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  3. Selective serotonin reuptake inhibitors during pregnancy and risk of persistent pulmonary hypertension in the newborn: population based cohort study from the five Nordic countries
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Research

Selective serotonin reuptake inhibitors during pregnancy and risk of persistent pulmonary hypertension in the newborn: population based cohort study from the five Nordic countries

BMJ 2012; 344 doi: https://doi.org/10.1136/bmj.d8012 (Published 12 January 2012) Cite this as: BMJ 2012;344:d8012
  1. Helle Kieler, associate professor in obstetrics and gynaecology1,
  2. Miia Artama, senior researcher2,
  3. Anders Engeland, senior researcher34,
  4. Örjan Ericsson, researcher5,
  5. Kari Furu, professor and senior researcher36,
  6. Mika Gissler, research professor72,
  7. Rikke Beck Nielsen, biostatistician8,
  8. Mette Nørgaard, associate professor and senior consultant in epidemiology8,
  9. Olof Stephansson, associate professor and senior consultant in obstetrics and gynaecology19,
  10. Unnur Valdimarsdottir, associate professor10,
  11. Helga Zoega, postdoctoral fellow in epidemiology10,
  12. Bengt Haglund, associate professor and senior researcher1
  1. 1Centre for Pharmacoepidemiology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, T2, SE-171 76 Stockholm, Sweden
  2. 2THL National Institute for Health and Welfare, Helsinki, Finland
  3. 3Department of Pharmacoepidemiology, Norwegian Institute of Public Health, Oslo, Norway
  4. 4Department of Public Health and Primary Health Care, University of Bergen, Norway
  5. 5National Board of Health and Welfare, Stockholm, Sweden
  6. 6Department of Pharmacy, University of Tromsø, Norway
  7. 7Nordic School of Public Health, Gothenburg, Sweden
  8. 8Department of Clinical Epidemiology, Institute of Clinical Medicine, Aarhus University Hospital, Denmark
  9. 9Department of Women’s and Children’s Health, Karolinska University Hospital and Institutet, Stockholm, Sweden
  10. 10Centre of Public Health Sciences, School of Health Sciences, University of Iceland, Reykjavik, Iceland
  1. Correspondence to: H Kieler helle.kieler{at}ki.se
  • Accepted 31 October 2011

Abstract

Objective To assess whether maternal use of selective serotonin reuptake inhibitors (SSRIs) increases the risk of persistent pulmonary hypertension in the newborn, and whether such an effect might differ between specific SSRIs.

Design Population based cohort study using data from the national health registers.

Setting Denmark, Finland, Iceland, Norway, and Sweden, 1996-2007.

Participants More than 1.6 million infants born after gestational week 33.

Main outcome measures Risks of persistent pulmonary hypertension of the newborn associated with early and late exposure to SSRIs during pregnancy and adjusted for important maternal and pregnancy characteristics. Comparisons were made between infants exposed and not exposed to SSRIs.

Results Around 30 000 women had used SSRIs during pregnancy and 11 014 had been dispensed an SSRI later than gestational week 20. Exposure to SSRIs in late pregnancy was associated with an increased risk of persistent pulmonary hypertension in the newborn: 33 of 11 014 exposed infants (absolute risk 3 per 1000 liveborn infants compared with the background incidence of 1.2 per 1000); adjusted odds ratio 2.1 (95% confidence interval 1.5 to 3.0). The increased risks of persistent pulmonary hypertension in the newborn for each of the specific SSRIs (sertraline, citalopram, paroxetine, and fluoxetine) were of similar magnitude. Filling a prescription with SSRIs before gestational week 8 yielded slightly increased risks: adjusted odds ratio 1.4 (95% confidence interval 1.0 to 2.0).

Conclusions The risk of persistent pulmonary hypertension of the newborn is low, but use of SSRIs in late pregnancy increases that risk more than twofold. The increased risk seems to be a class effect.

Footnotes

  • We thank Jørgen G Bramness, University of Oslo, Norway for his contributions to the design of the study.

  • Contributors: HK had full access to all of the data in the study, takes responsibility for the integrity of the data and the accuracy of the data analysis, and is guarantor. HK, KF, MG, MN, UV, and BH conceived and designed the study. MA, AE, MN, RBN, UN, and BH acquired the data in their countries. HK drafted the manuscript, obtained funding, and supervised the study. BH was responsible for the statistical analysis. All authors participated in interpreting the data and critically revising the manuscript.

  • Funding: This study was funded by the Swedish Pharmacy Company and by the authors’ affiliations. The Swedish Pharmacy Company was not involved in the design and conduct of the study; collection, management, analysis, or interpretation of the data; and preparation, review, or approval of the manuscript.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: This study was approved by the regional ethical review board at the Karolinska Institutet, Sweden (No 2008/1371-31/4); the Danish Data Protection Agency and the National Board of Health, Denmark; the National Institute for Health and Welfare (THL), the Social Insurance Institution of Finland and Statistics Finland, Finland; the National Bioethics Committee and the Data Protection Authority in Iceland, Iceland; and the Norwegian Data Inspectorate, Norway.

  • Data sharing: Codes from the International Classification of Diseases and Anatomical Therapeutic Chemical for the listed diseases and drugs are available from the corresponding author at helle.kieler{at}ki.se.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

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