Pregnancy outcome after first trimester use of angiotensin AT1 receptor blockers: an observational cohort study

  • Maria Hoeltzenbein
  • Tatjana Tissen-Diabaté
  • Anne-Katrin Fietz
  • Sandra Zinke
  • Angela Kayser
  • Reinhard Meister
  • Corinna Weber-Schoendorfer
  • Christof Schaefer
Original Paper
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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.

Keywords

Angiotensin AT1 receptor blockers Birth defect Chronic hypertension Pregnancy outcome Spontaneous abortion Congenital malformation 
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Notes

Acknowledgements

This work was performed with financial support from the German Ministry of Health (BMG) and the German Federal Institute for Drugs and Medical Devices (BfArM). The study was registered with the German Clinical Trial register (DRKS00010502) and the study protocol was approved by the ethics committee of the Charité-Universitätsmedizin Berlin (EA1/107/16).

Compliance with ethical standards

Conflict of interest

The authors report no conflict of interest.

Supplementary material

392_2018_1234_MOESM1_ESM.docx (387 kb)
Supplementary Material 1 (DOCX 388 KB)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Maria Hoeltzenbein
    • 1
  • Tatjana Tissen-Diabaté
    • 1
  • Anne-Katrin Fietz
    • 1
  • Sandra Zinke
    • 1
  • Angela Kayser
    • 1
  • Reinhard Meister
    • 2
  • Corinna Weber-Schoendorfer
    • 1
  • Christof Schaefer
    • 1
  1. 1.Pharmakovigilanzzentrum Embryonaltoxikologie, Institut für Klinische Pharmakologie und ToxikologieCharité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of HealthBerlinGermany
  2. 2.Department of MathematicsBeuth Hochschule für Technik BerlinBerlinGermany

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