Prevalence and risk factors of gastro-oesophageal reflux disease in Saudi Arabia: a systematic review and meta-analysis

Abstract

Objective

To estimate the pooled prevalence and associated factors of gastro-oesophageal reflux disease (GERD) in Saudi Arabia and other Gulf Cooperation Council (GCC) countries.

Design

Systematic review and meta-analysis

Data sources

Searches were carried out in Web of Science, Scopus, PubMed, Google Scholar and Dimensions AI with no date or language filters.

Eligibility criteria for selection of studies

Cross-sectional studies that reported estimates of GERD prevalence from Saudi Arabia and other GCC countries were included.

Data extraction and synthesis

Two reviewers independently extracted the data, and the accuracy and clarity of the final extracted data were cross-checked by another two reviewers. Study quality was assessed using JBI Critical Appraisal Tool for Prevalence Studies. Random-effects model was used for meta-analyses.

Results

Fourteen studies from Saudi Arabia met the inclusion criteria (total participants=17 927); from the other GCC countries, only one study from Bahrain and none from Qatar, United Arab Emirates, Kuwait or Oman met the inclusion criteria, and thus were not included in the pooled analysis. The pooled prevalence of GERD from Saudi Arabia was 32% (95% CI 22% to 44%); however, there was substantial heterogeneity (I² = 99.4%). In subgroup analysis to account for heterogeneity, the prevalence was found to be significantly lower when endoscopy findings were used as the diagnostic criteria (13% (95% CI 10% to 16%); τ²=0.028; I² = 93.4%) compared with Gerd-Q questionnaire (33% (95% CI 24% to 43%); τ²=0.54; I² = 98.6%) (p<0.0001). Similar findings were noted based on study quality: high, 26% (95% CI 17% to 36%); moderate, 49% (95% CI 32% to 66%) (τ²=0.87, I² = 99.3%) (p=0.0185). Factors that increased the odds of GERD were non-steroidal anti-inflammatory drugs/analgesics use (OR: 1.78, 95% CI 1.14 to 2.79; p=0.01; τ²=0.09, I² = 59%) and smoking (OR: 1.59, 95% CI 1.28 to 1.99; p<0.0001; τ²=0.03, I² = 33%).

Conclusion

The pooled prevalence of GERD in Saudi Arabia is 32%. However, given the high heterogeneity, there is a need to standardise methods for better contextualisation of such epidemiological data. Notably, GERD prevalence was significantly lower in high-quality studies and when endoscopy findings were used as the diagnostic criteria. Finally, the lack of GERD prevalence studies from other GCC countries highlights the need for studies to fill this gap.

Registration

PROSPERO (ID: CRD42023453031)

STRENGTHS AND LIMITATIONS.

• The main strength of this meta-analysis is its broad and inclusive search strategy. In addition to major databases such as PubMed, Scopus, and Web of Science, searches were also carried out in Google Scholar and Dimensions AI to capture studies that may not have been indexed in traditional databases. In addition, no language restrictions were applied.

• The meta-analysis used strict inclusion and exclusion criteria, and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

• A key limitation of this meta-analysis is that all included studies were cross-sectional in design; therefore, although associations between gastro-oesophageal reflux disease and various risk factors were analysed, causal relationships and temporal direction cannot be established.

Introduction

Gastro-oesophageal reflux disease (GERD) is a chronic, multifactorial condition resulting from the retrograde flow of acidic stomach contents into the oesophagus.¹ Several factors are associated with an increased risk of GERD, including older age, obesity, smoking, alcohol intake, use of non-steroidal anti-inflammatory drugs (NSAIDs) and various dietary and lifestyle habits.^{2 3}

A meta-analysis published in 2020 found that the global pooled prevalence of GERD is about 14%, with substantial variation across regions.² Recent estimates have found that the number of GERD cases worldwide reached about 826.6 million in 2021, an 83% increase from estimates in 1990. Similarly, the years lost to disability (YLD) due to GERD was also reported to have increased by about 82.5% (to 6.3 million) between 1990 and 2021.⁴ In addition, the economic burden of GERD is substantial, with a recent study estimating that the annual GERD-related medical cost/patient in the United States is US$6765.⁵ Collectively, this signifies that not only is GERD an increasingly common condition but also a growing global health and economic concern.

