Hydrochlorothiazide Safety in Pregnancy
Hydrochlorothiazide should be used during pregnancy only if clearly needed, as it crosses the placental barrier and carries risks of fetal/neonatal jaundice, thrombocytopenia, and other adverse reactions, though animal studies show no evidence of teratogenicity. 1
FDA Classification and Animal Data
- Hydrochlorothiazide is not assigned a specific FDA pregnancy category in the provided label, but falls under the principle that drugs should be used "only if clearly needed" during pregnancy 1
- Animal reproduction studies in pregnant mice and rats at doses up to 3,000 mg/kg and 1,000 mg/kg respectively showed no evidence of fetal harm during organogenesis 1
- However, no adequate and well-controlled studies exist in pregnant women, and animal studies are not always predictive of human response 1
Fetal and Neonatal Risks
Thiazides cross the placental barrier and appear in cord blood, creating direct fetal exposure 1. The specific risks include:
- Fetal or neonatal jaundice 1
- Thrombocytopenia 1
- Possibly other adverse reactions that occur in adults 1
Clinical Context: Diuretic Use Controversy
The use of diuretics during pregnancy remains controversial for several important reasons 2:
- Diuretics reduce plasma volume expansion, raising concern they might promote preeclampsia 2
- They should only be used in combination with other antihypertensive drugs, particularly when vasodilators cause fluid retention 2
- Diuretics are contraindicated when utero-placental perfusion is already reduced, such as in pre-eclampsia with fetal growth retardation 2
- If a diuretic is needed, a thiazide should be chosen over furosemide for chronic hypertension 2
Current Treatment Patterns
Recent data shows a significant shift away from hydrochlorothiazide use in pregnancy 3:
- Between 2008 and 2021, hydrochlorothiazide use among pregnant individuals with chronic hypertension decreased from 11% to 5% 3
- Labetalol replaced methyldopa as the most commonly used antihypertensive, increasing from 19% to 42% 3
- Nifedipine use also increased from 9% to 17% during this period 3
Preferred Alternatives
When antihypertensive treatment is needed during pregnancy, safer first-line options include 4, 5:
- Methyldopa - has the longest safety record with no evidence of adverse effects on mothers or babies, including long-term pediatric follow-up 2
- Labetalol - appears as effective and safe as hydralazine with fewer side effects 5
- Nifedipine - may be superior to hydralazine for severe hypertension 4
Critical Caveat
Only about 60% of individuals with chronic hypertension in pregnancy receive antihypertensive medications, despite evidence that treatment reduces adverse perinatal outcomes 3. When blood pressure exceeds 170/110 mmHg, there is significant risk of maternal cerebrovascular damage requiring urgent treatment 5.
Breastfeeding Considerations
Thiazides are excreted in breast milk 1. A decision must be made whether to discontinue nursing or discontinue hydrochlorothiazide, considering the drug's importance to the mother 1.