Why does lithium level decrease at 32 weeks gestation in a pregnant patient?

Why Lithium Levels Decrease at 32 Weeks Gestation

Lithium levels decrease at 32 weeks gestation primarily because glomerular filtration rate (GFR) increases by 30-50% during late pregnancy, dramatically accelerating renal lithium clearance and lowering serum concentrations despite stable dosing. 1, 2

Primary Mechanism: Enhanced Renal Clearance

The fundamental driver of declining lithium levels in late pregnancy is the marked increase in maternal renal function:

• Glomerular filtration rate increases by approximately 40% during pregnancy to accommodate fetal detoxification and expanded maternal blood volume 3
• Lithium clearance specifically increases by 30-50% during the last months of pregnancy, directly mirroring the rise in GFR 2
• Lithium is almost exclusively excreted via the kidney as a free ion, making it uniquely vulnerable to changes in renal function 2
• Dose-adjusted serum lithium concentrations in the third trimester are 34% lower than baseline (95% CI: -44% to -23%) 1

Timing and Trajectory of Lithium Level Changes

The decline follows a predictable pattern throughout gestation:

• First trimester: 24% decrease in lithium blood levels compared to baseline 4
• Second trimester: 36% decrease (the nadir of lithium concentrations) 4
• Third trimester (including 32 weeks): 21% decrease, representing a partial recovery from the second-trimester nadir but still substantially below baseline 4

At 32 weeks specifically, this decline coincides with peak cardiac output (30-50% above baseline) and maximum plasma volume expansion (40% increase), both of which contribute to the heightened renal perfusion driving lithium clearance 5, 3.

Contributing Physiological Factors Beyond GFR

Several pregnancy-related hemodynamic changes compound the effect on lithium levels:

• Renal blood flow increases by 40% during pregnancy, further enhancing drug clearance 3
• Cardiac output peaks between 24-32 weeks gestation, delivering more blood to the kidneys per unit time 5
• Expanded intravascular volume (40% increase by 24 weeks) creates a larger volume of distribution, though this effect is modest compared to enhanced clearance 5, 3

Clinical Implications for Dosing

To maintain therapeutic lithium concentrations during the third trimester, doses generally need to be increased by approximately 50% 1. However, individual variability is substantial:

• Close monitoring is essential: lithium levels should be checked weekly until 34 weeks, then weekly until delivery 4
• Creatinine levels should be measured concurrently to monitor renal clearance changes 4
• Dose adjustments must be individualized based on serial lithium measurements, as the magnitude of decline varies considerably between patients 1

Critical Postpartum Consideration

Lithium clearance normalizes rapidly after delivery, creating acute toxicity risk if the elevated third-trimester dose is continued postpartum 4, 6:

• Lithium dose should be reduced with the onset of labor to prevent maternal and neonatal toxicity 6
• Postpartum lithium levels remain slightly elevated (+9% above baseline) for at least 2 weeks, requiring twice-weekly monitoring during this period 4
• Delivery itself does not cause an acute change in lithium or creatinine levels, but the subsequent rapid decline in GFR over days to weeks necessitates dose reduction 4

Common Pitfall to Avoid

Do not assume lithium levels remain stable throughout pregnancy—the 34% average decline in third-trimester levels means that maintaining the pre-pregnancy dose will result in subtherapeutic concentrations and potential relapse of bipolar disorder 1. Conversely, failing to reduce the dose postpartum risks severe lithium toxicity in both mother and neonate 6.