1. Management of hypertension in pregnant women Atefe Vafaei 95/5/10
IN THE NAME OF GOD
Management of hypertension in pregnant women
Atefe Vafaei
95/5/10

2. INTRODUCTION :
●Preeclampsia: new onset of hypertension and either proteinuria or end-organ dysfunction most often after 20 weeks of gestation in a previously normotensive woman.
●Chronic (preexisting) hypertension –systolic pressure ≥140 mmHg and/or diastolic pressure ≥90 mmHg that antedates pregnancy, is present before the 20th week of pregnancy, or persists longer than 12 weeks postpartum.
●Preeclampsia-eclampsia superimposed upon chronic hypertension –a woman with chronic hypertension develops worsening hypertension with new onset proteinuria or other features of preeclampsia (eg, elevated liver enzymes, low platelet count).
●Gestational hypertension –elevated blood pressure first detected after 20 weeks of gestation in the absence of proteinuria or other diagnostic features of preeclampsia. Over time, some patients with gestational hypertension will develop proteinuria or end-organ dysfunction characteristic of preeclampsia and be considered preeclamptic, while others will be diagnosed with preexisting hypertension because of persistent blood pressure elevation postpartum.

4. GENERAL APPROACH — The decision to treat hypertension during pregnancy should consider the risks and benefits for both mother and fetus. The level of blood pressure is the most important factor: Treatment of severe hypertension (systolic BP ≥160 mmHg and/or diastolic BP ≥110 mmHg) is always recommended because it is believed to reduce the risk of maternal stroke.
The decision to use antihypertensive therapy in women with mild (systolic 140 to 150 mmHg, diastolic 90 to 100 mmHg) to moderate (systolic 150 to 159 mmHg, diastolic 100 to 109 mmHg) hypertension and no comorbidities is less clear.

5. Antihypertensive therapy — 
All antihypertensive drugs cross the placenta. women with chronic hypertension, either treated or untreated, are at increased risk of congenital malformations, particularly cardiac malformations, compared with normotensive women.

6. Options — The following drugs are effective antihypertensive agents with an acceptable safety profile in pregnancy. The choice of drug depends on the acuity and severity of hypertension and whether or not parenteral or oral therapy is used; these factors are discussed below.

7. Methyldopa — long-term safety for the fetus , a mild antihypertensive agent and has a slow onset of action (three to six hours). Many women will not achieve blood pressure goals on this oral agent or are bothered by its sedative effect at high doses. Beta-blockers —the risk of congenital malformations associated with first trimester oral beta-blocker exposure compared with no exposure, there was no overall increase in major congenital malformations (OR 0.90, 95% CI ) .

8. Beta-blockers
Labetalol: both alpha- and beta-adrenergic blocking activity, rapid onset of action than methyldopa (within two hours versus three to six hours), associated with maternal hepatotoxicity, which although rare, is important to recognize as it may be confused with the elevated liver enzymes of the HELLP (Hemolysis, Elevated Liver enzymes, and Low Platelet count) syndrome. Most cases are reversible, but fatalities have been reported(related to the duration of therapy in chronic hypertension and differences in baseline characteristics of the mothers ). , pindolol and the long-acting form of metoprolol are acceptable alternative agents .

9. The safety of beta-adrenergic blockers is somewhat controversial due to reports of premature labor, fetal growth restriction, and neonatal apnea, bradycardia, and hypoglycemia . Furthermore, myometrial relaxation of the gravid uterus is a beta2-receptor-mediated process, and nonselective beta-adrenergic blockers (such as propranolol) may counteract the effect of beta2 stimulation. Beta-adrenergic blockers that lack alpha-blocking properties (eg, atenolol) have been associated with lower placental and fetal weight at delivery when used early in pregnancy, and are generally avoided if an effective drug with a better safety profile is available .

10. Calcium channel blockers —nifedipine ,amlodipine, Nondihydropyridine calcium antagonists such as verapamiland diltiazem.
We caution against the use of immediate release oral nifedipine, although an American College of Obstetricians and Gynecologists committee opinion endorsed its use as an option for emergent treatment of acute, severe hypertension in pregnancy or postpartum (other options were sustained release nifedipine, labetalol, and hydralazine). In most cases use of immediate release nifedipine will be safe and well tolerated; however, there is a small risk of an acute, precipitous fall in blood pressure, which may result in a reduction in uteroplacental perfusion and headache.  

11. Hydralazine —intravenus of that is used for the acute treatment of severe hypertension. Hydralazine can also be taken orally; however, it causes reflex tachycardia and fluid retention, which limit its usefulness in pregnancy.
Thiazide diuretics —these agents can be continued in women with chronic hypertension who were taking them prior to pregnancy. Diuretics are not generally used in women with preeclampsia unless pulmonary edema has developed.

12. Clonidine —an effective drug for treatment of mild hypertension in pregnancy . However, it has bothersome side effects and the possibility of rebound hypertension if it is stopped suddenly, so other agents are preferred. Because clonidine is available as a transdermal patch, it is particularly useful for patients who cannot take an oral antihypertensive drug.

13. ACE inhibitors, ARBs, direct renin inhibitors — contraindicated at all stages of pregnancy. renal abnormalities when maternal exposure has been in the latter half of pregnancy, and first trimester exposure has been associated with fetal cardiac abnormalities. it is best to avoid initiating these drugs during pregnancy and to discontinue these agents in women planning pregnancy and switch to another agent.

