. 2018 Apr;41(4):415-427.

doi: 10.1007/s40264-017-0627-x.

Beta-Blocker Use in Pregnancy and Risk of Specific Congenital Anomalies: A European Case-Malformed Control Study

Jorieke E H Bergman¹, L Renée Lutke², Rijk O B Gans³, Marie-Claude Addor⁴, Ingeborg Barisic⁵, Clara Cavero-Carbonell⁶, Ester Garne⁷, Miriam Gatt⁸, Kari Klungsoyr^{9

10}, Nathalie Lelong¹¹, Catherine Lynch¹², Olatz Mokoroa¹³, Vera Nelen¹⁴, Amanda J Neville^{15

16}, Anna Pierini¹⁷, Hanitra Randrianaivo¹⁸, Anke Rissmann¹⁹, David Tucker²⁰, Awi Wiesel²¹, Helen Dolk²², Maria Loane²², Marian K Bakker²

Affiliations

¹ Department of Genetics, EUROCAT Northern Netherlands, University of Groningen, University Medical Centre Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands. j.e.h.van.kammen@umcg.nl.
² Department of Genetics, EUROCAT Northern Netherlands, University of Groningen, University Medical Centre Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands.
³ Department of Internal Medicine, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
⁴ Division of Medical Genetics, CHUV, Lausanne, Switzerland.
⁵ Children's Hospital Zagreb, Medical School University of Zagreb, Zagreb, Croatia.
⁶ Foundation for the Promotion of Health and Biomedical Research of the Valencian Region, Rare Diseases Research Unit, Valencia, Spain.
⁷ Paediatric Department, Hospital Lillebaelt, Kolding, Denmark.
⁸ Directorate for Health Information and Research, Guardamangia, Malta.
⁹ Division for Health Data and Digitalisation, The Norwegian Institute of Public Health, Bergen, Norway.
¹⁰ Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
¹¹ Paris Registry of Congenital Malformations, Obstetrical, Perinatal and Paediatric Epidemiology Research Team, Centre for Biostatistics and Epidemiology, INSERM, UMR 1153, Paris, France.
¹² Department of Public Health, Health Service Executive South East, Kilkenny, Ireland.
¹³ Public Health and Addictions Directorate, Basque Government, Vitoria-Gasteiz, BioDonostia Health Research Institute, Donostia-San Sebastian, Spain.
¹⁴ Department of Environment, PIH, Antwerp, Belgium.
¹⁵ IMER Registry (Emilia Romagna Registry of Birth Defects), Centre for Clinical and Epidemiological Research, University of Ferrara, Ferrara, Italy.
¹⁶ Azienda Ospedaliero, Universitaria di Ferrara, Ferrara, Italy.
¹⁷ CNR Institute of Clinical Physiology/RTDC Registry (Tuscany Registry of Congenital Defects), Fondazione Toscana "Gabriele Monasterio", Pisa, Italy.
¹⁸ Registre des Malformations Congenitales de la Reunion, Saint-Pierre, Reunion, France.
¹⁹ Medical Faculty, Malformation Monitoring Centre, Otto-von-Guericke University, Magdeburg, Saxony-Anhalt, Germany.
²⁰ Congenital Anomaly Register & Information Service for Wales, Public Health Wales, Swansea, UK.
²¹ Birth Registry Mainz Model, University Medical Centre of Johannes Gutenberg University, Mainz, Germany.
²² Centre for Maternal, Foetal and Infant Research, Institute of Nursing and Health Research, Ulster University, Belfast, Northern Ireland, UK.

PMID: 29230691
PMCID: PMC5878198
DOI: 10.1007/s40264-017-0627-x

Beta-Blocker Use in Pregnancy and Risk of Specific Congenital Anomalies: A European Case-Malformed Control Study

Jorieke E H Bergman et al. Drug Saf. 2018 Apr.

. 2018 Apr;41(4):415-427.

doi: 10.1007/s40264-017-0627-x.

