risk of SIDS, only the supine position is recommended for infants.

We don’t know whether metoclopramide is more effective than placebo or no treatment at reducing gastro-oesophageal reflux symptoms in infants and children up to 17 years old. However, a more serious consideration is the risk of adverse effects when used in the long term. Metoclopramide is now contraindicated for the treatment of GORD due to its adverse effects.

We don't know whether H₂ antagonists reduce symptoms in babies and children with GORD, and they may cause adverse effects.

Proton pump inhibitors may be no more effective than placebo at improving symptoms in infants and children younger than 12 months. We found no RCTs comparing proton pump inhibitors with placebo in older children.

There is no evidence that domperidone reduces symptoms in children and we do not know whether domperidone reduces symptoms in infants. Domperidone is not recommended for long-term use due to its adverse effects on the heart.

Weight loss is not a treatment option for infants and young children. We don’t know whether weight loss reduces symptoms of GORD in older children as we found no RCTs.

Clinical context

General background

Focus of the review

This overview focuses on selected interventions for GORD in pre-adolescent children (aged 0–12 years), including infants and preterm infants. In clinical practice, the first intervention that is commonly recommended and appears to frequently work in practice is to make simple changes in feeding practices (e.g., smaller and more frequent feeds). There is a lack of good-quality studies supporting these practices, as designing appropriate RCTs is challenging, so we have focused on other interventions. Surgery has also not been addressed in this overview, due to the poor quality of studies. However, in clinical practice, surgery may be considered, in particular in groups of children with severe GORD symptoms, following further gastrointestinal investigations and when medical treatment has proven unsuccessful. The selected interventions we have focused on in this overview have been used by clinicians to treat GORD in this group of children in clinical practice over many years. The aim of the overview is to ensure that the use of these interventions is backed by good evidence in this paediatric population, and not only as a result of extrapolation from adult studies.

Comments on evidence

Good-quality evidence from RCTs has been very limited for a number of reasons. Distinguishing GORD from physiological GOR is often difficult, as there are no tests that reliably correlate clinical symptoms and the disease itself. Presentation of symptoms varies according to the different age groups concerned, and reliance on parental reports can be difficult.

Search and appraisal summary

The update literature search for this overview was carried out from the date of the last search, August 2007, to October 2013. A back search from 1966 was performed for the new options added to the scope at this update. For more information on the electronic databases searched and criteria applied during assessment of studies for potential relevance to the overview, please see the Methods section. Searching of electronic databases retrieved 228 studies. After deduplication and removal of conference abstracts, 124 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 93 studies and the further review of 31 full publications. Of the 31 full articles evaluated, three systematic reviews and two RCTs were added at this update. In addition, one systematic review that was published after our search date was discussed in the Comments section.

About this condition

Definition

Gastro-oesophageal reflux (GOR) is the passive retrograde transfer of gastric contents into the oesophagus due to relaxation of the lower oesophageal sphincter, which is a normal physiological process and causes effortless regurgitation in otherwise healthy infants and children. This does not cause additional symptoms and as such no investigations or treatment is required, only parental reassurance. Gastro-oesophageal reflux disease (GORD) occurs as a result of complications of GOR and results in more troublesome symptoms, such as unexplained crying, feeding refusal, choking or gagging, sleep disturbance, abdominal pain, poor weight gain, and respiratory symptoms. A survey of 69 children (median age 16 months) with GORD attending a tertiary referral centre found that presenting symptoms were recurrent vomiting (72%), epigastric and abdominal pain (36%), feeding difficulties (29%), failure to thrive (28%), and irritability (19%). However, results may not be generalisable to infants or children presenting in primary care, who make up the most of the cases. More than 90% of children with GORD have vomiting before 6 weeks of age. GORD symptoms often vary depending on the age of the child. Older children and adolescents may present with symptoms very similar to those in adults (see overview for GORD in adults).

Incidence/ Prevalence

Gastro-oesophageal regurgitation is considered a problem if it is frequent, persistent, and associated with other symptoms such as increased crying, discomfort with regurgitation, and frequent back arching. A cross-sectional survey of parents of 948 infants attending 19 primary care paediatric practices found that regurgitation of at least one episode a day was reported in 51% of infants aged 0 to 3 months. 'Problematic' regurgitation occurred in significantly fewer infants (14% with problematic regurgitation v 51% with regurgitation of at least 1 episode a day; P <0.001). Peak regurgitation reported as 'problematic' was reported in 23% of infants aged 6 months. A prospective study of 2879 infants followed up from just after birth (from birth up to 2 weeks) to age 6 months by primary-care paediatricians found that regurgitation occurred in 23% of infants during the study period.

Aetiology/ Risk factors

Risk factors for GORD include immaturity of the lower oesophageal sphincter, chronic relaxation of the sphincter, increased abdominal pressure, gastric distension, hiatus hernia, and oesophageal dysmotility. Premature infants and children with severe neurodevelopmental problems or congenital oesophageal anomalies are particularly at risk.

Prognosis

Regurgitation is considered benign, and most cases resolve spontaneously by 12 to 18 months of age. The prevalence of 'problematic' regurgitation also reduced from 23% in infants aged 6 months to 3% in infants aged 10 to 12 months. One cohort study found that infants with frequent spilling in the first 2 years of life (at least 90 days in the first 2 years) were more likely to have symptoms of gastro-oesophageal reflux at 9 years of age than those with no spilling (RR 2.3, 95% CI 1.3 to 4.0). Rare complications of GORD include oesophagitis with haematemesis and anaemia, respiratory problems (such as cough, apnoea, and recurrent wheeze), and failure to thrive. A small comparative study (40 children) suggested that, when compared with healthy children, infants with GORD had slower development of feeding skills, and problems affecting behaviour, swallowing, food intake, and mother-child interaction.

Aims of intervention

To relieve symptoms, maintain normal growth, and prevent complications such as oesophagitis, with minimal adverse effects of treatment.

