The Safety of H₂‐Blockers Use During Pregnancy

Abstract

Little data exist on the safety of H(2)-blockers during pregnancy. A computerized database of medications dispensed from 1998 to 2007 to all women registered in the "Clalit" health maintenance organization, in the Southern District of Israel, was linked with computerized databases containing maternal and infant hospitalization records from the district hospital. The following confounders were controlled for: parity, maternal age, ethnic group, maternal diabetes, smoking, and peripartum fever. Also, therapeutic pregnancy termination data were analyzed. A total of 117 960 infants were born during the study period, 84 823 of them (72%) to women registered at Clalit; 1148 of the latter were exposed to H(2)-blockers during the first trimester of pregnancy. Exposure to H(2)-blockers was not associated with an increased risk for congenital malformations (adjusted odds ratio [OR] = 1.03, 95% confidence interval [CI]: 0.80-1.32); also, no such association was found when therapeutic pregnancy terminations were included in the analysis (adjusted OR = 1.17, 95% CI: 0.93-1.46). Exposure to H(2)-blockers was not associated with perinatal mortality, premature delivery, low birth weight, or low Apgar scores.

Antihistamines and birth defects: a systematic review of the literature

“…Measures of association for each medication were calculated from pooled data: cimetidine (RR (95% CI)): 1.3 (0.7-2.6); ranitidine: 1.5 (0.9-2.6) 64 . In the most recently published cohort analysis, Matok and colleagues used data from the largest health maintenance organization in Israel to examine the safety of H 2 -receptor antagonists during pregnancy 63 . The associations between any major birth defect and first trimester exposure to any H 2 -receptor antagonist (n=1,148 exposed pregnancies) or famotidine (n=878 exposed pregnancies) were both null (OR: 1.03; 95% CI: 0.80-1.32 for any H 2 -receptor antagonist and OR: 1.21; 95% CI: 0.92-1.58 for famotidine).…”

“…The associations between any major birth defect and first trimester exposure to any H 2 -receptor antagonist (n=1,148 exposed pregnancies) or famotidine (n=878 exposed pregnancies) were both null (OR: 1.03; 95% CI: 0.80-1.32 for any H 2 -receptor antagonist and OR: 1.21; 95% CI: 0.92-1.58 for famotidine). No measure of association was calculated for ranitidine because there were fewer than seven birth defects noted (n=276 exposed pregnancies) 63 .…”

“…The Swedish cohorts were built from extensive linkages of national registries; while the Collaborative Perinatal Project gathered data through maternal interviews of pregnant women enrolled at medical centers around the United States 70, 71 . Cohorts derived from health maintenance organizations are designed to simulate population-based cohorts 18, 25-27, 63 and in some situations do capture the vast majority of the population in a given geographic area. These cohorts have access to rich clinical information as well as prescription claims.…”

“…Additionally, in some studies 39, 54, 55 rigorous clinical review of every case 80-82 was undertaken to verify reported diagnoses and determine whether the case met the study's inclusion criteria. Similarly, a few studies in the review are based on data from health maintenance organizations 18, 25-27, 42, 63 with medical records forming the foundation of the birth defects ascertainment and in some of these studies, additional clinical review of potential cases was also undertaken.…”

Safety of Drugs during Pregnancy and Breastfeeding in Cystic Fibrosis Patients

“…Fixed combinations of aluminum and magnesium salts should be preferred and used at recommended doses. No associations with an increased rate of birth defects have been detected after more than 1,500 exposures during the first trimester with ranitidine [71,72] . No associations have been found between proton pump inhibitor use during pregnancy and increased rate of birth defects in studies including several thousands of patients [73,74] .…”