Beta-blocker use in pregnancy and risk of specific congenital anomalies: A European case-malformed control study

Jorieke E.H Bergman, L. Renée Lutke, Rijk O.B Gans, Marie-Claude Addor, Ingeborg Barisic, Clara Cavero-Carbonell, Ester Garne, Miriam Gatt, Kari Klungsoyr, Nathalie Lelong, Catherine Lynch, Olatz Mokoroa, Vera Nelen, Amanda J. Neville, Anna Pierini, Hanitra Randrianaivo, Anke Rissmann, David Tucker, Awi Wiesel, Helen DolkMaria Loane, Marian K. Bakker

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Introduction
The prevalence of chronic hypertension is increasing in pregnant women. Beta-blockers are among the most prevalent anti-hypertensive agents used in early pregnancy.

Objective
The objective of this study was to investigate whether first-trimester use of beta-blockers increases the risk of specific congenital anomalies in offspring.

Methods
A population-based case-malformed control study was conducted in 117,122 registrations of congenital anomalies from 17 European Concerted Action on Congenital Anomalies and Twins (EUROCAT) registries participating in EUROmediCAT with data for all or part of the period between 1995 and 2013. Associations previously reported in the literature (signals) were tested and an exploratory analysis was performed to identify new signals. Odds ratios of exposure to any beta-blocker or to a beta-blocker subgroup were calculated for each signal anomaly compared with two control groups (non-chromosomal, non-signal anomalies and chromosomal anomalies). The exploratory analyses were performed for each non-signal anomaly compared with all the other non-signal anomalies.

Results
The signals from the literature (congenital heart defects, oral clefts, neural tube defects and hypospadias) were not confirmed. Our exploratory analysis revealed that multi-cystic renal dysplasia had significantly increased odds of occurring after maternal exposure to combined alpha- and beta-blockers (adjusted odds ratio 3.8; 95% confidence interval 1.3–11.0).

Conclusion
Beta-blocker use in the first trimester of pregnancy was not found to be associated with a higher risk of specific congenital anomalies in the offspring, but a new signal between alpha- and beta-blockers and multi-cystic renal dysplasia was found. Future large epidemiological studies are needed to confirm or refute our findings.
Original languageEnglish
Pages (from-to)415-427 (2018)
Number of pages13
JournalDrug Safety
Volume41
DOIs
Publication statusPublished - 11 Dec 2017

Fingerprint

First Pregnancy Trimester
Case-Control Studies
Odds Ratio
Kidney
Maternal Exposure
Pregnancy
Hypospadias
Defects
Neural Tube Defects
Congenital Heart Defects
Antihypertensive Agents
Registries
Pregnant Women
Epidemiologic Studies
Confidence Intervals
Hypertension
Control Groups
Population

Keywords

  • antihypertensive agents
  • beta-antagonists
  • hypertension
  • pregnancy
  • first trimester exposure
  • birth defects
  • teratogenic effects

