Hypertensive Disorders of Pregnancy - Through the Life Cycle

Hypertensive disorders of pregnancy are the second lead-ing cause of maternal mortality in the United States. They affect 6 to 10% of pregnancies and contribute signifi-cantly to stillbirths, fetal and newborn deaths, and other adverse outcomes of pregnancy. The causes of most cases of hypertension during pregnancy remain unknown, and cures for these disorders remain elusive.¹³

Several types of hypertensive disorders in pregnancy have been identified (Table 5.2). In the past, the major types of hypertensive disorders in pregnancy were grouped

Oxidative Stress A condition that occurs when cells are exposed to more oxidizing molecules (such as free radicals) than to antioxidant molecules that neutralize them and help repair cell damage. Over time, oxidative stress causes damage to lipids, DNA, cells, and tissues.

Endothelium The layer of cells lining the inside of blood vessels.

Chronic Hypertension

Hypertension that is present before pregnancy or diagnosed before 20 weeks of pregnancy. Hypertension is defined as blood pressure ≥140 mm Hg systolic or ≥90 mm Hg diastolic blood pressure.

Hypertension first diagnosed during pregnancy that does not resolve after pregnancy is also classified as chronic hypertension.

Gestational Hypertension

This condition exists when elevated blood pressure levels are detected for the first time after mid-pregnancy. It is not accompanied by proteinuria. If blood pressure returns to normal by 12 weeks postpartum, the condition is considered to be transient hypertension of pregnancy. If it remains elevated, then the woman is considered to have chronic hypertension.

Women with gestational hypertension are at lower risk for poor pregnancy outcomes than are women with preeclampsia.

Preeclampsia–Eclampsia

A pregnancy-specific syndrome that usually occurs after 20 weeks gestation (but that may occur earlier) in previously normotensive women. It is determined by

increased blood pressure during pregnancy to ≥140 mm Hg systolic or ≥90 mm Hg diastolic and is accompanied by proteinuria. In the absence of proteinuria, the disease is highly suspected when increased blood pressure is accompanied by headache, blurred vision, abdominal pain, low platelet count, and abnormal liver enzyme values.

• Proteinuria is defined as the urinary excretion of

≥0.3 grams of protein in a 24-hour urine specimen.

This usually correlates well with readings of

≥30 mg/dL protein, or ≥2 on dipstick readings taken in samples from women free of urinary tract infection.

In the absence of urinary tract infection, proteinuria is a manifestation of kidney damage.

• Eclampsia is defined as the occurrence of seizures that cannot be attributed to other causes in women with preeclampsia.

Preeclampsia Superimposed on Chronic Hypertension This disorder is characterized by the development of proteinuria during pregnancy in women with chronic hypertension. In women with hypertension and proteinuria before 20 weeks of pregnancy, it is indicated by a sudden increase in proteinuria, blood pressure, or abnormal platelet or liver enzyme levels.

*Blood pressure values used to determine status should be based on two or more measurements of blood pressure in relaxed settings.

Table 5.2 Definitions and features of hypertensive disorders of pregnancy^*2

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Women with salt-sensitive hypertension, or hyper-tension that responds to dietary sodium intake, must be managed along a fine line between consuming too much sodium for good blood pressure control and consuming too little at the potential cost of impaired fetal growth.²⁴ For women with hypertension that was managed successfully in part by a low-sodium diet prior to pregnancy, continuing that dietary approach is gener-ally recommended.²⁵

Gestational Hypertension

Gestational hypertension is usually diagnosed after 20 weeks of pregnancy. Unlike women with preeclampsia, women with gestational hypertension do not have pro-teinuria. Women with this disorder are at greater risk for hypertension and stroke later in life.Women with gesta-tional hypertension tend to be overweight or obese and have excess central body fat.²⁶

Preeclampsia–Eclampsia

Preeclampsia–eclampsia represents a syndrome character-ized by:

Oxidative stress, inadequate antioxidant defenses,

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inflammation, and endothelial dysfunction Platelet aggregation and blood coagulation due to

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deficits in prostacyclin relative to thromboxane Blood vessel spasms and constriction, restricted