The prevalence of GERD and its associated effects can vary by region. The highest number of YLDs due to GERD has been reported from South Asia, followed by East Asia and the Middle East and North Africa region.⁶ In coherence, in a previous global estimate on the prevalence of GERD, Middle East was found to have one of the highest estimates, a finding in coherence with that of Nirwan et al^{3 7} However, the number of studies retrieved from the Middle East in this meta-analysis was few, thereby reducing the statistical power and robustness of the pooled estimates for these countries, especially the Gulf Cooperation Council (GCC) countries. In addition, there has been a recent increase in studies reporting the prevalence of GERD from this region.8,10

To provide more recent and robust estimates, we conducted this meta-analysis to primarily estimate the pooled prevalence of GERD in Saudi Arabia and other GCC countries and to evaluate if differences in study characteristics, such as study design, study quality, diagnostic criteria and year of publication contribute to heterogeneity. We hypothesise that study design, study quality and diagnostic criteria would contribute to heterogeneity in the pooled estimates. The secondary objectives were to identify risk factors of GERD. The study findings would provide an overview of the quality of the existing epidemiological data in the region. Further, the findings of this study may guide policymakers in developing screening programmes to identify GERD earlier, thereby reducing its subsequent health and economic burden.

Methods

This systematic review and meta-analysis is reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines.¹¹ Its protocol was registered on PROSPERO (ID: CRD42023453031).

Eligibility criteria, information sources and search strategy

Cross-sectional studies and cohort studies (baseline data) that reported (a) the prevalence of GERD from (b) GCC countries, irrespective of the age of the participants, were considered for inclusion, while all other types of studies were excluded. Cross-sectional studies were included as they are the best suited design for answering questions on prevalence,¹² while baseline data from cohort studies were also considered suitable as they may provide representative prevalence estimates. Studies that only reported on interventions, lifestyle approaches or clinical evaluations were excluded. In addition, studies that reported the prevalence of GERD without the use of appropriate/verifiable diagnostic criteria (eg, self-reported previous diagnosis or diagnosis using unvalidated questionnaires) or that were not representative of the population (such as only including university students in surveys) were excluded.

Systematic searches were carried out in the following five databases: Web of Science, PubMed, Scopus, Google Scholar and Dimensions AI (https://www.dimensions.ai/). Search terms included gastro-oesophageal reflux, gastro-oesophageal reflux disease, GERD, gastric acid reflux, nonerosive reflux disease, NERD or heartburn and prevalence as well as the names of the six countries in the GCC region. Online supplementary table 1 presents the detailed search strategy and results for each database. In addition, the end list references of all relevant papers were hand searched. No date or language filters were applied.

Study selection process

All searches were independently carried out by two reviewers (AKS and AAS). Rayyan (https://www.rayyan.ai/) was used for removing duplicates and for title and abstract screening. The initial screening (title and abstract) and full-text screening process was independently carried out by both these reviewers (using the ‘Blind On’ feature). Differences in decisions were resolved through discussion between both reviewers or with the supervisor (AAA).

Data extraction process

Data from studies included in the final analysis were manually extracted onto a standardised Excel sheet (Microsoft 365) to elicit information regarding demographics (age range and distribution and gender-wise sample distribution), study characteristics (author names and year of publication, study design, study setting, country, method of sampling and sample size), diagnostic characteristics (data collection tool, criteria for defining GERD and duration of symptoms), and outcomes (GERD prevalence and its risk factors). Data extraction was piloted independently by two reviewers (IAA and HDA) (on three studies) to review for consistency and comprehensiveness. Then, both the reviewers independently extracted the data, compared their results and resolved discrepancies through discussion. The accuracy and clarity of the final extracted data was cross-checked by two reviewers (MHI and RMA). No assumptions/imputations were made about any missing or unclear information. For subgroup analysis, studies were included on an available-case basis.

Outcome and associated factors

Appropriate diagnosis of GERD was defined as being based on endoscopic findings, Montreal definition or the use of a GERD-specific score-based questionnaire. Studies reporting only a single symptom (eg, only heartburn or acid regurgitation) once a week were excluded.

