Chlorthalidone Use in Pregnancy
Chlorthalidone should generally not be used during pregnancy, as diuretics are not recommended for blood pressure control in pregnant women with diabetes or hypertension, though it may be used safely at lower doses in specific circumstances such as chronic kidney disease with reduced glomerular filtration rate. 1
Primary Guideline Recommendations
The American Diabetes Association explicitly states that diuretic use during pregnancy is generally not recommended, though acknowledges it may be used safely when prescribed at lower doses for individuals in certain circumstances (e.g., chronic kidney disease and reduced glomerular filtration rate). 1
The 2022 American Diabetes Association guidelines state that chronic diuretic use during pregnancy is not recommended as it has been associated with restricted maternal plasma volume, which may reduce uteroplacental perfusion. 1
FDA Classification and Safety Data
The FDA classifies chlorthalidone as Pregnancy Category B, meaning reproduction studies in rats and rabbits at doses up to 420 times the human dose revealed no evidence of harm to the fetus. 2 However, the FDA label emphasizes several critical caveats:
- Thiazides cross the placental barrier and appear in cord blood 2
- Potential fetal hazards include fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that have occurred in adults 2
- The anticipated benefits must be weighed against possible hazards to the fetus 2
Clinical Context for Use
The FDA label specifically addresses when chlorthalidone might be appropriate in pregnancy:
- The routine use of diuretics in an otherwise healthy pregnant woman is inappropriate and exposes mother and fetus to unnecessary hazard 2
- Diuretics do not prevent development of toxemia of pregnancy 2
- Chlorthalidone is indicated in pregnancy only when edema is due to pathologic causes 2
- Dependent edema from the expanded uterus should be treated with elevation and support hose, not diuretics 2
Preferred Alternatives for Hypertension in Pregnancy
The American Diabetes Association identifies the following as safe and effective antihypertensive drugs in pregnancy:
- First-line agents: methyldopa, nifedipine (long-acting), and labetalol 1, 3
- Alternative safe options: clonidine, diltiazem, and prazosin 1, 3
- Atenolol should be avoided due to associations with fetal growth restriction 3
Mechanism of Concern
The European Society of Cardiology explains that diuretics reduce plasma volume expansion, which may promote preeclampsia, and should only be used in combination with other antihypertensive drugs, particularly when vasodilators cause fluid retention. 4 Diuretics are contraindicated when utero-placental perfusion is already reduced. 4
Blood Pressure Targets in Pregnancy
When treating hypertension in pregnant women with diabetes, target blood pressure of 110-135/85 mmHg to balance reducing maternal hypertension risk against minimizing fetal growth impairment. 1, 3
Common Pitfalls to Avoid
- Do not use diuretics for routine management of pregnancy-related edema or hypertension 2
- Do not confuse physiologic hypervolemia of normal pregnancy (which is beneficial) with pathologic fluid retention 2
- If chlorthalidone was used before pregnancy recognition, reassure that Category B classification suggests low teratogenic risk, but switch to preferred agents 2
- Remember that chlorthalidone is excreted in breast milk, requiring consideration of discontinuing nursing or the drug 2
When Chlorthalidone Might Be Considered
The only scenario where chlorthalidone use may be justified is in pregnant women with chronic kidney disease and reduced glomerular filtration rate who require diuretic therapy at lower doses for volume management. 1 Even in this circumstance, the decision requires careful weighing of maternal benefits against potential fetal risks.