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Gastrointestinal Pregnancy Women's health

Dyspepsia - pregnancy-associated

Last revised in June 2024

Dyspepsia in pregnancy is commonly due to gastro-oesophageal reflux, thought to involve a combination of mechanical and hormonal factors.

Dyspepsia - pregnancy-associated: Summary

  • Dyspepsia in pregnancy is commonly due to gastro-oesophageal reflux, thought to involve a combination of mechanical and hormonal factors.
  • Up to 80% of women suffer from dyspepsia at some time during their pregnancy, with symptoms starting at any stage of pregnancy. There appears to be an increased risk of symptoms in women who have had symptoms of gastro-oesophageal reflux prior to pregnancy, in women who have had a previous pregnancy, and as the pregnancy advances.
  • Once symptoms have developed, there is a high likelihood that they will persist throughout the pregnancy. However, in most women symptoms will disappear shortly after delivery.
  • Symptoms include heartburn and acid reflux. Investigations are usually not necessary.
  • Lifestyle advice should be offered as first-line management.
  • If lifestyle adjustments alone are insufficient, dyspepsia in pregnancy can usually be managed with antacids and alginates. 
  • Acid-suppressing drugs such as H2 receptor antagonists or proton pump inhibitors should only be used in pregnancy if symptoms are not responding to lifestyle advice, antacids, and alginates. 
  • Referral should be arranged:
    • Immediately if there is dyspepsia and significant acute gastrointestinal bleeding.
    • Urgently if there are features suggestive of malignancy.
    • Non-urgently if symptoms do not adequately respond to treatment, or there is doubt about the diagnosis.
    • With urgency depending on clinical judgement if symptoms suggest a pregnancy-related disorder other than dyspepsia.

Have I got the right topic?

From age 13 years to 60 years (Female).

This CKS topic covers the management of pregnancy-associated dyspepsia.

This CKS topic does not cover the management of dyspepsia due to other causes during pregnancy (for example peptic ulcer disease).

There are separate CKS topics on Dyspepsia - unidentified cause, Dyspepsia - proven GORD, Dyspepsia - proven non-ulcer, Dyspepsia - proven peptic ulcer, and Nausea/vomiting in pregnancy.

The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, and providing first contact or primary healthcare.

How up-to-date is this topic?

Changes

June 2024 — minor update. Further revision of content regarding the specific use of antacids and alginates in pregnancy in the basis of recommendation section. 

Previous changes

May 2024 — minor update. Revised content in the summary regarding the use of antacids and alginates following communication from UKTIS. 

April 2023 — minor update. Typographical error corrected. 

March to April 2017 — reviewed. A literature search was conducted in February 2017 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of this topic. No major changes to clinical recommendations have been made. There have been minor changes to the recommendations on referral in line with updated guidelines from the National Institute for Health and Care Excellence on Gastro-oesophageal reflux disease and dyspepsia in adults: investigation and management (2014) and Suspected cancer: recognition and referral (2015). The age range covered by this topic has been changed to 13–60 years. Prescribing information has been restructured.

November 2012 — reviewed. A literature search was conducted in October 2012 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of this topic. No changes to clinical recommendations have been made.

October 2012 — minor update. The 2012 QIPP options for local implementation have been added to this topic.

September 2011 — minor update. Text changed in line with the UKMi (UK Medicines information) publication regarding choice of proton pump inhibitors for the treatment of reflux in women who are breastfeeding. 

March 2011 — topic structure revised to ensure consistency across CKS topics — no changes to clinical recommendations have been made.

January to May 2008 — converted from CKS guidance to CKS topic structure. The evidence-base has been reviewed in detail, and recommendations are more clearly justified and transparently linked to the supporting evidence. Omeprazole is now recommended in equal preference to ranitidine following a review on the evidence of its safety and in acknowledgement of its product license.

January 2007 — minor update to prescribing information on antacids. 

July 2006 — updated. Omeprazole is now licensed for use in pregnancy and is included for treatment of dyspepsia in pregnancy if ranitidine fails. 

November 2005 — minor technical update. 

February 2005 — written. Validated in June 2005 and issued in July 2005.

Update

New evidence

Evidence-based guidelines

No new guidelines published since 1st July 2022.

HTAs (Health Technology Assessments)

No new HTAs since 1 July 2022.

Economic appraisals

No new economic appraisals relevant to England since 1 July 2022.

Systematic reviews and meta-analyses

No new systematic reviews published since 1 July 2022.

Primary evidence

No new primary evidence which reaches the CKS threshold for inclusion published since 1 July 2022.

New policies

No new national policies or guidelines since 1 July 2022.

New safety alerts

No new safety alerts since 1 July 2022.

Changes in product availability

No changes in product availability since 1 July 2022.

Goals and outcome measures

Goals

To support primary healthcare professionals to:

  • Make a diagnosis of dyspepsia in pregnancy.
  • Offer self-care advice to women with pregnancy-associated dyspepsia.
  • Provide symptomatic relief of dyspepsia symptoms during pregnancy.
  • Appropriately refer or seek specialist advice.

Outcome measures

No outcome measures were found during the review of this topic.

Audit criteria

No audit criteria were found during the review of this topic.

QOF indicators

No QOF indicators were found during the review of this topic.

QIPP - Options for local implementation

No QIPP indicators were found during the review of this topic.

NICE quality standards

  • Adults with dyspepsia or reflux symptoms who present to community pharmacists are given advice about making lifestyle changes, using over-the-counter medicines and when to consult their GP.
  • Adults presenting with dyspepsia or reflux symptoms are referred for urgent direct access endoscopy to take place within 2 weeks if they have dysphagia, or are aged 55 and over with weight loss.

