Effects of antihypertensive drugs on the unborn child: what is known, and how should this influence prescribing?

This review discusses the use of antihypertensive drugs in acute and long term treatment of hypertensive disorders of pregnancy, including their placental transfer and adverse effects on the fetus. All antihypertensive agents cross the placental barrier and are present in varying concentrations in the fetal circulation, with varying resultant effects on fetal metabolism. Antihypertensive drugs that are lipid soluble will pass through the placental barrier with ease whereas the most polar will not. Placental transfer diminishes under conditions that decrease the surface area or increase the thickness of the placenta. Highly protein-bound drugs form complexes which impair placental transfer while unbound drugs cross the placenta easily. The ionised drug form is highly charged and cannot cross lipid membranes while the un-ionised form can easily cross the placenta. A decrease in placental blood flow can slow down the transfer of lipid soluble drugs to the fetus. Close monitoring of the fetal and maternal condition is necessary for the rest of the pregnancy after antihypertensive therapy is commenced. Methyldopa is the initial drug of choice for long term oral antihypertensive therapy in pregnancy. Neither short term nor long term use of methyldopa is associated with adverse effects. In the short term (<6 weeks) beta-receptor antagonists are effective and well tolerated provided there are no signs of intrauterine growth impairment. ACE (angiotensin converting enzyme) inhibitors are contraindicated in the second and third trimesters of pregnancy because they are teratogenic. Intravenous dihydralazine is widely used for rapid reductions of severely elevated blood pressure. The use of nifedipine concurrently with MgSO4 must be approached with caution because the combination is associated with severe hypotension, neuromuscular blockade and cardiac depression. In the last decade, knowledge of antihypertensive drugs used in pregnancy has improved and new drugs, e.g. calcium antagonists, which have been shown to have great potential for use in pregnancy, have been introduced. Safety for the fetus with newer drugs has not yet been adequately evaluated. Currently, well established and cost effective drugs such as methyldopa (long term use) and intravenous dihydralazine (rapid reduction) are the agents of choice to treat hypertensive disorders of pregnancy.