Skip to main content
Log in

Treating Gastro-Oesophageal Reflux Disease During Pregnancy and Lactation

What are the Safest Therapy Options?

  • Drug Safety Concepts
  • Published:
Drug Safety Aims and scope Submit manuscript

Abstract

Gastro-oesophageal reflux and heartburn are reported by 45 to 85% of women during pregnancy. Typically, the heartburn of pregnancy is new onset and is precipitated by the hormonal effects of estrogen and progesterone on lower oesophageal sphincter function. In mild cases, the patient should be reassured that reflux is commonly encountered during a normal pregnancy: lifestyle and dietary modifications may be all that are required.

In a pregnant woman with moderate to severe reflux symptoms, the physician must discuss with the patient the benefits versus the risks of using drug therapy. Medications used for treating gastrooesophageal reflux are not routinely or vigorously tested in randomised, controlled trials in women who are pregnant because of ethical and medico-legal concerns. Safety data are based on animal studies, human case reports and cohort studies as offered by physicians, pharmaceutical companies and regulatory authorities.

If drug therapy is required, first-line therapy should consist of nonsystemically absorbed medications, including antacids or sucralfate, which offer little, if any, risk to the fetus. Systemic therapy with histamine H2 receptor antagonists (avoiding nizatidine) or prokinetic drugs (metoclopramide, cisapride) should be reserved for patients with more severe symptoms. Proton pump inhibitors are not recommended during pregnancy except for severe intractable cases of gastrooesophageal reflux or possibly prior to anaesthesia during labour and delivery. In these rare situations, animal teratogenicity studies suggests that lansoprazole may be the best choice. Use of the least possible amount of systemic drug needed to ameliorate the patient’s symptoms is clearly the best for therapy. If reflux symptoms are intractable or atypical, endoscopy can safely be performed with conscious sedation and careful monitoring the mother and fetus.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Olans LB, Wolf JL. Gastroesophageal reflux in pregnancy. Gastrointest Endosc Clin N Am 1994; 4(4): 699–713

    PubMed  CAS  Google Scholar 

  2. Torbey CF, Richter JE. Gastrointestinal motility disorders in pregnancy. Semin Gastrointest Dis 1995; 6(4): 201–16

    Google Scholar 

  3. Castro L. Reflux esophagitis as the cause of heartburn in pregnancy. Am J Obstet Gynecol 1967; 98: 1–10

    Google Scholar 

  4. Marrero JM, Goggin PM, de Caestecker JS, et al. Determinants of pregnancy heartburn. Br J Obstet Gynaecol 1992; 99: 731–4

    Article  PubMed  CAS  Google Scholar 

  5. Everson GT. Gastrointestinal motility in pregnancy. Gastroenterol Clin N Am 1992; 21(4): 751–76

    CAS  Google Scholar 

  6. Bainbridge ET, Nicholas SD, Newton JR, et al. Gastro-esophageal reflux in pregnancy. Scand J Gastroenterol 1984; 19: 85–9

    PubMed  CAS  Google Scholar 

  7. Bassey OO. Pregnancy heartburn in Nigerians and Caucasians with theories about aetiology based on manometric recordings from the oesophagus and stomach. Br J Obstet Gynaecol 1977; 84: 439–43

    Article  PubMed  CAS  Google Scholar 

  8. Bainbridge ET, Temple JG, Nicholas SP, et al. Symptomatic gastrooesophageal reflux in pregnancy: a comparative study of white Europeans and Asians in Birmingham. Br J Clin Pract 1983; 37: 53–7

    PubMed  CAS  Google Scholar 

  9. Baron TH, Richter JE. Gastroesophageal reflux disease in pregnancy. Gastroenterol Clin N Am 1992; 21(4): 777–91

    CAS  Google Scholar 

  10. Van Thiel DH, Gavaler JS, Stremple J. Heartburn of pregnancy. Gastroenterology 1977; 72: 666–8

    PubMed  Google Scholar 

  11. Fisher RS, Roberts GS, Grabowski CJ, et al. Altered lower esophageal sphincter function during early pregnancy. Gastroenterology 1978; 74: 1233–7

    PubMed  CAS  Google Scholar 

  12. Fisher RS, Roberts GS, Grabowski CJ, et al. Inhibition of lower esophageal sphincter circular muscle by female sex hormones. Am J Physiol 1978; 234: E243–7