[NICE, 2015]

Background information

What is it?

  • Dyspepsia is a term used to describe a number of symptoms associated with the upper gastrointestinal tract that may include upper abdominal pain or discomfort, reflux, heartburn, belching, nausea, and vomiting [NICE, 2019]. In the context of pregnancy, this usually refers to gastro-oesophageal reflux disease, experienced as heartburn, regurgitation, or an acid taste in the mouth [Ali, 2022].

What causes it?

  • Dyspepsia in pregnancy is commonly due to gastro-oesophageal reflux.
  • The cause of gastro-oesophageal reflux in pregnancy is thought to involve both mechanical and hormonal factors, including:
    • Hormone changes, causing reduced gastric tone and motility and a decrease in lower oesophageal sphincter pressure. The latter appears to be the most significant factor in causation.
    • Increased gastrointestinal transit time.
    • Increased intra-abdominal pressure due to the growing uterus.

   [Vazquez, 2015; Phupong and Hanprasertpong, 2015; Body and Christie, 2016; Thélin, 2020; Ali, 2022]

How common is it?

  • Dyspepsia in pregnancy is common, with the literature suggesting that globally anywhere between 17–80% of women suffer from symptoms such as heartburn at some time during their pregnancy [Vazquez, 2015; Phupong and Hanprasertpong, 2015; Meyer, 2021; Ali, 2022]. Wide variations in reported incidence are likely to be due to differing definitions [Thélin, 2020].
  • Prevalence increases with gestational age, with symptoms most commonly starting late in the first trimester, then becoming more frequent and more severe as the pregnancy progresses [Phupong and Hanprasertpong, 2015].
  • One prospective longitudinal cohort study of the evolution of gastro-oesophageal reflux symptoms during pregnancy found that [Malfertheiner et al, 2012]:
    • In pregnant women, 12.5% had heartburn at least once a week in the first trimester, 21.5% in the second trimester, and 35.3% in the third trimester. Daily heartburn occurred in around 10% of women in the third trimester.
    • In the third trimester, 40.7% of women experienced regurgitation at least once a week (compared with 3.6% of non-pregnant women).

What are the risk factors?

  • The following risk factors have been associated with gastro-oesophageal reflux symptoms in pregnancy:
    • Symptoms of gastro-oesophageal reflux prior to pregnancy.
    • Increasing gestational age.
    • Parity.
  • The following, previously believed to be possible risk factors, do not appear to be associated:
    • Pre-pregnancy body mass index (BMI).
    • Weight gain during pregnancy.
    • Higher maternal age.

 [Body and Christie, 2016; Thélin, 2020]

What are the complications?

  • Symptoms usually resolve without complications; however:
    • Quality of life may be adversely affected. Dyspepsia most commonly has an impact on sleep, but also on eating and drinking, and subsequently may affect productivity and physical or social function [Malfertheiner, 2017; Ali, 2022].
    • Dyspepsia during pregnancy may increase the risk of developing subsequent gastro-oesophageal reflux symptoms in the future [Bor et al, 2007].
    • There is some evidence that heartburn and gastro-oesophageal reflux are associated with an increased severity of nausea and vomiting in pregnancy; managing heartburn and reflux may improve the severity of nausea and vomiting in pregnancy [Gill et al, 2009a].
    • Serious complications such as erosive oesophagitis, strictures, and bleeding are rare, and usually occur in women with pre-existing reflux disease [Body and Christie, 2016; Thélin, 2020].

What is the prognosis?

  • Once gastro-oesophageal reflux symptoms have developed, there is a high likelihood of the symptoms persisting during pregnancy. However, in most women, symptoms can be managed with lifestyle modifications with or without medication, and disappear shortly after delivery.
  • The severity and frequency of gastro-oesophageal reflux symptoms often increase as pregnancy advances with a commensurate impact on quality of life.
  • A small proportion of women continue to have symptoms after delivery, and safety in lactation must be considered for any medication used at this point. Persisting symptoms most often occur in women with pre-existing disease.

 [Vazquez, 2015; Body and Christie, 2016; Malfertheiner, 2017; Thélin, 2020; Ali, 2022]

Diagnosis

When should I suspect dyspepsia in pregnancy?

  • Dyspepsia in pregnancy is predominantly caused by gastro-oesophageal reflux disease (GORD). The diagnosis can be made on symptoms alone, which do not differ from the non-pregnant population.
  • Take a detailed history. Ask about: 
    • Presenting symptoms and how they are affecting the woman's quality of life: heartburn and acid reflux are common, but people may also describe other symptoms including upper abdominal discomfort and anorexia. 
    • Alarm features (for example haematemesis, weight loss, dysphagia) that might suggest more serious underlying disease. For more information, see the section on Red Flag symptoms.
    • Previous history of dyspepsia or reflux symptoms.
    • Aggravating factors such as lying supine, eating a meal, and use of medications which can contribute to dyspepsia, such as nonsteroidal anti-inflammatory drugs.
    • Features suggesting an illness unrelated to pregnancy (for example symptoms of fever, rigors, vomiting, and malaise). For more information, see the section on Differential diagnosis.
    • Treatments already tried, especially over-the-counter medication (for example antacids).
  • Examination is usually normal.
  • Investigations are usually not necessary. Where they are required, they are usually carried out in secondary care and may include:
    • Manometry and pH probes.
    • An upper GI endoscopy.
    • Non-invasive testing for Helicobacter pylori, which may be delayed until after delivery. Evidence suggests Helicobacter pylori does not affect severity or recurrence of symptoms in pregnancy and in general eradication is not advised unless indicated by, for example, peptic ulcer disease.

