Summary
Lithium is a mood stabilising agent licensed for the treatment and prophylaxis of mania, bipolar disorder and recurrent depression, and the treatment of aggressive or mutilating behaviour. Lithium levels need to be monitored regularly in the non-pregnant patient and more frequently throughout pregnancy and the postnatal period.
The majority of studies have not suggested an overall increased risk of congenital malformation, although a possible increased risk of cardiac defects has been found. An early retrospective study suggested an association between in utero lithium exposure and Ebstein’s anomaly. This has not been replicated by other studies, and as the expected background rate of Ebstein’s anomaly is 1 in 20,000, even with the hypothesized increased risk following lithium exposure, the estimated absolute risk to an exposed fetus remains very low (1 in 1,500).
There is no compelling evidence of increased rates of spontaneous abortion, low or high birth weight, intrauterine death, or adverse neurodevelopmental outcome following lithium exposure in utero, however the data are currently too limited to completely exclude an increased risk of these outcomes. An increased risk of preterm delivery and neonatal complications has been identified.
Lithium use in pregnancy is complicated by its fluctuating pharmacokinetics and narrow therapeutic index, which together present a risk of both suboptimal maternal treatment and maternal/neonatal lithium toxicity. Maternal dehydration (e.g. as a result of pregnancy sickness) may also rapidly increase serum lithium levels, whereas increased clearance in later pregnancy may reduce levels. NICE Guidelines state that where lithium therapy is continued during pregnancy, serum lithium levels should be monitored every four weeks until the 36th week, and then weekly until delivery. Serum lithium levels and fluid balance should also be carefully monitored during labour and adjusted to maintain concentrations within the therapeutic range. Due to the risk of neonatal lithium toxicity and the need for monitoring during labour, delivery in hospital is advised. All neonates exposed to lithium in utero should have their serum lithium level measured shortly after delivery.
Exposure to lithium at any stage in pregnancy would not usually be regarded as medical grounds for termination of pregnancy. However, other risk factors may be present in individual cases which may independently increase the risk of adverse pregnancy outcome. Clinicians are reminded of the importance of consideration of such factors when performing case-specific risk assessments.
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