All following associated factors of GERD that had been reported were included for analysis: age, gender, body mass index category, education level, marital status, self-reported use of analgesics/NSAIDs, self-reported current smoking status and dietary habits (ie, frequent consumption of spicy food, fatty/fast food, coffee/tea and carbonated drinks; ‘frequent’ was defined as >2 times/day or week, as applicable).

Study quality assessment

JBI Critical Appraisal Tool for Prevalence Studies was used to determine study quality. This tool evaluates nine domains related to the quality of methods in studies (online supplementary table 2).¹³ Study quality was categorised as follows: >75%=high; 50%–75%=moderate; <50%=low.¹⁴ Two reviewers (AKS and AAS) independently assessed the studies against the questions in the appraisal checklist, and all discrepancies were resolved through discussion between themselves or with the supervisor (AAA). The original study investigators were not contacted to obtain additional data for any study.

Data synthesis

GERD prevalence was reported as cases per 100 population. The Wilson method was used to determine 95% CIs for individual studies based on the reported crude estimates and population sizes.¹⁵ Pooled prevalence estimates were generated using a random-effects model, with 95% CIs derived using the DerSimonian and Laird method.¹⁶ To stabilise variance across studies, the Freeman–Tukey double arcsine transformation method was used.

Between-study heterogeneity was evaluated using Cochran’s Q (χ²-based) test and the tau-squared (τ²) estimate. For τ², a value higher than 0 denotes the absolute value of heterogeneity and higher values mean greater heterogeneity. I-squared (I²) statistic was used to quantify the proportion of variability attributable to heterogeneity, with 51%–75% heterogeneity considered substantial and >75% as considerable; the percentage here indicates the total heterogeneity resulting from between-study variance that could not be explained by sampling error. Therefore, to account for heterogeneity, 95% prediction interval (PI) was also reported to estimate the expected range of true prevalence of GERD in future studies in similar settings.17,20 To explore potential causes for significant heterogeneity, we carried out subgroup analyses according to study design (ie, electronic health records and survey), study quality, diagnostic criteria (ie, endoscopy and questionnaire-based) and year of publication. Similarly, meta-regression analysis was carried out for mean age to determine its role in heterogeneity, and this was reported using bubble plot and regression coefficients (β). Beyond this, pooled estimates were reported according to geographic region, and the associated risk factors were identified.

Publication bias for the overall prevalence estimate was evaluated through visual assessment of funnel plot, and its symmetry was evaluated using Egger’s linear regression test by plotting the SE against log-transformed prevalence estimates (significant at p <0.1).²¹ Publication bias was not reported for individual risk factors because the number of included studies was <10 for all factors except for gender, and thus the test would have had insufficient power to reliably detect asymmetry.²²

Pooled prevalence was also stratified by risk factor and reported as percentages along with 95% CIs. Further, the association between GERD and its risk factors was reported using ORs along with 95% CIs. p<0.05 was considered statistically significant for the effect of study-level covariates. RevMan V.5.4 and R V.4.3 were used for all statistical analyses.

Results

Search findings

In the initial searches, 255 records were retrieved, of which 136 were duplicates and removed. Of the remaining 119 records, 92 were excluded during the title and abstract screening (no non-English articles were found in the searches) (online supplementary table 3) provides details of studies excluded owing to study participants not being representative of the general population. From the full-text screening of the remaining 27 articles, 12 were excluded23,34 and 15 were included in this systematic review (figure 1).8,1035 Online supplementary table 4 lists the 12 excluded studies along with the reasons. All 15 studies were cross-sectional. In terms of country, 14 were from Saudi Arabia, and 1 was from Bahrain; no study from Qatar, United Arab Emirates, Kuwait and Oman met the inclusion criteria. Therefore, in the meta-analysis, only the 14 studies from Saudi Arabia were included.

Figure 1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart diagram for the identification of studies.

Study characteristics

Most studies from Saudi Arabia were from the Southwest region and Makkah Province (four studies each); two studies covered the entire Saudi Arabia. Participants in the studies ranged from 320⁴⁴ to 3166.³⁸ Of the 14 studies from Saudi Arabia, 4 studies were published between 2010 and 2019, and 10 studies were published between 2020 and 2024, highlighting the recency of the data. In terms of method of diagnosis, 11 studies used the Gerd-Q questionnaire (score≥8) (table 1)836,45; in all these studies, the duration of symptoms was considered as 1 week, whereas the same was not stated in the remaining 3 studies.^{9 35 46} Gerd-Q and 1-week symptom duration were also used in the study from Bahrain.¹⁰

Table 1. Characteristics of the included studies (n=15).