Basis for recommendation

The information that dyspepsia in pregnancy is predominantly caused by gastro-oesophageal reflux disease is based on expert opinion in a review article [Ali, 2022]. The recommendation that the diagnosis can be made on symptoms alone is based on World Gastroenterology Organisation Global guidelines: Global perspective on gastroesophageal reflux disease [Hunt, 2017] and expert opinion in review articles [Body and Christie, 2016; Thélin, 2020].

History and examination

  • The recommendation to:
    • Ask about presenting symptoms is based on World Gastroenterology Organisation Global guidelines: Global perspective on gastrooesophageal reflux disease [Hunt, 2017] and expert opinion in review articles [Body and Christie, 2016; Thélin, 2020].
    • Exclude alarm features is extrapolated from information in the World Gastroenterology Global Guidelines [Hunt, 2017] and in the National Institute for Health and Care Excellence (NICE) guideline Suspected cancer: recognition and referral [NICE, 2021a].
    • Ask about a previous history of dyspepsia or reflux symptoms is based on expert opinion in a review article [Thélin, 2020].
    • Check for aggravating factors including medication is based on the World Gastroenterology Organisation Global guidelines [Hunt, 2017], the NICE guideline Gastro-oesophageal reflux disease and dyspepsia in adults: investigation and management [NICE, 2019], and on expert opinion in a review article [van der Woude et al, 2014].
    • Excluding other diagnoses and asking about treatments already tried is pragmatic, based on what CKS considers to be good clinical practice. 

Investigations

What symptoms or signs should alert me to a more serious cause?

Red flag or alarm symptoms which should prompt consideration of a more serious condition or the need for urgent investigation include:

  • Difficulty swallowing (dysphagia).
  • Hoarse voice.
  • Recurring or persistent cough.
  • Upper or lower gastrointestinal tract bleeding.
  • Weight loss.
  • Lymphadenopathy.
  • Epigastric or supraclavicular mass.

Basis for recommendation

Information on red flag symptoms is based largely on the World Gastroenterology Organisation Global guidelines, and the National Institute for Health and Care Excellence (NICE) guideline Suspected cancer: recognition and referral [Hunt, 2017; NICE, 2021a].

What else might it be?

Pregnancy-related disorders:

  • Nausea and vomiting of pregnancy, including hyperemesis gravidarum. For more information, see the CKS topic on Nausea/vomiting in pregnancy.
  • Pre-eclampsia — for more information, see the CKS topic on Hypertension in pregnancy.
  • HELLP syndrome (haemolysis, elevated liver enzymes, and low platelets).
  • Acute fatty liver of pregnancy (rare).

Disorders unrelated to pregnancy, for example:

Basis for recommendation

This information is largely based on World Gastroenterology Organisation guidelines: Global perspective on gastroesophageal reflux disease [Hunt, 2017] and expert opinion in a review article [van der Woude et al, 2014].

Management

Scenario: Management

From age 13 years to 60 years (Female).

What self-care advice should I give?

  • Give lifestyle advice as first-line management. 
  • Advise the woman to:
    • Eat smaller meals more frequently (every 3 hours), not eat late at night (or less than 3 hours before bedtime), eat healthily, and avoid known irritants (for example alcohol, caffeine, fruit juices and carbonated drinks, chocolate, and fatty and spicy foods).
    • Keep a food diary to identify triggers.
    • Try to avoid excessive weight gain and to maintain regular physical activity.
    • Try raising the head of their bed by 10–15 cm.
    • Try to sleep on the left side rather than on the right side or supine.
    • Avoid medications that may cause or worsen symptoms, if appropriate (for example calcium-channel antagonists, anticholinergics, antidepressants, and nonsteroidal anti-inflammatory drugs).
    • Stop smoking (if applicable).
  • Offer patient information, such as that provided by the NHS on Indigestion and heartburn in pregnancy.
  • Advise the woman to return if symptoms are not controlled by lifestyle changes, or if worsening or new symptoms develop.

Basis for recommendation

CKS found no trial evidence of lifestyle modifications for managing dyspepsia in pregnancy.

Offering self-care and lifestyle advice as first-line management
  • The recommendation to offer lifestyle advice as first-line management is based on guidelines from the National Institute for Health and Care Excellence (NICE) on Antenatal care [NICE, 2021b] and on Gastro-oesophageal reflux disease and dyspepsia in adults: investigation and management [NICE, 2019], and on the World Health Organization's recommendations on antenatal care for a positive pregnancy experience [WHO, 2016], and is consistent with advice in the British National Formulary to avoid the use of drugs if possible during the first trimester[BNF, 2022].  
  • There are few data on the efficacy of lifestyle modifications in people with gastro-oesophageal reflux disease (GORD) in pregnancy or otherwise, and studies that there exist are small and of low quality. This advice is, however, based on consensus in guidelines and expert review articles [van der Woude et al, 2014; Vazquez, 2015; Body and Christie, 2016; Ali, 2022]. 
Self-care and lifestyle advice recommendations
  • The recommendations on what advice to give are extrapolated from the NICE guideline Gastro-oesophageal reflux disease and dyspepsia in adults: investigation and management [NICE, 2019]; the World Gastroenterology Organisation Global perspective on gastroesophageal reflux disease [Hunt, 2017]; and from review articles [van der Woude et al, 2014; Vazquez, 2015; Body and Christie, 2016; Ali, 2022]. 
  • The evidence review for the NICE guideline states that many dietary aspects of this advice are based on factors which are known to reduce lower oesophageal sphincter tone (such as smoking, alcohol, coffee, chocolate) or delay gastric emptying (such as fatty foods) [NICE, 2019].
  • There is some low quality evidence supporting advice regarding sleep and bed position [Ali, 2022].
Offering patient information
  • This recommendation is and is based on NICE guideline Gastro-oesophageal reflux disease and dyspepsia in adults: investigation and management [NICE, 2019] and on what CKS considers to be good clinical practice.
Follow-up advice
  • This recommendation is pragmatic and is based on what CKS considers to be good clinical practice. Although dyspepsia in pregnancy is a common symptom, other treatments are available if symptoms are not controlled by self-care and lifestyle measures. It is also important to consider the potential for differential diagnoses to cause similar symptoms. 

