Not treating bipolar disorder during pregnancy can have adverse pregnancy and birth outcomes: BMJ:Nov.2012

15.11.2012

Increased risk of pregnancy complications (preterm birth, small for gestational babies) is reported with bipolar disorders.  We know that Lithium, Valproate, and Carbamazepine have been associated with congenital malformations. (Lithium :the data is conflicting and difficult to interpret). Antipsychotics like Olanzapine and Clozapine are reported to cause microcephaly.

Are these reported effects  due to the effect of illness or the drugs that are used to treat them? This has never been studied and this Swedish study is addressing this important question.

Boden and colleagues used the data from three linked Swedish nationwide registers (Swedish prescribed drug register,  medical birth register, and the national patient register). Only women with at least two recorded diagnoses for bipolar disorder (ICD-10 code F30-31) in the national patient register were classified as having bipolar disorder. Providing  a prescription that supplied a quantity of the drug (lithium, antipsychotic drugs, and any of the anticonvulsants Carbamazepine, Lamotrigine, and Valproate)  to cover intake during pregnancy according to the prescribed dosage was defined as ‘use of mood stabiliser’. Women with bipolar disorder were classified by use of mood stabilisers as either treated or untreated. Only major congenital malformations were included.

Findings

1.Women with bipolar disorder, whether treated or not, were more often smokers, overweight, and misused alcohol or substances than women without bipolar disorder.

2. In the treated mothers, 40% had used Lamotrigine, 39%  antipsychotics, 12% Valproate,   2% carbamazepine and  lithium by 24%.

3.The risks of preterm birth in both treated and untreated women were increased by 50%.

4. Infants of women with untreated bipolar disorder were at increased risk of microcephaly and neonatal hypoglycemia.

5. The prevalence of congenital malformations was 2.0% (n=6517) in infants born to women without bipolar disorder, 1.9% (n=11) in untreated women, and ranging from 0% to 3.5% in treated women. (note that maximum 4 cases out of 116 patients taking Lamotrigine give a figure of 3.5%. same for antipsychotics).

Conclusions:

It is important to note that there is an increased risks for several of the investigated outcomes  in the untreated women. This suggest that mood stabilising treatment is probably not the sole reason for the increased risk of adverse pregnancy and birth outcomes previously observed in women with bipolar disorder.

In an accompanying editorial , Salvatore Gentile elaborates that severe maternal psychiatric disorders, such as bipolar disorder, them selves are considered to be “teratogenic” conditions. More microcephaly and recurrent episodes of neonatal hypoglycaemia found in untreated cases in this study is particularly noteworthy.  Analysing different stabilisers with differing potential as one class is a limitation. Study does not provide information about the proportion of pregnant women who needed polypharmacotherapy.  Women treated had more admissions, was it because they had more severe illness or because  they were treated with suboptimal doses?

The question here is whether to treat or not to treat but how to optimise treatment. The adverse effects of not treating on mother and baby are well known.

Risks of adverse pregnancy and birth outcomes in women treated or not treated with mood stabilisers for bipolar disorder: population based cohort study. Bodén R, Lundgren M, Brandt L, Reutfors J, Andersen M, Kieler H. BMJ. 2012 Nov 8;345:e7085.

full text: http://www.bmj.com/content/345/bmj.e7085

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