    PubMed  CAS  Google Scholar 

  13. Schulze K, Christensen. Lower esophageal sphincter of the opossum esophagus in pseudopregnancy. Gastroenterology 1977; 73: 1082–5

    PubMed  CAS  Google Scholar 

  14. Van Thiel DH, Gravaler JS, Stremple J. Lower esophageal sphincter pressure in women using sequential oral contraceptives. Gastroenterology 1976; 71: 232–4

    PubMed  Google Scholar 

  15. Fillippone M, Malmud L, Kryston L, et al. Esophageal and LES pressures (LESP) in male transsexuals treated with female sex hormones [abstract]. Clin Res 1983; 31: 282A

    Google Scholar 

  16. Macfie AG, Magides AD, Richmond MN et al. Gastric emptying in pregnancy. Br J Anaesth 1991; 67: 54–7

    Article  PubMed  CAS  Google Scholar 

  17. Whitehead EM, Smith M, Dean Y, et al. An evaluation of gastric emptying times in pregnancy and the puerperium. Anaesthesia 1993; 48: 53–7

    Article  PubMed  CAS  Google Scholar 

  18. Sandhar BK, Elliott RH, Windram I, et al. Peripartum changes in gastric emptying. Anaesthesia 1992; 47: 196–8

    Article  PubMed  CAS  Google Scholar 

  19. O’Sullivan GM, Sutton AJ, Thompson SA, et al. Noninvasive measurement of gastric emptying in obstetric patients. Anesth Analg 1987; 66: 505–11

    Article  PubMed  Google Scholar 

  20. Spence AA, Moir DD, Finlay WEI. Observations on intragastric pressure. Anaesthesia 1967; 22: 249–56

    Article  PubMed  CAS  Google Scholar 

  21. Van Thiel DH, Wald A. Evidence refuting a role for increasing abdominal pressure in the pathogenesis of heartburn associated with pregnancy. Am J Obstet Gynecol 1981; 140: 420–2

    PubMed  Google Scholar 

  22. Cappell MS, Colon VJ, Sidhom OA. A study of eight medical centers of the safety and clinical efficacy of es-ophagogastroduodenoscopy in 83 pregnant females with follow-up of fetal outcome with comparison to control groups. Am J Gastroenterol 1996; 91(2): 348–54

    PubMed  CAS  Google Scholar 

  23. Lewis JH, Weingold AB, The committee on FDA-related matters, American college of gastroenterology. The use of gastrointestinal drugs during pregnancy and lactation. Am J Gastroenterol 1985; 80(11): 912–23

    PubMed  CAS  Google Scholar 

  24. Niebyl JR. Teratology and drug use during pregnancy and lactation. In: Scott JR, Isaia PD, Hammond C, et al., editors. Dansforths obstetrics and gynecology. 7th ed. Philadelphia: WB Saunders, 1994: 225–44

    Google Scholar 

  25. Saunders EJ, Saunders JA. Drug therapy in pregnancy: the lesson of diethylstibestrol, thalidomide and bendectin. Health Care Women Int 1989; 11: 423–32

    Article  Google Scholar 

  26. Witter FR, King TM, Blake D. The effects of chronic gastrointestinal medication on the fetus and neonate. Obstet Gynecol 1981; 58(5 Suppl.): 79–84

    Google Scholar 

  27. Hill LM, Kleinberf F. Effects of drugs and chemicals on the fetus and newborn. Mayo Clin Proc 1984; 59: 707–16

    PubMed  CAS  Google Scholar 

  28. Ching C, Lam S. Antacids: indications and limitations. Drugs 1994; 47: 305–17

    Article  PubMed  CAS  Google Scholar 

  29. Physicians desk reference. 51st ed. Montvale (NJ): Medical Economics Company Inc., 1997

  30. Ranchet G, Gangemi O, Petrone M. Sucralfate in the treatment of gravidic pyrosis. G Ital Ostericia Ginecol 1990; 12: 1–16

    Google Scholar 

  31. Anand S, Van Thiel DH. Prenatal and neonatal exposure to cimetidine results in gonadal and sexual dysfunction in adult males. Science 1982; 218: 441–5

    Article  Google Scholar 

  32. Parker S, Schade RR, Pohl CR, et al. Prenatal and neonatal exposure of male rat pups to cimetidine but not ranitidine adversely affects subsequent adult sexual functioning. Gastroenterology 1984; 86: 675–80