Outcomes

Symptom severity vomiting, regurgitation, and incidence of complications (e.g., oesophagitis and respiratory symptoms). These were chosen as markers of the disease for the purposes of this review as there are no reliable clinical tests to diagnose the condition and it is defined by its clinical presentation. Reflux Index, a measure of the percentage of time with a low oesophageal pH (frequently <pH 4), is a surrogate outcome that is often used in RCTs. Clinical interpretation of Reflux Index measurements is problematic, as the correlation between these measurements and the symptoms of gastro-oesophageal reflux has not been well studied. We have only reported Reflux Index findings where data on clinical outcomes were unavailable. Adverse effects.

Methods

Search strategy BMJ Clinical Evidence search and appraisal date October 2013. Databases used to identify studies for this systematic overview include: Medline 1966 to October 2013, Embase 1980 to October 2013, The Cochrane Database of Systematic Reviews 2013, issue 10 (1966 to date of issue), the Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA) database. Inclusion criteria Study design criteria for inclusion in this systematic overview were systematic reviews and RCTs published in English, at least single-blinded, and containing more than 20 individuals, of whom more than 80% were followed up. There was no minimum length of follow-up. We excluded all studies described as ‘open’, ‘open label’, or not blinded unless blinding was impossible. BMJ Clinical Evidence does not necessarily report every study found (e.g., every systematic review). Rather, we report the most recent, relevant, and comprehensive studies identified through an agreed process involving our evidence team, editorial team, and expert contributors. Evidence evaluation A systematic literature search was conducted by our evidence team, who then assessed titles and abstracts, and finally selected articles for full text appraisal against inclusion and exclusion criteria agreed a priori with our expert contributor. In consultation with the expert contributor, studies were selected for inclusion and all data relevant to this overview extracted into the benefits and harms section of the overview. In addition, information that did not meet our predefined criteria for inclusion in the benefits and harms section, may have been reported in the 'Further information on studies' or 'Comment' section. Adverse effects All serious adverse effects, or those adverse effects reported as statistically significant, were included in the harms section of the overview. Pre-specified adverse effects identified as being clinically important were also reported, even if the results were not statistically significant. Although BMJ Clinical Evidence presents data on selected adverse effects reported in included studies, it is not meant to be, and cannot be, a comprehensive list of all adverse effects, contraindications, or interactions of included drugs or interventions. A reliable national or local drug database must be consulted for this information. Comment and Clinical guide sections In the Comment section of each intervention, our expert contributors may have provided additional comment and analysis of the evidence, which may include additional studies (over and above those identified via our systematic search) by way of background data or supporting information. As BMJ Clinical Evidence does not systematically search for studies reported in the Comment section, we cannot guarantee the completeness of the studies listed there or the robustness of methods. Our expert contributors add clinical context and interpretation to the Clinical guide sections where appropriate. Structural changes this update At this update, we have removed the following interventions from this overview: soy formula with added fibre, and surgery. We have added the following intervention: hydrolysed formula. Data and quality To aid readability of the numerical data in our overviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). BMJ Clinical Evidence does not report all methodological details of included studies. Rather, it reports by exception any methodological issue or more general issue which may affect the weight a reader may put on an individual study, or the generalisability of the result. These issues may be reflected in the overall GRADE analysis. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).

Table.

GRADE Evaluation of interventions for GORD in infants and children.

Important outcomes	Symptom severity
Studies (Participants)	Outcome	Comparison	Type of evidence	Quality	Consistency	Directness	Effect size	GRADE	Comment
What are the effects of treatment for symptomatic gastro-oesophageal reflux in infants and children?
at least 6 (at least 440)	Symptom severity	Feed thickeners versus non-thickened feeds	4	−2	0	0	0	Low	Quality points deducted for poor-quality studies and no intention-to-treat analysis in some studies
4 (160)	Symptom severity	Sodium alginate versus placebo	4	−2	−1	−1	0	Very low	Quality points deducted for sparse data and incomplete reporting of results; consistency point deducted for lack of consistent benefit in all studies; directness point deducted for uncertainty about clinical relevance of outcome measured
3 (156)	Symptom severity	Prone or left lateral sleeping position versus other sleeping positions	4	–2	0	–1	0	Very low	Quality points deducted for sparse data and incomplete reporting of results; directness point deducted for uncertainty of clinical relevance of outcomes assessed
at least 5 (at least 120)	Symptom severity	Metoclopramide versus placebo or no treatment	4	−2	0	−2	0	Very low	Quality points deducted for sparse data and incomplete reporting of results; directness points deducted for uncertainty about clinical relevance of outcomes measured, and for heterogeneous population, doses and outcomes assessed
1 (32)	Symptom severity	H₂ antagonists versus placebo	4	−1	0	−1	0	Low	Quality point deducted for sparse data; directness point deducted for uncertainty about clinical relevance of outcome measured
3 (268)	Symptom severity	Head elevated sleep position versus horizontal sleep position	4	–1	–1	–1	0	Very low	Quality point deducted for incomplete reporting of results; consistency point deducted for conflicting results (different direction of effect between studies); directness point deducted for uncertainty of clinical relevance of outcomes assessed
at least 4 (at least 400)	Symptom severity	Proton pump inhibitors versus placebo	4	−2	0	0	0	Low	Quality points deducted for weak methods and incomplete reporting
1 (45)	Symptom severity	Proton pump inhibitors versus hydrolysed formula	4	−1	0	−1	0	Low	Quality point deducted for sparse data; directness point deducted for uncertainty about clinical relevance
1 (22)	Symptom severity	Proton pump inhibitors versus sodium alginate	4	−2	0	−1	0	Very low	Quality points deducted for sparse data and incomplete reporting of results; directness point deducted for uncertainty about clinical relevance of outcome measured

Open in a new tab

We initially allocate 4 points to evidence from RCTs, and 2 points to evidence from observational studies. To attain the final GRADE score for a given comparison, points are deducted or added from this initial score based on preset criteria relating to the categories of quality, directness, consistency, and effect size. Quality: based on issues affecting methodological rigour (e.g., incomplete reporting of results, quasi-randomisation, sparse data [<200 people in the analysis]). Consistency: based on similarity of results across studies. Directness: based on generalisability of population or outcomes. Effect size: based on magnitude of effect as measured by statistics such as relative risk, odds ratio, or hazard ratio.

