Lithium is an effective mood stabilizer frequently prescribed for the long-term management of bipolar disorder. For women with bipolar disorder, maintaining effective mental health treatment during pregnancy is a significant challenge. The decision to continue or discontinue medication involves carefully weighing the risk of maternal relapse against the potential for fetal harm. This tension centers on lithium’s classification as a teratogen, a substance capable of causing developmental abnormalities in an embryo or fetus.
The Primary Cardiac Concern
The specific teratogenic effect most consistently associated with prenatal lithium exposure is a rare congenital heart defect known as Ebstein’s anomaly. This anomaly is the signature cardiac malformation linked to the drug. It involves the improper formation of the tricuspid valve, which separates the right atrium and the right ventricle of the heart.
In a normal heart, the tricuspid valve ensures blood flows forward from the right atrium into the right ventricle. With Ebstein’s anomaly, the valve leaflets are displaced downward into the right ventricle instead of sitting at the proper junction. This displacement causes a portion of the right ventricle to become integrated into the right atrium, and the valve often leaks significantly.
This defect causes blood to flow backward, a condition called tricuspid regurgitation, which reduces the heart’s pumping efficiency. The reduced blood flow to the lungs and the resulting enlargement of the right atrium can lead to cyanosis, or a bluish tint to the skin, and heart failure in infants, depending on the severity.
Understanding the Absolute Risk
The actual risk of Ebstein’s anomaly in pregnancies exposed to lithium is considerably lower than initially feared. Early registry reports suggested an alarmingly high risk, but more recent, controlled studies have provided a more modest estimate. The general population risk of any major cardiac malformation is approximately 1.15% of live births.
For infants exposed to lithium during the first trimester, the risk of a major cardiac malformation increases to approximately 1.9% to 2.4%. This translates to an increased risk of about one additional case of a cardiac malformation per 100 live births. The risk for right ventricular outflow tract obstruction defects, which includes Ebstein’s anomaly, is specifically elevated compared to other defects.
The critical exposure window for this cardiac risk is the first trimester of pregnancy, specifically between the third and eighth weeks after conception. This is the period of organogenesis when the fetal heart is rapidly developing and is most vulnerable to teratogens. Lithium’s proposed biological mechanism involves interfering with cellular signaling pathways necessary for the proper development of heart cells.
The risk appears to be dose-dependent, meaning the incidence of malformations is higher at greater maternal lithium dosages. One study found that the risk ratio for cardiac malformations was substantially higher for daily doses exceeding 900 mg compared to doses of 600 mg or less. This dose-response relationship offers a potential target for risk mitigation through careful therapeutic drug monitoring.
Monitoring and Clinical Management During Pregnancy
Managing lithium treatment during pregnancy requires a coordinated approach between the psychiatrist, obstetrician, and patient, ideally beginning with pre-conception counseling. Counseling allows the care team to discuss the risks and benefits of continuing lithium versus switching to an alternative mood stabilizer, such as lamotrigine, or attempting temporary discontinuation. The high risk of maternal relapse upon stopping lithium must be carefully weighed against the potential fetal risks.
For women who continue lithium therapy into the first trimester, the standard screening tool to detect cardiac malformations is a fetal echocardiogram. This specialized ultrasound provides detailed images of the fetal heart structure and function. The fetal echocardiogram is typically performed between 18 and 22 weeks of gestation, allowing for the comprehensive assessment of cardiac development, including the tricuspid valve.
Clinical management involves frequent monitoring of maternal lithium blood levels, which often decrease significantly during pregnancy due to changes in kidney function and increased fluid volume. Clinicians must adjust the dosage to maintain a therapeutic level that prevents maternal mood episodes while minimizing fetal exposure. Dosage adjustments are often focused on keeping the daily dose below the 900 mg threshold, where the cardiac risk is observed to increase.
The goal is ensuring the mother’s mental stability while actively mitigating the specific risk of cardiac teratogenicity. In some cases, temporarily tapering or discontinuing lithium during the critical first trimester, followed by restarting it in the second trimester, may be considered. However, this strategy must be assessed on an individual basis due to the high risk of relapse.