    PubMed  CAS  Google Scholar 

  33. Zulli P, Di Nisio Q. Cimetidine treatment during pregnancy. Lancet 1982; 2: 945–6

    Google Scholar 

  34. Corrazza GR. Cimetidine (’Tagamet) in peptic ulcer therapy during pregnancy. Clin Trial J 1982; 19: 91–3

    Google Scholar 

  35. Glade G, Saccar CL, Pereira GR. Cimetidine in pregnancy: apparent transient liver impairment in the newborn. Am J Dis Child 1980; 134: 87–8

    PubMed  CAS  Google Scholar 

  36. Briggs G, Freeman R, Yaffe S, editors. Drugs in pregnancy and lactation: a reference guide to fetal and neonatal medicine. 4th ed. Baltimore: Williams and Wilkins, 1994

    Google Scholar 

  37. Somogyi A, Gugler R. Cimetidine excretion into breast milk. Br J Clin Pharmacol 1979; 7: 627–9

    Article  PubMed  CAS  Google Scholar 

  38. Leslie GB, Walker TF. A toxicological profile of cimetidine. In: Burland WL, Simkins MA, editors. Cimetidine: proceedings of the Second International Symposium on histamine H2-receptor antagonists. Amsterdam: Excerpta Medica, 1977: 24–33

    Google Scholar 

  39. Blyth DI. Some effects of histamine in the depolarized rat uterus. Br J Pharmacol 1973; 49: 445–56

    Article  PubMed  CAS  Google Scholar 

  40. McGowan WAW Safety of cimetidine in obstetric patients. J R Soc Med 1979; 72: 902–7

    PubMed  CAS  Google Scholar 

  41. Ostheimer GW, Morrison JA, Lavoie C, et al. The effect of cimetidine on mother, newborn and neonatal behavior [abstract]. Anesthesiology 1982; 57: A405

    Article  Google Scholar 

  42. Cipriani S, Conti R, Vella G. Ranitidine in pregnancy: three case reports. Clin Eur 1983; 22(1): 1–6

    Google Scholar 

  43. Beeley L. Does ranitidine have an adverse effect on a pregnant women or her fetus? BMJ 1985; 290: 308

    Article  Google Scholar 

  44. Armentano G, Bracco PL, Di Silverio C. Ranitidine in the treatment of reflux esophagitis in pregnancy. Clin Exp Obstet Gynecol 1989; 16: 130–3

    PubMed  CAS  Google Scholar 

  45. Koren G, Zemlickis DM. Outcome of pregnancy after first trimester exposure to H2 receptor antagonists. Ann J Perinatol 1991; 8: 37–8

    Article  CAS  Google Scholar 

  46. Larson JD, Patatanian E, Miner PB, et al. Double-blind, placebo-controlled study of ranitidine for gastroesophageal reflux symptoms during pregnancy. Obstet Gynecol 1997; 90(1): 83–7

    Article  PubMed  CAS  Google Scholar 

  47. Savarino V, Giusti M, Scalabrini P, et al. Famotidine has nosignificant effect on gonadal function in man. Gastroenterol Clin Biol 1988; 12(1): 19–22

    PubMed  CAS  Google Scholar 

  48. Anderson PO. Drug use during breast feeding. Clin Pharm 1991; 10: 594–624

    PubMed  CAS  Google Scholar 

  49. Michaletz-Onody PA. Peptic ulcer disease in pregnancy. Gastroenterol Clin N Am 1992; 21: 817–26

    CAS  Google Scholar 

  50. Neubauer BL, Goode RL, Best KL, et al. Endocrine effects of a new histamine H2-receptor antagonist, nizatidine (LY139037), in the male rat. Toxicol Appl Pharmacol 1990; 102: 219–32

    Article  PubMed  CAS  Google Scholar 

  51. Morton DM. Pharmacology and toxicology of nizatidine. Scand J Gastroenterol 1987; 22 (Suppl. 136): 1–8

    Article  Google Scholar 

  52. Magee LA, Inoncencion G, Kamboj L, et al. Safety of first trimester exposure to histamine H2-blockers: a prospective cohort study. Dig Dis Sci 1996; 41: 1145–9

    Article  PubMed  CAS  Google Scholar 

  53. Desmond PV, Watson KJR. Metoclopramide: a review. Med J Aust 1986; 144: 366–9

    PubMed  CAS  Google Scholar 

  54. Arvela P, Jouppila R, Kauppila A, et al. Placental transfer and hormonal effects of metoclopramide. Eur J Clin Pharmacol 1983; 25: 345–8

