Maria Hoeltzenbein1, Tatjana Tissen-Diabaté2, Anne-Katrin Fietz2, Sandra Zinke2, Angela Kayser2, Reinhard Meister3, Corinna Weber-Schoendorfer2, Christof Schaefer2. 1. Pharmakovigilanzzentrum Embryonaltoxikologie, Institut für Klinische Pharmakologie und Toxikologie, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany. maria.hoeltzenbein@charite.de. 2. Pharmakovigilanzzentrum Embryonaltoxikologie, Institut für Klinische Pharmakologie und Toxikologie, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany. 3. Department of Mathematics, Beuth Hochschule für Technik Berlin, Berlin, Germany.
Abstract
BACKGROUND: Ongoing discussion about the safety of renin-angiotensin inhibitors in the first trimester and limited data on pregnancy outcomes after exposure to angiotensin AT1 receptor blockers (ARBs). METHODS: Observational cohort study compares outcomes of 215 prospectively ascertained pregnancies with first trimester exposure to ARBs with 642 non-hypertensive pregnancies. RESULTS: The rate of major birth defects in the ARB cohort (9/168, 5.4%) was higher than in the comparison group (17/570, 3%), but not significantly increased (ORadj 1.9, 95% CI 0.7-4.9). There was no distinct pattern of anomalies among infants with birth defects. The risk of spontaneous abortions was not increased (HRadj 0.9, 95% CI 0.5-1.6), although the cumulative incidence was in the upper normal range (0.22, 95% CI 0.15-0.32). Higher rates of prematurity (ORadj 3.0; 95% CI 1.7-5.1) and a reduced birth weight after adjustment for sex and gestational age were observed. There was no evidence for an increased risk for major birth defects, spontaneous abortions, or preterm birth in a sensitivity analysis comparing ARB exposed hypertensive women to hypertensive women without ARB exposure during the first trimester. CONCLUSION: Our study supports the hypothesis that ARBs are not major teratogens. Patients inadvertently exposed to ARBs during the early pregnancy may be reassured. Nevertheless, women planning pregnancy should avoid ARBs. In selected cases, ARBs might be continued under careful monitoring of menstrual cycle and discontinued as soon as pregnancy is recognized.
BACKGROUND: Ongoing discussion about the safety of renin-angiotensin inhibitors in the first trimester and limited data on pregnancy outcomes after exposure to angiotensin AT1 receptor blockers (ARBs). METHODS: Observational cohort study compares outcomes of 215 prospectively ascertained pregnancies with first trimester exposure to ARBs with 642 non-hypertensive pregnancies. RESULTS: The rate of major birth defects in the ARB cohort (9/168, 5.4%) was higher than in the comparison group (17/570, 3%), but not significantly increased (ORadj 1.9, 95% CI 0.7-4.9). There was no distinct pattern of anomalies among infants with birth defects. The risk of spontaneous abortions was not increased (HRadj 0.9, 95% CI 0.5-1.6), although the cumulative incidence was in the upper normal range (0.22, 95% CI 0.15-0.32). Higher rates of prematurity (ORadj 3.0; 95% CI 1.7-5.1) and a reduced birth weight after adjustment for sex and gestational age were observed. There was no evidence for an increased risk for major birth defects, spontaneous abortions, or preterm birth in a sensitivity analysis comparing ARB exposed hypertensivewomen to hypertensivewomen without ARB exposure during the first trimester. CONCLUSION: Our study supports the hypothesis that ARBs are not major teratogens. Patients inadvertently exposed to ARBs during the early pregnancy may be reassured. Nevertheless, women planning pregnancy should avoid ARBs. In selected cases, ARBs might be continued under careful monitoring of menstrual cycle and discontinued as soon as pregnancy is recognized.
Authors: Lucy C Chappell; Stephen Enye; Paul Seed; Annette L Briley; Lucilla Poston; Andrew H Shennan Journal: Hypertension Date: 2008-02-07 Impact factor: 10.190
Authors: Brian T Bateman; Kate M Shaw; Elena V Kuklina; William M Callaghan; Ellen W Seely; Sonia Hernández-Díaz Journal: PLoS One Date: 2012-04-30 Impact factor: 3.240