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blood flow

Increased blood pressure

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Insulin resistance

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Adverse maternal immune system responses to the

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placenta ^{21, 27, 28}

Elevated blood levels of triglycerides, free fatty

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acids, and cholesterol

Many of the metabolic abnormalities observed in preec-lampsia are present before it is diagnosed and are the same as those for cardiovascular disease.²⁹ Occurrence of preeclampsia during pregnancy is predictive of later devel-opment of cardiovascular disease.³⁰

Virtually all maternal organs can be affected in preec-lampsia. Organs most affected by small blood clots, vasocon-striction, and reduced blood flow are the placenta and the mother’s kidney, liver, and brain.³¹

Eclampsia can be a life-threatening condition and one that is difficult to predict. Eclamptic seizures appear to be related to hypertension, the tendency of blood to clot, and spasms of and damage to blood vessels in the brain. It complicates about 1 in 2000 pregnancies.³²

Signs and symptoms of preeclampsia range from mild to severe (Table 5.4), as do the health consequences (Table 5.5).

The cause of preeclampsia is unknown but appears to origi-nate from abnormal implantation and vascularization of

Chronic Hypertension

The incidence of chronic hypertension—or that diagnosed prior to pregnancy or before 20 weeks after conception—

ranges from 1 to 5% depending on the population studied. The condition is more likely to occur in African Americans, obese women, women over 35 years of age, and women who experienced high blood pressure in a previous pregnancy.²³

Women with mild hy-pertension may be taken off antihypertension medica-tions preconceptionally or early in pregnancy, because the drugs do not appear to improve the course or out-come of pregnancy.²⁴ Mild hypertension in healthy women that does not be-come worse during preg-nancy appears to pose few risks to maternal and newborn health. Pregnancies among women with blood pressures

≥160/110 mm Hg—either or both values—are associ-ated with an increased risk of fetal death, preterm deliv-ery, and fetal growth retardation. Selection of the proper antihypertension medicines for women during pregnancy reduces these risks somewhat.

Nutritional Interventions for Women with Chronic Hypertension in Pregnancy Preconceptional and pregnancy diets of women with hypertension should be carefully monitored with the aim of achieving adequate and balanced diets for pregnancy. Weight-gain recommen-dations are the same as for other pregnant women.

Table 5.3 Dietary and other environmental exposures that increase or decrease chronic

inflammation and oxidative stress^13,20 1. Decrease

Regular intake of colorful fruits and vegetables,

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dried beans, and whole-grain products

Adequate intake of the omega-3 fatty acids EPA

•

and DHA

Vitamin D sufficiency

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Physical activity

• 2. Increase

Frequent intake of processed and high-fat meats

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Regular intake of baked products and snack

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foods with trans fats

Frequent consumption of soft drinks, other

high-•

sugar beverages Physical inactivity

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High levels of body fat, especially visceral fat

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Smoking

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Prostacyclin A potent inhibitor of platelet aggregation and a powerful vasodilator and blood pressure reducer derived from n-3 fatty acids.

Thromboxane The parent of a group of thromboxanes derived from the n-6 fatty acid arachidonic acid. Thromboxane increases platelet aggregation and constricts blood vessels, causing blood pressure to increase.

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Increased rates of preterm delivery and low-birth-weight in infants born to women with preeclampsia are partly related to clinical decisions to deliver fetuses early in order to treat the disease. Most infants born to women with this disorder are normal weight, however, and some newborns are large for gestational age. Variations in birth weight associated with preeclampsia appear to be related to the severity of the disease in individual women.⁴¹

The risk of developing preeclampsia is higher in women who were born small for gestational age (SGA).