Glossary

Choke-gag reflux: Regurgitation of food into the pharynx and upper oesophagus that causes choking and gagging as the person tries to protect the airway in an automatic reflex action.
GERD Symptom Questionnaire – Infants (GSQ-I): A questionnaire for assessment of gastro-oesophageal reflux disease. Symptoms scored are vomiting/regurgitation, irritability/fussiness, refusal to feed, choking/gagging when eating, and arching back.
Infant gastro-oesophageal reflux questionnaire-revised (I-GERQ-R): A 12-item questionnaire based on symptoms such as regurgitation, irritability, feeding refusal, apnoea, hiccups, and arching.
Low-quality evidence: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Spilling: When liquid or substance in small particles falls or spills out of the mouth.
Very low-quality evidence: Any estimate of effect is very uncertain.

Disclaimer

The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients. To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.

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BMJ Clin Evid. 2015 Jul 24;2015:0310.

Feed thickeners in infants

Summary

Thickened feeds may reduce the severity and frequency of regurgitation and vomiting in the short term. However, some thickened fluids may increase diarrhoea.

We searched for the following feed thickeners: rice cereal, carob-bean gum, carob-seed flour, sodium carboxymethylcellulose, pre-thickened milk formula.

Benefits and harms

Feed thickeners versus non-thickened feeds:

We found three systematic reviews (search date 2003; 2008; 2011). The first systematic review identified eight RCTs. The second systematic review identified 14 RCTs and pooled data for some RCTs for some outcomes. One RCT identified by this systematic review was not included in the meta-analysis, therefore, we have reported it individually. The third systematic review assessed non-surgical treatments in infants with GORD and included three RCTs on thickened feeds. This systematic review described individual studies, but did not perform a meta-analysis. The data from two of the three RCTs were meta-analysed in the previous systematic review, so we have used its reporting. Information from the remaining RCT is reported from the third systematic review. None of the RCTs were longer than 8 weeks in duration.

Symptom severity

Thickened formula feeds compared with non-thickened feeds Thickened formula feeds may be more effective than non-thickened feeds in infants and children under 2 years at reducing regurgitation and vomiting, and at improving weight gain in infants under 6 months (low-quality evidence).

Ref (type)	Population	Outcome, Interventions	Results and statistical analysis	Effect size	Favours
Regurgitation
Systematic review	Infants (<4 months) with a diagnosis of GORD who were otherwise healthy 2 RCTs in this analysis	Number of infants without regurgitation 35/96 (36%) with thickened feeds (carob) 13/98 (13%) with standard formula	RR 2.75 95% CI 1.55 to 4.88 P = 0.0005	Moderate effect size	thickened feed
Systematic review	Infants (<6 months) with a diagnosis of GORD who were otherwise healthy 3 RCTs in this analysis	Mean number of episodes of regurgitation per day with thickened feeds (corn) with standard formula Absolute results not reported	MD −2.09 95% CI −2.87 to −1.31 P <0.00001	Effect size not calculated	thickened feed
Systematic review	Infants (<6 months) with a diagnosis of GORD who were otherwise healthy 3 RCTs in this analysis	Mean number of episodes of regurgitation per day with thickened feeds (carob) with standard formula Absolute results not reported	MD −1.97 95% CI −2.85 to −1.09 P <0.0001 I² = 86% (P = 0.0008) Reason for heterogeneity not explained in review; see Further information on studies	Effect size not calculated	thickened feed
Systematic review	Infants (1–3 months) with >4 episodes of regurgitation or vomiting/day for 1 week Data from 1 RCT	Frequency of regurgitation 4 weeks with thickened feeds (bean-gum) with thickened feeds (rice cereal) with standard formula Absolute results not reported	P=0.14 Among-group analysis; individual arms versus each other were not reported
Systematic review	Children (aged 1 month–2 years) with GORD and who were developmentally normal 2 RCTs in this analysis	Regurgitation severity score with thickened feeds with no thickeners Absolute results not reported	MD –0.94 95% CI –1.35 to –0.52 See Further information on studies for methodological issues	Effect size not calculated	thickened feeds
RCT	104 infants aged 14–120 days, with regurgitation at least 5 times/day In review	% change in feeds that were followed by regurgitation 1 week –34% with pre-thickened milk formula (Enfamil AR) –22% with standard milk formula	P = 0.045	Effect size not calculated	thickened feed
RCT	104 infants aged 14–20 days, with regurgitation at least 5 times/day In review	% change in feeds that were followed by regurgitation 5 weeks –38% with pre-thickened milk formula (Enfamil AR) –24% with standard milk formula	P = 0.036	Effect size not calculated	thickened feed
RCT	104 infants aged 14–120 days, with regurgitation at least 5 times/day In review	% change in regurgitation volume 1 week –4.5% with pre-thickened milk formula (Enfamil AR) –3.4% with standard milk formula	P = 0.035	Effect size not calculated	thickened feed
RCT	104 infants aged 14–120 days, with regurgitation at least 5 times/day In review	% change in regurgitation volume 5 weeks –4.6% with pre-thickened milk formula (Enfamil AR) –3.4% with standard milk formula	P = 0.05	Effect size not calculated	thickened feed
RCT	104 infants aged 14–120 days, with regurgitation at least 5 times/day In review	% change in feeds with choke–gag reflux (decrease from baseline) 1 week –27% with pre-thickened milk formula (Enfamil AR) –15% with standard milk formula	P = 0.004	Effect size not calculated	thickened feed
RCT	104 infants aged 14–120 days, with regurgitation at least 5 times/day In review	% change in feeds with choke–gag reflux (decrease from baseline) 5 weeks with pre-thickened milk formula (Enfamil AR) with standard milk formula Absolute results not reported	P = 0.049	Effect size not calculated	thickened feed
Vomiting
Systematic review	Infants (<6 months) with a diagnosis of GORD who were otherwise healthy 2 RCTs in this analysis	Mean number of episodes of regurgitation and vomiting per day with thickened feeds (rice, cornstarch) with standard formula Absolute results not reported	MD –1.37 95% CI –2.53 to –0.20 P = 0.02 I² = 94% (P <0.0001) Reason for heterogeneity not explained in review; see Further information on studies	Effect size not calculated	thickened feed
Systematic review	Infants (<6 months) with a diagnosis of GORD who were otherwise healthy 2 RCTs in this analysis	Mean number of episodes of vomiting per day with cornstarch thickened feeds with standard formula Absolute results not reported	MD –0.97 95% CI –1.54 to –0.39 P = 0.001 I² = 55% (P = 0.13) Reason for heterogeneity not explained in review; see Further information on studies	Effect size not calculated	thickened feed
Systematic review	Children (aged 1 month–2 years) with GORD and who were developmentally normal 3 RCTs in this analysis	Frequency of emesis with thickened feeds with no thickeners Absolute results not reported	MD –0.91 95% CI –1.22 to –0.61 See Further information on studies for methodological issues	Effect size not calculated	thickened feeds
Weight gain
	Infants (<6 months) with a diagnosis of GORD who were otherwise healthy 4 RCTs in this analysis	Mean (SD) weight gain (g/day) with with thickened feeds (bean-gum, cornstarch, corn, or cereal) with standard formula Absolute results not reported	MD 3.68 95% CI 1.55 to 5.81 P = 0.0007 I² = 68% (P = 0.02) Reason for heterogeneity not explained in review; see Further information on studies	Effect size not calculated	thickened feed
Systematic review	Infants (1–3 months) with >4 episodes of regurgitation or vomiting/day for 1 week Data from 1 RCT	Weight gain 4 weeks with bean-gum thickened feeds with standard formula Absolute results not reported	P <0.05	Effect size not calculated	thickened feed