Author(s)	Study design	Study city, region, and country	Total sample size	Age range (years)	Mean age (years) (±SD)	Gender distribution		GERD diagnostic criteria
						Male (%)	Female (%)
Alqassab et al10	Survey	Bahrain	385	≥18	41.5 (14.4)	46.8	53.2	Gerd-Q (score≥8)
Al-Humayed et al35	Electronic Health Records	Aseer, Southwest, SA	1607	15–100	48.5 (18)	56.4	43.6	Upper GI endoscopy findings
Almadi et al36	Survey	Riyadh, Central, SA	1265	≥18	30 (11.6)	67.8	32.2	Gerd-Q (score≥8)
Alsuwat et al37	Survey	Pan SA	2043	≥18	29.6 (10.5)	48.2	51.8	Gerd-Q (score≥8)
Awadalla and Al Musa38	Survey	Abha, Southwest, SA	3166	18–90	33.5 (12.5)	45.2	54.8	Gerd-Q (score≥8)
Alharthi et al39	Survey	Taif, Makkah Province, SA	756	≥18	NS	43.7	56.3	Gerd-Q (score≥8)
Kariri et al40	Survey	Jazan, Southwest, SA	853	≥18	NS	43.7	56.3	Gerd-Q (score≥8)
Halawani and Banoon41	Survey	Makkah, Makkah Province, SA	339	18–84	39.5 (15.5)	56.3	43.7	Gerd-Q (score≥8)
Kuddus et al42	Survey	Hail, Northwest, SA	704	≥15	23.6 (11.8)	51.7	48.3	Gerd-Q (score≥8)
Al Ghadeer et al43	Survey	Eastern Province, SA	1517	18–58	27.5 (11.4)	41.2	58.8	Gerd-Q (score≥8)
Alsaleem et al44	Survey	Abha, Southwest, SA	320	≥18	NS	52.2	47.8	Gerd-Q (score≥8)
Odah et al45	Survey	Al Qunfudhah, Makkah Province, SA	1180	16–94	31.7 (10.7)	63.5	36.5	Gerd-Q (score≥8)
AlHusaini et al8	Survey	Riyadh Central, SA	490	≥17	NS	41	59	Gerd-Q (score≥8)
Alsahafi et al9	Electronic Health Records	Jeddah, Makkah Province, SA	2805	≥18	48 (18.6)	38.7	61.3	Upper GI endoscopy findings
Alkhaldi et al46	Survey	Pan SA	882	≥18	31.5 (14.9)	22.6	77.4	FSSG Questionnaire (score>8)

FSSG, Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease; GERD, gastro-oesophageal reflux disease; GI, gastrointestinal; SA, Saudi Arabia.

Study quality assessment

The study quality assessment for all included studies (n=15) is provided in online supplementary figure 1.⁴⁷ In summary, 10 studies were of high quality8,1035 38 and 5 were of moderate quality^{36 37 42 45 46}; none were of low quality. Of note, several studies were found to have used an Arabic version of the Gerd-Q questionnaire that was only translated and piloted but not validated, and most studies also did not report the response rates. In addition, several studies used the online mode for disseminating the questionnaire, which resulted in a random and convenience sampling, but likely introduced self-selection bias.

Pooled prevalence of GERD in Saudi Arabia

In the single study from Bahrain (n=385), the prevalence of GERD was reported as 41.5% (95% CI 37% to 47%).¹⁰ The pooled prevalence of GERD in Saudi Arabia (n=17 927) using the random-effects model was 32% (95% CI 22% to 44%), but there was substantial heterogeneity (τ²=0.9223; χ²=2067.59, I² = 99.4%) (figure 2). In addition, the PI was 5.2%–80.2%, further highlighting between-studies substantial heterogeneity and considerable variability in GERD prevalence estimates across populations and methodologies. This is also represented in the findings of individual studies: with the lowest reported prevalence being 11% (95% CI 10% to 12%)⁹ and the highest being 78% (95% CI 75% to 81%).⁴⁶

Figure 2. Pooled prevalence of gastro-oesophageal reflux disease (GERD) in Saudi Arabia. GLMM, generalized linear mixed model.

