Abstract
Introduction
Heartburn is a common complaint during pregnancy; the incidence is reported to be between 17% and 45%.
Methods and outcomes
We conducted a systematic overview and aimed to answer the following clinical question: What are the effects of interventions to prevent or treat heartburn in pregnancy? We searched Medline, Embase, The Cochrane Library, and other important databases up to December 2014 (BMJ Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review).
Results
At this update, searching of electronic databases retrieved 80 studies. After deduplication and removal of conference abstracts, 59 records were screened for inclusion in the review. Appraisal of titles and abstracts led to the exclusion of 58 studies and the further review of one full publication. The full article evaluated did not meet our reporting criteria, and thus no new evidence was added at this update. We performed a GRADE evaluation for two PICO combinations.
Conclusions
In this systematic overview, we categorised the efficacy for six interventions, based on information about the effectiveness and safety of acid-suppressing drugs, antacids with or without alginates, raising the head of the bed, reducing caffeine intake, reducing intake of fatty foods, and reducing the size and frequency of meals.
Key Points
Heartburn is common during pregnancy; the incidence is reported to be between 17% and 45%.
We searched for evidence of effectiveness from RCTs and systematic reviews of RCTs for interventions to prevent and treat heartburn in pregnancy.
Antacids may provide effective heartburn relief in pregnancy.
We don't know whether acid-suppressing drugs, such as ranitidine, are beneficial in treating heartburn in pregnancy.
We don't know whether dietary and lifestyle modifications are beneficial in preventing or treating heartburn in pregnancy. However, recommendations have been made that lifestyle and dietary modifications, including reducing the intake of fatty foods and reducing the size and frequency of meals, should remain first-line treatment for heartburn in pregnant women. Other lifestyle modifications that could be considered are reducing caffeine intake and raising the head of the bed.
Clinical context
General background
Heartburn is a common complaint during pregnancy; the incidence is reported to be between 17% and 45%. Serious complications are rare, although it may be associated with severe nausea and vomiting, and the condition usually resolves soon after delivery.
Focus of the review
The review assesses the efficacy and safety (primarily related to teratogenic adverse effects) of several interventions used to manage heartburn during pregnancy, ranging from lifestyle changes to antacids and acid-suppressing drugs.
Comments on evidence
We found no direct evidence from RCTs regarding the role of lifestyle measures or acid-suppressing agents (H2 receptor antagonists and PPIs) compared with placebo or no treatment in the management of heartburn in pregnancy. One systematic review, which included one relevant RCT, found that antacids may provide effective heartburn relief in pregnancy compared with placebo. Another systematic review, also with one relevant RCT, found no difference between antacid alone and antacid plus acid-suppressing drug in terms of symptoms relief. Overall, the quality of evidence was low.
Search and appraisal summary
The update literature search for this review was carried out from the date of the last search, February 2010, to December 2014. For more information on the electronic databases searched and criteria applied during assessment of studies for potential relevance to the review, please see the Methods section. Searching of electronic databases retrieved 80 studies. After deduplication and removal of conference abstracts, 59 records were screened for inclusion in the review. Appraisal of titles and abstracts led to the exclusion of 58 studies and the further review of one full publication. The full article evaluated did not meet our reporting criteria, and thus no new evidence was added at this update. One systematic review was added to the Comment section.
Additional information
The National Institute of Health and Care Excellence (NICE) antenatal care guidelines recommend that women who present with symptoms of heartburn in pregnancy should be offered information regarding lifestyle and diet modification. Antacids may be offered to women whose heartburn remains troublesome despite lifestyle and diet modification.
About this condition
Definition
Heartburn is defined as a sensation of 'burning' in the upper part of the digestive tract, including the throat. It can be associated with oesophagitis. One study reported the results of endoscopy on 73 pregnant women with heartburn and found endoscopic and histological evidence of oesophagitis in most women. As complications associated with heartburn during pregnancy are rare (e.g., erosive oesophagitis), upper endoscopy and other diagnostic tests, such as oesophageal manometry and pH studies, are infrequently needed. Therefore, the diagnosis of heartburn is mainly clinical, based on the history.
Incidence/ Prevalence
Heartburn is one of the most common gastrointestinal symptoms in pregnant women, with an incidence in pregnancy of 17% to 45%. In some studies, the prevalence of heartburn has been found to increase from 22% in the first trimester to 39% in the second trimester to between 60% and 72% in the third trimester. However, one prospective cohort study found that, in most pregnant women, heartburn, acid regurgitation, or both began in the first trimester and disappeared during the second trimester; and another cohort study also found that gastrointestinal symptoms, such as heartburn and nausea, were more common in the first trimester. The study also found that primigravidae reported more gastrointestinal symptoms than multiparae.