It appears that growth restriction in utero may impair mechanisms involved in the regulation of blood pressure and increase the probability that high blood pressure will develop with the physiological stresses of pregnancy.⁴² Vitamin and Mineral Supplementation and the Risk of Preeclampsia Oxidative stress and a lack of antioxidant defenses appear to play key roles in the de-velopment of preeclampsia. Based on this knowledge, it was theorized that therapeutic doses of vitamins C and E (which function as antioxidants) would decrease oxida-tive stress and the risk of preeclampsia. Results from early studies suggested that this did happen, but later, better-designed clinical trials failed to identify a true relation-ship between supplemental vitamin C and E intake and preeclampsia. It is now concluded that vitamin C and E supplements should not be used to prevent preeclampsia.⁴³ Supplemental vitamin D, however, has been related to a reduced risk of preeclampsia in women with poor vitamin D status.^40,44

the placenta, and poor blood flow through the placenta.³¹ Abnormal blood flow through the placenta is an important characteristic of preeclampsia because it decreases the deliv-ery of nutrients and gases to the fetus. It appears to be re-lated to oxidative stress, reduced antioxidant defenses, and endothelial dysfunction.¹³ Insulin resistance is also a com-mon characteristic of preeclamspia and contributes to some of the negative consequences observed.²⁷ The only cure is delivery.²⁵ Signs and symptoms of preeclampsia generally disappear rapidly after delivery, but eclampsia may occur within 12 days following delivery.³⁴

Women with preeclampsia are at increased risk for de-veloping gestational diabetes during pregnancy, and type 2 diabetes, hypertension, heart disease, and stroke later in life.³⁶ About 15% of women with gestational diabetes and 30% of those with type 2 diabetes prior to pregnancy will develop preeclampsia.³² A history of preeclampsia increases the risk that it will occur in subsequent pregnancies.³⁸ Risk Factors for the Development of Preec-lampsia The roots of preeclampsia lie very early in pregnancy, but as yet there is no reliable means of iden-tifying women who will develop it before the condition is established.³⁸ However, women with insulin resistance, obesity, abnormally high triglyceride levels, or other char-acteristics listed in Table 5.6 are at increased risk for de-veloping the disease.

Table 5.5 Outcomes related to the existence of preeclampsia during pregnancy^23,35 Mother

Early delivery by cesarean section

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Acute renal (kidney) dysfunction

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Increased risk of gestational diabetes, hypertension,

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and type 2 diabetes later in life

Abruptio placenta (rupture of the placenta)

• Newborn

Growth restriction

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Respiratory distress syndrome

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Table 5.6 Risk factors for preeclampsia^23,38–40 First pregnancy (nulliparous)

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Obesity, especially high levels of central body fat

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Underweight

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Mother’s smallness at birth

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African Americans, American Indians

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History of preeclampsia

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Preexisting diabetes mellitus

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Age over 35 years

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Multifetal pregnancy

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Insulin resistance

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Abnormally high blood triglyceride levels

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Chronic hypertension

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Renal disease

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Poor vitamin D status

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Poor calcium status

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Consumption of a pro-inflammatory, pro-oxidative

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stress diet Table 5.4 Signs and symptoms of preeclampsia³³

Hypertension

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Increased urinary protein (albumin)

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Decreased plasma volume expansion (hemoglobin

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levels .13 g/dL) Low urine output

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Persistent and severe headaches

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Sensitivity of the eyes to bright light

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Blurred vision

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Abdominal pain

• Nausea

•

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Nutritional Recommendations and Interventions for Preeclampsia

In the best of circumstances, dietary interventions for preeclampsia would begin prior to pregnancy. This ap-proach might give women the opportunities to decrease body weight and stores of central body fat, become physi-cally fit, and consume a diet that reduces inflammation and oxidative stress. Short of those circumstances, dietary rec-ommendations and interventions should begin in at-risk women as early in pregnancy as possible.

Nutritional and physical activity recommendations that may benefit women at risk of preeclampsia include:

1000–2000 mg per day of dietary or supplemental

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calcium

Adequate vitamin D status

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Use of a multivitamin-mineral supplement

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Five or more servings of colorful vegetables and

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fruits daily

Consumption of the assortment of other basic

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foods recommended in MyPyramid

Moderate exercise (for example, walking,

swim-●

ming, noncompetitive tennis, or dancing for 30 minutes) daily unless medically contraindicated Weight gain that follows recommendations based

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on prepregnancy weight status

Iron supplements, especially if taken in high doses, may ag-gravate inflammation by increasing the body’s free-radical load.⁵⁰ Women with preeclampsia should not be given high-dose iron supplements.

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