What treatment should I consider?

  • Antacids and alginates are recommended as first-line treatments if symptoms are not controlled adequately by lifestyle changes. 
    • Antacid preparations such as those containing combinations of aluminium and magnesium or alginate products are recommended on an 'as required' basis. 
    • Calcium-containing products may be used on a short-term or occasional use basis.
    • Products containing sodium bicarbonate or magnesium trisilicate are not recommended in pregnancy.
    • Liquid products are usually faster acting and more effective than tablets.
    • Advise women to avoid taking antacids within two hours of iron or folate supplements as antacids can affect absorption of other medication.
  • If symptoms are very severe, and persist despite lifestyle changes and treatment with an antacid or alginate, consider prescribing an acid-suppressing drug.
    • CKS recommends using acid-suppressing drugs only as a last resort in severe cases in primary care, and only after a shared-care discussion about the potential risks and benefits, and about the limited evidence available regarding efficacy and safety in pregnancy. These options may be more appropriate for use in secondary care for the more serious cases or those with complications.
    • Signpost women to sources of further information such as leaflets provided by the UK Teratology Information Service (UKTIS):
    • Since ranitidine has been withdrawn, the preferred H2 receptor antagonist option would be famotidine, but the manufacturer does not recommend use in pregnancy, and advises it should only be prescribed if clearly needed.
    • Of the proton pump inhibitors (PPIs) available, the manufacturer of omeprazole advises that it can be used in pregnancy but there is a lack of good quality evidence regarding safety, some possible concerns about a small increased risk of congenital malformations, and a possible association with childhood asthma and allergy. There is a lack of data for other PPIs, although the manufacturer of pantoprazole states that what data there is indicates no evidence of harm to the baby.

Basis for recommendation

Antacids and alginates
  • The recommendation to use antacid and alginate treatment as first-line pharmacological treatment is based on the National Institute for Health and Care Excellence (NICE) guideline Antenatal care [NICE, 2021b], World Gastroenterology Organisation Global Guidelines: Global perspective on gastroesophageal reflux disease [Hunt, 2017], World Health Organization Recommendations on antenatal care for a positive pregnancy experience [WHO, 2016], expert opinion in review articles [van der Woude et al, 2014; Body and Christie, 2016; Thélin, 2020; Ali, 2022], and the British National Formulary, which states that 'if dietary and lifestyle changes fail to control gastro-oesophageal reflux disease in pregnancy, an antacid or an alginate can be used' [BNF, 2022].
    • Antacids are considered to be a nonsystemic drug therapy as most have little systemic absorption, are fast-acting, and effective at providing quick symptomatic relief [Body and Christie, 2016; Garg, 2022].
    • An evidence review for the recommendations within the NICE guideline Antenatal care found no significant evidence of maternal or fetal harm for antacids and alginates, and no significant difference in efficacy between the two options, both of which were considered effective [NICE, 2021c]. The review noted a lack of available evidence confirming no harm to the baby following the use of these medications during pregnancy, and that hypothetical risks could not be ruled out.
  • A Cochrane systematic review (search date June 2015) found no large randomised controlled trials on heartburn relief in pregnancy [Phupong and Hanprasertpong, 2015].
    • A US double-blind randomised trial (n = 156) compared a magnesium and aluminium based antacid plus simeticone with placebo. The Cochrane authors did not draw any conclusion on the overall effectiveness of antacids and alginates on reducing dyspepsia in pregnancy and concluded that there is very little evidence to support the theory that symptoms can be completely alleviated by pharmaceutical treatment. They noted that more randomised controlled trials are needed to assess the effectiveness of interventions, including raft-forming alginate reflux suppressants. 
  • Antacids have not been found to cause teratogenic effects in animal studies [van der Woude et al, 2014] and calcium, aluminium, and magnesium-containing preparations (except magnesium trisilicate) are thought to be safe in pregnancy at the usual doses [Body and Christie, 2016; WHO, 2016; Ali, 2022]. 
    • The British National Formulary does not list pregnancy as a contraindication or caution to antacid use [BNF, 2022].
  • The choice of antacid/alginate product in pregnancy is based on the following:
    • Experts in review articles recommend avoiding products containing sodium bicarbonate and avoiding long-term or high dose use of those containing magnesium trisilicate because they may cause adverse effects in the mother or foetus. Antacids containing magnesium trisilicate may cause foetal issues such as cardiovascular impairment, respiratory distress, hypotonia, and nephrolithiasis if used for prolonged periods at high doses, and sodium bicarbonate may be associated with fluid overload and metabolic alkalosis in both mother and baby [van der Woude et al, 2014; Body and Christie, 2016; Thélin, 2020; Ali, 2022; Garg, 2022].
    • Products whose principal ingredient is a calcium salt are widely available over-the-counter, but are only recommended by CKS for short-term or occasional use because calcium may cross the placenta, and rarely, excessive calcium intake (greater than 1000mg of elemental calcium per day) can cause milk-alkali syndrome (characterized by hypercalcaemia, metabolic alkalosis, and renal impairment) [Thélin, 2020; Ali, 2022].
    • Liquids are generally preferred as they are considered more effective [Garg, 2022]. 
  • The advice to avoid taking antacids within two hours of iron or folate supplements is based on World Health Organization Recommendations on antenatal care for a positive pregnancy experience  [WHO, 2016] and advice within expert review articles [Body and Christie, 2016; Ali, 2022].
Acid-suppressing drugs 