Cite this

Bergman, J. E. H., Lutke, L. R., Gans, R. O. B., Addor, M-C., Barisic, I., Cavero-Carbonell, C., ... Bakker, M. K. (2017). Beta-blocker use in pregnancy and risk of specific congenital anomalies: A European case-malformed control study. Drug Safety, 41, 415-427 (2018). https://doi.org/10.1007/s40264-017-0627-x
Bergman, Jorieke E.H ; Lutke, L. Renée ; Gans, Rijk O.B ; Addor, Marie-Claude ; Barisic, Ingeborg ; Cavero-Carbonell, Clara ; Garne, Ester ; Gatt, Miriam ; Klungsoyr, Kari ; Lelong, Nathalie ; Lynch, Catherine ; Mokoroa, Olatz ; Nelen, Vera ; Neville, Amanda J. ; Pierini, Anna ; Randrianaivo, Hanitra ; Rissmann, Anke ; Tucker, David ; Wiesel, Awi ; Dolk, Helen ; Loane, Maria ; Bakker, Marian K. / Beta-blocker use in pregnancy and risk of specific congenital anomalies: A European case-malformed control study. In: Drug Safety. 2017 ; Vol. 41. pp. 415-427 (2018).
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abstract = "IntroductionThe prevalence of chronic hypertension is increasing in pregnant women. Beta-blockers are among the most prevalent anti-hypertensive agents used in early pregnancy.ObjectiveThe objective of this study was to investigate whether first-trimester use of beta-blockers increases the risk of specific congenital anomalies in offspring.MethodsA population-based case-malformed control study was conducted in 117,122 registrations of congenital anomalies from 17 European Concerted Action on Congenital Anomalies and Twins (EUROCAT) registries participating in EUROmediCAT with data for all or part of the period between 1995 and 2013. Associations previously reported in the literature (signals) were tested and an exploratory analysis was performed to identify new signals. Odds ratios of exposure to any beta-blocker or to a beta-blocker subgroup were calculated for each signal anomaly compared with two control groups (non-chromosomal, non-signal anomalies and chromosomal anomalies). The exploratory analyses were performed for each non-signal anomaly compared with all the other non-signal anomalies.ResultsThe signals from the literature (congenital heart defects, oral clefts, neural tube defects and hypospadias) were not confirmed. Our exploratory analysis revealed that multi-cystic renal dysplasia had significantly increased odds of occurring after maternal exposure to combined alpha- and beta-blockers (adjusted odds ratio 3.8; 95{\%} confidence interval 1.3–11.0).ConclusionBeta-blocker use in the first trimester of pregnancy was not found to be associated with a higher risk of specific congenital anomalies in the offspring, but a new signal between alpha- and beta-blockers and multi-cystic renal dysplasia was found. Future large epidemiological studies are needed to confirm or refute our findings.",
keywords = "antihypertensive agents, beta-antagonists, hypertension, pregnancy, first trimester exposure, birth defects, teratogenic effects",
author = "Bergman, {Jorieke E.H} and Lutke, {L. Ren{\'e}e} and Gans, {Rijk O.B} and Marie-Claude Addor and Ingeborg Barisic and Clara Cavero-Carbonell and Ester Garne and Miriam Gatt and Kari Klungsoyr and Nathalie Lelong and Catherine Lynch and Olatz Mokoroa and Vera Nelen and Neville, {Amanda J.} and Anna Pierini and Hanitra Randrianaivo and Anke Rissmann and David Tucker and Awi Wiesel and Helen Dolk and Maria Loane and Bakker, {Marian K.}",
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Bergman, JEH, Lutke, LR, Gans, ROB, Addor, M-C, Barisic, I, Cavero-Carbonell, C, Garne, E, Gatt, M, Klungsoyr, K, Lelong, N, Lynch, C, Mokoroa, O, Nelen, V, Neville, AJ, Pierini, A, Randrianaivo, H, Rissmann, A, Tucker, D, Wiesel, A, Dolk, H, Loane, M & Bakker, MK 2017, 'Beta-blocker use in pregnancy and risk of specific congenital anomalies: A European case-malformed control study', Drug Safety, vol. 41, pp. 415-427 (2018). https://doi.org/10.1007/s40264-017-0627-x

Beta-blocker use in pregnancy and risk of specific congenital anomalies: A European case-malformed control study. / Bergman, Jorieke E.H; Lutke, L. Renée; Gans, Rijk O.B; Addor, Marie-Claude; Barisic, Ingeborg; Cavero-Carbonell, Clara; Garne, Ester; Gatt, Miriam; Klungsoyr, Kari; Lelong, Nathalie; Lynch, Catherine; Mokoroa, Olatz; Nelen, Vera; Neville, Amanda J.; Pierini, Anna; Randrianaivo, Hanitra; Rissmann, Anke; Tucker, David; Wiesel, Awi; Dolk, Helen; Loane, Maria; Bakker, Marian K.

In: Drug Safety, Vol. 41, 11.12.2017, p. 415-427 (2018).

Research output: Contribution to journalArticle

TY - JOUR

T1 - Beta-blocker use in pregnancy and risk of specific congenital anomalies:

T2 - A European case-malformed control study

AU - Bergman, Jorieke E.H

AU - Lutke, L. Renée

AU - Gans, Rijk O.B

AU - Addor, Marie-Claude

AU - Barisic, Ingeborg

AU - Cavero-Carbonell, Clara

AU - Garne, Ester

AU - Gatt, Miriam

AU - Klungsoyr, Kari

AU - Lelong, Nathalie

AU - Lynch, Catherine

AU - Mokoroa, Olatz

AU - Nelen, Vera

AU - Neville, Amanda J.

