Consider Both the Unborn Child and the Mother When Treating Hypertension in Pregnancy

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Oral Drugs for Mild/Moderate Hypertension

There is no clear consensus on the management of mild to moderate hypertension in pregnancy to optimise pregnancy outcomes.[4] Nevertheless, national hypertension societies of the US, Canada and Australasia all list methyldopa, labetalol and long-acting nifedipine as acceptable oral antihypertensive agents if drug therapy is required in pregnant women with mild to moderate hypertension.[4,5,6] Some of the most commonly used antihypertensive medications in pregnancy and suggested dosage regimens are provided in table 2 .

Methyldopa is a drug of first choice for control of mild to moderate hypertension in pregnancy and is the most widely prescribed antihypertensive for this indication in several countries, including the US and the UK.[1,2] The wide use of this drug in pregnancy reflects the fact that it has the best documented maternal and fetal safety record, including favourable long term (4.5 to 7.5 year) paediatric follow-up data.[1] During long term use in pregnancy, methyldopa does not alter maternal cardiac output or blood flow to the uterus or kidneys,[1,2] and for all these reasons is generally considered the agent of choice for chronic blood pressure control in pregnancy.[1]

The combined and ß-adrenoceptor blocker labetalol is a peripheral vasodilator which has been shown to be effective in pre-eclamptic and non-proteinuric hypertension in pregnancy.[1] Available data suggest that the antihypertensive effect is not associated with compromised renal or uterine blood flow.[1] In a randomised comparative trial of 263 pregnant women with mild to moderate hypertension, treatment with either labetalol or methyldopa achieved significantly lower maternal blood pressures throughout gestation compared with no medication, and there were no differences among the 3 groups with respect to various clinical outcomes (e.g. gestational age at delivery, birthweight, fetal growth retardation).[7] However, because the safety record of labetalol in pregnancy is not as well established as that of methyldopa, labetalol should probably be considered a second-line agent for pregnant women with chronic hypertension requiring long term drug therapy.[1]

While earlier studies suggested that administration of ß-blockers (particularly those without intrinsic sympathomimetic activity[8]) during pregnancy might increase the chance of intrauterine growth retardation, recent studies have been more reassuring on this point.[1] Nevertheless, the available data are insufficient to rule out unrecognised adverse effects of early and prolonged use of ß-blockers in pregnancy. When used for short periods (<6 weeks) during the third trimester, ß-blockers are effective and well tolerated provided there are no signs of intrauterine growth impairment.[1]

Use of the cardioselective ß-blocker atenolol early in pregnancy in women with chronic hypertension has been shown to result in significantly lower birthweights compared with placebo and other antihypertensive agents.[9,10] The results of these and other studies indicate that treatment with atenolol is associated with fetal growth impairment and that this effect is related to duration of therapy.[9,10,11] Thus, atenolol should be avoided in early pregnancy and used only with caution in later pregnancy;[1] some advise avoidance of atenolol altogether in pregnancy.[2]

When administered in late pregnancy, oral calcium antagonists have been shown to reduce maternal blood pressure in pregnant women with mild to moderate hypertension, including those with pre-eclampsia, without apparent adverse fetal or perinatal effects.[1,2] However, little is known about the effects of long term administration of these drugs in pregnant women, particularly in the first trimester.[1] Among the calcium antagonists, nifedipine has been the best studied in pregnancy and the drug has been used extensively in later pregnancy.[1,2]

Oral hydralazine, a direct vasodilator, is effective as monotherapy or as add-on therapy to methyldopa in the long term management of chronic hypertension in pregnancy.[1] Hydralazine appears to be reasonably safe for the fetus although a few cases of fetal thrombocytopenia have been reported.[1] In general, effective long term antihypertensive therapy with hydralazine (e.g. for chronic hypertension in pregnancy) often requires combination therapy (typically with a sympatholytic agent such as methyldopa or a ß-blocker) and such combinations also help attenuate reflex sympathetic activation associated with hydralazine.[2]

Administration of ACE inhibitors during the second and third trimesters can result in a number of fetal adverse effects, including growth retardation, renal failure, persistent patent ductus arteriosus, respiratory distress syndrome, fetal hypotensive syndrome, and prepartum death.[12] Although the magnitude of the risk is unknown, these agents are contraindicated in at least the second and third trimesters.[1,2] Furthermore, while ACE inhibitors may be safe in early pregnancy, women taking these agents should be warned about the possible risks of this class of drugs in pregnancy and advised to discontinue ACE inhibitor therapy before or when they become pregnant.[1] Since the teratogenic risk of ACE inhibitors is thought to be related to a direct pharmacological effect of the drugs on fetal physiology, angiotensin II receptor antagonists are also not recommended in pregnancy.[1,2]

While diuretics have been reported to prevent pre-eclampsia by reducing blood pressure, they are rarely prescribed as antihypertensive agents during pregnancy because they reduce maternal plasma volume and can cause electrolyte disturbances.[1]

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