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Adverse effects

Ref (type)	Population	Outcome, Interventions	Results and statistical analysis	Effect size	Favours
Adverse effects
Systematic review	Infants (<6 months) with a diagnosis of GORD who were otherwise healthy Data from 1 RCT	Number of bowel movements with locust-bean gum thickened feeds with standard formula Absolute results not reported	Reported as significant P values not reported	Effect size not calculated	standard formula
Systematic review	90 infants 2 RCTs in this analysis	Coughing with thickened feeds with non-thickened feeds Absolute results not reported	SMD in coughs/hour 0.38 95% CI 0.16 to 0.59	Effect size not calculated	non-thickened feeds
Systematic review	166 infants Data from 1 RCT	Withdrawal because of diarrhoea with thickened feeds with non-thickened feeds Absolute results not reported
RCT	104 infants aged 14–120 days, with regurgitation at least 5 times/day In review	Discontinuation rates 13% with pre-thickened milk formula (Enfamil AR) 20% with standard milk formula Absolute numbers not reported	Reported as not significant P value not reported It is not clear what was substituted in those who stopped standard formula		Not significant
RCT	96 formula-fed infants, mean age of 93 days, with >5 episodes of regurgitation and vomiting occurring a day and abnormal oesophageal pH In review	Change in number of stools passed daily 4 weeks from 2.62 to 2.60 with corn starch-thickened casein-predominant formula from 3.80 to 3.54 with standard milk formula	P = 0.08		Not significant

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Further information on studies

RCTs identified by the review were generally small, of short duration, and low quality. Few RCTs provided data that could be included in meta-analyses. It was not clear if meta-analysis was based on intention-to-treat data. Many of the RCTs were crossover RCTs, and it was not clear from the review whether meta-analyses used data from before the crossover period.

The systematic review did not explain heterogeneity but did perform a random effects analysis for any outcome with significant heterogeneity. Of the studies in the systematic review, 6/14 (43%) had no intention-to-treat analysis. The authors also noted that several studies were sponsored by the manufacturer of the formula, and that it might not always have been possible to maintain blinding as the specific texture of the thickened formula meant that parents or clinicians might be able to easily identify which formula they had been given. Studies ranged from 1 to 8 weeks in duration.

Comment

The clinical relevance of changes in regurgitation scores used in RCTs is unclear. Feeds are thickened with feed thickeners (rice, corn, or carob flour); some of these pre-thickened infant formulas thicken on contact with stomach acid.

Substantive changes

Feed thickeners in infants Two systematic reviews added. Categorisation unchanged (likely to be beneficial).

BMJ Clin Evid. 2015 Jul 24;2015:0310.

Hydrolysed formula

Summary

As allergies may be indistinguishable from the symptoms of GORD, hydrolysed formula (also known as extensively hydrolysed, prehydrolysed, or hypoallergenic formula) has been suggested as a treatment.

We found no clinically important results from RCTs about the effects of hydrolysed formula compared with placebo.

Benefits and harms

Hydrolysed formula versus placebo:

We found one systematic review, which found no RCTs comparing hydrolysed formula to placebo.

Hydrolysed formula versus proton pump inhibitor:

See option for Proton pump inhibitors.

Comment

None.

Substantive changes

Hydrolysed formula New option added. One systematic review added and data reported from 1 RCT. Categorised as 'unknown effectiveness'.

BMJ Clin Evid. 2015 Jul 24;2015:0310.

Sodium alginate

Summary

The high sodium content of sodium alginate may result in complications of hypernatraemia in preterm babies with immature renal function and is not recommended in this group of infants.

Benefits and harms

Sodium alginate versus placebo:

We found no systematic review, but found four RCTs.

Symptom severity

Sodium alginate compared with placebo Sodium alginate may be more effective than placebo in infants and children aged under 2 years of age at reducing the number of episodes of vomiting at 14 days, but we don't know whether it is more effective at reducing the number of regurgitation episodes (very low-quality evidence).