Online supplementary figure 2 shows the funnel plot of the included studies. The distribution of the studies was asymmetrical; however, the Egger’s meta-regression analysis showed that there was no evidence of small-study effects or publication bias for the overall estimate of GERD prevalence (t=0.01, df=13, p=0.99; bias estimate=0.12, SE=9.52). Of note, the between-study heterogeneity remained considerable (τ² = 160.18).

Exploration of sources of heterogeneity in the pooled prevalence of GERD in Saudi Arabia

In the subgroup analysis, the prevalence rates were found to significantly differ by study quality: high (n=12 238), 26% (95% CI 17% to 36%); moderate (n=6074), 49% (95% CI 32% to 66%) (τ²=0.87; χ²=2082.38, I² = 99.3%) (online supplementary figure 3). The meta-analyses also found substantial differences when stratified by study design and diagnostic criteria. In terms of study design, a markedly lower prevalence of GERD was found in studies that used electronic health records (n=4412; 13% (95% CI 10% to 16%); τ²=0.028; I² = 93.4%) compared with surveys (n=13 515; 36% (95% CI 26% to 49%); τ²=0.81; I² = 99.1%) (online supplementary figure 4).

A substantially lower prevalence was found when endoscopy findings were used as the diagnostic criteria for GERD (n=4412; 13% (95% CI 10% to 16%); τ²=0.028; I² = 93.4%) compared with the Gerd-Q questionnaire (n=12 633; 33% (95% CI 24% to 43%); τ²=0.54; I² = 98.6%) and the FSSG questionnaire (n=882; 78% (95% CI 75% to 81%); τ²=0.92; I² = 99.4%). Subgroup analysis revealed the differences between diagnostic criteria were statistically significant (χ² = 468.85, p<0.0001) (figure 3). While the substantial heterogeneity in all the subgroup analysis suggests the influence of other unmeasured sources of variation, visual assessment of the forest plot and the significant difference in prevalence by diagnostic criteria suggests that diagnostic criteria is likely the major contributor of heterogeneity.

Figure 3. Diagnostic criteria-wise pooled prevalence of gastro-oesophageal reflux disease (GERD).

Heterogeneity was not explained even when studies were stratified according to year of publication: 2010–2019 (n=8081): τ²=0.33, I² = 99.2%; 2020–2024 (n=9846): τ²=1.16, I² = 99.5% (online supplementary figure 5). Meta-regression analysis demonstrated that increasing mean age was significantly associated with a reduction in the pooled prevalence estimate (β = −0.0814, SE=0.0288, p=0.0048); however, substantial residual heterogeneity remained after adjustment (residual I² = 99.31%) (online supplemental figure 5 and 6). Of note, in the bubble plot, the two studies that contributed to reduction in prevalence estimate with increase in age were both endoscopy-based studies, further highlighting the influence of diagnostic criteria as the major source of heterogeneity.

Pooled prevalence of GERD in different regions of Saudi Arabia

The pooled prevalence of GERD according to regions of Saudi Arabia also varied, as shown in online supplementary figure 7. The highest prevalence was reported from the Northwest Region (n=704; 58%; 95% CI 54% to 62%), although this only included a single study. This was followed by the Southwest (n=5946; 36% (95% CI 20% to 58%); τ²=0.77; I² = 99.3%) and Central (n=1755; 29% (95% CI 14% to 52%); τ²=0.48; I² = 99.1%) regions, although the large difference in the lower and upper CIs is suggestive of considerable uncertainty in the estimate. The lowest prevalence of GERD was reported from the Makkah Province (n=882; 19% (95% CI 12% to 27%); τ²=0.24; I² = 98.8%).

Prevalence of GERD according to risk factors

Table 2 provides the pooled prevalence by risk factors and its association with GERD. Online supplementary figures 8–21 provide the forest plots stratified by risk factor.

Table 2. Pooled prevalence of GERD and its associated factors.

Risk factor	Studies (n)	Participants (n)	Pooled prevalence % (95% CI)	Odds ratio (95% CI)	I2 (%)	τ 2	P value
Gender
Male	10	4791	27.8 (26.5 to 29.1)	0.90 (0.69 to 1.17)	85	0.15	0.43
Female	10	5915	29.5 (28.3 to 30.6)
BMI category
Normal	6	1467	51.1 (48.5 53.6)	Comparator
Underweight	3	140	47.1 (39.1 to 55.4)	1.05 (0.68 to 1.61	0	0	0.83
Overweight	5	1004	43.1 (40.1 to 46.2)	1.06 (0.79 to 1.41)	51	0.05	0.71
Obese	7	2534	21.4 (19.8 to 23.0)	1.27 (0.90 to 1.80)	57	0.09	0.17
Education level
Primary	6	284	28.5 (23.6 to 34.0)	Comparator
Secondary	5	1188	24.0 (21.6 to 26.5)	1.11 (0.66 to 1.86)	63	0.25	0.68
University	6	4308	27.9 (26.5 to 29.2)	1.11 (0.70 to 1.74)	56	0.18	0.66
Marital status
Single	6	2534	28.4 (26.7 to 30.2)	Comparator
Married	6	3189	26.0 (24.5 to 27.5)	1.07 (0.70 to 1.65	90	0.24	0.76
Divorced/widowed	3	105	33.3 (25.0 to 42.8)	2.04 (0.97 to 4.29)	56	0.24	0.06
NSAIDs/analgesics use
Yes	3	495	35.6 (31.5 to 39.9)	1.78 (1.14 to 2.79)	59	0.09	0.01*
No	3	2052	22.2 (20.4 to 24.0)
Current smoker
Yes	7	948	42.1 (39.0 to 45.3)	1.59 (1.28 to 1.99)	33	0.03	<0.0001*
No	7	4157	39.6 (38.1 to 41.1)
Frequent spicy food consumption
Yes	6	1156	37.1 (34.4 to 39.9)	1.13 (0.96 to 1.35)	0	0.00	0.15
No	6	3067	30.2 (28.6 to 31.8)
Frequent fatty/fast food consumption
Yes	5	1669	37.9 (35.6 to 40.2)	1.33 (0.97 to 1.83)	74	0.09	0.08
No	5	2064	31.0 (29.0 to 33.0)
Frequent coffee/tea consumption
Yes	6	2314	31.6 (29.7 to 33.5)	1.21 (0.71 to 2.06)	90	0.38	0.48
No	6	1970	31.3 (29.3 to 33.4)
Frequent carbonated drinks consumption
Yes	4	632	38 (34.3 to 41.8)	1.11 (0.73 to 1.71)	71	0.13	0.62
No	4	2397	25.4 (23.7 to 27.2)

^*Indicates significant independent risk factor.

BMI, body mass index; GERD, gastro-oesophageal reflux disease; NSAIDs, non-steroidal anti-inflammatory drugs.

The studies included the meta-analysis had grouped patients by age in a highly variable range, and thus we were unable to analyse age groups as a risk factor for GERD. In terms of sex, the pooled prevalence of GERD was higher in females (n=5915; 29.5%, 95% CI 28.3% to 30.6.1%) than males (n=4791; 27.8%; 95% CI 26.5% to 29.1%); however, sex was not found to be a significant risk factor for GERD (OR=0.90, 95% CI 0.69 to 1.17; I²=85%) (online supplementary figure 8). With respect to BMI category, the prevalence of GERD was highest among those who were underweight (47.1%), and, surprisingly, lowest among those who were obese (21.4%). However, weight categories were not found to be significant risk factors for GERD (online supplementary figures 9–11).

Regarding educational level, which was used as an indicator for socioeconomic status, it was found that individuals with primary education had a marginally higher prevalence of GERD (28.5%) than those with secondary and university-level education (24.0% and 27.9%, respectively), although education level was not significantly associated with GERD (online supplementary figures 12 and 13). Marital status analysis showed the highest prevalence of GERD was among divorced/widowed individuals (33.3%), but marital status was not a significant risk factor for GERD (online supplementary figures 14 and 15).