    Article  Google Scholar 

  55. Bailey B, Addis A, Lee A, et al. Cisapride use during human pregnancy: a prospective, controlled multicenter study. Dig Dis Sci 1997; 42(9): 1848–52

    Article  PubMed  CAS  Google Scholar 

  56. Adamo S, Carrara M, Azzurro M, et al. Omeprazole treatment during first month of pregnancy: a case report. Ital J Gastroenterol 1993; 25 (Suppl. 1): 1–198

    Google Scholar 

  57. Harper MA, McVeigh JE, Thompson W, et al. Successful pregnancy in association with zollinger-ellison syndrome. Am J Obstet Gynecol 1995; 13: 863–4

    Article  Google Scholar 

  58. Glasbrenner B, Swobodnik W, Malfertheiner P, et al. Severe hyperemesis gravidarum-pathophysiologic observations and new therapeutic approach [in German]. Z Gastroenterol 1991; 29(4): 163–6

    PubMed  CAS  Google Scholar 

  59. Tsirigotis M, Yazdani N, Craft I. Potential effects of omeprazole in pregnancy [letter]. Hum Reprod 1995 Aug; 10(8): 2177–8

    PubMed  CAS  Google Scholar 

  60. Kurinczuk J, Bower C. Birth defects in infants conceived by intracytoplasmic sperm injection: an alternative interpretation. BMJ 1997; 315: 1260–6

    Article  PubMed  CAS  Google Scholar 

  61. Bylsma-Howell M, Riggs KW, McMorland GH, et al. Placental transport of metoclopramide: assessment of maternal and neonatal effects. Can Anaesth Soc J 1983; 30: 487–92

    Article  PubMed  CAS  Google Scholar 

  62. Vanner RG, Goodman NW. Gastro-oesophageal reflux in pregnancy at term and after delivery. Anaesthesia 1989; 44: 808–11

    Article  PubMed  CAS  Google Scholar 

  63. Parkman HP, Baron TH, Richter JE, et al. Gastrointestinal motility disorders during pregnancy. In: Karlstadt RG, Surawicz Cm, Croitoru R, editors. Gastrointestinal disorders during Pregnancy. Am Coll Gastroenterol 1994: 4-14

  64. Lewis RT, Burgess JH, Hempson LG. Cardiorespiratory studies in critical illness: changes in aspiration pneumonitis. Arch Surg 1971; 103: 335–40

    Article  PubMed  CAS  Google Scholar 

  65. Picca SM, Fiordalisi J. Treatment of gastrointestinal motility disorders in pregnancy. Ann Intern Med 1993; 119(7 Pt 1): 635

    PubMed  CAS  Google Scholar 

  66. Cheek TG, Gutsche BB. Pulmonary aspiration of gastric contents. In: Scnider SM, Levinson G, editors. Anesthesia for Obstetrics. Baltimore: Williams and Wilkins, 1993: 407–31

    Google Scholar 

  67. Hodgkinson R, Glassenberg R, Joyce TH, et al. Comparison of cimetidine (Tagamet) with antacid for safety and effectiveness in reducing gastric acidity before elective cesarean section. Anesthesiology 1983; 59: 86–90

    Article  PubMed  CAS  Google Scholar 

  68. Moore J, Flynn RJ, Sampaio M, et al. Effect of single-dose omeprazole on intragastric acidity and volume during obstetric anaesthesia. Anaesthesia 1989; 44: 559–62

    Article  PubMed  CAS  Google Scholar 

  69. Orr DA, Bill KM, Gillon KRW, et al. Effects of omeprazole, with and without metoclopramide, in elective obstetric anaesthesia. Anaesthesia 1993; 48: 114–9

    Article  PubMed  CAS  Google Scholar 

  70. Brock-Utne JG, Dow TG, Welman S, et al. The effect of metoclopramide in the lower oesophageal sphincter in late pregnancy. Anaesth Intensive Care 1978; 6: 26–9

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Broussard, C.N., Richter, J.E. Treating Gastro-Oesophageal Reflux Disease During Pregnancy and Lactation. Drug-Safety 19, 325–337 (1998). https://doi.org/10.2165/00002018-199819040-00007

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002018-199819040-00007

Keywords

Navigation