Relapse of Bipolar Disorder During Pregnancy Increases Risk of Postpartum Illness

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In planning for pregnancy, women with bipolar disorder and their care providers are forced to make difficult choices.  In the setting of medication discontinuation, relapse rates are significant, and there is evidence that untreated psychiatric illness in the mother is associated with worse maternal and fetal outcomes.  However, many of the medications commonly used to treat bipolar disorder, specifically lithium, carry a small but measurable increase in risk of teratogenesis.  The reproductive safety of other medications, including atypical antipsychotic medications, is not well characterized. These decisions are further complicated by the paucity of data regarding the course of bipolar illness during pregnancy.

A recent study from the United Kingdom looks specifically at recurrence of illness during pregnancy and the postpartum period in a group of women with bipolar disorder.  This study included 128 women with DSM-5 bipolar disorder (BD) who were recruited to the Bipolar Disorder Research Network Pregnancy Study and were followed from 12 weeks of gestation to 12 weeks postpartum. Semi-structured questionnaires, supplemented with clinician interviews and review of the medical record, were used to assess for lifetime psychiatric history and psychiatric illness during pregnancy and the postpartum follow-up.  

In this cohort, 98 women had bipolar I disorder/schizoaffective-BD (BD-I group) and 26 bipolar II disorder/other specified BD and related disorder (BD-II group).   The two groups were similar, although the women in the BD-II group had earlier onset of illness and had more frequent depressive episodes than women with BD-I.  Information regarding the use of medications during pregnancy was not reported.  About 40% of the women in each group used a mood stabilizer during the postpartum period.   

  • Perinatal recurrence of illness was common in both groups: 57% (BD-I) and 62% (BD-II) experienced a mood episode during pregnancy. 
  • Women with BD-I were more likely to experience mania/psychosis during pregnancy than women with BD-II (13.5% vs. 0%).
  • Women with BD-I were more likely to experience mania/psychosis within 6 weeks postpartum (23%) compared to women with BD-II (4%). 
  • In women with BD-I, mania/psychosis during pregnancy was associated with a sevenfold increased risk of postpartum mania/psychosis (RR 7.0, p<0.001). 

 In women with BD-I, depression during pregnancy was associated with a threefold increase in risk of postpartum depression  (RR 3.18, p=0.023).

This study is consistent with previous reports suggesting that risk for perinatal recurrence of bipolar disorder is high, with approximately 60% of women with bipolar disorder (type I or II) experiencing recurrent illness during pregnancy and/or the postpartum period.  Also consistent with previous reports is the finding that depressive episodes are more common than mania in women with BD-I and BD-II; however, mania/psychosis is much more common in women with BD-I than those with BD-II. (In this study, only one of the 26 women with BD-II experienced postpartum mania/psychosis.)

The Importance of Remaining Well During Pregnancy

Of great clinical significance is the observation that women who experience recurrent illness during pregnancy are more likely to experience illness during the postpartum period.  The highest risk was observed in women with BD-I; in this study, women who experienced mania/psychosis during pregnancy had a sevenfold increased risk of experiencing postpartum mania/psychosis.  Overall, recurrence of illness during pregnancy (depression or mania) was associated with a twofold increase in risk for postpartum illness.  

It is clear that risk for postpartum psychiatric illness, including postpartum psychosis, is high in women with bipolar disorder.  Previous studies have demonstrated that risk for postpartum illness can be reduced significantly with the use of a mood stabilizer, such as lithium, during the postpartum period.  However, given the risks associated with the use of certain mood stabilizers during pregnancy, many women and their providers elect to discontinue mood stabilizers during pregnancy.  This study confirms previous studies documenting high rates of recurrent illness during pregnancy in women with bipolar disorder, but the findings of this study also suggest that the discontinuation of mood stabilizers during pregnancy may have significant implications for vulnerability to postpartum psychiatric illness.

In women with unipolar depression, relapse during pregnancy is a robust predictor of postpartum depression; this study indicates that for women with bipolar disorder, recurrent illness during pregnancy, especially mania or psychosis, is a robust predictor of postpartum psychiatric illness. While certain mood stabilizers, including lithium carry some risk of teratogenesis, we need to weigh the relatively small risk of teratogenesis in mood stabilizers, excluding valproic acid, against the very high risk of recurrent illness during pregnancy in the mother. Avoiding medication during pregnancy and restarting it after delivery may not be the best option.  This study, and others, suggests that keeping the mother well during pregnancy will reduce the risk of postpartum psychiatric illness.

Ruta Nonacs, MD PhD

 

Perry A, Gordon-Smith K, Di Florio A, Craddock N, Jones L, Jones I. Mood episodes in pregnancy and risk of postpartum recurrence in bipolar disorder: The Bipolar Disorder Research Network Pregnancy Study. J Affect Disord. 2021;294:714-722. 

 

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