Aetiology/ Risk factors
The cause of heartburn during pregnancy is multifactorial. Increased amounts of progesterone or its metabolites cause relaxation of smooth muscle, which results in a reduction in gastric tone and motility, and a decrease in lower oesophageal sphincter pressure. It has also been found that, during pregnancy, the lower oesophageal sphincter is displaced into the thoracic cavity (an area of negative pressure), which allows food and gastric acid to pass from the stomach into the oesophagus, leading to oesophageal inflammation and a sensation of 'burning'. Pressure of the growing uterus on gastric contents as the pregnancy progresses may worsen heartburn, although some authors believe that mechanical factors have a smaller role. Heartburn may also be caused by abnormal gastric emptying, delayed small bowel transit, or by some medications taken during pregnancy, such as anti-emetics.
Prognosis
Most cases of heartburn improve with lifestyle modifications. Women who smoke or drink alcohol should be advised to abstain. Dietary changes (e.g., consumption of smaller meals, not eating late at night, and avoiding known triggers) may be of benefit to some. Despite these measures, however, heartburn severity may increase throughout the course of pregnancy.
Aims of intervention
To prevent heartburn in pregnancy; to relieve or reduce the severity of symptoms; to minimise and avoid adverse effects of treatment on the mother and fetus (including teratogenicity).
Outcomes
Symptom severity (prevalence of heartburn, pain from heartburn, symptom diaries, number of additional antacids used, number of visits to physician/healthcare facilities, number of days off work, and inability to perform daily activities); quality of life (e.g., maternal satisfaction); adverse effects on mother, adverse effects on fetus (including teratogenicity).
Methods
Search strategy BMJ Clinical Evidence search and appraisal December 2014. Databases used to identify studies for this systematic overview include: Medline 1966 to December 2014, Embase 1980 to December 2014, The Cochrane Database of Systematic Reviews 2014, issue 4 (1966 to date of issue), the Database of Abstracts of Reviews of Effects (DARE), and the Health Technology Assessment (HTA) database. Inclusion criteria Study design criteria for inclusion in this review were systematic reviews and RCTs published in English, at least single-blinded for pharmacological interventions (blinding was not necessary for RCTs evaluating lifestyle and dietary interventions), and containing 20 or more individuals (10 in each arm), of whom more than 80% were followed up. There was no minimum length of follow-up. 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 contributors. In consultation with the expert contributors, studies were selected for inclusion and all data relevant to this overview extracted into the benefits and harms section of the review. 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. Data and quality To aid readability of the numerical data in our reviews, 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 (into high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).
Table 1.
GRADE evaluation of interventions for heartburn in pregnancy
| Important outcomes | Symptom severity, adverse effects | ||||||||
| Number of studies (participants) | Outcome | Comparison | Type of evidence | Quality | Consistency | Directness | Effect size | GRADE | Comment |
| What are the effects of interventions to prevent or treat heartburn in pregnancy? | |||||||||
| 2 (206) | Symptom severity | Antacids v placebo | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for unclear method of randomisation and no between group statistical analysis in one RCT |
| 1 (30) | Symptom severity | Antacid v antacid plus acid-suppressing drug | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and for unclear method of randomisation |
Type of evidence: 4 = RCT; 2 = Observational; 1 = Non-analytical/expert opinion. Consistency: similarity of results across studies Directness: generalisability of population or outcomes Effect size: based on relative risk or odds ratio
Glossary
- 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.
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.
