Gynecology

Management of hypertension during pregnancy

Key points –Learning bite
د. حسين محمد جمعه
اختصاصي الامراض الباطنة
البورد العربي
كلية طب الموصل
2012

Hypertension is the most common medical problem seen in pregnancy 15% of pregnancies

In all pregnant women, the measurement of blood pressure should be performed in the sitting position, because for many the lateral recumbent position is associated with a blood pressure lower than that recorded in the sitting position. The diagnosis of hypertension requires the measurement of two elevated blood pressures, at least 6 h apart.

Normal changes in blood pressure during pregnancy

First trimester there is a fall in BP caused by vasodilation(prostacyclin and nitric oxide),primarily affects the diastolic pressure, and a drop of 10 mm Hg is usual by 13-20 weeks' gestation.BP continues to fall until 22-24 weeks. After this, there is a gradual increase until term, when BP returns to the level it was before pregnancy.
Immediately after delivery BP usually falls and then increases over the next five days

First, the priority is in making the correct diagnosis, with the emphasis on distinguishing preexisting (chronic) from pregnancy induced (gestational hypertension and the syndrome of preeclampsia).
Second, much of the obstetric literature distinguishes blood pressure (BP) levels as either mild (140 to 159/90 to 109 mm Hg) or severe (160/110 mm Hg), rather than as stages .
Update on the Use of Antihypertensive Drugs in Pregnancy
2008 American Heart Association.


Third, in contrast to hypertension guidelines in adults, which emphasize the importance of systolic BP, much of the obstetric literature focuses on diastolic rather than systolic BP, in part because of the lack of clinical trials to support one approach versus another.

Even women whose blood pressure was normal throughout pregnancy may experience transient hypertension in the early period post partum. This perhaps reflects a degree of vasomotor instability.

The main types of hypertensive disease in pregnancy

• pre-existing hypertension
• gestational hypertension
• pre-eclampsia

Pre-existing hypertension

A known pre-pregnancy
or before 20 weeks' gestation).
caveats to this diagnosis.
Women with pre-existing HP that has not been diagnosed may appear normotensive in early pregnancy because of the normal fall in the first trimester. This may mask the pre-existing HP, and when you find HP later in the pregnancy you may interpret this as gestational.
Pre-eclampsia can occasionally present before 20 weeks.

The presence of mild pre-existing hypertension approximately

doubles the risk of pre-eclampsia and increases the risk of abruption of the placenta and restriction of growth in the fetus.

Gestational hypertension

hypertension occurring in the second half of pregnancy without significant proteinuria or other features of pre-eclampsia in a woman with previously normal blood pressure. It complicates 6-7% of pregnancies.
The risk of pre-eclampsia is 15-26%.
Blood pressure usually returns to normal by six weeks after birth.


Pre-eclampsia and eclampsia
usually occurs after 20 weeks' gestation and is a multisystem disorder.
It was classically defined as a triad of:
Hypertension
Oedema
Proteinuria.
But a more modern definition of pre-eclampsia concentrates on a rise in blood pressure during pregnancy together with >0.3 g proteinuria in 24 hours. Oedema is no longer included because it is not specific.

In most normal pregnancies, the woman has some lower extremity edema by the third trimester. In contrast,
a sudden worsening in dependent edema, edema in nondependent areas (such as the face and hands),
or rapid weight gain suggest a pathologic process and warrant further evaluation for preeclampsia.

The onset of significant proteinuria, in the absence of renal disease, is one of the best indicators of pre-eclampsia. headache, visual disturbance, and abdominal pain are well recognised signs of severe pre-eclampsia .

Preeclampsia-eclampsia is a syndrome that manifests clinically as new-onset hypertension in later pregnancy (any time after 20 weeks, but usually closer to term), with associated proteinuria: 1 on dipstick and, officially, 300 mg per 24-hour urine collection.
2008 American Heart Association.

occurs in 5% to 8% of all pregnancies and is thought to be a consequence of abnormalities in the maternal vessels supplying the placenta,leading to poor placental perfusion and release of factors,causing widespread endothelial dysfunction with multiorgan system clinical features, such as hypertension, proteinuria,and cerebral (edema, occipital headaches, or seizures) and hepatic dysfunction (extension to hemolysis elevation of liver enzymes, low platelets).
Preeclampsia-eclampsia

The HELLP syndrome(hemolysis, elevated liver enzymes, low platelets) is a special subgroup of severe preeclampsia and is a major cause of morbidity and mortality in this disease. The presence of platelet dysfunction and coagulation disorders further increases the risk of stroke.


Preeclampsia
Although the exact pathophysiologic mechanism is not clearly understood, preeclampsia is primarily a disorder of placental dysfunction leading to a syndrome of endothelial dysfunction with associated vasospasm.

In most cases, pathology demonstrates evidence of placental insufficiency with associated abnormalities such as diffuse placental thrombosis, an inflammatory placental decidual vasculopathy, and/or abnormal trophoblastic invasion of the endometrium. This supports abnormal placental development or placental damage from diffuse microthrombosis as being central to the development of this disorder.

Evidence also indicates that an altered maternal immune response to fetal/placental tissue may contribute to the development of preeclampsia. Risk factors for the development of preeclampsia include nulliparity, diabetes mellitus, a history of renal disease or chronic hypertension, a prior history of preeclampsia, extremes of maternal age (>35 or <15 years), obesity, factor V Leiden mutation, antiphospholipid antibody syndrome, and multiple gestation.

Deterrence/Prevention

Multiple interventions to prevent preeclampsia have been investigated. Pharmacologic treatment and normalization of chronic hypertension does not reduce the risk of developing superimposed preeclampsia. Other therapies that have been tried include low-dose acetylsalicylic acid (ASA), supplemental calcium, salt restriction, supplemental magnesium, and fish oil therapy.

While several large trials of ASA in high-risk populations showed minimal benefit in reducing the frequency of preeclampsia, a meta-analysis reported an approximate
15% reduction in preeclampsia among pregnant women taking low-dose ASA. This therapy appears very safe and might be considered in high-risk women. None of the other therapies have demonstrated any significant preventive benefit.

Magnesium sulfate is the treatment of choice for the prevention and treatment of eclamptic seizures. Two large randomized clinical trials have demonstrated the superiority of magnesium sulfate over phenytoin and diazepam, and a recent large randomized clinical trial has demonstrated the efficacy of magnesium sulfate in reducing the risk of seizure and possibly reducing the risk of maternal death.

Given the difficulty of predicting eclamptic seizures on the basis of disease severity, it is recommended that once the decision to proceed with delivery is made, all patients carrying a diagnosis of preeclampsia be treated with magnesium sulfate.

When to treat hypertension during pregnancy

Significant hypertension must be treated to reduce the incidence of maternal intracranial haemorrhage.
The level at which you should start antihypertensive treatment for non-severe hypertension is controversial. Most doctors start antihypertensives when:
Systolic blood pressure is >140-160 mm Hg or
Diastolic pressure is >90-110 mm Hg.


The blood pressure you should
aim to achieve is also controversial, but many practitioners would treat to keep the mean arterial pressure <125 mm Hg . for example, a blood pressure
of < 150/100 mm Hg.

Lowering the blood pressure too much may lead to placental hypoperfusion because placental blood flow is not autoregulated. This will affect the fetus.

Unfortunately there is no evidence that treating chronic or gestational hypertension protects against the development of pre-eclampsia.

Drug treatment

All antihypertensive drugs cross the placenta and reach the fetal circulation. Most of the antihypertensive agents in routine use are not teratogenic, although ACE inhibitors and angiotensin receptor blockers are, and should be avoided.

A teratogenic substance is one that interferes with the formation of major body structures during the first trimester, during the period of organogenesis
A fetotoxic drug interferes with the subsequent growth and development of the fetus

Mild to moderate hypertension

Treating mild to moderate pre-existing HP benefits the mother, but there is no clear evidence of an enhanced outcome for the baby.
Some women with mild treated pre-existing hypertension are able to stop their medication in the first half of pregnancy because of the physiological fall in blood pressure. But should be monitored and treatment restarted as soon as necessary.

First line drugs

Methyldopa
Centrally acting agent and first choice.
You should warn women that it can cause sedation; this can limit the dose used. The drug may cause liver transaminases to rise (in up to 5% of women) or a positive Coomb's test (although haemolytic anaemia is uncommon). You should not give methyldopa to women with a prior history of depression, because of the increased risk of postnatal depression.


Second line drugs
You should use these drugs when monotherapy with methyldopa is insufficient or when women cannot tolerate methyldopa.
Nifedipine
It is safe at any stage of gestation. You should avoid sublingual nifedipine(placental hypoperfusion).
Giving concomitant magnesium sulphate can exacerbate abrupt hypotension. Amlodipine has been used in pregnancy, but there are little safety data.

Oral labetalol

This is used by some as a first line agent. alpha and beta blocker and appears safe in pregnancy. Since beta blockers have been associated with growth restriction when used from the first trimester, our preference is to avoid labetalol until later in pregnancy.
Oral hydralazine
Safe throughout pregnancy, although there have been reports of lupus-like syndromes in the mother and neonate.more frequently used as an infusion for treating acute severe hypertension.

Third line drugs

Alpha and beta adrenergic blockers
BB associated with an increased risk of fetal growth restriction. Atenolol in particular has often been singled out but labetalol seems safe.
you should avoid BB in the first half of pregnancy because of concerns about growth restriction.
Prazosin is safe and effective in pregnancy. Doxazosin appears to be safe, although data are limited.

Thiazide diuretics

These drugs do not appear to be teratogenic. Although they reduce the expansion in plasma volume associated with normal pregnancy, this has not been proved to impair fetal growth.
They are usually avoided in the treatment of hypertension in pregnancy, their use is reserved for cardiac disease and pulmonary oedema.


Hydrochlorothiazide may be continued during pregnancy;the use of low doses (12.5 to 25 mg daily) may minimize untoward metabolic effects, such as impaired glucose tolerance and hypokalemia. Triamterene and amiloride are not teratogenic based on small numbers of case reports. Spironolactone is not recommended because of its antiandrogenic effects during fetal development.

However,mild volume contraction with diuretic therapy may lead to hyperuricemia and in so doing invalidate serum uric acid levels as a laboratory marker in the diagnosis of superimposed preeclampsia.

Different units have their preferences for intravenous hydralazine or labetalol, which are equally effective, but the latter has fewer side effects. Oral nifedipine may also be used.
You should give hydralazine only after giving intravenous fluid: this reduces the reflex tachycardia, and abrupt hypotension, precipitated by vasodilation.
Severe hypertension

Good control of hypertension in severe pre-eclampsia does not halt the progression of the disease, only delivery can do this, but it can reduce the incidence of complications such as cerebral haemorrhage. In patients with severe hypertension you may gain only hours or days.

Women with gestational hypertension or pre-eclampsia are usually able to stop all antihypertensives within six weeks after birth. Women with pre-existing hypertension can resume the drugs they were taking before they became pregnant.
But women who want to breast feed should avoid diuretics because they can increase thirst.
Proteinuria in pre-eclamptic women will usually resolve by three months post partum if there is no underlying renal abnormality.

Breast feeding

You can give most antihypertensive drugs used in routine practice to women who are breast feeding.

Antihypertensive treatment post partum and during breast feeding

Blood pressure typically rises after delivery over the first five days. May be normotensive immediately after the birth, but then become hypertensive again in the first postnatal week.
You should avoid methyldopa post partum because of the risk of postnatal depression. Our first line agent is atenolol, plus nifedipine or an ACE inhibitor if another agent is required.


Neonatal exposure to methyldopa via nursing is likely low, and it is generally considered safe .Atenolol and metoprolol are concentrated in breast milk,possibly to levels that could affect the infant; by ontrast,exposure to labetalol and propranolol seems low. Although milk concentrations of diuretics are low and considered safe,these agents can decrease milk production significantly.
2008 American Heart Association.

There are reports of calcium channel blocker transfer into breast milk, apparently without adverse effects. Sufficient data exist for the safety of 2 ACE-Is, captopril and enalapril;the concentration of captopril was 1% of that found in blood,with the infant receiving 0.03% of the regular dose,
2008 American Heart Association.

Diuretics and beta blockers, commonly preferred antihypertensives, are safe for use in lactating women, with some precautions. In general, it is preferable to avoid high dosages of any one medication by either changing medications or adding an additional agent.
Low dosages of thiazide diuretics (e.g.,25 mg per day or less of hydrochlorothiazide are excreted in small amounts into the breast milk but do not suppress lactation and, consequently, are compatible with nursing.

Beta blockers vary widely in the amount excreted into breast milk. Propranolol , metoprolol and labetalol are excreted in small quantities and are compatible with breastfeeding even in compromised infants.Atenolol ,nadolol and sotalol are excreted in higher amounts, which can lead to hypotension,bradycardia and tachypnea in the infant.

Nonsteroidal anti-inflammatory drugs

Oral contraceptives
Corticosteroids
Cyclosporine
Erythropoietin
Cocaine
Alcohol abuse
Licorice (excessive amounts)
Drugs that increase BP