Rationale for advising against using acid-suppressing drugs in primary care where possible:

  • These are not included in the NICE guideline on Antenatal care, nor in the WHO Recommendations on antenatal care for a positive pregnancy experience [NICE, 2021b; WHO, 2016].
  • There is a lack of good quality evidence for efficacy and safety of these drugs in pregnancy [Phupong and Hanprasertpong, 2015; NICE, 2021c].
  • Although previous meta-analyses have suggested no significant risk of congenital abnormality in babies born to women exposed to PPIs [Gill et al, 2009b; Thélin, 2020; Ali, 2022], a systematic review with meta-analysis published in 2020 which included 26 observational studies found there may be an increased risk [Li, 2020].
  • There is also some evidence that there may be an association between prenatal exposure to acid-suppressive drugs and an increased risk of childhood asthma and allergy [Mulder, 2014; Lai, 2018; Thélin, 2020; Ali, 2022]. 
  • CKS accepts these drugs are commonly used, particularly omeprazole. A study in France of more than 6 million pregnancies between 2010 and 2018 found that within that time frame, the use of proton pump inhibitors had more than doubled, with exposure in 12.2% of pregnancies in 2010 increasing to 26% in 2018 [Meyer, 2021]. The authors concluded that, in the light of recent findings of a possible increased risk of congenital abnormalities, more risk-benefit consideration was needed in prescribing, and more research needed on safety.

Choice of acid-suppressing drug

  • Ranitidine was previously considered to have a good safety profile, but has now been withdrawn due to reported presence of N-nitrosodimethylamine (NDMA) or other nitrosamines [MHRA, 2022]. The British National Formulary (BNF) advises that the manufacturers recommend avoiding all other H2 receptor antagonists, and the manufacturer's information for these agents states that safety has not been established or that they should not be used unless absolutely necessary or the benefit exceeds the risk. In animal studies, cimetidine had a weak anti-androgen effect and there are no adequate studies of use of nizatadine in pregnant women. Famotidine was not associated with adverse effects in animal studies [Thélin, 2020]. A recent expert review considers famotidine to be the H2 receptor antagonist of choice [Ali, 2022]. 
  • Although in the UK, omeprazole is the only PPI recommended for use in pregnancy by the manufacturer, in the USA the U.S. Food and Drug Administration (FDA) classes it as a Category C drug due to risk in animal studies. A recent expert review favours the use of pantoprazole where a PPI is indicated [Ali, 2022]. 

[BNF, 2022; EMC, 2017; EMC, 2018; EMC, 2019; EMC, 2020; EMC, 2021; EMC, 2022]

The recommendation to have a shared-care discussion with the woman about risks and benefits, and to signpost to sources of information is pragmatic and based on what CKS considers to be good practice, and is in keeping with the recommendations by the manufacturers in drug information leaflets.

When should I refer or seek specialist advice?

  • Refer immediately (same-day) if there is dyspepsia and significant acute gastrointestinal bleeding.
  • Refer urgently to a gastroenterologist there are features suggestive of malignancy. For more information, see the CKS topic on Gastrointestinal tract (upper) cancers - recognition and referral.
    • Note that the classical alarm features of weight loss, an epigastric mass, persistent abdominal pain or iron deficiency anaemia may be difficult to interpret in pregnancy.
  • Refer non-urgently to a gastroenterologist if: 
    • Symptoms do not adequately respond to antacids, alginates, or other treatments given in primary care. (Refer more urgently if the symptoms are so severe that they affect the woman's ability to eat sufficiently.)
    • There is doubt about the diagnosis.
  • Refer to an obstetrician if symptoms suggest a pregnancy-related disorder other than dyspepsia, for example pre-eclampsia or HELLP syndrome (haemolysis, elevated liver enzymes, and low platelets) — use clinical judgement regarding urgency of referral depending on the presenting problem.

Basis for recommendation

CKS found no UK guidelines on referral criteria for dyspepsia in pregnancy. 

Immediate referral
  • The recommendation to refer people with dyspepsia and significant acute gastrointestinal bleeding immediately is based on the National Institute for Health and Care Excellence (NICE) guideline on Gastro-oesophageal reflux disease and dyspepsia in adults: investigation and management [NICE, 2019].
Urgent referral
  • The recommendation to urgently refer people with alarm features suggestive of malignancy to a gastroenterologist is extrapolated from the NICE guideline on Suspected cancer: recognition and referral [NICE, 2021a]. 
Non-urgent referral
  • The recommendation to refer non-urgently to a gastroenterologist if symptoms do not adequately respond to antacids, alginates, or other treatment given in primary care is extrapolated from the NICE guideline on Gastro-oesophageal reflux disease and dyspepsia in adults: investigation and management [NICE, 2019]. This advises considering referral to a specialist service if gastro-oesophageal symptoms are non-responsive to treatment or unexplained.
  • The recommendations to refer if there is doubt about the diagnosis, or the woman is unable to eat sufficiently are pragmatic, based on what CKS considers to be good clinical practice.
Referral to an obstetrician
  • This recommendation to refer to an obstetrician if symptoms suggest a pregnancy-related disorder other than dyspepsia is extrapolated from the NICE guideline on Antenatal care which advises the management and treatment of pregnant women by the appropriate specialist teams when problems are identified [NICE, 2021b]. It is also pragmatic, based on what CKS considers to be good clinical practice.

Prescribing information

Important aspects of prescribing information relevant to primary healthcare are covered in this section specifically for the drugs recommended in this CKS topic. For further information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC), or the British National Formulary (BNF).

