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October 25, 2014

Choosing antihypertensive drugs during pregnancy

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Pregnancy and hypertensionAntihypertensive drugs are used during pregnancy to stabilise BP and prevent exacerbations in women with pre-existing chronic hypertension, gestational hypertension, or preeclampsia*.

  • ACE inhibitors must be avoided throughout pregnancy: During the 1st trimester, they increase the risk of cardiovascular and neurological information. During the second and third semester, they can lead to renal impairment, oligohydramnios, limb defects, craniofacial abnormalities and pulmonary hypoplasia. Women of child-bearing age must be warned of the risks associated with ACE inhibitors and effective means of contraception should be used.
  • Angiotensin II receptor blockers, despite a shorter follow up, have been linked to the same risk of malformations as with ACE inhibitors. Renin inhibitor aliskiren has a similar mechanism of action and therefore should not be used during pregnancy.
  • Beta-blockers, when taken shortly before delivery, can cause bradycardia and hypoglycaemia in the new-born. In addition, beta-blockers reduce placental perfusion, which may result in intra-uterine foetal death, immature and premature deliveries. Propranolol has been extensively used during pregnancy with adverse effects similar to all beta-blockers. While there is no evidence of associated teratogenicity, it should not be given during pregnancy unless its use is essential. Atenolol was associated with lower birth weight and therefore should be avoided during pregnancy. Evidence suggests that labetalol is less toxic to the unborn child.
  • Calcium channel blocker nifedipine has not been associated with birth defects in human. However, it should not be administered during pregnancy (especially during the first trimester) as it was found teratogenic in some animal species.
  • Thiazide diuretics have been used during pregnancy with no reported malformations, but the consequences of a water-electrolyte imbalance during pregnancy are unclear.
  • Methyldopa, a centrally active alpha-adrenergic agonist, has been extensively used during pregnancy with no reported foetal abnormalities. Methyldopa does cross the placental barrier and appears in cord blood so anticipated benefits should be weighed against possible risks.
  • Vasodilator hydralazine is not recommended during the first two trimesters, causing more frequent maternal hypotension, foetal cardiac arrhythmias, and Caesarean sections. However, the drug may be employed in later pregnancy if there is no safer alternative or when the disease itself carries serious risks for the mother or child, e.g. pre-eclampsia or eclampsia.
  • The consequences of the use of other hypertensive drugs during pregnancy haven’t been fully investigated.

Moreover, little is known of the long-term effects of antihypertensive drugs on children exposed in utero.

Key message: Methyldopa has been extensively used for the treatment of hypertension in pregnancy with the longest safety record. Labetalol is an antihypertensive treatment of choice during pregnancy. Hydralazine may be use in the third trimester. Angiotensin-converting enzyme inhibitors, angiotensin II antagonists and aliskiren should be avoided due to the risks of malformation and toxicity for the foetus.

*High BP (≥140/90 mmHg) after 20 weeks of pregnancy is generally due to gestational hypertension, which is a placental disorder. Pre-eclampsia (failure of blood supply to the placenta) is confirmed when there are other symptoms, particularly protein in the urine. Pre-eclampsia can lead to severe complications for the mother (damage to various organs, risk of stroke, etc.) and the infant (especially growth retardation). BP should be monitored for each antenatal visit and after birth.

Reference: Prescrire International Feb 2011; 20(113) p.50-51.