AU - Pierini, Anna

AU - Randrianaivo, Hanitra

AU - Rissmann, Anke

AU - Tucker, David

AU - Wiesel, Awi

AU - Dolk, Helen

AU - Loane, Maria

AU - Bakker, Marian K.

N1 - UIR compliant. UIR dates updated on UIR link

PY - 2017/12/11

Y1 - 2017/12/11

N2 - IntroductionThe prevalence of chronic hypertension is increasing in pregnant women. Beta-blockers are among the most prevalent anti-hypertensive agents used in early pregnancy.ObjectiveThe objective of this study was to investigate whether first-trimester use of beta-blockers increases the risk of specific congenital anomalies in offspring.MethodsA population-based case-malformed control study was conducted in 117,122 registrations of congenital anomalies from 17 European Concerted Action on Congenital Anomalies and Twins (EUROCAT) registries participating in EUROmediCAT with data for all or part of the period between 1995 and 2013. Associations previously reported in the literature (signals) were tested and an exploratory analysis was performed to identify new signals. Odds ratios of exposure to any beta-blocker or to a beta-blocker subgroup were calculated for each signal anomaly compared with two control groups (non-chromosomal, non-signal anomalies and chromosomal anomalies). The exploratory analyses were performed for each non-signal anomaly compared with all the other non-signal anomalies.ResultsThe signals from the literature (congenital heart defects, oral clefts, neural tube defects and hypospadias) were not confirmed. Our exploratory analysis revealed that multi-cystic renal dysplasia had significantly increased odds of occurring after maternal exposure to combined alpha- and beta-blockers (adjusted odds ratio 3.8; 95% confidence interval 1.3–11.0).ConclusionBeta-blocker use in the first trimester of pregnancy was not found to be associated with a higher risk of specific congenital anomalies in the offspring, but a new signal between alpha- and beta-blockers and multi-cystic renal dysplasia was found. Future large epidemiological studies are needed to confirm or refute our findings.

AB - IntroductionThe prevalence of chronic hypertension is increasing in pregnant women. Beta-blockers are among the most prevalent anti-hypertensive agents used in early pregnancy.ObjectiveThe objective of this study was to investigate whether first-trimester use of beta-blockers increases the risk of specific congenital anomalies in offspring.MethodsA population-based case-malformed control study was conducted in 117,122 registrations of congenital anomalies from 17 European Concerted Action on Congenital Anomalies and Twins (EUROCAT) registries participating in EUROmediCAT with data for all or part of the period between 1995 and 2013. Associations previously reported in the literature (signals) were tested and an exploratory analysis was performed to identify new signals. Odds ratios of exposure to any beta-blocker or to a beta-blocker subgroup were calculated for each signal anomaly compared with two control groups (non-chromosomal, non-signal anomalies and chromosomal anomalies). The exploratory analyses were performed for each non-signal anomaly compared with all the other non-signal anomalies.ResultsThe signals from the literature (congenital heart defects, oral clefts, neural tube defects and hypospadias) were not confirmed. Our exploratory analysis revealed that multi-cystic renal dysplasia had significantly increased odds of occurring after maternal exposure to combined alpha- and beta-blockers (adjusted odds ratio 3.8; 95% confidence interval 1.3–11.0).ConclusionBeta-blocker use in the first trimester of pregnancy was not found to be associated with a higher risk of specific congenital anomalies in the offspring, but a new signal between alpha- and beta-blockers and multi-cystic renal dysplasia was found. Future large epidemiological studies are needed to confirm or refute our findings.

KW - antihypertensive agents

KW - beta-antagonists

KW - hypertension

KW - pregnancy

KW - first trimester exposure

KW - birth defects

KW - teratogenic effects

UR - https://pure.ulster.ac.uk/en/publications/beta-blocker-use-in-pregnancy-and-risk-of-specific-congenital-ano

U2 - 10.1007/s40264-017-0627-x

DO - 10.1007/s40264-017-0627-x

M3 - Article

C2 - 29230691

VL - 41

SP - 415-427 (2018)

JO - Drug Safety

JF - Drug Safety

SN - 0114-5916

ER -

Bergman JEH, Lutke LR, Gans ROB, Addor M-C, Barisic I, Cavero-Carbonell C et al. Beta-blocker use in pregnancy and risk of specific congenital anomalies: A European case-malformed control study. Drug Safety. 2017 Dec 11;41:415-427 (2018). https://doi.org/10.1007/s40264-017-0627-x