Antacids and alginates

What contraindications and cautions are associated with antacids and alginates?

  • Avoid antacid or alginate products if the person is known to be hypersensitive to any of the ingredients or excipients. 
  • For people with hepatic impairment [BNF, 2022]:
    • Avoid antacids containing large amounts of sodium if the person has fluid retention.
    • Avoid antacids that cause constipation (can cause coma).
  • For people with renal impairment [BNF, 2022]:
    • Avoid antacids containing large amounts of sodium if the person has fluid retention.
    • Avoid, or use a lower dose of, antacids containing magnesium salts due to an increased risk of toxicity.
    • Aluminium accumulation and toxicity is a risk.
  • Antacids or other agents that lower gastric acidity should not be taken within two hours of iron or folate supplements, and should be used carefully in pregnant patients with evidence of iron or other mineral deficiency because the normal absorption of minerals such as iron is enhanced by gastric acidity [Ali, 2022]. 

What adverse effects are associated with antacids and alginates?

  • Side effects are rare if antacids and alginates are taken as required at the recommended dose.
  • Antacids may cause either diarrhoea or constipation.
  • Calcium-containing antacids can cause rebound acid secretion, hypercalcaemia and alkalosis, and milk-alkali syndrome at prolonged high doses.

[BNF, 2022; Thélin, 2020; Ali, 2022]

What are the drug interactions with antacids and alginates?

  • Antacids affect the absorption of many drugs and may damage enteric coatings, so ideally should not be taken at the same time [BNF, 2022].

Prescribing information for acid-suppressing drugs

Due to the lack of good quality data and clarity regarding safety of acid-suppressing drugs in pregnancy, no specific positive recommendations are made at this time for for the use of these medications. For prescribing information for acid-suppressing drugs, if used for pregnant women in primary care, refer to Prescribing Information for H2- receptor antagonists and proton pump inhibitors in the separate topic Dyspepsia - proven GORD. Further information on contraindications, cautions, drug interactions and adverse effects is available in the British National Formulary (BNF) and electronic Medicines Compendium (eMC).

Refer to the section on Treatment and Basis for recommendation in this topic for information regarding safety of these drugs in pregnancy, and choice of medication. Only prescribe where the benefit outweighs the possible risk.

[NICE, 2021b; Thélin, 2020; Ali, 2022; BNF, 2022]

Supporting evidence

This CKS topic is based on guidelines from the National Institute for Health and Care Excellence on Antenatal care [NICE, 2021b], Gastro-oesophageal reflux disease and dyspepsia in adults: investigation and management [NICE, 2019], and Suspected cancer: recognition and referral [NICE, 2021a]; the World Health Organization's WHO recommendations on antenatal care for a positive pregnancy experience [WHO, 2016]; the World Gastroenterology Organisation's Global perspective on gastroesophageal reflux disease [Hunt, 2017]. Recommendations are also supported by information in review articles [Body and Christie, 2016; Thélin, 2020; Ali, 2022].

The rationale for the diagnosis, referral, and management of a pregnant woman with dyspepsia is summarized in the relevant basis for recommendation sections.

How this topic was developed

This section briefly describes the processes used in developing and updating this topic. Further details on the full process can be found in the About Us section and on the Clarity Informatics website.

Search strategy

A literature search was conducted for guidelines, systematic reviews and randomized controlled trials on primary care management of Dyspepsia - pregnancy associated.

Search dates

April 2017 - July 2022

Key search terms

Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline.

  • (dyspepsia/ or dyspepsia.tw. or dyspeptic.tw. or heartburn/ or heartburn.tw. or indigestion.tw. or gastroesophageal reflux.tw. or gerd.tw. or gord.tw.) AND (exp pregnancy/ or pregnant.tw. or pregnancy.tw.)

Sources of guidelines

Sources of systematic reviews and meta-analyses

  • The Cochrane Library:
    • Systematic reviews
    • Protocols
    • Database of Abstracts of Reviews of Effects
  • Medline (with systematic review filter)
  • EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

Sources of randomized controlled trials

  • The Cochrane Library:
    • Central Register of Controlled Trials
  • Medline (with randomized controlled trial filter)
  • EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

Sources of national policy

Patient experiences

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

Stakeholder engagement

Our policy

The external review process is an essential part of CKS topic development. Consultation with a wide range of stakeholders provides quality assurance of the topic in terms of:

  • Clinical accuracy.
  • Consistency with other providers of clinical knowledge for primary care.
  • Accuracy of implementation of national guidance (in particular NICE guidelines).
  • Usability.

Principles of the consultation process

  • The process is inclusive and any individual may participate.
  • To participate, an individual must declare whether they have any competing interests or not. If they do not declare whether or not they have competing interests, their comments will not be considered.
  • Comments received after the deadline will be considered, but they may not be acted upon before the clinical topic is issued onto the website.
  • Comments are accepted in any format that is convenient to the reviewer, although an electronic format is encouraged.
  • External reviewers are not paid for commenting on the draft topics.
  • Discussion with an individual or an organization about the CKS response to their comments is only undertaken in exceptional circumstances (at the discretion of the Clinical Editor or Editorial Steering Group).
  • All reviewers are thanked and offered a letter acknowledging their contribution for the purposes of appraisal/revalidation.
  • All reviewers are invited to be acknowledged on the website. All reviewers are given the opportunity to feedback about the external review process, enabling improvements to be made where appropriate.

