International Journal of Technology Assessment In Health Care, 8:Suppl. 1 (1992), 63-71. Copyright © 1992 Cambridge University Press. Printed in the U.S.A.

SCREENING FOR HYPERTENSION IN PREGNANCY Robert L. Goldenberg University of Alabama, Birmingham

Abstract The literature dealing with screening for hypertension in pregnancy was reviewed. No level of blood pressure or any other factor provides a guarantee of no risk for the development of preeclampsia. However, higher blood pressure in early pregnancy and a failure to decrease blood pressure in midpregnancy are both associated with the development of preeclampsia. The development of proteinuria, rather than the level of blood pressure, is the best predictor of poor pregnancy outcome. Multiparas, especially those with severe chronic hypertension who develop preeclampsia, are at greatest risk of poor pregnancy outcome.

Hypertension in pregnancy has been associated with a number of poor outcomes for the mother, fetus, and infant. This article discusses some of the outcomes associated with hypertension in pregnancy. Several factors are then evaluated that influence the severity of those outcomes. The first observation to make is that despite the fact that hypertension in pregnancy is conceptually divided into chronic or preexisting hypertension on the one hand and pregnancy-induced hypertension on the other, in practice, separating out these entities is frequently difficult if not impossible. Furthermore, in many studies, the care taken to divide hypertension into appropriate classifications differs substantially. Therefore, the disease process that in one study may be classified as chronic hypertension may be classified as pregnancy-induced hypertension in another. Additionally, the distinction between pregnancy-induced hypertension and preeclampsia has varied between studies and further contributes to the confusion surrounding these conditions. For example, some authors use either hypertension and edema or hypertension and proteinuria to define preeclampsia. Others require a minimum level of protein to make the diagnosis of preeclampsia. With these caveats in mind, this article explores the relationship between hypertension and pregnancy outcome. One major source of difficulty in studying the relationship of blood pressures to pregnancy outcome is that blood pressures are not stable during pregnancy. For example, in normal women, the blood pressure declines in the late first and early second trimester, plateaus at a relatively low level during the second and early third trimester, and then rises late in pregnancy (3) (Figure 1). The diastolic blood pressure is relatively similar in the sitting or lying down positions, whereas the sitting systolic pressures are considerably lower. Both systolic and diastolic pressures tend to be higher in first than in subsequent pregnancies. Establishing when in pregnancy a blood pressure is mea63

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16 20 24 28 32 36 40 Gestational Age (Weeks) Figure 1. Mean blood pressure by gestational age and parity for white gravidas 25-34 years of age who delivered single live term newborns.

sured and the position used, therefore, are crucial in describing the relationship of blood pressure to pregnancy outcome. Clearly it is not appropriate to compare pressures taken at different times or in different positions. Another major difficulty in understanding this literature is that different authors measure blood pressure differently and some use different measurements. For example, some authors have used the maximum recorded blood pressure, either in the pregnancy or in a given trimester, whereas others use the mean of all values taken during that time period. Various investigators have presented data about systolic and/or diastolic blood pressures as well as the mean arterial pressures (MAP = systolic + 2 x diastolic/3) in relationship to outcome (17). At the present time it is not absolutely clear which measure is best associated with outcome, although in general high diastolic pressures correlate best with intrauterine growth retardation (IUGR) and fetal death, whereas (in our studies) higher systolic pressures, in the absence of a high diastolic pressure, were associated with larger rather than smaller babies. Because the MAP is weighted to reflect the diastolic component of blood pressure, this measure also is more closely associated with IUGR. However, the measurement is not in general use and probably offers no real advantage over the standard systolic and diastolic blood pressure measurement. For this article, chronic hypertension will be defined as an elevated blood pressure documented prior to pregnancy or prior to 20 weeks gestational age; preeclampsia as a constellation of findings, usually including elevated blood pressure and proteinuria in the absence of previously documented hypertension and/or renal disease; and superimposed preeclampsia as increasing proteinuria and blood pressure in women with a history of chronic hypertension and/or renal disease. Also, it is possible to have blood 64

INTL. J. OF TECHNOLOGY ASSESSMENT IN HEALTH CARE 8:SUPPL. 1, 1992

Screening for hypertension in pregnancy Perinatal Mortality, per 1000

175 150 -

< 55

55-65 65-74 75-84 85-94 95-104 105+

Diastolic Blood Pressure (mm/Hg) Figure 2. Perinatal mortality per 1,000 live births by maximum diastolic blood pressure (mm Hg) and degree of proteinuria.

pressure increasing into the abnormal range with no proteinuria in the absence of previous history of chronic hypertension or renal disease. This process is called pregnancy-induced hypertension. Blood Pressure and Outcome