Compared with non-users (n=2052), NSAIDs/analgesics users (n=495) had a higher prevalence (35.6% vs 22.2%). In addition, use of NSAIDs/analgesics was significantly associated with increased risk of GERD (OR: 1.78, 95% CI 1.14 to 2.79; p=0.01), with a moderate to significant heterogeneity (τ²=0.09; I² = 59%) (online supplementary figure 16). Similarly, compared with non-smokers, smokers were found to have a higher prevalence of GERD (42.1% vs 39.6%). In addition, smoking significantly increased the risk of GERD (OR: 1.59, 95% CI 1.28 to 1.99; p<0.0001), with low to moderate heterogeneity (τ²=0.03; I² = 33%) (online supplementary figure 17). Meta-analysis was not conducted for khat chewing and alcohol consumption, as they were reported only in a single study each.

In terms of dietary habits, compared with non-frequent consumers, the prevalence of GERD was higher among those who frequently consumed spicy food (37.1% vs 30.2%), fatty/fast foods (37.9% vs 31.0%), coffee/tea (31.6% vs 31.3%) and carbonated drinks (38% vs 25.4%); however, none of these were found to significantly increase the odds for GERD (online supplementary figures 18–21).

Discussion

This was the first meta-analysis conducted to determine the prevalence and risk factors of GERD across all countries of GCC; however, it was found that such studies have primarily been conducted in Saudi Arabia, with only a single recent study from Bahrain. No studies from Qatar, Kuwait, United Arab Emirates and Oman met the inclusion criteria of this review, thereby signifying the strong need for studies to report the prevalence of GERD from these countries. It should be noted that two recent studies from Qatar and one older study from Kuwait reported the prevalence of esophagitis from endoscopy findings but did not sufficiently delineate GERD to specifically report its prevalence, highlighting the need for better diagnostic reporting of GERD in studies from the region.23,25

A recent meta-analysis estimated the prevalence of GERD in Saudi Arabia; however, it included studies that did not use verifiable diagnostic criteria (such as self-reported previous diagnosis and diagnosis using author-developed questionnaires) or that were not representative of the population (such as only including university students in surveys). Such inclusion can introduce significant sampling and selection bias that can distort pooled prevalence estimates.⁴⁸ In addition, the meta-analysis also did not provide insights of differences based on diagnostic criteria and study designs, which are important for clinicians and policymakers to better contextualise the reported prevalence.⁴⁸

The pooled prevalence of GERD in Saudi Arabia was estimated to be 32%, highlighting the substantial burden of this disease. Further, the only identified study from Bahrain reported a prevalence of 41.5%. These rates are substantially higher than the global prevalence of 14% reported by Nirwan et al, but are in line with previous studies estimating that the prevalence of GERD is among the highest in Middle Eastern populations.^{2 3 7} However, the findings of the current meta-analysis should be interpreted with caution, as significant differences were noted in the prevalence rates across diagnostic criteria, with lower prevalence being reported in endoscopy-based studies than questionnaire-based studies, and between high- and medium-quality studies. In addition, there was substantial heterogeneity across studies.

Gerd-Q was used to report the prevalence in 11 of 14 (about 80%) of studies from Saudi Arabia. However, using symptom-based questionnaires such as Gerd-Q to report the prevalence of GERD can result in the risk of overestimating GERD, as highlighted by Nirwan et al, who reported that the prevalence of GERD was highest when using the Gerd-Q and lowest when using the Montreal definition.² In fact, endoscopy has been shown to have higher sensitivity and specificity than Gerd-Q.⁴⁹ Further, the Gerd-Q has been reported to lack accuracy for quantifying the frequency of reflux and its associated symptoms.⁵⁰ As questionnaire and endoscopy-based studies identify fundamentally different patient populations, this explains the wide variations in pooled prevalence rates of GERD between the studies in the current meta-analyses. The 13% prevalence of GERD using endoscopy is close to the 20.1% prevalence of GERD found in a very recent endoscopy-based diagnosis study reported from Saudi Arabia.⁵¹ Collectively, this indicates the diagnosis of GERD using specific clinical procedures such as endoscopy and/or 24-hour pH-impedance is more accurate for reporting prevalence.⁵² In fact, the Lyon Consensus 2.0 recommends that for patients with no previous GERD diagnosis, prolonged wireless pH monitoring or catheter-based pH or pH-monitoring off antisecretory medication should be used for making a diagnosis, and thus this should ideally be considered in future studies reporting prevalence.⁵²

