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Risks of adverse pregnancy and birth outcomes in women treated or not treated with mood stabilisers for bipolar disorder: population based cohort study

BMJ 2012; 345 doi: http://dx.doi.org/10.1136/bmj.e7085 (Published 08 November 2012) Cite this as: BMJ 2012;345:e7085
  1. Robert Bodén, consultant psychiatrist and researcher12,
  2. Maria Lundgren, paediatrician and researcher3,
  3. Lena Brandt, biostatistician and epidemiologist2,
  4. Johan Reutfors, consultant psychiatrist and researcher2,
  5. Morten Andersen, clinical pharmacologist and visiting professor2,
  6. Helle Kieler, associate professor in obstetrics and gynaecology and head2
  1. 1Department of Neuroscience, Psychiatry, Uppsala University, Ing 15 3tr, SE-751 85 Uppsala, Sweden
  2. 2Centre for Pharmacoepidemiology, Department of Medicine Solna, Karolinska Institutet, Sweden
  3. 3Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden
  1. Correspondence to: R Bodén robert.boden{at}neuro.uu.se
  • Accepted 15 October 2012

Abstract

Objective To investigate the risks of adverse pregnancy and birth outcomes for treated and untreated bipolar disorder during pregnancy.

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

Setting Sweden.

Participants 332 137 women with a last menstrual period anytime after 1 July 2005 and giving birth anytime before the end of 31 December 2009. Women with a record of at least two bipolar diagnoses were identified and grouped as treated (n=320)—those who had filled a prescription for mood stabilisers (lithium, antipsychotics, or anticonvulsants) during pregnancy—or untreated (n=554). Both groups were compared with all other women giving birth (n=331 263).

Main outcome measures Preterm birth, mode of labour initiation, gestational diabetes, infants born small or large for gestational age, neonatal morbidity, and congenital malformations.

Results Of the untreated women, 30.9% (n=171) were induced or had a planned caesarean delivery compared with 20.7% (n=68 533) without bipolar disorder (odds ratio 1.57, 95% confidence interval 1.30 to 1.90). The corresponding values for the treated women were 37.5% (n=120) (2.12, 1.68 to 2.67). The risks of preterm birth in both treated and untreated women were increased by 50%. Of the untreated women, 3.9% (n=542) had a microcephalic infant compared with 2.3% (324 844) of the women without bipolar disorder (1.68, 1.07 to 2.62). The corresponding values for the treated women were 3.3% (n=311) (1.26, 0.67 to 2.37). Similar trends were observed for risks of infants being small for gestational age infants for weight and length. Among infants of untreated women, 4.3% (n=24) had neonatal hypoglycaemia compared with 2.5% (n=8302) among infants of women without bipolar disorder (1.51, 1.04 to 2.43), and 3.4% (n=11) of the treated women (1.18, 0.64 to 2.16). The analyses of variation in outcomes did not support any significant differences between treated and untreated women.

Conclusions Bipolar disorder in women during pregnancy, whether treated or not, was associated with increased risks of adverse pregnancy outcomes.

Footnotes

  • Contributors: RB conceived the study. LB carried out the statistical analyses. RB and HK wrote the first draft of the manuscript. All authors contributed to the study design, critically reviewed the manuscript, and approved the final version for submission. All authors had full access to all of the data (including statistical reports and tables) in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis. RB is the guarantor.

  • Funding: This study was funded by unrestricted grants from Lennanders Foundation, Gillbergska Foundation, Uppsala County Council (ALF-grants), and by the authors’ affiliations.

  • 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; and no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: This study was approved by the regional ethics board at the Faculty of Medicine, Uppsala University (Dnr: 2008/305).

  • Data sharing: No additional data available.

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