Alginate Therapy for Gastroesophageal Reflux in Pregnancy: A Scoping Review

ABSTRACT

Objective

Alginate therapies are a promising option for managing gastroesophageal reflux (GERD), but most treatments are not recommended during pregnancy. This scoping review aimed to summarize the current outcomes research on the use of alginate therapy for treating GERD during pregnancy.

Data Sources

EMBASE, MEDLINE, CINAHL, and Web of Science were searched from database inception to November 1, 2024. Reference lists of included studies were also searched.

Review Methods

We included randomized controlled trials (RCTs) and non‐randomized studies evaluating alginate use in pregnant individuals with GERD. Screening and data extraction were performed by three reviewers in duplicate. Extracted data included study design, location, population, study group allocation, and clinical outcomes. Descriptive statistics were calculated using Microsoft Excel.

Results

Two RCTs and two prospective cohort studies met the inclusion criteria. Of the two RCTs identified, one evaluated an alginate formulation against a proton pump inhibitor (PPI), and the other against a magnesium–aluminum antacid. Cohort studies reported investigator‐ and patient‐rated treatment success at 89.7% and 90.0%, respectively, with 92.2% of participants having symptom relief within 20 min. Similar improvements in heartburn intensity and frequency were found when comparing alginates and antacids. Few maternal adverse effects were reported, and no fetal or neonatal outcomes were related to treatment. Safety profiles of alginates were comparable to PPIs and antacids.

Conclusion

Current literature on alginate therapy in pregnant women may suggest potential for symptom relief and favorable tolerability, but current evidence is limited by the few available prospective studies.

Level of Evidence

N/A.

1. Introduction

Gastroesophageal reflux disease (GERD) affects 40%–80% of pregnant women and can occur in any trimester, often worsening as pregnancy progresses [1]. It is mainly characterized by heartburn and regurgitation, but can also cause nausea, epigastric pain, and vomiting [2]. Elevated progesterone and estrogen levels during pregnancy relax the lower esophageal sphincter (LES), allowing acid to move back into the esophagus. Additionally, increased abdominal pressure from the growing fetus further exacerbates these symptoms [2].

Antacids and proton pump inhibitors (PPIs) are commonly used to manage GERD and are generally considered safe during pregnancy [3]. However, some studies suggest a potential association between PPI use and an increased risk of pre‐eclampsia, though findings from human studies remain mixed and inconclusive [4]. Alginate raft therapies have shown promise in managing GERD, offering a non‐systemic mode of action with few reported adverse effects [5]. They form a physical barrier above gastric contents, mechanically preventing reflux without systemic absorption [5]. This localized action makes alginates especially attractive for pregnant patients, where minimizing fetal drug exposure is critical. However, rigorous evaluations of their safety and efficacy during pregnancy remain limited. In 2013, a narrative review by Quartarone suggested that alginates were safe and effective for treating GERD in pregnancy [6]. The purpose of this scoping review was to describe and summarize current outcomes research on alginate therapy for GERD in pregnancy. Although a systematic review and meta‐analysis were initially planned, the limited quantity and heterogeneity of available studies justified conducting a scoping review instead.

2. Methods

This review was registered with PROSPERO (CRD42024611165) and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses extension for Scoping Reviews (PRISMA‐ScR) [7].

2.1. Information Sources and Search Strategy

We performed a search from database inception to November 1, 2024, in the following databases: Medline, Embase, CINAHL. The search was limited to English‐language primary research articles published in peer‐reviewed journals. We also manually searched the reference lists from included articles. Supporting Information 1 includes the search strategy for each database.

2.2. Eligibility Criteria

Studies were eligible for inclusion if they were randomized controlled trials (RCTs) or non‐randomized studies including cohort and case–control designs, published in English, and published in peer‐reviewed journals. The study population consisted of pregnant women aged 18 years or older presenting with symptoms of GERD. The intervention of interest was alginate‐based raft‐forming agents, such as Algicon, Gaviscon, and Pyrogastrone, used for the management of GERD during pregnancy. Eligible comparators included placebo, antacids, proton pump inhibitors (PPIs), histamine‐2‐receptor antagonists (H2RAs), or no active treatment. Outcomes included the safety and efficacy of alginate therapies.

Studies were excluded if they did not involve pregnant women, were conducted in non‐human subjects, evaluated interventions other than alginate‐based raft‐forming agents, or were published as review articles, case reports, conference abstracts, or other non‐primary research formats. Studies were also excluded if they did not report on safety or efficacy outcomes.