Ref (type)	Population	Outcome, Interventions	Results and statistical analysis	Effect size	Favours
Regurgitation
RCT 3-armed trial	30 children aged 4 months–17 years	Frequency of regurgitation episodes (episode defined as pH <4) over 24 hours with sodium alginate with placebo Absolute results not reported	Difference among the three groups reported as not significant; between-group comparisons not reported P value not reported
Vomiting
RCT	90 infants aged 0–12 months attending 25 general practices	Median number of episodes of vomiting in previous 24 hours 14 days 3.0 with aluminium-free alginate 5.0 with placebo	P = 0.009	Effect size not calculated	aluminium-free alginate
General symptom improvement
RCT	90 infants aged 0–12 months attending 25 general practices	Number of symptom-free days (at least 10% symptom-free days) 31% with aluminium-free alginate 11% with placebo Absolute numbers not reported	P = 0.027	Effect size not calculated	aluminium-free alginate
RCT	20 children, mean age 28 months	Total number of reflux episodes in 24 hours (as detected with pH monitoring; change in episodes from baseline) from 131.6 to 65.0 with sodium alginate from 87.0 to 91.0 with placebo	Significance not assessed
RCT Crossover design	20 bottle-fed infants, mean age 163.5 days, with symptoms clinically suggestive of GORD	Median number of reflux events an hour 1.58 with sodium plus magnesium alginate in milk 1.68 with placebo in milk	P = 0.78		Not significant
RCT Crossover design	20 bottle-fed infants, mean age 163.5 days, with symptoms clinically suggestive of GORD	Median number of acid reflux events an hour 0.25 with sodium plus magnesium alginate in milk 0.43 with placebo in milk	P = 0.94		Not significant

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Adverse effects

Ref (type)	Population	Outcome, Interventions	Results and statistical analysis	Effect size	Favours
Adverse effects
RCT	90 infants aged 0–12 months attending 25 general practices	Proportion of children experiencing one adverse effect 14 day 55% with aluminium-free alginate 59% with placebo Absolute numbers not reported	P >0.2		Not significant
RCT	20 children, mean age 28 months	Adverse effects with sodium alginate with placebo Absolute results not reported

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No data from the following reference on this outcome.

Sodium alginate versus proton pump inhibitor:

See option for Proton pump inhibitors.

Comment

The high sodium content of sodium alginate may result in complications of hypernatraemia in preterm babies with immature renal function and therefore is not recommended in this group of infants.

Substantive changes

No new evidence

BMJ Clin Evid. 2015 Jul 24;2015:0310.

Left lateral or prone sleep positioning

Summary

Positions other than the supine position have been associated with a higher risk of sudden infant death syndrome (SIDS) and are not recommended for infants.

Sleeping in the left lateral or prone position may improve oesophageal pH and number of episodes of reflux compared with sleeping supine or on the right side in infants younger than 6 months of age. The effects of left lateral or prone sleeping on clinically important outcomes are unknown. However, due to the increased risk of SIDS, only the supine position is recommended for infants.

Benefits and harms

Prone or left lateral sleeping position versus other sleeping positions:

We found one systematic review (search date 2003, 4 RCTs), and one additional RCT. The review did not identify any RCTs assessing clinical outcomes, but found RCTs assessing the effect of posture on oesophageal pH variables such as Reflux Index.

Symptom severity

Prone or left lateral sleeping positions compared with supine and right lateral positions Prone or left lateral sleeping positions may be more effective than supine or right lateral positions at improving symptoms of GORD (number of episodes and Reflux Index) in infants younger than 6 months of age (very low-quality evidence).

Ref (type)	Population	Outcome, Interventions	Results and statistical analysis	Effect size	Favours
Episodes of reflux
RCT Crossover design	24 infants, aged <5 months with Reflux Index of >5% In review	Mean number of episodes 48 hours 4.3 with prone sleeping position 5.8 with left lateral sleeping position 5.5 with right lateral sleeping position 7.1 with supine sleeping position	P = 0.007 in favour of prone over supine positioning	Effect size not calculated	prone position
RCT Crossover design	15 infants, aged <6 months In review	Mean number of episodes 5.2 with prone sleeping position 19.6 with supine sleeping position	P <0.001	Effect size not calculated	prone position
RCT Crossover design	18 infants, <37 weeks' gestation but >7 days old	Mean number of reflux episodes 24 hours with prone sleeping position with left lateral sleeping position with right lateral sleeping position Absolute results not reported	P <0.001 for between-group comparisons of prone and left lateral positions versus right lateral position	Effect size not calculated	prone and left lateral positions
Reflux Index
RCT Crossover design	24 infants, aged <5 months with Reflux Index of >5% In review	Mean Reflux Index 48 hours 7% with prone sleeping position 8% with left lateral sleeping position 12% with right lateral sleeping position 15% with supine sleeping position	P <0.001 in favour of prone or left lateral positioning	Effect size not calculated	prone or left lateral position
RCT Crossover design	15 infants, aged <6 months In review	Mean Reflux Index 7.9% with prone sleeping position 37.4% with supine sleeping position	P <0.001	Effect size not calculated	prone position
RCT Crossover design	18 infants, <37 weeks' gestation but >7 days old	Mean Reflux Index 24 hours with prone sleeping position with left lateral sleeping position with right lateral sleeping position Absolute results not reported	P <0.001 for between-group comparisons of prone and left lateral positions versus right lateral position	Effect size not calculated	prone and left lateral positions

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Adverse effects

No data from the following reference on this outcome.

Comment

The RCTs identified by the systematic review measured the surrogate outcome of Reflux Index, and it is difficult to interpret the clinical importance of the observed changes. The review cited one case control study (244 SIDS cases and 868 controls matched for age and place of birth) that examined the combined effects of sleeping position and prenatal risk factors in SIDS. The study found that both prone (OR 13.9, 95% CI 8.2 to 24.0) and side (OR 3.5, 95% CI 2.1 to 5.7) sleeping positions significantly increased the risk of SIDS compared with supine positioning. One large, prospective cohort study found that the left lateral sleeping position increased the risk of SIDS compared with the supine position (at 2 months: adjusted OR 6.6, 95% CI 1.7 to 25.2).

Clinical guide

Due to the increased risk of SIDS, only the supine position is recommended for infants.

Substantive changes

No new evidence

BMJ Clin Evid. 2015 Jul 24;2015:0310.