Stakeholders

  • Key stakeholders identified by the CKS team are invited to comment on draft CKS topics. Individuals and organizations can also register an interest to feedback on a specific topic, or topics in a particular clinical area, through the Getting involved section of the Clarity Informatics website.
  • Stakeholders identified from the following groups are invited to review draft topics:
    • Experts in the topic area.
    • Professional organizations and societies (for example, Royal Colleges).
    • Patient organizations, Clarity has established close links with groups such as Age UK and the Alzheimer’s Society specifically for their input into new topic development, review of current topic content and advice on relevant areas of expert knowledge.
    • Guideline development groups where the topic is an implementation of a guideline.
    • The British National Formulary team.
    • The editorial team that develop MeReC Publications.
  • Reviewers are provided with clear instructions about what to review, what comments are particularly helpful, how to submit comments, and declaring interests.

Patient engagement

Clarity Informatics has enlisted the support and involvement of patients and lay persons at all stages in the process of creating the content which include:

  • Topic selection
  • Scoping of topic
  • Selection of clinical scenarios
  • First draft internal review
  • Second draft internal review
  • External review
  • Final draft and pre-publication

Our lay and patient involvement includes membership on the editorial steering group, contacting expert patient groups, organizations and individuals.

Evidence exclusion criteria

Our policy

Scoping a literature search, and reviewing the evidence for CKS is a methodical and systematic process that is carried out by the lead clinical author for each topic. Relevant evidence is gathered in order that the clinical author can make fully informed decisions and recommendations. It is important to note that some evidence may be excluded for a variety of reasons. These reasons may be applied across all CKS topics or may be specific to a given topic.

Studies identified during literature searches are reviewed to identify the most appropriate information to author a CKS topic, ensuring any recommendations are based on the best evidence. We use the principles of the GRADE and PICOT approaches to assess the quality of published research. We use the principles of AGREE II to assess the quality of published guidelines.

Standard exclusions for scoping literature:

  • Animal studies
  • Original research is not written in English

Possible exclusions for reviewed literature:

  • Sample size too small or study underpowered
  • Bias evident or promotional literature
  • Population not relevant
  • Intervention/treatment not relevant
  • Outcomes not relevant
  • Outcomes have no clear evidence of clinical effectiveness
  • Setting not relevant
  • Not relevant to UK
  • Incorrect study type
  • Review article
  • Duplicate reference

Organizational, behavioural and financial barriers

Our policy

The CKS literature searches take into consideration the following concepts, which are discussed at the initial scoping of the topic.

  • Feasibility
    • Studies are selected depending on whether the intervention under investigation is available in the NHS and can be practically and safely undertaken in primary care.
  • Organizational and Financial Impact Analysis
  • Studies are selected and evaluated on whether the intervention under investigations may have an impact on local clinical service provision or national impact on cost for the NHS. The principles of clinical budget impact analysis are adhered to, evaluated and recorded by the author. The following factors are considered when making this assessment and analysis.
    • Eligible population
    • Current interventions
    • Likely uptake of new intervention or recommendation
    • Cost of the current or new intervention mix
    • Impact on other costs
    • Condition-related costs
    • In-direct costs and service impacts
    • Time dependencies
  • Cost-effectiveness or cost-benefit analysis studies are identified where available. 

We also evaluate and include evidence from NICE accredited sources which provide economic evaluations of recommendations, such as NICE guidelines. When a recommended action may not be possible because of resource constraints, this is explicitly indicated to healthcare professionals by the wording of the CKS recommendation.

Declarations of interest

Our policy

Clarity Informatics requests that all those involved in the writing and reviewing of topics, and those involved in the external review process to declare any competing interests. Signed copies are securely held by Clarity Informatics and are available on request with the permission of the individual. A copy of the declaration of interest form which participants are asked to complete annually is also available on request. A brief outline of the declarations of interest policy is described here and full details of the policy is available on the Clarity Informatics website. Declarations of interests of the authors are not routinely published, however competing interests of all those involved in the topic update or development are listed below. Competing interests include:

  • Personal financial interests
  • Personal family interest
  • Personal non-financial interest
  • Non-personal financial gain or benefit

Although particular attention is given to interests that could result in financial gains or losses for the individual, competing interests may also arise from academic competition or for political, personal, religious, and reputational reasons. An individual is not obliged to seek out knowledge of work done for, or on behalf of, the healthcare industry within the departments for which they are responsible if they would not normally expect to be informed.

Who should declare competing interests?

Any individual (or organization) involved in developing, reviewing, or commenting on clinical content, particularly the recommendations should declare competing interests. This includes the authoring team members, expert advisers, external reviewers of draft topics, individuals providing feedback on published topics, and Editorial Steering Group members. Declarations of interest are completed annually for authoring team and editorial steering group members, and are completed at the start of the topic update and development process for external stakeholders.

Competing interests declared for this topic:

None.