14. Nitroprusside — Limited clinical experience pregnancies and the possibility of fetal cyanide poisoning have restricted the use of nitroprusside in pregnancy.

15. Activity — Recommendations for level of activity should be individualized; for example, a woman with stable chronic hypertension early in pregnancy is unlikely to benefit from bedrest, while a woman with newly diagnosed preeclampsia in the third trimester should be advised to limit activity if she is being managed as an outpatient. Diet — A normal diet without significant salt restriction is generally advised, as salt restriction may induce low intravascular volume.

16. MANAGEMENT OF COMMON HYPERTENSIVE DISORDERS DURING PREGNANCY
1. Preeclampsia: The definitive treatment of preeclampsia is delivery, which is always beneficial for the mother. However, delivery may not be beneficial for the fetus if it is born preterm. Although the fetus is at increased risk of intrauterine growth restriction and stillbirth in the preeclamptic environment, conservative management, including antihypertensive therapy, may be pursued in selected cases to gain fetal maturity.

17. Indications for antihypertensive therapy — We do not prescribe antihypertensive therapy for mild hypertension, which we define as blood pressures consistently less than 150/100 mmHg. The benefit of antihypertensive therapy in pregnant women with mild hypertension is a reduction in risk of developing severe hypertension , which may not be sufficient to warrant exposing the fetus to the potential adverse effects from these drugs .

18. Severe hypertension should be treated to prevent maternal vascular complications. We initiate antihypertensive therapy in adult women at systolic pressures ≥150 mmHg or diastolic blood pressures ≥100 mmHg. We may initiate treatment earlier in women with signs of cardiac decompensation or cerebral symptoms (eg, severe headache, visual disturbances, chest discomfort, shortness of breath, confusion) and in younger women whose baseline blood pressures were low . then women with preeclampsia may be more susceptible to the neurologic features of severe disease at lower blood pressures (eg, ≥150 mmHg systolic).

19. Choice of drug and dose : Acute therapy —intravenous labetalol (Begin with 20 mg intravenously over 2 minutes followed at 10-minute intervals by doses of 20 to 80 mg up to a maximum total cumulative dose of 300 mg or constant infusion of 1 to 2 mg/min )or hydralazine (Begin with 5 mg intravenously over 1 to 2 minutes , maximum bolus dose is 20 mg) as first-line agents for acute therapy of severe hypertension. but nimodipine, diazoxide, and ketanserin were probably best avoided. oral nifedipine is an acceptable alternative to parenteral labetalol or hydralazine for severe hypertension . -Options for second-line therapy include labetalol or nicardipine by infusion pump. Nitroprusside is administered as a last resort. -Magnesium sulfate, which is usually administered to women with preeclampsia, is never a substitute for prompt initiation of antihypertensive treatment of severe hypertension as it has minimal effects on blood pressure.

20. Long-term oral therapy — preeclamptic women with severe hypertension remote from term are stabilized and not delivered immediately. Oral antihypertensive therapy is often indicated for these patients. Options for oral antihypertensive therapy are the same as for women .with preexisting hypertension

21. Target blood pressure — reducing mean arterial pressure by no more than 25 percent over 2 hours and achieving a target of 130 to .150 mmHg systolic and 80 to 100 mmHg diastolic

22. 2. Gestational hypertension — The indications for and choice of antihypertensive therapy in women with gestational hypertension are the same as for women with preeclampsia.

23. 3. Chronic (preexisting) hypertension — Beneficial effects of treatment appear to be limited to prevention of maternal morbidity and depend upon the severity of the disease. nonobese women under age 30 years with a confirmed negative family history of hypertension may have secondary hypertension, so causes of secondary hypertension should be considered in those with suggestive clinical features such as severe or resistant hypertension, acute onset of hypertension, metabolic abnormalities associated with either renovascular hypertension (high plasma renin activity) or primary aldosteronism (low plasma renin activity, low serum potassium), or proven onset of hypertension before puberty.

24. Baseline laboratory tests: ●Urinalysis
●Urine culture
●Creatinine
●Glucose
●Electrolytes
●Quantitative analysis of urine protein  

25. Indications for treatment —
we avoid treatment of pregnant women with mild hypertension and no evidence of target organ damage, especially in the first trimester, since blood pressure normally decreases as pregnancy progresses into the second trimester.
In women already on antihypertensive therapy who have early pregnancy blood pressures less than 120/80 mmHg, we would consider tapering/discontinuing antihypertensive drugs and closely monitoring the blood pressure response.
Our indications for initiating or reinstituting antihypertensive therapy are persistent diastolic pressures of 95 to 99 mmHg, systolic pressures ≥150 mmHg, or signs of hypertensive target-organ damage.
Severe hypertension in pregnancy (blood pressure ≥160/110 mmHg) should be treated.

26. Complicated and secondary hypertension: ●Secondary hypertension.
●Target-organ damage (eg, left ventricular hypertrophy, microalbuminuria, retinopathy).
●Dyslipidemia.
●Maternal age over 40 years old.
●History of stroke.
●Previous perinatal loss.
●Diabetes 
(a blood pressure target of 110 to 129/65 to 79 mmHg in pregnant women with diabetes and chronic hypertension)

28. Blood pressure goal — in women without target-organ damage :systolic pressure between 140 and 150 mmHg and diastolic pressure between 90 and 100 mmHg In women with target-organ damage: to keep the blood pressure below 140/90 mmHg

29. THE END