Metoclopramide

Summary

We don’t know whether metoclopramide is more effective than placebo or no treatment at reducing gastro-oesophageal reflux symptoms (including regurgitation and reflux index) in infants and children up to 17 years old.

Metoclopramide has been associated with adverse effects including irritability, dystonia, and tardive dyskinesia.

The European Medicines Agency (EMA) issued a drug alert regarding metoclopramide in 2013 and it is now contraindicated for the treatment of GORD in children due to its adverse effects.

Benefits and harms

Metoclopramide versus placebo or no treatment:

We found two systematic reviews (search dates 2003; and not reported) comparing metoclopramide with no treatment or placebo (see Further information on studies), and one additional RCT. Three of the RCTs reported in the second review are also included in the first review.

Symptom severity

Metoclopramide compared with placebo/no treatment We don't know whether metoclopramide is more effective than placebo or no treatment at reducing gastro-oesophageal reflux symptoms (including regurgitation and reflux index) in infants and children up to 17 years old (very low-quality evidence).

Ref (type)	Population	Outcome, Interventions	Results and statistical analysis	Effect size	Favours
Regurgitation
RCT 3-armed trial	30 children aged 4 months–17 years	Frequency of regurgitation episodes (episode defined as pH <4) over 24 hours with metoclopramide with sodium alginate with placebo Absolute results not reported	Difference among the three groups reported as not significant; between-group comparisons not reported P value not reported
General symptom improvement
Systematic review	101 infants 2 RCTs in this analysis	Mean number of daily symptoms with metoclopramide with placebo/no treatment Absolute results not reported	SMD –0.73 95% CI –1.16 to –0.30 See Further information on studies for more details about RCTs identified by review	Effect size not calculated	metoclopramide
Systematic review	22 children (aged 12 months or less) Data from 1 RCT	Gastric fractional emptying rates with metoclopramide with placebo/no treatment Absolute results not reported	Significance not assessed in review See Further information on studies for more details about RCTs identified by review
Systematic review	30 infants (aged 1–9 months with gastro-oesophageal reflux diagnosed by pH probe) Data from 1 RCT	Symptom scores and scintigraphy with metoclopramide with placebo/no treatment Absolute results not reported	See Further information on studies for more details about RCTs identified by review

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Adverse effects

Ref (type)	Population	Outcome, Interventions	Results and statistical analysis	Effect size	Favours
Adverse effects not specified
Systematic review	120 infants 4 RCTs in this analysis	Adverse effects 11/71 (15%) with metoclopramide 1/49 (2%) with control	Risk difference +0.26 95% CI –0.02 to +0.53		Not significant
Systematic review	Infants	Adverse effects (any) with metoclopramide with control Absolute results not reported

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No data from the following reference on this outcome.

Further information on studies

The review identified seven RCTs in developmentally normal children between the ages of 1 month and 2 years with GORD. Few of the RCTs provided adequate data for meta-analysis. RCTs in the review used metoclopramide in doses ranging from 0.1 mg/kg four times daily to 0.3 mg/kg three times daily. RCTs included in the review were generally small. Meta-analyses tended to be based on data from a small number of infants in two studies.

The review identified 12 RCTs in infants (age range, preterm to 18 months) with GORD. Of the 12 studies included in the review, only five were RCTs, and one of these RCTs included only 10 infants and, therefore, does not meet the inclusion criteria for this review. There was no pooling of data owing to heterogeneity of trial populations, and variable dosing and outcome measures. The review reported that the quality of the included trials was poor, with only one of the RCTs reporting a power calculation. Two RCTs included in the review found similar pH measurements with metoclopramide and placebo (absolute numbers, CI, and P value not reported).

Comment

One observational study (42 infants) assessing the effect of metoclopramide 0.2 or 0.3 mg on pH parameters, found that metoclopramide was associated with dystonia in one infant and increased irritability in three infants.

Clinical guide

The EMA issued a drug alert regarding metoclopramide in 2013 and it is now contraindicated for the treatment of GORD in children due to its adverse effects.

Substantive changes

Metoclopramide Evidence re-evaluated. Categorisation changed from 'trade-off between benefits and harms' to 'likely to be ineffective or harmful'.

BMJ Clin Evid. 2015 Jul 24;2015:0310.

Domperidone

Summary

We don't know whether domperidone reduces symptoms in babies with gastro-oesophageal reflux.

We found no direct information from RCTs about domperidone in the treatment of children with GORD.

Domperidone is not recommended for long-term use due to its adverse effects on the heart.

Benefits and harms

Domperidone:

We found no systematic review or RCTs about domperidone in the treatment of children with GORD.

Comment

Clinical Guide

The European Medicines Agency (EMA) recommends domperidone is restricted to short-term use due to its long-term effects on the heart. It should be avoided in children with co-existing heart disease and those receiving treatment with CYP3A4 inhibitors.

Substantive changes

Domperidone Evidence re-evaluated. Categorisation changed from 'unknown effectiveness' to 'likely to be ineffective or harmful'.

BMJ Clin Evid. 2015 Jul 24;2015:0310.

H₂ antagonists

Summary

We don't know whether H 2 antagonists reduce symptoms in babies and children with gastro-oesophageal reflux and oesophagitis.

H 2 antagonists may cause adverse effects in babies.

Benefits and harms

H₂ antagonists versus placebo:

We found one systematic review, which found no RCTs that met BMJ Clinical Evidence inclusion criteria. We found two small additional RCTs. One of the RCTs (27 children, aged 3–14 years with GORD) identified compared different doses of cimetidine, but reported only physiological outcomes (gastric pH, gastric acid suppression) and is not discussed further. We found no RCTs of ranitidine in children with GORD.

Symptom severity

Cimetidine compared with placebo We don't know whether cimetidine is more effective than placebo at improving symptoms in children with GORD, as clinical relevance of results is unclear (low-quality evidence).

