Are diuretics, such as hydrochlorothiazide (thiazide diuretic), safe to use during pregnancy?

Diuretics in Pregnancy: Safety Considerations

Diuretics should generally be avoided during pregnancy unless there is a specific medical indication such as heart failure symptoms or volume overload, as they may reduce plasma volume expansion and potentially compromise uteroplacental perfusion. 1

General Safety Considerations

• Thiazide diuretics like hydrochlorothiazide are not recommended for routine use during pregnancy as they may reduce normal plasma volume expansion, potentially increasing the risk of pre-eclampsia 1
• The FDA label for hydrochlorothiazide specifically states: "The routine use of diuretics in an otherwise healthy woman is inappropriate and exposes mother and fetus to unnecessary hazard" 2
• Diuretics do not prevent development of toxemia (pre-eclampsia) of pregnancy, and there is insufficient evidence supporting their use in treating developed toxemia 2

Specific Clinical Scenarios

When Diuretics May Be Considered

• Diuretics may be reasonable for pregnant patients with mitral stenosis who develop heart failure symptoms (stage D) 1
• Furosemide has been used safely in pregnancy complicated by renal or cardiac failure 1
• In late-stage pregnancy, diuretics may be used if needed for volume control, but not as first-line agents for blood pressure control 1

When Diuretics Should Be Avoided

• Diuretics are contraindicated when utero-placental circulation perfusion is already reduced, such as in pre-eclampsia with fetal growth retardation 1
• Chronic diuretic use during pregnancy is not recommended as it has been associated with restricted maternal plasma volume, which may reduce uteroplacental perfusion 1

Evidence on Fetal Outcomes

• Recent data from the Registry Of Pregnancy And Cardiac disease (ROPAC) did not conclusively establish an association between diuretic use during pregnancy and adverse fetal outcomes 3
• However, older research has suggested potential risks, including a study that found prenatal exposure to diuretics and maternal hypertension might disrupt fetal neurodevelopment 4
• A Cochrane review found insufficient evidence to draw reliable conclusions about the effects of diuretics on prevention of pre-eclampsia and its complications 5

Preferred Alternatives for Hypertension in Pregnancy

• Methyldopa remains the first-line agent for hypertension in pregnancy due to its established safety record 1
• Labetalol (an alpha-beta blocker) is also considered safe and effective 1
• Calcium channel blockers, mainly nifedipine, can be used but should be administered with caution 1
• ACE inhibitors and angiotensin receptor blockers are contraindicated during pregnancy due to risk of fetal renal dysplasia and other complications 1

Clinical Decision Algorithm

1. For pregnant women with hypertension without volume overload:

   • First-line: Methyldopa or labetalol 1
   • Second-line: Calcium channel blockers 1
   • Avoid diuretics as primary treatment 1, 2

2. For pregnant women with heart failure symptoms or volume overload:

   • Consider diuretics (preferably loop diuretics like furosemide) as adjunctive therapy 1
   • Monitor closely for maternal and fetal effects 1

3. For pregnant women with pre-eclampsia:

   • Diuretics are contraindicated due to already reduced plasma volume 1
   • Focus on other antihypertensive medications and timely delivery if necessary 1

Important Monitoring Considerations

• If diuretics must be used, close maternal and fetal surveillance is essential 1
• Monitor for electrolyte imbalances, particularly hypokalemia, which is more common in women taking diuretics 1
• Assess fetal growth regularly, as diuretics may potentially affect placental perfusion 1

Remember that while diuretics may be necessary in specific clinical scenarios, their use should be carefully considered against potential risks, and they should not be used routinely for managing uncomplicated hypertension or physiologic edema in pregnancy 2.