5.3 Chronic Hypertension in Pregnancy A. Definition of the Problem Hypertension is the most common medical disorder during pregnancy. The hypertensive disorders of pregnancy are usually divided into chronic hypertension, preeclampsia/eclampsia, preeclampsia superimposed on chronic hypertension, and gestational hypertension. Chronic hypertension is defined as the presence of sustained hypertension before 20 weeks gestation. Most pregnant women with hypertension have preeclampsia, but chronic hypertension may affect up to 1/3 of pregnant women with hypertension, or about 120,000 pregnancies a year in the US. Women with chronic hypertension have a significantly increased risk of developing superimposed preeclampsia, and a risk of maternal and fetal morbidity and mortality. There is no systematic evidence supporting a treatment approach to these women. B. Current State of the Science NHLBI’s 2000 Working Group Report on High Blood Pressure in Pregnancy defined chronic hypertension as a systolic blood pressure of at least 140 mmHg, or a diastolic blood pressure of at least 90 mmHg on more than one occasion. Most women with chronic hypertension in pregnancy have mild to moderate hypertension, and are at low risk for adverse cardiovascular or perinatal events. There is no evidence that pharmacological treatment results in improved outcomes in this situation, and the normal decreased systemic vascular resistance during pregnancy may normalize their blood pressures. Much of the increased risk associated with chronic hypertension occurs in the 25% of such pregnancies in which superimposed preeclampsia develops. This combination significantly increases both maternal and fetal risks, which are further exacerbated if renal disease is also present. In the extreme situation of pregnancy after renal transplantation, fetal prematurity occurs in more than half of all pregnancies. Maternal complications include placental abruption, stroke, pulmonary edema, hypertensive encephalopathy, retinopathy, acute renal failure, and death; fetal complications include, in addition to prematurity, low birth weight and perinatal death. Treatment of chronic hypertension in pregnancy requires balancing risks and benefits to both mother and fetus. For women with mild hypertension and no other risk factors, the preponderance of scientific evidence suggests that drug treatment during pregnancy confers little benefit and is not likely to be necessary. There has been at least one small study that identified an increase in fetal complications (low birth weight) in women treated with an antihypertensive agent. For women with severe hypertension, placebo-controlled trials have not been performed due to ethical considerations, but there also are not good studies comparing therapeutic agents in different classes in this population. Neither have there been studies of treatment of hypertension in pregnant women with other risk factors, such as pre-existing renal disease, diabetes mellitus, cardiac disease, or sleep-disordered breathing. Information about safety of antihypertensive drugs for the fetus in humans is limited, except for a specific proscription against the use of angiotensinconverting enzyme inhibitors and angiotensin II receptor blockers in the second or third trimester 49 due to known renal anomalies that develop in the fetus. C. Ongoing Activity The Institute currently supports no studies of chronic hypertension in pregnancy. D. Proposal One of the priority recommendations of the Working Group on Research on Hypertension During Pregnancy in 2001 was for a randomized clinical trial of antihypertensive medications in pregnancy to evaluate blood pressure control, fetal growth and safety, and genetic variation in response to therapy. This recommendation has not been implemented, and should be strongly considered.

Exposure to ARBs for a period longer than the first trimester of pregnancy appears to be associated with a high risk for adverse fetal outcomes.

[Hypertension in pregnancy]

Service de médecine communautaire, Département de médecine interne, HUG, 1211 Genève 14.

Hypertension affects approximately 10% of all pregnancies and may jeopardize maternal and fetal health. Chronic hypertension must be distinguished from pre-eclampsia, that can be associated with a bad outcome. An antihypertensive treatment is advocated when systolic blood pressure is > or = 160 mmHg or diastolic blood pressure is > or = 110 mmHg. Hospitalisation is mandatory if there is an associated proteinuria. Labetalol, nifedipine and methyldopa are the commonly used blood-pressure lowering drugs and they are considered safe during pregnancy. Angiotensin converting enzymes inhibitors and angiotensin II receptor blockers are contraindicated, even during the first trimester of pregnancy. The prescription of diuretics during pregnancy should be avoided.

Antihypertensive drugs in pregnancy.

When mean arterial pressure exceeds 140 mmHg (equivalent to 180/120), there is a significant risk of maternal cerebral vascular damage. Therefore it is recommended that blood pressures greater than 170/110 should be treated with urgency, aiming to maintain the blood pressure at all times at less than 170/110 but not lower than 130/90. Parenteral hydralazine is effective and safe therapy. Labetalol (intravenously or orally) appears to be as effective and as safe, and causes fewer troublesome side effects; however, clinical experience of its use is more limited, particularly in relation to its safety for the fetus and neonate. Delivery of the fetus is usually the definitive management of severe hypertension in pregnancy. However, this action may not reduce the blood pressure immediately. After initial treatment with rapid-acting agents, it is often advantageous to maintain control of arterial pressure with ongoing oral therapy (methyldopa, labetalol). In addition to the protective effect on the mother, such therapy may allow delivery of the fetus to be deferred; this should be considered only if the fetus is significantly premature (e.g., less than 34 weeks), there is no other evidence of maternal or fetal distress, and there can be meticulous monitoring of the maternal and fetal state proceeding to prompt delivery if deterioration occurs. The indications for treatment of mild or moderate hypertension in pregnancy are less clear. Severe hypertensive episodes can be reduced by several drugs (methyldopa, labetalol, beta-blockers). Methyldopa appears to reduce the small risk of mid-trimester abortions seen in association with early hypertension. Other benefits may be possible with other individual drugs; however, none of these have been found consistently in controlled studies to date. There seems, therefore, to be no definite indication for treatment of mild hypertension in pregnancy; treatment of moderate hypertension may be reasonable but its value is unproved at present. Antihypertensive drugs are valuable in pregnancy to reduce the risks directly due to elevated blood pressure. These drugs are not expected to affect the evolution of preeclampsia nor to treat the other complications of this condition.

Methyldopa and beta-adrenoceptor antagonists have been used most extensively. In acute severe hypertension, intravenous labetalol or oral nifedipine are reasonable choices.