Ref (type)	Population	Outcome, Interventions	Results and statistical analysis	Effect size	Favours
Symptom improvement
RCT	37 children aged 1 month–14 years with GORD complicated by oesophagitis	Proportion of children who improved 12 weeks 67% with cimetidine 30% with placebo Absolute numbers not reported	P <0.01 The clinical score was developed for the study, and the clinical importance of this result is unclear	Effect size not calculated	cimetidine

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Adverse effects

Ref (type)	Population	Outcome, Interventions	Results and statistical analysis	Effect size	Favours
Adverse effects (any)
RCT	37 children aged 1 month–14 years with GORD complicated by oesophagitis	Adverse effects with cimetidine with placebo Absolute results not reported

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Comment

Both identified RCTs were small and provided insufficient evidence about clinical effects. Cimetidine has been reported to cause bradycardia in a small subgroup of people. Uncontrolled studies of ranitidine have reported bronchospasm, acute dystonic reactions, sinus node dysfunction, bradycardia, and vasovagal reactions.

Substantive changes

H₂ antagonists One systematic review added. Categorisation unchanged (unknown effectiveness).

BMJ Clin Evid. 2015 Jul 24;2015:0310.

Head elevated sleep positioning

Summary

We found no clinically important results from RCTs on clinically relevant outcomes about head elevated supine positioning compared with flat supine positioning, or the prone horizontal positioning compared with prone elevated positioning, in children under 6 months of age with GORD.

Due to the increased risk of sudden infant death syndrome (SIDS), only the supine position is recommended for infants.

Benefits and harms

Head elevated sleep position versus horizontal sleep position:

We found one systematic (search date 2003, 3 RCTs) which identified RCTs assessing reflux index and the number of episodes of reflux.

Symptom severity

Head elevated sleep position versus horizontal sleep position We don't know whether sleeping with head elevated is more effective than sleeping in the horizontal position at improving symptoms of GORD (Reflux Index and episodes of reflux) (very low-quality evidence).

Ref (type)	Population	Outcome, Interventions	Results and statistical analysis	Effect size	Favours
Reflux Index
RCT Crossover design	24 infants, aged <5 months with Reflux Index of >5% In review	Mean Reflux Index 10.7% with horizontal positioning 10.1% with head elevation	Reported as not significant P value not reported		Not significant
Systematic review	10 infants, aged 2–8 weeks, with excessive regurgitation Data from 1 RCT	Median Reflux Index 18% with horizontal supine position 11% with head elevated supine position (10° elevation)	P = 0.003 Statistical analysis carried out by review using individual data Results differ from those reported in original paper (mean Reflux Index: 19% with head elevated supine position v 11% with horizontal supine position; P = 0.08)	Effect size not calculated	head elevated supine position
Systematic review	100 infants aged <6 months; 90 had GORD based on Reflux Index >10% Data from 1 RCT	Median Reflux Index (subgroup of children with GORD) 29% with prone horizontal position 23% with prone plus head elevated	Reported as not significant P value not reported		Not significant
Episodes of reflux
Systematic review	10 infants, aged 2 to 8 weeks, with excessive regurgitation Data from 1 RCT	Mean number of episodes 24 hours 33.9 with horizontal supine position 32.3 with head elevated supine position (10° elevation)	P = 0.95		Not significant
Systematic review	100 infants aged <6 months, 90 had GORD based on Reflux Index >10% Data from 1 RCT	Mean number of episodes 7.8 with prone horizontal position 5.7 with prone plus head elevated	Reported as not significant P value not reported		Not significant

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Adverse effects

No data from the following reference on this outcome.

Comment

The RCTs identified by the systematic review measured the surrogate outcome of Reflux Index, and it is difficult to interpret the clinical importance of the observed changes.

Clinical guide

Due to the increased risk of SIDS, only the supine position is recommended for infants.

Substantive changes

No new evidence

BMJ Clin Evid. 2015 Jul 24;2015:0310.

Proton pump inhibitors

Summary

Proton pump inhibitors have been associated with hepatitis, and omeprazole with chronically elevated serum gastrin.

Benefits and harms

Proton pump inhibitors versus placebo:

We found two systematic reviews (search dates 2010; and 2011), which contained three RCTs comparing proton pump inhibitor with placebo. The three RCTs were common to both systematic reviews; however, neither systematic review pooled data. One RCT did not fulfil the inclusion criteria for this BMJ Clinical Evidence review; therefore, it is not reported further in this review. We found two subsequent RCTs.

Symptom severity

Proton pump inhibitors compared with placebo Proton pump inhibitors may be no more effective than placebo at improving symptoms of GORD in children younger than 12 months (low-quality evidence).

Ref (type)	Population	Outcome, Interventions	Results and statistical analysis	Effect size	Favours
Symptom severity
Systematic review	Infants (4−51 weeks) with symptomatic GORD and no response to conservative therapy In review Data from 1 RCT	GORD symptoms (per daily diary − % of feeds/week with: regurgitation; stopping feedings early; feeding refusal; arching back; coughing; wheezing; hoarseness) with lanzoprazole with placebo Absolute results not reported	Reported as no differences between groups P value not reported
Systematic review	Infants (<12 months) with clinical diagnosis of suspected, symptomatic, or endoscopy-confirmed GORD and GSQ-I score >16 In review Data from 1 RCT	Change in weekly GORD symptom scores 4 weeks −2.39 with pantoprazole −2.52 with placebo	Reported as not significant		Not significant
RCT	80 infants (1−11 months) with GORD who exhibited symptom improvement following 2 weeks' open-label administration of esomeprazole	Mean change from baseline in vomiting/regurgitation (assessed using Physician Global Assessment) 0.04 with esomeprazole 0.09 with placebo	P value not reported
RCT	80 infants (1−11 months) with GORD who exhibited symptom improvement following 2 weeks' open-label administration of esomeprazole	Discontinuation rates due to symptom worsening 4 weeks 15/39 (38%) with esomeprazole 20/41 (49%) with placebo	HR 0.69 95% CI 0.35 to 1.35 P = 0.28 See Further information on studies		Not significant
Vomiting
RCT	52 neonates with signs and symptoms of GORD	Percentage change from baseline in vomiting episodes post-treatment −8% with esomeprazole +10% with placebo	P = 0.4227		Not significant

