Lithium is an important treatment option for women with bipolar disorder. Because women with bipolar disorder are at high risk for relapse during the postpartum period, we typically recommend that women continue treatment with lithium throughout the postpartum period. While this intervention clearly decreases risk for postpartum psychiatric illness, the use of lithium while breastfeeding presents certain challenges.
All medications taken by the mother are secreted into the breast milk. The concentration of a particular medication found in breast milk is determined by multiple factors. Women have historically been instructed to avoid breastfeeding while taking lithium based on early reports suggesting high levels of lithium in the breast milk and several cases of lithium toxicity in nursing infants (Schou 1973). While the American Academy of Pediatrics guidelines are less restrictive in their current recommendations, they do urge caution.
Studies quantifying the level of lithium exposure and the risks of lithium exposure in nursing infants are sparse. Based on studies measuring the amount of lithium in breast milk in a case series of 11 mothers, researchers estimated that the average dosage of lithium in an exclusively breastfed infant would be 12.2% (range 0 to 30%) of the maternal weight-adjusted dosage (Moretti et al, 2003). Peak levels occur within 1 to 3 hours after ingestion of standard preparations and within 4 to 4.5 hours with the slow and extended release forms.
Few studies have directly measured lithium levels in the nursing infant. The largest study to date comes from Dr. Adele Viguera derived from a research project carried out at the MGH Center for Women’s Mental Health. Ten women taking lithium and their nursing infants were evaluated. Lithium levels in milk, as well as infant and maternal serum levels of lithium, were measured at approximately 6 weeks postpartum. Infant thyroid and renal function were also assessed.
In this group of women, lithium carbonate dose averaged 841 mg/day (range 600-1200 mg/day). The average lithium concentration in breast milk was 0.36 ± 0.11 mmol/L (range <0.1 – 0.51) or 51% (range 17%-73%) of the maternal serum levels (average of 0.72 ± 0.22 mmol/L, range 0.41 – 1.16). Corresponding infant serum levels averaged 0.15 ± 0.07 mmol/L (range 0.09-0.30). Eight of the 10 infants had levels below 0.2 mmol/L. There were no adverse events reported in 9 of the 10 infants; one infant had slightly elevated TSH (thyroid stimulating hormone) that soon normalized after the mother discontinued lithium treatment.
Although the sample size in this study was relatively small, it is thus far the largest systematic study quantifying exposure to lithium in infants nursed by mothers taking lithium. While early reports raised concerns regarding exposure to high levels of lithium in nursing infants, this study suggests that serum lithium levels in nursing infants were relatively low and, on average, were about 25% of maternal levels.
What is the Risk of Adverse Events?
Given the small number of exposed infants included in the medical literature, and the fact that many of these are case reports, it is impossible to quantify the risk of adverse events in nursing infants. The information we do have suggests that adverse events are more likely to occur if lithium levels are high. Two cases in the literature indicate symptoms of lithium toxicity developing as a result of dehydration; the first case was associated with maternal use of a diuretic, the second case developed after the baby had an upper respiratory infection.
There have been several reports of elevated TSH in infants exposed to lithium via breast milk. There have also been two reports of altered renal function. Other adverse events include lethargy, decreased muscle tone and inadequate weight gain.
Reviewing the Options for Postpartum Treatment
For women with bipolar disorder, the postpartum period is a time of increased vulnerability to severe psychiatric illness, including postpartum depression and psychosis. To minimize the risk of postpartum illness, we typically recommend that women continue treatment with lithium, or some type of mood stabilizer, throughout the postpartum period. Based on the information we have regarding lithium and breastfeeding, some women may elect to continue lithium but plan to bottle feed their infant rather than breastfeed.
Given the many benefits of breastfeeding, some women taking lithium may wish to breastfeed their infants, either partially or exclusively. A woman who is stable on lithium and wishes to breastfeed has a number of options to consider as she approaches the postpartum period.
Switching to another mood stabilizer: After delivery, a woman may choose to discontinue lithium and switch to a different mood stabilizer. But there are risks which must be considered. Changing or stopping medications at a time known for a high risk of relapse is not advisable for many women with serious illness. Furthermore, a woman who responds to lithium may not respond to another mood stabilizer. Additionally, for many mood stabilizers, safety data for breastfeeding are lacking. There are some limited data available for anticonvulsants, but even less data for atypical antipsychotic medications.
Continuing lithium while breastfeeding: A woman taking lithium in the postpartum period who does plan to breastfeed may choose either to breastfeed exclusively or to compromise by partially breastfeeding and supplementing with formula. Viguera and colleagues note that whether a woman on lithium is breastfeeding exclusively or partially, there are a number of factors that she must consider.
Breastfeeding might be a reasonable option if the following criteria are met:
- Stable maternal mood
- Lithium monotherapy (or a simple medication regimen)
- A healthy, full-term infant
- Adherence to infant monitoring guidelines
- A collaborative pediatrician who is supportive of the mother’s decision and who understands the importance of infant monitoring
Monitoring of Nursing Infants
Infants exposed to lithium via breast milk are vulnerable to the same side effects as adults, including changes in thyroid and renal functioning; thus, close clinical monitoring of infants exposed to lithium through breast milk is recommended. This monitoring should include measurement of lithium levels, TSH, BUN and creatinine while the child is nursing.
Guidelines, however, differ on the frequency of infant monitoring. Based on a systematic review, Imaz and colleagues (2019) recommend that in cases where the mother is treated with lithium during pregnancy, infant lithium level, TSH, and BIN should be assessed at the time of delivery, at 48 hours postpartum and 10 days postpartum. In women who initiate lithium at the time of delivery, testing should occur in the infant at 10 days postpartum. Further monitoring is recommended only if the infant’s lithium level is greater than 0.3 mEq/L or if clinical signs of toxicity appear. (The cutoff of 0.3 mEq/L is based on the finding that most infants with levels below 0.3 mEq/L do not have adverse effects.)
However, others recommend close pediatric follow-up of the infant in combination with more frequent laboratory monitoring (i.e., serum lithium, TSH, BUN). For example, Viguera and colleagues recommend testing during the immediate postpartum period and then every 8-12 weeks if the initial testing is normal. Whatever frequency of testing is indicated, access to an experienced pediatric phlebotomist is important to facilitate blood testing.
Blood tests are indicated if the infant exhibits unusual behavior or signs of lithium toxicity, including lethargy or sedation, restlessness, feeding difficulties, or abnormal growth and development. In addition, the mother must be educated regarding signs of dehydration in the infant. Any fever and/or signs of infection warrant heightened vigilance as they may cause dehydration and increase risk for lithium toxicity in the infant.
Other Considerations in Postpartum Women with Bipolar Disorder
Aside from concerns related to infant exposure to lithium, many clinicians emphasize the risk to maternal mood posed by sleep disturbance. Although it has not been well studied in this population, it is believed that sleep deprivation can trigger mood episodes in postpartum women with bipolar disorder. Formula feeding or supplementing with formula enables others to participate in nighttime feeds and may protect a mother’s sleep.
Ruta Nonacs, MD PhD
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Lithium Drugs and Lactation Database (LactMed)