NU677 Unit 4 Lithium in Pregnancy Risk-Benefit Example

Six Weeks Pregnant After Nine Stable Years on Lithium: A Perinatal Risk-Benefit Paper for a 32-Year-Old Whose Last Untreated Episode Was Psychotic Mania

[Student Name]

Purdue University Global

NU677: PMHNP Diagnosis and Management Across the Lifespan III

Unit 4 Perinatal Risk-Benefit Paper

[Instructor Name]

[Date]

The patient is composite; doses, levels and dates are bracketed.

The Patient

Dr. [F.], [32], is a field wildlife biologist with bipolar I disorder diagnosed at [21]. She had two manic episodes before lithium, the second with psychosis and a [three]-week hospitalization. She has been well on lithium carbonate [900] mg daily, level [0.7] mmol/L, for nine years. She and her partner had not planned a pregnancy but want to continue it. She called the clinic the day of her positive test, at about [six] weeks after her last menstrual period. Her question: "Do I have to stop lithium to protect the baby?"

What Lithium May Do to the Pregnancy

The historical fear was of Ebstein's anomaly, a rare heart defect. More recent large studies put the risk in proportion. In a cohort of over a million pregnancies, cardiac malformations occurred in [2.41] percent of infants exposed to lithium in the first trimester compared with [1.15] percent of unexposed infants, an adjusted risk ratio of [1.65]; the risk rose with dose, with no clear increase at [600] mg a day or less and a risk ratio of about [3.2] above [900] mg (Patorno et al., 2017). A meta-analysis of cohort data found that first-trimester lithium exposure was associated with more major malformations, [7.4] percent against [4.3] percent, and with more neonatal readmissions, but not with other pregnancy complications (Munk-Olsen et al., 2018).

At six weeks, she is already within the period when the heart is forming. Stopping lithium now would reduce exposure for the remaining weeks of organ development but cannot undo exposure that has already occurred.

What Stopping Lithium May Do to Her

The risk of relapse is high. A meta-analysis of postpartum relapse in women with bipolar disorder found relapse rates of [66] percent among women who were medication-free during pregnancy compared with [23] percent among those who continued prophylactic medication (Wesseloo et al., 2016). Her history makes the stakes higher still: her last untreated episode was psychotic mania requiring hospitalization. A manic or psychotic episode in pregnancy carries its own risks to her and the baby, from poor self-care and sleep to impulsive behavior and loss of the ability to plan for the birth, and postpartum psychosis can endanger both mother and child.

The drug's added risk is a few percentage points of malformation, much of it already incurred by week six; the illness's risk, if lithium stops, is a relapse that is more likely than not.

Her Work and Her Pregnancy

Her job adds practical considerations that matter to the plan. She spends days at a time at remote field sites with limited phone signal, often in heat, which raises the risk of dehydration and therefore of a rising lithium level. She and her supervisor agreed that she would not do solo field work in the third trimester, would carry extra water and electrolyte drinks, and would schedule her lithium blood tests around field trips. Her partner was taught the signs of lithium toxicity, such as worsening tremor, vomiting, diarrhea, unsteadiness and confusion, and knows to take her to an emergency department if they appear. These steps are not in the pregnancy studies, but they follow directly from them: the level must stay steady for the benefit to hold and the risk to stay low.

What She Was Told About the Numbers

Numbers were given as absolute risks as well as ratios, because a risk ratio of 1.65 sounds larger than it is. In the large cohort, about 2 or 3 babies in 100 exposed to lithium had a heart malformation, compared with about 1 in 100 unexposed; at the dose she will now take, the added risk may be smaller still. On the other side, about 2 in 3 women with bipolar disorder who were off medication in pregnancy relapsed after delivery, compared with about 1 in 4 who stayed on it. She said the second pair of numbers decided it for her, because she remembered what the last relapse had done to her and did not want her baby's first months to look like that.

Options Discussed

1. Continue lithium at the lowest effective dose.

2. Stop lithium now and restart in the second trimester or after delivery.

3. Switch to another medication, such as an antipsychotic with more reproductive safety data, accepting the risk of relapse during the switch and the uncertainty of response.

Her Decision and the Plan

Dr. [F.] chose to continue lithium. The plan:

1. Reduce the dose to the lowest level that has kept her well, aiming for [0.6] mmol/L, and split it into [two or three] daily doses to lower peak levels.

2. Detailed anatomy ultrasound and fetal echocardiography at [18 to 22] weeks.

3. Lithium levels every [four] weeks in the first two trimesters and every [one to two] weeks in the third, since kidney clearance rises in pregnancy and falls abruptly after delivery.

4. Delivery plan with obstetrics: attention to hydration, a level on admission, holding or reducing the dose at the onset of labor, and restarting after delivery with close level monitoring.

5. Postpartum: frequent visits in the first weeks, sleep protection with her partner handling night feeds, and a relapse plan with early warning signs.

6. Infant: pediatric team informed; monitoring of the newborn for lithium effects. Breastfeeding discussed as a separate decision.

7. Folic acid continued.

If She Had Chosen Differently

Had she chosen to stop lithium, the plan would not have been to stop abruptly, which raises the risk of early mania. A gradual reduction over several weeks, weekly visits, sleep protection and a plan to restart promptly at the first warning sign would have been offered, with the understanding that restarting in the second trimester, after the heart has formed, carries less malformation risk. Had she chosen to switch, an antipsychotic would have been started first and lithium reduced only once she was stable on it. Each choice was described with its own plan, so that the one she chose was not the only one explained in detail.

Limits of the Evidence

The malformation studies are observational, and even large cohorts cannot fully separate the effect of lithium from that of the illness or other exposures. The relapse figures come from pooled studies with varied definitions. Her own risk may differ from the averages. The decision was hers, made with these limits explained.

References

Munk-Olsen, T., Liu, X., Viktorin, A., Brown, H. K., Di Florio, A., D'Onofrio, B. M., Gomes, T., Howard, L. M., Khalifeh, H., Krohn, H., Larsson, H., Lichtenstein, P., Taylor, C. L., Van Kamp, I., Wesseloo, R., Meltzer-Brody, S., Vigod, S. N., & Bergink, V. (2018). Maternal and infant outcomes associated with lithium use in pregnancy: An international collaborative meta-analysis of six cohort studies. The Lancet Psychiatry, 5(8), 644-652. https://doi.org/10.1016/S2215-0366(18)30180-9

Patorno, E., Huybrechts, K. F., Bateman, B. T., Cohen, J. M., Desai, R. J., Mogun, H., Cohen, L. S., & Hernandez-Diaz, S. (2017). Lithium use in pregnancy and the risk of cardiac malformations. New England Journal of Medicine, 376(23), 2245-2254. https://doi.org/10.1056/NEJMoa1612222

Wesseloo, R., Kamperman, A. M., Munk-Olsen, T., Pop, V. J. M., Kushner, S. A., & Bergink, V. (2016). Risk of postpartum relapse in bipolar disorder and postpartum psychosis: A systematic review and meta-analysis. American Journal of Psychiatry, 173(2), 117-127. https://doi.org/10.1176/appi.ajp.2015.15010124