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Adverse effects

Ref (type)	Population	Outcome, Interventions	Results and statistical analysis	Effect size	Favours
Adverse effects
Systematic review	Infants aged 3–12 months with irritability and Reflux Index >5%, oesophagitis, or both In review Data from 1 RCT	Adverse effects with omeprazole with placebo Absolute results not reported
Systematic review	Infants (4−51 weeks) with symptomatic GORD and no response to conservative therapy In review Data from 1 RCT	Serious adverse events 4 weeks 12% with lansoprazole 2% with placebo Absolute numbers not reported	P = 0.032	Effect size not calculated	placebo
RCT	80 infants (1−11 months) with GORD who exhibited symptom improvement following 2 weeks' open-label administration of esomeprazole	Serious adverse events 4/39 (10%) with esomeprazole 1/41 (2%) with placebo	Significance not assessed
RCT	52 neonates with signs and symptoms of GORD	Serious adverse events 0/26 (0%) with esomeprazole 3/26 (12%) with placebo	Significance not assessed

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Proton pump inhibitors versus hydrolysed formula:

We found one systematic review (search date 2010), which contained one RCT comparing proton pump inhibitors (lansoprazole given once a day or a split dose twice a day) with hydrolysed formula. We report data directly from the RCT.

Symptom severity

Proton pump inhibitors versus hydrolysed formula We don't know whether proton pump inhibitors are more effective than hydrolysed formula at reducing gastro-oesophageal reflux symptoms in infants under 7 months (low-quality evidence).

Ref (type)	Population	Outcome, Interventions	Results and statistical analysis	Effect size	Favours
Symptom severity
RCT 3-armed trial	45 infants (3−7 months) with an I-GERQ-R score of at least 16 over a 1 week period In review	Number of infants with an Infant Gastro-oesophageal Reflux Questionnaire Revised (I-GERQ-R) score reduction of 6 or more 2 weeks 9/15 (60%) with lansoprazole once daily 10/15 (67%) with lansoprazole twice daily 3/15 (20%) with hydrolysed formula	P <0.05 Not clear if this P value was among group, combined lansoprazole versus hydrolysed formula, or head to head

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Proton pump inhibitors versus sodium alginate:

We found one systematic review (search date 2010), which contained one RCT.

Symptom severity

Proton pump inhibitors versus sodium alginate We don’t know whether proton pump inhibitors are more effective than sodium alginate at reducing gastro-oesophageal reflux symptoms in infants and children (very low-quality evidence).

Ref (type)	Population	Outcome, Interventions	Results and statistical analysis	Effect size	Favours
Symptom severity
Systematic review	Children (1−12 years) with GORD symptoms combined with results of pH monitoring and/or moderate oesophagitis shown on endoscopy Data from 1 RCT	Change in clinical symptom scores (not further defined) 8 weeks 4.3 with lansoprazole 4.2 with alginate	Significance not assessed

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Further information on studies

A 4-week blinded randomisation phase followed on from an initial 2-week open label treatment phase. A total of 98 children were entered into the open label phase. Of this group, 18/98 (18%) discontinued prior to randomisation due to lack of therapeutic response (n = 9), adverse effects (n = 5), or withdrawal of consent by parent (n = 4), while 80 children continued to the randomised phase. Authors of the trial were funded by AstraZeneca.

Authors of the trial were funded by AstraZeneca. The study was discontinued early due to poor enrolment.

Comment

Proton pump inhibitors have been reported to cause hepatitis, and omeprazole chronically elevates serum gastrin. One RCT measured the surrogate outcome of Reflux Index, and it is difficult to interpret the clinical importance of the observed changes. Since the search date of this BMJ Clinical Evidence review, a systematic review has been published on pharmacological treatment of children with gastro-oesophageal reflux, which included studies on PPIs. The findings do not change our categorisation and will be reported fully in the next update.

Substantive changes

Proton pump inhibitors Two systematic reviews and two subsequent RCTs added. Categorisation unchanged (unknown effectiveness).

BMJ Clin Evid. 2015 Jul 24;2015:0310.

Weight loss

Summary

We found no direct information from RCTs about weight loss in the treatment of children with GORD. Weight loss is not a treatment option for infants and young children.

Benefits and harms

Weight loss:

We found no systematic review or RCTs for weight loss to treat GORD in children.

Comment

Weight loss is not a treatment option for infants and young children. While there is an increased incidence of GORD in obese adults, there is no evidence that weight reduction reduces symptoms of GORD in adults (see overview on GORD in adults).

Substantive changes

No new evidence

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PERMALINK

GORD in infants and children

Dr Rajini Sarvananthan

Roles

Abstract

Introduction

Methods and outcomes

Results

Conclusions

Key Points

Clinical context

General background

Focus of the review

Comments on evidence

Search and appraisal summary

About this condition

Definition

Incidence/ Prevalence

Aetiology/ Risk factors

Prognosis

Aims of intervention

Outcomes

Methods

Table.

Glossary

Disclaimer

References

Feed thickeners in infants

Summary

Benefits and harms

Feed thickeners versus non-thickened feeds:

Symptom severity

Adverse effects

Further information on studies

Comment

Substantive changes

Hydrolysed formula

Summary

Benefits and harms

Hydrolysed formula versus placebo:

Hydrolysed formula versus proton pump inhibitor:

Comment

Substantive changes

Sodium alginate

Summary

Benefits and harms

Sodium alginate versus placebo:

Symptom severity

Adverse effects

Sodium alginate versus proton pump inhibitor:

Comment

Substantive changes

Left lateral or prone sleep positioning

Summary

Benefits and harms

Prone or left lateral sleeping position versus other sleeping positions:

Symptom severity

Adverse effects

Comment

Clinical guide

Substantive changes

Metoclopramide

Summary

Benefits and harms

Metoclopramide versus placebo or no treatment:

Symptom severity

Adverse effects

Further information on studies

Comment

Clinical guide

Substantive changes

Domperidone

Summary

Benefits and harms

Domperidone:

Comment

Clinical Guide

Substantive changes

H2 antagonists

Summary

H₂ antagonists

H₂ antagonists versus placebo: