Histamine H2-receptor antagonists (H2RAs) (cimetidine, famotidine, nizatidine and ranitidine) reduce gastric acidity through inhibition of gastric acid production. H2RAs are used in the symptomatic relief of episodic dyspepsia and gastro-oesophageal reflux disease, in the prevention and treatment of gastric or duodenal ulceration, and prior to general anaesthesia in patients at risk of acid aspiration. H2RAs may be considered for use in pregnancy after lifestyle modification, first-line antacid or alginate treatment and second-line PPI treatment (with omeprazole) have proved unsuccessful in controlling symptoms, or are not considered appropriate.
Data regarding the risk of adverse pregnancy or fetal outcomes following exposure to H2RAs as a class are drawn from studies reporting over 4,600 pregnancy exposures collectively. The majority of these studies do not analyse pregnancy outcomes for the individual H2RAs separately. There are more data available for ranitidine (over 1,500 pregnancy exposures) and less data available for cimetidine, famotidine and nizatidine.
There is no evidence of an overall increase in the risk of congenital malformation for H2-antagonists. Nor is there good evidence of increased risks of specific malformations. Risks of miscarriage, intrauterine death, low infant birth weight, neonatal complications or adverse neuro-developmental outcomes do not appear to be increased following exposure to H2RAs. A meta-analysis has suggested a small increased risk of preterm delivery following H2RA use in pregnancy; however, the data are likely confounded by indication and therefore a causal link is unlikely. Studies of individual drugs are too small to draw definitive conclusions.
An increased risk of childhood asthma following maternal exposure to H2RAs has been reported; however, as data are conflicted and likely confounded, further research is required.
Exposure to H2RAs at any stage of pregnancy would not be regarded as medical grounds for termination of pregnancy or any additional fetal monitoring. However, other risk factors may be present in individual cases which may independently increase the risk of adverse pregnancy outcome. Clinicians are reminded of the importance of consideration of such factors when performing case-specific risk assessments.
This is a summary of the full UKTIS monograph for health care professionals and should not be used in isolation. The full UKTIS monograph and access to any hyperlinked related documents is available to NHS health care professionals who are logged in.
If you have a patient with exposure to a drug or chemical and require assistance in making a patient-specific risk assessment, please telephone UKTIS on 0344 892 0909 to discuss the case with a teratology specialist.
If you would like to report a pregnancy to UKTIS please click here to download our pregnancy reporting form. Please encourage all women to complete an online reporting form.