References
- 1.National Institute for Health and Care Excellence. Antenatal care. March 2008. Available at http://www.nice.org.uk/guidance/cg62 (last accessed 21 May 2015). [Google Scholar]
- 2.Eisenberg A, Murkoff HE, Hathaway SE. What to expect when you are expecting. New York: Workman Publishing, 1998. [In Spanish] [Google Scholar]
- 3.Richter JE. Review article: the management of heartburn in pregnancy. Aliment Pharmacol Ther 2005;22:749–757. [DOI] [PubMed] [Google Scholar]
- 4.Tytgat GN, Heading RC, Müller-Lissner S, et al. Contemporary understanding and management of reflux and constipation in the general population and pregnancy: a consensus meeting. Aliment Pharmacol Ther 2003;18:291–301. [DOI] [PubMed] [Google Scholar]
- 5.Castro Lde P. Reflux esophagitis as the cause of heartburn in pregnancy. Am J Obstet Gynecol 1967;98:1–10. [DOI] [PubMed] [Google Scholar]
- 6.Baron TH, Ramirez B, Richter JE. Gastrointestinal motility disorders during pregnancy. Ann Intern Med 1993;118:366–375. [DOI] [PubMed] [Google Scholar]
- 7.Audu BM, Mustapha SK. Prevalence of gastrointestinal symptoms in pregnancy. Niger J Clin Pract 2006;9:1–6. [PubMed] [Google Scholar]
- 8.Ho KY, Kang JY, Viegas OA. Symptomatic gastro-oesophageal reflux in pregnancy: a prospective study among Singaporean women. J Gastroenterol Hepatol 1998;13:1020–1026. [DOI] [PubMed] [Google Scholar]
- 9.Richter JE. Gastroesophageal reflux disease during pregnancy. Gastroenterol Clin North Am 2003;32:235–261. [DOI] [PubMed] [Google Scholar]
- 10.Marrero JM, Goggin PM, de Caestecker JS, et al. Determinants of pregnancy heartburn. Br J Obstet Gynaecol 1992;99:731–734. [DOI] [PubMed] [Google Scholar]
- 11.Bruce NW. Gestational adaptation. In: Iffy L, Kaminetzki HA, eds. Obstetrics and perinatology. Principles and practice. Buenos Aires: Médica Panamericana, 1986. pp. 706–711. [In Spanish] [Google Scholar]
- 12.Al-Amri SM. Twenty-four hour pH monitoring during pregnancy and at postpartum: a preliminary study. Eur J Obstet Gynecol Reprod Biol 2002;102:127–130. [DOI] [PubMed] [Google Scholar]
- 13.Santisteban S, Oliva J. Obstetric semiology. In: Rigol O, ed. Obstetrics and gynaecology. La Habana: Ciencias Médicas, 2004:59. [In Spanish] [Google Scholar]
- 14.van Thiel DH, Gavaler JS, Joshi SN, et al. Heartburn of pregnancy. Gastroenterology 1977;72:666–668. [PubMed] [Google Scholar]
- 15.Sripramote M, Lekhyananda N. A randomized comparison of ginger and vitamin B6 in the treatment of nausea and vomiting of pregnancy. J Med Assoc Thai 2003;86:846–853. [PubMed] [Google Scholar]
- 16.Dowswell T, Neilson JP. Interventions for heartburn in pregnancy. In: The Cochrane Library, Issue 4, 2014. Chichester, UK: John Wiley & Sons, Ltd. Search date 2008. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Reisfield DR. Pyrosis and pregnancy. Curr Ther Res Clinical Exp 1971;13:680–684. [PubMed] [Google Scholar]
- 18.Kovacs GT, Campbell J, Francis D, et al. Is mucaine an appropriate medication for the relief of heartburn during pregnancy? Asia Oceania J Obstet Gynaecol 1990;16:357–362. [DOI] [PubMed] [Google Scholar]
- 19.Rayburn W, Liles E, Christensen H, et al. Antacids vs. antacids plus non-prescription ranitidine for heartburn during pregnancy. Int J Gynaecol Obstet 1999;66:35–37. [DOI] [PubMed] [Google Scholar]
- 20.Hofmeyr GJ, Lawrie TA, Atallah AN, et al. Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems. In: The Cochrane Library, Issue 4, 2014. Chichester, UK: John Wiley & Sons, Ltd. Search date 2014. 24960615 [Google Scholar]
- 21.Duley L, Gülmezoglu AM, Henderson-Smart DJ. Magnesium sulphate and other anticonvulsants for women with pre-eclampsia. In: The Cochrane Library, Issue 4, 2014. Chichester, UK: John Wiley & Sons, Ltd. Search date 2002. 21069663 [Google Scholar]
- 22.Gill SK, O'Brien L, Koren G, et al. The safety of histamine 2 (H2) blockers in pregnancy: a meta-analysis. Dig Dis Sci 2009;54:1835–1838. [DOI] [PubMed] [Google Scholar]
- 23.Gill SK, O'Brien L, Einarson TR, et al. The safety of proton pump inhibitors (PPIs) in pregnancy: a meta-analysis. Am J Gastroenterol 2009;104:1541–1545. [DOI] [PubMed] [Google Scholar]
- 24.Law R, Maltepe C, Bozzo P, et al. Treatment of heartburn and acid reflux associated with nausea and vomiting during pregnancy. Can Fam Physician 2010;56:143–144. [PMC free article] [PubMed] [Google Scholar]