bipolar disorders in pregnancy,to treat or not to treat

The real question is how to treat most effectively

In a linked research paper (doi:10.1136/bmj.e7085), Bodén and colleagues analysed the risks for the fetus associated with treated and untreated bipolar disorder during pregnancy.1 They found that women with untreated bipolar disorder were at increased risk of producing offspring with microcephaly and neonatal hypoglycaemia, and that infants born to women who are treated with mood stabilisers during pregnancy were at slightly increased risk of preterm birth and congenital anomalies. How should these findings be interpreted?

Previous research has shown that the offspring of women with bipolar disorder have increased rates of memory and attention disturbances, impaired social functioning, behavioural and emotional problems, and even severe psychiatric disorders.2 Severe maternal psychiatric disorders, such as bipolar disorder, are therefore considered to be “teratogenic conditions.”3 Microcephaly has been associated with delayed growth and development, epilepsy, hypotonia, spastic hemiplegia, altered balance and coordination, intellectual impairment, and hyperactivity.4 Recurrent episodes of neonatal hypoglycaemia are strongly correlated with persistent neurodevelopmental and physical growth deficits until 5 years of age,5 severe mental retardation, and epilepsy.6

Bodén and colleagues estimated the risk of any congenital malformation to be 3.4% for bipolar women treated with mood stabilisers compared with 1.9% in untreated women and 2.0% in healthy women. However, it is difficult to draw meaningful conclusions from this finding because of what is not known. Data derived from potential exposure to several mood stabilising agents with different degrees of teratogenic risk (structural, gestational, perinatal, and neurodevelopmental; box) were analysed together. Forty per cent of mothers with bipolar disorder were prescribed lamotrigine, and recent data support the safe use of this drug during pregnancy.3 Valproate or carbamazepine, which are both well known teratogenic agents, were prescribed to 14% of mothers, whereas 24% were prescribed lithium, the safety of which is still unclear.7 The corresponding figure for antipsychotic drugs was 39%; however, agents belonging to this class of neurotherapeutics also show different levels of teratogenic risks, structurally, gestationally, and perinatally.8 Furthermore, this study does not provide information about the proportion of pregnant women who needed polypharmacotherapy.
Aspects of the complex phenomenon of teratogenicity

Structural teratogenicity: Increased risk of major fetal malformations

Perinatal teratogenicity: Increased risk of perinatal complications

Gestational teratogenicity: Increased risk of complicated pregnancy outcomes

Neurobehavioural teratogenicity: Increased risk of impaired neurodevelopment

The finding that women treated with mood stabilisers during pregnancy had more admissions to psychiatric hospital than untreated women needs careful consideration.1 The authors conclude that this finding might reflect a more severe and active disorder. However, these women may have received suboptimal treatment (relatively low doses of drugs) because of their pregnant status, and suboptimally treated disease may have contributed to increased risks of adverse outcomes in offspring.

Moreover, treatment was measured by drugs dispensed, not used, which again could have led to confounding due to untreated disease. Although the authors report that there is fairly good agreement between the use of mood stabilisers during pregnancy and dispensed drugs, other sources of information have highlighted that, in the general psychiatric population, 45% of patients with bipolar disorder do not adhere to drug treatment.9

Non-adherence might increase during pregnancy because both patients and treating doctors may worry about fetal malformations. Non-adherence to mood stabilising drugs predicts higher use of healthcare resources, including psychiatric emergency visits and admissions to psychiatric hospital.10 Pregnant women who are admitted to psychiatric emergency services often receive relatively high doses of psychotropic drugs to treat their current mental state, regardless of reproductive safety considerations.11

Bodén and colleagues found that both treated and untreated women with bipolar disorder were at greater risk of adverse pregnancy outcomes than women without mental illness. It is important to remember the potential consequences of bipolar relapse in pregnancy and the puerperium: a woman’s mental state may preclude her from caring for herself or for her child adequately and this may lead to offspring being removed from maternal care.12

Given the current study’s findings, it is clear that prophylactic treatment with psychotropic drugs should be actively encouraged for all pregnant women with bipolar disorder.7 The question is not “to treat or not to treat?” but “how to treat optimally?” Because no drug is without risks, clinicians cannot hope to identify a “safe choice,” but merely a “less harmful” one.

Furthermore, drug treatment is only one part of the overall management of pregnant women diagnosed with severe and persistent psychiatric disorders. An integrated tailored approach to management must be provided for these vulnerable mothers.

It is vital to anticipate that the stigma associated with mental illness may lead to refusal to engage with psychiatric services and to ensure that barriers to engagement are attenuated. Patients must be properly counselled about the risks of treatment versus the risks associated with the untreated psychiatric disorder. Wherever possible ensure that patients are offered available financial support and help to engage with medical services.

Discuss with patients, partners, and family the changes to lifestyle and challenges that come with being a parent, and help identify supportive care givers for the mother-infant pair. Encourage and facilitate social integration, especially for women from disadvantaged social groups and those who are isolated. Drug treatment will undoubtedly improve maternal adherence to these adjunctive interventions

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