References

  • Ali, R.A.R., Hassan, J. and Egan, L.J. (2022) Review of recent evidence on the management of heartburn in pregnant and breastfeeding women. BMC Gastroenterology 22(1), 219. [Abstract] [Free Full-text]
  • BNF (2022) British National Formulary. National Institute for Health and Care Excellence (NICE). https://bnf.nice.org.uk
  • Body, C. and Christie, J.A. (2016) Gastrointestinal diseases in pregnancy: nausea, vomiting, hyperemesis gravidarum, gastroesophageal reflux disease, constipation, and diarrhea. Gastroenterology Clinics of North America 45(2), 267-283. [Abstract]
  • Bor, S., Kitapcioglu, G., Dettmar, P. and Baxter, T. (2007) Association of heartburn during pregnancy with the risk of gastroesophageal reflux disease. Clinical Gastroenterology and Hepatology 5(9), 1035-1039. [Abstract]
  • EMC (2017) SPC for Nizatidine 150mg capsules, Hard. Electronic Medicines Compendium. Datapharm Communications Ltd. https://www.medicines.org.uk/emc [Free Full-text]
  • EMC (2018) SPC for Omeprazole 20mg gastro-resistant capsules. Electronic Medicines Compendium. Datapharm Communications Ltd. https://www.medicines.org.uk/emc [Free Full-text]
  • EMC (2019) SPC for Cimetidine 400mg tablets. Electronic Medicines Compendium. Datapharm Communications Ltd. https://www.medicines.org.uk/emc [Free Full-text]
  • EMC (2020) SPC for Pantoprazole 20mg gastro-resistant tablets. Electronic Medicines Compendium. Datapharm Communications Ltd. https://www.medicines.org.uk/emc [Free Full-text]
  • EMC (2021) SPC for Lansoprazole 30mg Gastro-Resistant Capsules. Electronic Medicines Compendium. Datapharm Communications Ltd. https://www.medicines.org.uk/emc [Free Full-text]
  • EMC (2022) SPC for Famotidine 20mg tablets. Electronic Medicines Compendium. Datapharm Communications Ltd. https://www.medicines.org.uk/emc [Free Full-text]
  • Garg, V., Narang, P. and Taneja, R. (2022) Antacids revisited: review on contemporary facts and relevance for self-management. Journal of International Medical Research 50(3), 3000605221086457. [Abstract] [Free Full-text]
  • Gill, S.K., Maltepe, C. and Koren, G. (2009a) The effect of heartburn and acid reflux on the severity of nausea and vomiting of pregnancy. Canadian Journal of Gastroenterology 23(4), 270-272.
  • Gill, S.K., O'Brien, L., Einarson, T.R. and Koren, G. (2009b) The safety of proton pump inhibitors (PPIs) in pregnancy: a meta-analysis. American Journal of Gastroenterology 104(6), 1541-1546. [Abstract]
  • Hunt, R., Armstrong, D., Katelaris, P., et al. (2017) World Gastroenterology Organisation Global Guidelines: GERD Global Perspective on Gastroesophageal Reflux Disease. Journal of Clinical Gastroenterology 51(6), 467-748. [Abstract]
  • Lai, T., Wu, M., Liu, J., et al. (2018) Acid-suppressive drug use during pregnancy and the risk of childhood asthma: A meta-analysis. Paediatrics 141(2), e20170889. [Abstract]
  • Li, M.L., Zhernakova, A., Engstrand, L. and Wijmenga, C. (2020) Systemic review with meta-analysis: the risks of proton pump inhibitors during pregnancy. Alimentary Pharmacology and Therapeutics 51(4), 410-420. [Abstract]
  • Malfertheiner S.F., Malfertheiner, M.V., Kropf, S., et al. (2012) A prospective longitudinal cohort study: evolution of GERD symptoms during the course of pregnancy. Bio Med Central Gastroenterology 12(131). [Abstract]
  • Malfertheiner, S.F., Seelbach-Göbel, B., Costa, S., et al. (2017) Impact of gastrooesophageal reflux disease symptoms on the quality of life in pregnant women: a prospective study. European Journal of Gastroenteroly and Hepatology 29(8), 892-896. [Abstract]
  • Meyer, A., Fermaut, M., Drouin, J., et al. (2021) Drug use for gastrointestinal symptoms during pregnancy: A French nationwide study 2010 - 2018. PLOS One 16(1), e0245854. [Abstract] [Free Full-text]
  • Medicines & Healthcare products Regulatory Agency (MHRA) (2022) Freedom of Information request on the status of ranitidine products in the UK. Gov.uk. [Free Full-text]
  • Mulder, B., Schuiling-Veninga, C.C.M., Bos, H.J., et al. (2014) Prenatal exposure to acid-suppressive drugs and the risk of allergic diseases in the offspring: a cohort study. Clinical and Experimental Allergy 44(2), 261-269. [Abstract]
  • NICE (2015) Quality standard: dyspepsia and gastro-oesophageal reflux disease in adults. Quality standard (QS96). National Institute for Health and Care Excellence. http://www.nice.org.uk [Free Full-text]
  • NICE (2019) Gastro-oesophageal reflux disease and dyspepsia in adults: investigation and management. National Institute for Health and Care Excellence. https://www.nice.org.uk [Free Full-text]
  • NICE (2021a) Suspected cancer: recognition and referral. National Institute for Health and Care Excellence. http://www.nice.org.uk [Free Full-text]
  • NICE (2021b) Antenatal care [NG201]. National Institute for Health and Care Excellence. http://www.nice.org.uk [Free Full-text]
  • National Institute for Health and Care Excellence (NICE) (2021c) Antenatal care[S] Management of heartburn in pregnancy NICE guideline NG201 Evidence reviews underpinning recommendations 1.4.8 and 1.4.9 August 2021. National Institute for Health and Care Excellence (NICE). http://www.nice.org.uk [Free Full-text]
  • Phupong, V. and Hanprasertpong, T. (2015) Interventions for heartburn in pregnancy (Cochrane review). The Cochrane library. John Wiley and Sons Ltd. http://www.cochranelibrary.com
  • Thélin, C.S. and Richter, J.E. (2020) Review article: The management of heartburn during pregnancy and lactation. Alimentary Pharmacology and Therapeutics 51(4), 421-434. [Abstract]
  • van der Woude, C.J., Metselaar, H.J. and Danese, S. (2014) Management of gastrointestinal and liver diseases during pregnancy. Gut 63(6), 1014-1023. [Abstract]
  • Vazquez, J.C. (2015) Heartburn in pregnancy. British Medical Journal Clinical Evidence. http://www.clinicalevidence.bmj.com
  • World Health Organization (2016) WHO recommendations on antenatal care for a positive pregnancy experience. World Health Organization..
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