The current meta-analysis found that use of NSAIDs/analgesics and smoking were factors that significantly increased the odds of GERD by 78% and 59%, respectively. In addition, the heterogeneity for both were moderate and low, respectively, indicating relatively consistent findings. This is an expected result given that both NSAIDs and smoking have detrimental effects on oesophageal mucosa and lower oesophageal sphincter tone.^{53 54} Our findings are coherent with those of a community-based study from Australia, which found that, compared with never users, the prevalence of GERD symptoms was significantly higher among those who regularly used aspirin or other NSAIDs.⁵⁵ Similarly, in the United States, the relative risk of GERD was reported to be higher among NSAID users compared with non-users.⁵⁶ In terms of smoking, a very recent meta-analysis reported that inhalational exposures were significantly associated with a higher risk of GERD.⁵⁷ In Japan, a case–control comparison revealed an increased risk of reflux esophagitis among former smokers and current smokers compared with never-smokers.⁵⁸

Obesity is a well-recognised factor of GERD.⁷ This association has also been demonstrated in a large-scale global healthcare database study.⁵⁹ Similarly, a very recent meta-analysis found that BMI is significantly and linearly associated with an increased risk of GERD, with overweight being an inflection point for increased disease risk.⁶⁰ However, the current meta-analysis surprisingly found that the pooled prevalence of GERD was the lowest among obese participants compared with normal, underweight and overweight participants (table 2). A possible explanation for this unexpected finding could be residual confounding factors across studies as well as self-reporting bias among participants. In addition, the strength of association between GERD and obesity can be influenced by factors such as ethnicity and sex.⁵⁹ In line with this, a recent endoscopy-based study from Saudi Arabia also found that obesity was not an associated factor for GERD.⁵¹ Therefore, the findings of the current meta-analysis should be interpreted with caution, and further large-scale, well-designed studies are required from Saudi Arabia to determine the relationship between obesity and GERD and identify potential effect modifiers.

Regarding dietary factors, those who frequently consumed spicy food, fatty/fast foods, coffee/tea and carbonated drinks had a higher prevalence of GERD, but these were not found to be independent risk factors of GERD. However, limited reporting and inconsistent definitions of ‘frequent’ across studies may have weakened the robustness of the analyses, although we defined ‘frequent’ as >2 times/day or week. It should be noted that these data were only available from self-reported questionnaire studies, and thus self-reporting bias cannot be excluded. Finally, because patients with symptoms of GERD may intentionally avoid foods perceived to worsen reflux symptoms, reverse causality cannot be excluded.

Limitations

The extremely high heterogeneity across studies (I² >99%) is a major limitation of this meta-analysis. This is most likely due to differences in the diagnostic criteria. Other factors that could have contributed to the high heterogeneity were study designs, sampling strategies and regional variations. In terms of methods, 80% of the studies used the Gerd-Q questionnaire, which may overestimate GERD. In addition, several of these studies used a non-validated Arabic version of Gerd-Q, further reducing the generalisability and precision of the pooled estimates. Another limitation is that while frequent alcohol consumption is a known associated factor of GERD,⁵⁴ it was not included in the current meta-analyses, as its use was only reported in a single study. Finally, we were only able to categorise smokers as current smokers and non-smokers based on the reporting patterns in identified studies, and thus could not include former smokers, which could have added a broader scope of analysis.⁵⁸

Conclusion

The pooled prevalence of GERD in Saudi Arabia is 32%. In addition, NSAIDs/analgesics use and smoking significantly increased the risk of GERD. However, the high heterogeneity between studies as well as the prevalence being significantly lower in high-quality studies and when endoscopy findings were used as the diagnostic criteria strongly indicate the need to standardise methods for estimating the prevalence and risk factors of GERD for better contextualisation. Finally, the lack of reporting of GERD prevalence from the other countries of GCC (namely, Qatar, United Arab Emirates, Kuwait and Oman) highlights the need for such studies to fill this gap.

Data availability statement

Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.