Although the classic definition of abnormal blood pressure in pregnancy has been defined as a pressure of 140/90 mm Hg or more on two occasions, or a rise over baseline of 30/15 mm Hg, the usefulness of these definitions remains an open question. For example, in chronic hypertensive women, Page and Christianson (17) found a rise of 25 mm Hg "essentially harmless," whereas a rise of 20 mm Hg in chronic hypertensives with superimposed preeclampsia was "disastrous." Very clearly, there is not a specific threshold level of high blood pressure that divides good outcomes from poor outcomes. For example, in the U.S. Collaborative Perinatal Project, the relationship of maximum prenatal diastolic blood pressure taken after 28 weeks gestational age and perinatal mortality were compared (Figure 2). In this study, the optimal outcome in terms of perinatal survival occurred at maximum diastolic pressures between 75 and 84 mm Hg (5). Pressures either higher or lower than this range were associated with slightly higher perinatal mortality rates. However, in each pressure range the mortality was increased substantially when proteinuria was present. Several authors have emphasized that women who do not achieve the normal late first or early second trimester fall in blood pressure are at greater risk for the development of hypertension later in pregnancy. For example, Moutquin et al. (14) demonstrated that previously normotensive women destined to develop preeclampsia had higher diastolic pressures as early as 9-12 weeks gestation. Reiss et al. (18) also examined the timing of the mid-pregnancy decline in systemic blood pressures and also INTL. J. OF TECHNOLOGY ASSESSMENT IN HEALTH CARE 8:SUPPL. 1, 1992

65

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211 Pregnancies with Mild Chronic Hypertension (MAP =108 ±8.3 mm Hg)

8-19 weeks gestation 104 (49%) 1f

20-26 weeks MAP gestation decreased

4 (4%) 27-41 weeks gestation

71 (34%) r

MAP unchanged

11 (16%)

40 (17%) t

MAP increased

13 (32%)

Severe Exacerbation of Hypertension

Figure 3. Changes in mean arterial blood pressure (MAP) and pregnancy outcome in women with mild chronic hypertension.

demonstrated that women who failed to have the normal decline at 9-12 weeks were more likely to develop preeclampsia. Other authors have found similar results, although the sensitivity and specificity of the results make this test appear to be not useful for screening (1;2;17;23). In many of these studies, the conclusions are tainted because the definition of preeclampsia was variable and depended mostly on a high blood pressure. Although there is little question that high blood pressure early in pregnancy is associated with higher blood pressures later in pregnancy, there is little solid evidence that blood pressures in the "high normal" range early in pregnancy consistently predict preeclampsia defined as hypertension accompanied by proteinuria. Proteinuria In women with mild chronic hypertension, Sibai et al. (19) showed that when there was a second trimester decline in pressure, only 4% developed preeclampsia. If the pressures remained stable, 16% developed preeclampsia. However, if the midtrimester pressures rose, 32% of these chronic hypertensive women developed preeclampsia (Figure 3). Our review of the literature indicates that while early blood pressures or changes in blood pressures may predict the later onset of preeclampsia, high blood pressure alone early in pregnancy does not appear to be the major factor in determining outcome. In an excellent series of studies, Sibai et al. (19;20;21) evaluated pregnancy outcome in women with both mild chronic hypertension (diastolic 90-110 mm Hg) and severe chronic hypertension (diastolic >110 mm Hg). In women with mild chronic hypertension, if they did not develop preeclampsia (as defined by proteinura of 2 + or greater), the pregnancy outcome was not distinguishable from nonhypertensive women (Table 1). However, for the 10-20% of mild chronic hypertensives who developed preeclampsia, the pregnancy outcome was very poor, with a 10% incidence of abruption, a 33% incidence of IUGR, and a perinatal mortality rate of 24%. These results were confirmed by Page and Christianson (17). Similar results were also described by Gleicher et al. (8), who found that multiparous women with chronic hypertension and superimposed preeclampsia had significantly worse pregnancy outcomes than those with classic primiparous preeclampsia. Lin et al. (11) also found that fetal outcome was worse in multiparous preeclamptic women. From Sibai and Anderson's (20) study of severe chronic hypertension (>110 mm 66

INTL. J. OF TECHNOLOGY ASSESSMENT IN HEALTH CARE 8:SUPPL. 1, 1992

Screening for hypertension in pregnancy Table 1. Pregnancy Outcome in Women with Chronic Mild Hypertension (110 mm Hg diastolic) Early in Pregnancy

With preeclampsia (n = 23) Gestational age at delivery (weeks) Birthweight (g) Placental weight