[Physician Comment] Bipolar Disorder is associated with adverse pregnancy outcomes regardless of pharmacologic treatment

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From study author Robert Bodén, M.D., Ph.D. Department of Neuroscience, Psychiatry, Uppsala University Hospital, Sweden:

“Many pregnant women with bipolar disorder can become severely ill if not treated with prophylactic mood-stabilizing drugs, but due to fear of harming the fetus they might stop their medication. However, untreated bipolar disorder is also associated with poor pregnancy outcome for the offspring, which hopefully will be incorporated into the risk benefit analyses when deciding if and how to treat bipolar disorder during pregnancy. Because bipolar disorder is a rather common and severe psychiatric disorder and drug treatment during pregnancy is a truly multidisciplinary field forming an important cross-road for obstetrics, pediatrics and psychiatry. It also encompasses difficult ethical and medical considerations that are important to start to think about already as a student.

Our study has highlighted that pregnant women with bipolar disorder have many known risk factors for adverse pregnancy outcome such as excessive smoking and alcohol and substance abuse disorders, thus these pregnancies should be regarded as high risk pregnancies per se and monitored extra carefully.”

Key study points: 

1. Bipolar disorder itself, regardless of treatment with mood stabilizing drugs, was associated with adverse pregnancy outcomes.
2. The cost-benefit of pharmacologic treatment of bipolar disorder in pregnancy should be re-examined in light of adverse pregnancy outcomes, including preterm birth and microcephaly, in untreated women.

Primer: Bipolar disorder is a psychiatric disorder in which patients alternate between episodes of mania and depression. Various aspects of bipolar disorder present risks to the developing fetus of a woman with bipolar disorder. Manic patients present with an abnormally elevated mood, often associated with lack of inhibitions, extreme euphoria and racing thoughts. A manic patient, for instance, might not sleep for days at a time, spend excessively or make other rash decisions. A bipolar patient experiencing a depressive episode will present similarly to a patient with major depression, exhibiting symptoms of extreme sadness and apathy and trouble sleeping. Bipolar patients also have a very high risk of suicide (1-2).

The typical age of onset of bipolar disorder late adolescence to early adulthood, and thus is likely to affect women during their reproductive years.  Typically, it is treated with mood stabilizing drugs, such as Carbamazepine, Lamotrigine, Lithium, and Valproate, though many small studies have demonstrated associations with adverse pregnancy outcomes including congenital malformations, abnormal fetal growth, and preterm birth. For these reasons, attempts are often made to discontinue treatment during pregnancy. However, untreated bipolar disorder is also been associated with adverse pregnancy outcomes, not the least of which includes an increased risk of suicide. This creates a dilemma of how to treat women with bipolar disorder who become pregnant (3-4).

The present work is the first direct attempt to differentiate between the adverse effects of the illness itself from those caused by drugs used to treat the illness.

This study assessed the risk of adverse pregnancy outcomes in women with bipolar disorder by comparing healthy women to those with bipolar disorder, both treated and untreated. 

Background reading:

1. Up-to-date: Bipolar disorder in women–preconception and prenatal maintenance pharmacotherapy
2. Management of bipolar disorder during pregnancy 
3. Bipolar Disorder 
4. ACOG guidelines on the use of psychiatric medication during pregnancy

This [population based retrospective cohort] study: evaluated pregnancy outcomes for 332,137 Swedish women who became pregnant and gave birth during a four and a half year period. Information was obtained from three national Swedish registries maintained by the National Board of Health and Welfare, containing information on almost all births in Sweden. Of the study population, 331,263 had no bipolar disorder and were on no mood stabilizing drugs, 554 had confirmed bipolar disorder and were not treated, and 320 had confirmed bipolar disorder and were treated during pregnancy.

Results showed that both treated and untreated women with bipolar disorder were significantly more likely to have pre-term, Caesarean, and Non-spontaneous deliveries as compared to women with no bipolar disorder (pre-term p=0.03, all others p<0.01). Additionally, women with untreated bipolar disorder were at an increased risk of having a child born with microcephaly and neonatal hypoglycemia.

In sum: Compared to pregnant women without bipolar disorder, pregnant women with bipolar disorder were more likely to have adverse outcomes, regardless of whether or not they received treatment. This risk of adverse outcomes in untreated women should be considered when deciding whether or not to continue pharmacologic treatment for bipolar disorder during pregnancy.  

Click to read the study in the current issue of BMJ 

Click to read an accompanying editorial in BMJ 

By [MS] and [LH]

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