USE OF LITHIUM IN PREGNANCY

Lithium is a mood stabilising agent licensed for the treatment and prophylaxis of mania, bipolar disorder, recurrent depression, and other psychiatric illnesses. Lithium levels need to be monitored regularly in the non-pregnant patient, and more frequently throughout pregnancy and the postnatal period.

It is important to ensure that women with mental health conditions are treated appropriately during pregnancy. Where a woman’s illness is stable on lithium treatment, either prior to conception or during pregnancy, the risk of discontinuing or changing medication or reducing the dose, should be carefully weighed against the risk of relapse. Clinicians are encouraged to discuss the advantages and disadvantages of lithium use with the patient. Where the benefit of continued treatment is considered to outweigh any potential or known risks, lithium use in pregnancy may be the best option.

Lithium exposure has been associated with an increased risk of congenital cardiac defects, with an absolute risk of up to 2.25% and a possible dose effect. One study has identified an elevated risk of right ventricular outflow tract (RVOT) obstruction anomalies, corresponding to an absolute risk of 0.6% following lithium exposure. While early analyses suggested a possible association between in utero lithium exposure and Ebstein’s anomaly, subsequent studies have failed to confirm this association. Studies investigating the impact of dose are limited, but higher risks of malformation have been associated with the use of >900 mg/day in a single study. There is currently no safe dose identified for lithium, and further investigations of possible dose effects are required.

There is no good evidence of increased risks of miscarriage, low 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. Possible increased risks of high birth weight, preterm delivery and neonatal complications have been identified, although preterm delivery is independently associated with maternal bipolar disorder.

Lithium use in pregnancy is complicated by fluctuating pharmacokinetics and a narrow therapeutic index, which present risks of both suboptimal maternal treatment and maternal and/or 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. National Institute for Health and Care Excellence (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 be monitored during labour. 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. Additional monitoring of fetal growth should be considered, due to a possible risk of higher birth weight. Other risk factors may also 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.