What are the risks of using clonidine (antihypertensive medication) during pregnancy?

Clonidine Use During Pregnancy: Risks and Considerations

Clonidine can be used during pregnancy with caution, as limited evidence suggests it is likely not associated with adverse pregnancy outcomes, though monitoring for potential maternal and fetal effects is essential. 1

Safety Profile in Pregnancy

• Studies documenting clonidine use during pregnancy for hypertension or hyperemesis gravidarum have found no increased risk for major or minor malformations 2
• FDA classifies clonidine as Pregnancy Category C, indicating that animal studies have shown adverse effects on the fetus, but there are no adequate well-controlled studies in humans 3
• In animal studies, clonidine was associated with increased resorptions in rats at doses as low as ⅓ the maximum recommended human dose when dams were treated continuously before mating 3

Maternal and Fetal Considerations

• Maternal hemodynamic response to clonidine is heterogeneous and can impact fetal growth:

  • Women who experience decreased cardiac output rather than decreased vascular resistance have higher rates of low birth weight infants 4
  • Monitor fetal growth in women taking clonidine, particularly those who experience a reduction in heart rate after initiating therapy 4

• For pregnant individuals with diabetes and chronic hypertension, clonidine is among the antihypertensive drugs known to be effective and safe in pregnancy 2

• Blood pressure goals during pregnancy should be 110-135/85 mmHg to reduce risk of unmanaged maternal hypertension while minimizing impaired fetal growth 2

Dosing and Administration

• Starting dose: 0.05-0.1 mg at bedtime
• Titration: Increase by 0.1 mg BID-TID to a maximum of 0.4 mg per day 2
• Monitor maternal vital signs due to risk of hypotension and bradycardia 1

Specific Risks and Case Reports

• One isolated case report linked clonidine use throughout pregnancy for hypertension with Roberts syndrome in an infant, though causality is uncertain 2, 5
• Potential for delayed manifestation of adverse effects - some fetal abnormalities with clonidine have been reported to occur after several months 6

Breastfeeding Considerations

• Clonidine is excreted in human milk and is detectable in infant serum following exposure via breastfeeding 2
• Milk-to-plasma ratio is approximately 2 with a relative infant dose up to 7.1% 2
• One case report described an infant developing drowsiness, hypotonia, suspected generalized seizures, and episodes of apnea when exposed to 0.15 mg daily during pregnancy and early postpartum 2
• Symptoms resolved within 24 hours of breastfeeding cessation 2
• Breastfed infants should be monitored for drowsiness, hypotonia, jitteriness, sedation, and seizures 1

Clinical Recommendations

1. Consider alternative antihypertensives with more safety data in pregnancy first (methyldopa, labetalol, nifedipine) 2
2. If clonidine is necessary, use the lowest effective dose
3. Monitor maternal blood pressure and heart rate regularly
4. Perform regular fetal growth assessments, especially if maternal heart rate decreases after starting therapy
5. Avoid abrupt discontinuation as it may induce hypertensive crisis 1

In comparative studies, clonidine has demonstrated similar safety and efficacy to methyldopa in pregnancy, with 98% neonatal survival rates 7, supporting its use when clinically indicated.