Authors

Affiliations

¹ Department of Genetics, EUROCAT Northern Netherlands, University of Groningen, University Medical Centre Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands. j.e.h.van.kammen@umcg.nl.
² Department of Genetics, EUROCAT Northern Netherlands, University of Groningen, University Medical Centre Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands.
³ Department of Internal Medicine, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
⁴ Division of Medical Genetics, CHUV, Lausanne, Switzerland.
⁵ Children's Hospital Zagreb, Medical School University of Zagreb, Zagreb, Croatia.
⁶ Foundation for the Promotion of Health and Biomedical Research of the Valencian Region, Rare Diseases Research Unit, Valencia, Spain.
⁷ Paediatric Department, Hospital Lillebaelt, Kolding, Denmark.
⁸ Directorate for Health Information and Research, Guardamangia, Malta.
⁹ Division for Health Data and Digitalisation, The Norwegian Institute of Public Health, Bergen, Norway.
¹⁰ Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
¹¹ Paris Registry of Congenital Malformations, Obstetrical, Perinatal and Paediatric Epidemiology Research Team, Centre for Biostatistics and Epidemiology, INSERM, UMR 1153, Paris, France.
¹² Department of Public Health, Health Service Executive South East, Kilkenny, Ireland.
¹³ Public Health and Addictions Directorate, Basque Government, Vitoria-Gasteiz, BioDonostia Health Research Institute, Donostia-San Sebastian, Spain.
¹⁴ Department of Environment, PIH, Antwerp, Belgium.
¹⁵ IMER Registry (Emilia Romagna Registry of Birth Defects), Centre for Clinical and Epidemiological Research, University of Ferrara, Ferrara, Italy.
¹⁶ Azienda Ospedaliero, Universitaria di Ferrara, Ferrara, Italy.
¹⁷ CNR Institute of Clinical Physiology/RTDC Registry (Tuscany Registry of Congenital Defects), Fondazione Toscana "Gabriele Monasterio", Pisa, Italy.
¹⁸ Registre des Malformations Congenitales de la Reunion, Saint-Pierre, Reunion, France.
¹⁹ Medical Faculty, Malformation Monitoring Centre, Otto-von-Guericke University, Magdeburg, Saxony-Anhalt, Germany.
²⁰ Congenital Anomaly Register & Information Service for Wales, Public Health Wales, Swansea, UK.
²¹ Birth Registry Mainz Model, University Medical Centre of Johannes Gutenberg University, Mainz, Germany.
²² Centre for Maternal, Foetal and Infant Research, Institute of Nursing and Health Research, Ulster University, Belfast, Northern Ireland, UK.

PMID: 29230691
PMCID: PMC5878198
DOI: 10.1007/s40264-017-0627-x

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.

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Conflict of interest statement

Funding

This study is a part of the EUROmediCAT project, which was supported by the European Union under the Seventh Framework Programme (HEALTH-F5-2011-260598). EUROCAT registries are funded as described by Greenlees et al. [19]. EUROCAT Northern Netherlands is funded by the Dutch Ministry of Welfare, Health and Sports.

Conflict of interest

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, Awi Wiesel, Helen Dolk, Maria Loane and Marian K. Bakker have no conflicts of interest directly relevant to the content of this article. David Tucker declares that he is a shareholder in GlaxoSmithKline.

Ethics approval

This study was performed on anonymised patient data and ethics committee approval was therefore not required.

Figures

**Fig. 1**
Flowchart of the literature review

**Fig. 2**
Flowchart of inclusions and exclusions for the signal analysis. The sum of the separate exclusions is higher than the total number of exclusions because some cases had more than one exclusion criterion. *CHD* congenital heart defect, *CL/P* cleft lip with or without cleft palate, CP cleft palate, *FDA* US Food and Drug Administration, *NTD* neural tube defect

See this image and copyright information in PMC

References

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Beta-Blocker Use in Pregnancy and Risk of Specific Congenital Anomalies: A European Case-Malformed Control Study

Affiliations

Beta-Blocker Use in Pregnancy and Risk of Specific Congenital Anomalies: A European Case-Malformed Control Study

Authors

Affiliations

Abstract

Conflict of interest statement

Funding

Conflict of interest

Ethics approval

Figures

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical