Hypertensive Issues During Pregnancy

Elevated blood pressure during pregnancy is a significant problem affecting many pregnancies. In some cases, the hypertension is pre-existing, while in others, it develops over the course of pregnancy. Occasionally, it does both.

Normal Blood Pressure Changes During Pregnancy
During the middle trimester, blood pressure (both systolic and diastolic) normally drop below early pregnancy and prepregnancy levels. Not uncommonly, there is a widening of the pulse pressure (difference between systolic and diastolic levels). These changes are associated with the significant reduction in peripheral vascular resistence and some degree of AV shunting within the uterus and intervillous space. The decreased peripheral resistance is compensated by the relative tachycardia so often found among pregnant women.

In the third trimester, blood pressure usually rises to approximately pre-pregnancy levels. Elevations significantly higher than that are considered abnormal.

Hypertension
The definition of hypertension varies, but one common definition is the sustained elevation of BP above 140/90. Most obstetricians believe that if either the systolic or the diastolic pressure is elevated on a sustained basis, that hypertension exists. A few require that both be elevated. As a practical matter, in most cases of hypertension, both are elevated.

The diastolic pressure elevation is probably the more important of the two and mean arterial pressure (MAP) during the second or third trimester are used by some to assess risk. Conceptually, the MAP is one-third the distance from the diastolic pressure to the systolic pressure. This can be expressed mathematically as:

During the second trimester, if the average of all MAPs ≥ 90, there is a significant increased risk for perinatal mortality, morbidity and impaired fetal growth dynamics.

Women with pre-existing hypertension face increased risks during pregnancy for diminished uterine blood flow, pre-eclampsia, and if uncontrolled, maternal stroke. For these reasons, it is important that those with pre-existing hypertension be appropriately treated and followed during pregnancy.

Toxemia of Pregnancy
Toxemia of pregnancy is a clinical syndrome characterized by elevated blood pressure, protein in the urine, fluid retention and increased reflexes. It occurs only during pregnancy and resolves completely after pregnancy. It is seen most often as women approach full term, but it can occur as early as the 22nd week of pregnancy. It's cause is unknown, but it occurs more often in:

Ordinarily, blood pressure decreases during the middle trimester, compared to pre-pregnancy levels. After the middle trimester, blood pressure tends to rise back to the pre-pregnancy levels. Sometimes, blood pressure becomes elevated.

Sustained blood pressures exceeding 140/90 are considered abnormal and may indicate the presence of toxemia of pregnancy. For women with pre-existing hypertension, a sustained worsening of their hypertension over pre-pregnancy levels by 30 systolic and 15 diastolic is often used to indicate the possible presence of super-imposed toxemia.

Diagnosis
The presence of hypertension and proteinuria are essential to the diagnosis of toxemia of pregnancy.

Pregnant women can normally lose up to 200 mg of protein in the urine in 24 hours. If protein loss exceeds 300 mg in 24 hours, this is considered proteinuria. Urine dipstick analysis for protein measures only a single point in time and does not necessarily reflect protein loss over 24 hours. Nonetheless, assuming average urine production of about a liter a day, and consistent loss throughout the 24 hour period*:

Category	Negative	Trace	1+	2+	3+	4+
Dipstick Results	<15 mg/dL	15-29 mg/dL	30 mg/dL	100 mg/dl	300 mg/dl	>2000 mg/dL
Equivalent 24-hour Results*	<150 mg	150-299 mg	300-999 mg	1000-2999 mg	3-20 g	>20 g

Some but not all women with toxemia demonstrate fluid retention (as evidenced by edema or sudden weight gain exceeding 2 pounds per week). Some but not all women with toxemia will demonstrate increased reflexes (clonus).

Most women toxemia of pregnancy have no symptoms. Among the few with symptoms are such findings as:

Cause(s) of Toxemia of Pregnancy
The cause or causes are not known. Some common associations are first pregnancies, pre-existing hypertension, hydatidiform mole, and those conditions which lead to overdistension of the uterus, such as polyhydramnios and multiple gestation.

Physiologically, women with this condition demonstrate peripheral vascular spasm, leading to injury of the capillary walls and leakage of intravascular fluids into the extracellular spaces. Due to the modestly impaired kidney function that accompanies this condition, serum creatinine levels are usually modestly increased (>1.0 mg%). Hemoconcentration results in a modest increase in hemoglobin and hematocrit. Both contribute to an elevation of BUN, usually >12 mg%. Uric acid is typically >5.5 mg% due to increased production in association with peripheral vascular sluggishness.

Consequences
Toxemia of pregnancy, including pre-eclampsia, eclampsia and the HEELP syndrome, are very dangerous, with potentially serious consequences for both the mother and fetus. Among these are:

Fortunately, most cases of toxemia of pregnancy are mild, and most of the more severe forms are successfully treated (delivered) before the serious consequences can unfold. In some severe cases, even early diagnosis and treatment will prove unsuccessful in avoiding the more serious consequences.

Pre-eclampsia
Toxemia of pregnancy is subdivided into two categories: pre-eclampsia and eclampsia. The difference is the presence of seizures in women with eclampsia.

The clinical course of pre-eclampsia is variable. Some women demonstrate a mild, stable course of the disease, with modest elevations of blood pressure and no other symptoms (mild pre-eclampsia). Others display a more aggressive disease, with deterioration of both maternal and fetal condition (severe pre-eclampsia). Some of the points of differentiation are listed here. Notice that there is no "moderate" pre-eclampsia, only mild and severe.

Problem	Mild Pre-Eclampsia	Severe Pre-Eclampsia
Blood Pressure	>140/90	>160/110
Proteinuria	1+ (300 mg/24 hours)	2+ (1000 mg/24 hours)
Edema	+/-	+/-
Increased reflexes	+/-	+
Upper abdominal pain	-	+
Headache	-	+
Visual Disturbance	-	+
Decreased Urine Output	-	+
Elevation of Liver Enzymes	-	+
Decreased Platelets	-	+
Increased Bilirubin	-	+
Elevated Creatinine	-	+

The definitive treatment of pre-eclampsia is delivery. The urgency of delivery depends on the gestational age and the severity of the disease.

Severe pre-eclampsia usually requires urgent delivery (within hours) more or less regardless of gestational age. In this situation, the risk of serious complications (placental abruption, growth restriction, liver failure, renal failure, hemorrhage, coagulopathy, seizures, death) will generally take precedence over the fetal benefit of prolonging the pregnancy. Induction of labor is preferred, unless the maternal condition is so tenuous and the cervix so unfavorable that cesarean section is warranted.

In milder cases, particularly if remote from term or with an unfavorable cervix, treatment may range from hospitalization with close observation to initial stabilization followed by induction of labor following preparation of the cervix over the course of several days. In the most mild, selected cases, outpatient management might be considered with careful monitoring of maternal and fetal condition.

Traditionally, magnesium sulfate(MgSO4) has been used to treat pre-eclampsia. Magnesium sulfate, in high enough doses, is a reasonably effective anti-convulsant, mild anti-hypertensive and mild diuretic. While other agents may be more potent in each of these individual areas, none combines all three of these features into a single drug. The world's experience with magnesium sulfate to treat pre-eclampsia is extensive and these unique features provide considerable reassurance in employing it in these clinical settings. Magnesium sulfate is given IM, IV or both. All are effective reasonably effective in preventing seizures. Because the risk of eclampsia continues after delivery, MgSO4 is frequently continued for 24 to 48 hours after delivery.

The therapeutic margin (distance between effective dose and toxicity) is relatively thin with magnesium sulfate, so some precautions need to be taken to prevent overdose. The biggest problem with MgSO4 is respiratory depression (10 meq/L) and respiratory arrest (>12 meq/L). Cardiovascular collapse occurs at levels exceeding 25 meq/L. Magnesium levels can be measured in a hospital setting, but clinical management works about as well and is non-invasive.

The patellar reflexes (knee-jerk) disappear as magnesium levels rise above 10 meq/L. Periodic checking of the patellar reflexes and withholding MgSO4 if reflexes are absent will usually keep your patient away from respiratory arrest. This is particularly important if renal function is impaired (as it often is in severe pre-eclampsia) since magnesium is cleared entirely by the kidneys.

In the case of respiratory arrest or severe respiratory depression, the effects of MgSO4 can be reversed by the administration of calcium.

If BP is persistently greater than 160/110, administer an antihypertensive agent to lower the BP to levels closer to 140/90. One commonly-used agent for this purpose is:

Eclampsia
Eclampsia means that maternal seizures have occurred in association with toxemia of pregnancy.

These tonic/clonic episodes last for several minutes and may result in bite lacerations of the tongue. During the convulsion, maternal respirations stop and the patient turns blue because of the desaturated hemoglobin in her bloodstream. As the attack ends, she gradually resumes breathing and her color returns. Typically, she will remain comatose for varying lengths of time. If convulsions are frequent, she will remain comatose throughout. If infrequent, she may become arousable between attacks. If untreated, convulsions may become more frequent, followed by maternal death. In more favorable circumstances, recovery occurs.

Eclampsia should be aggressively treated with magnesium sulfate (described above), followed by prompt delivery, often requiring a cesarean section. If convulsions persist despite MgSO4, consider:

This serious condition is associated with severe pre-eclampsia and the treatment is similar...delivery with prophylaxis against maternal seizures.

Unlike pre-eclampsia, patients with HELLP syndrome may continue to experience clinical problems for days to weeks or even months.

If the HELLP syndrome is mild, it may gradually resolve spontaneously, but more severe forms often require intensive, prolonged care to achieve a favorable outcome.