2.3. Study Selection and Data Extraction

Study selection and data extraction were conducted using Covidence software (Melbourne, Australia) [8]. Three reviewers (M.S., C.L., S.W.‐A.) independently screened titles/abstracts and reviewed full texts in duplicate. Three reviewers (M.S., C.L., K.H.) then independently performed data extraction in duplicate. All discrepancies during study selection and extraction phases were resolved by a senior author (P.S.). Extracted data included author and year, study design, location, population, intervention, control, number of participants, mean age, gestational age at study entry, follow‐up periods, study outcomes and key findings.

2.4. Statistical Analysis

We performed descriptive statistics to characterize all included studies and calculated proportions and frequencies, where applicable. All data management was performed using Microsoft Excel (Redmond, WA, USA) [9].

3. Results

In summary, 568 studies were identified in the database search of Medline, Embase, CINAHL. Of the 488 studies that underwent abstract screening 25 studies met the inclusion criteria and were included for full‐text review. After full‐text screening, the review yielded 4 studies that met the inclusion criteria (Figure 1).

FIGURE 1.

PRISMA flow diagram. [Color figure can be viewed in the online issue, which is available at www.laryngoscope.com]

3.1. Study Characteristics

Of the four included studies, two were RCTs and two were prospective cohort studies. Across all studies, the total sample size was 430 pregnant participants, with a mean age of 29.5 (±5.3) years [10, 11, 12, 13].

The RCTs, published in 2017 and 2023, enrolled a combined total of 140 participants and were conducted in Thailand and India, respectively [10, 11]. Meteerattanapipat and Phupong included pregnant women aged 18–40 years who were less than 36 weeks' gestation and recruited from antenatal clinics [10]. Participants were randomized in equal numbers (n = 50 per group) to receive either Liquid Gaviscon or a magnesium–aluminum antacid. Most developed heartburn during the second trimester, with a mean gestational age at onset of 26.9 (±8.0) weeks in the intervention group and 23.6 (±9.2) weeks in the comparator group [10]. The primary outcome was a reduction in heartburn frequency, and the trial was prospectively registered in a clinical trial registry [10]. Jayanthy and Reddy enrolled 20 participants per group, with no age restrictions, and compared a liquid alginate preparation with intravenous pantoprazole [11]. Mean gestational age at study entry was 19.90 (±4.38) weeks in the intervention group and 19.55 (±4.40) weeks in the comparator group [11]. The primary objective was to compare the time to onset of pain relief between groups. This trial was not registered in a clinical trial registry [11].

The two eligible prospective cohort studies were conducted in 2003 and 2012, recruiting a combined total of 292 participants [12, 13]. Both studies were carried out in the United Kingdom and South Africa. Inclusion criteria were similar across studies: pregnant women (≤ 38 weeks' gestation), aged 18–40 years, with current symptoms of heartburn and/or reflux requiring treatment [12, 13]. Each study used a Gaviscon brand‐name preparation as the intervention; however the strength and formulation differed between studies [12, 13]. The primary endpoint in both was the investigator's overall rating of the treatment after 4 weeks, calculated using a frequency distribution [12, 13].

The study characteristics of all studies are presented in the Supporting Information 2 [10, 11, 12, 13].

3.2. Treatment Efficacy

In the two non‐randomized studies, treatment efficacy was assessed by both investigators and participants using a five‐point scale (i.e., very good, good, acceptable, poor, very poor) [12, 13]. For these studies, data from both intention‐to‐treat (ITT) populations were pooled (total n = 281) [12, 13]. Across both studies, pooled investigator‐rated treatment success was 89.7%, while patient‐rated success was 90.0%. Time to symptom relief was also pooled, with 61.9% of participants experiencing relief within 10 min and 92.2% within 20 min [12, 13]. Notably, heartburn in pregnant women was most frequently reported as severe at night, but only moderate during the day. This severity reduced after 4 weeks of alginate treatment [12, 13]. Lastly, the mean sodium alginate dosages were comparable across both studies, despite differences in formulation [12, 13].

In the two randomized studies, there were no significant differences between groups for maternal age and gestational age of heartburn onset. Meteerattanapipat and Phupong compared sodium alginate with magnesium‐aluminum antacid gel [10]. No statistically significant differences were found between the two treatments in any of their efficacy parameters. This included heartburn frequency, intensity, 50% pain score reduction, quality of life, symptom frequency, and maternal satisfaction [10]. However, they reported that 80% and 92% of the participants in the alginate group achieved improvement in heartburn frequency and intensity, respectively [10]. In contrast, Jayanthy and Reddy found that alginates provided a significantly faster onset of action than PPIs, with similar findings observed for mean 24‐h symptom‐free intervals [11]. Overall, 85% of participants in the alginate group rated the treatment as “good” or “very good” [11].

3.3. Treatment Safety

In the non‐randomized studies, 477 maternal adverse events were reported among 176 participants. Of these, 93 events were classified as serious, occurring in a total of 52 women [12, 13]. The most reported serious adverse event was the need for a cesarean delivery, which occurred in 34 of these women [12, 13]. In Lindow et al., nine events were judged as “possibly” or “probably” related to the intervention; however, these events were not classified or explained in the text [14]. Whereas, in Strugala et al., three events were considered “possibly” or “probably” related to the intervention [13]. These were reported as single occurrences of hypertension, diarrhea, and nausea. All three of these events led to participant withdrawal from the study [13]. In regard to fetal and neonatal safety outcomes, there were none deemed related to treatment, and overall adverse event rates aligned with expected population norms [12, 13]. Sodium levels were also not a concern, as values were within normal limits and remained similar from baseline to the study assessment visit [12, 13]. However, there was an increase in serum potassium observed in one patient [12].

In the randomized studies, no significant differences in maternal side effects were observed between alginate and PPI or antacid groups [10, 11]. Common alginate‐related side effects included constipation, chalky taste, bloating, and nausea [10, 11]. Neonatal outcomes, including birth weight, Apgar scores, and Neonatal Intensive Care Unit (NICU) admissions, were similar across groups in Meteerattanapipat and Phupong [10].

4. Discussion

This scoping review aimed to identify and summarize the existing literature on alginate therapy for GERD in pregnancy, with particular focus on symptom relief, onset of action, and comparison with standard anti‐reflux therapies. It is important to underscore that two RCTs have evaluated the role of alginate therapy in pregnancy, despite the known ethical and logistical challenges of conducting prospective research in pregnancy. The results of our review indicate that alginate‐based therapies may provide rapid symptom relief, with most participants reporting improvement within 10 to 20 min. Importantly, alginate therapy appears generally well tolerated in pregnancy. Most maternal adverse events were mild, serious events were uncommon, and no fetal or neonatal outcomes were attributed to treatment. These therapies were also comparably safe to other standard GERD treatments, since no statistically significant differences in maternal or neonatal adverse events were identified between groups. Electrolyte values including sodium and potassium, also remained largely stable, minimizing potential impact on blood pressure or fluid retention in pregnancy.

The results of this review align with the review completed by Quatarone in 2013 [6], supporting the efficacy and safety of alginate raft therapy during pregnancy. A review by Zhao et al. [14] demonstrated that alginates were more effective than placebo and antacids in the general GERD population, though direct comparisons with PPIs were limited. Consistent with the findings of our review, Zhao et al. found no significant differences in the number of adverse events across treatment groups [14]. The RCT by Jayanthy and Reddy suggested faster symptom relief with alginates compared to pantoprazole, though the small sample size limits the strength of this conclusion [11].

Clinically, alginate therapy may be limited by its physicochemical properties since not all formulations are equivalent, and raft strength is considered critical to efficacy [15]. Research suggests that alginates may be particularly beneficial for mild to moderate GERD, especially post‐prandial reflux [16]. Their localized, non‐systemic mechanism may make them a safer long‐term alternative to PPIs, particularly for patients at risk of PPI dependency [16]. Among available products, pure sodium alginate formulations without added calcium may offer additional safety advantages by avoiding excess calcium load during pregnancy [17]. Despite their broad use in clinical settings, alginates are often positioned as adjuncts to PPI therapy or as first‐line monotherapy for milder symptoms [18].

5. Limitations

A primary limitation of this scoping review was the potential omission of relevant studies, despite the use of a broad and comprehensive search strategy. This was because some studies were not able to be retrieved due to the date of publication, being published in a language other than English, or being too old such that only the abstract was available. Nonetheless, this review serves as an important first stage in evaluating the therapeutic profile of alginate therapy for pregnant patients diagnosed with GERD.

6. Conclusion

In summary, alginate therapy may help manage GERD during pregnancy, but these findings are constrained by the limited number of eligible studies and the inability to perform a meta‐analysis of efficacy and safety outcomes. Future randomized prospective research is needed to help confirm these findings and guide clinical practice.

Conflicts of Interest

The authors declare no conflicts of interest.

Supporting information

Supporting Information 1. Search Strategies.

Supporting Information 2. Study Characteristics of the Included Studies.

Senthilkumaran M., Hui K., Li C., Werden‐Abrams S., Staibano P., and van der Woerd B., “Alginate Therapy for Gastroesophageal Reflux in Pregnancy: A Scoping Review,” The Laryngoscope 136, no. 4 (2026): 1583–1587, 10.1002/lary.70242.

Data Availability Statement

Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.