Hypertensive disorders in pregnancy represent a major cause of maternal and perinatal morbidity and mortality. Hypertension affects approximately 10% of all pregnancies, and is the second leading cause of maternal death in the USA 1,2. The diagnosis of hypertension in pregnancy has relied on the use of conventional in-office blood pressure screening measurements during prenatal visits. This method of blood pressure assessment has come under scrutiny owing to poor measurement techniques, observer error, and the possibility of ‘white-coat hypertension’ leading to misdiagnosis. Thus, out-of-office blood pressure measurements using both self (home) and ambulatory blood pressure monitoring (ABPM) recently have been viewed as superior methods for detecting true hypertension 3. In fact, in the nonpregnant patient, ABPM has become a valuable means for diagnosing and managing hypertension 3.
Self (home) and ABPM are similar techniques in that they both use automated devices to obtain and store blood pressure measurements, and they both use Phase I and V Korotkoff sounds to determine systolic and diastolic blood pressure, respectively. They differ in that self blood pressure monitoring (SBPM) is performed by the patient intermittently during the day, whereas ABPM uses a device worn for 24 hours and automatically records and stores multiple blood pressure measurements during that time.
Pre-eclampsia, a pregnancy-specific disease, is defined as hypertension after 20 weeks’ gestation accompanied by proteinuria, clinical edema, or both of these signs 4. Some of the more severe clinical manifestations of pre-eclampsia include renal insufficiency, hemolysis, pulmonary edema, cerebral hemorrhage, hepatic dysfunction, seizures, intrauterine growth restriction, oligohydramnios, abruptio placentae, and intrauterine fetal death 1,2. Because of these risks, an elevation of blood pressure in the obstetrician's office creates substantial concern and leads to more intensive evaluation during the course of the pregnancy. The development of pregnancy hypertension often results in referral to maternal–fetal medicine specialists for consultation and follow-up.
The use of ambulatory and home blood pressure monitoring in pregnancy is a relatively new and promising method of managing patients with hypertension in pregnancy 5. This review discusses the benefits of out-of-office blood pressure monitoring compared to conventional blood pressure assessment and provides a summary of the available literature on both home and ABPM in pregnancy.
Classification of hypertensive disorders in pregnancy
The most important consideration in the classification of hypertension during pregnancy is differentiation of those hypertensive disorders that antedate pregnancy from pregnancy-related hypertension, or pre-eclampsia. Chronic hypertension is defined as blood pressure ≥140 mmHg systolic or ≥90 mmHg diastolic, which is present either prior to pregnancy or before the 20th week of gestation. Hypertension that is diagnosed during pregnancy and does not resolve postpartum is also classified as chronic hypertension 1.
Pre-eclampsia, as stated above, is a syndrome peculiar to pregnancy and is associated with reduced organ perfusion secondary to vasospasm and activation of the coagulation cascade 1. Pre-eclampsia is diagnosed when hypertension (≥140/90 mmHg or 30/15 mmHg above the first trimester blood pressure) develops after the 20th week of gestation and is accompanied by proteinuria of at least 0.3 g in a 24-h specimen, and/or edema. Usually the edema is non-dependent and often located in the hands or face. The hypertension must be persistent (two measurements taken 6 h apart).
The severity of pre-eclampsia is further classified based on clinical symptoms and laboratory values. The clinical manifestations of severe pre-eclampsia are outlined in Table 1
Pre-eclampsia superimposed on chronic hypertension is a clinical entity that worsens the prognosis for both mother and fetus and warrants closer monitoring for its development during pregnancy in a woman whose blood pressure is elevated. Patients with chronic hypertension are at increased risk for developing pre-eclampsia during the pregnancy 6,7 and differentiation between worsening chronic hypertension versus the development of pre-eclampsia should be made. Factors which may help in distinguishing these two entities are (1) new-onset proteinuria in women with hypertension who did not have proteinuria prior to 20 weeks’ gestation, (2) a sudden increase in proteinuria, (3) a sudden worsening of blood pressure in a previously well-controlled, compliant patient, (4) abnormal laboratory values known to be associated with pre-eclampsia, especially low platelet count or elevated transaminases (1).
Gestational hypertension is classified as hypertension detected after 20 weeks’ gestation in the absence of proteinuria or edema. This term is limited only to those patients who do not develop pre-eclampsia by the time of delivery and whose blood pressure returns to normal in the postpartum period. If the hypertension persists well beyond the pregnancy, then the diagnosis of chronic hypertension is given.
Conventional blood pressure assessment
There have been a number of criticisms of conventional blood pressure measurement in diagnosing and managing the hypertensive pregnant patient. Although the mercury column sphygmomanometer is still considered the most accurate clinical instrument for blood pressure measurement, both equipment and observer error have been implicated in providing inaccurate blood pressure measurements. Improper cuff size, for example, is a common reason for discrepancies noted with conventional blood pressure assessment. A standard cuff and bladder size should be used on patients with a mid-biceps arm circumference <32 cm, while a large cuff is more appropriate for those patients with an arm circumference ≥33 cm.
Observer error and bias are additional problems that may be encountered with conventional blood pressure assessment. Error may occur as a result of fatigue, poor memory, decreased visual or auditory acuity, and poor interpretation of Korotkoff sounds 8. Observer bias often results from the tendency to ‘normalize’ blood pressure 9 as well as the practice of rounding off measurements to the nearest 5 or 10 mmHg 10.
An additional limitation of conventional blood pressure measurement in pregnancy is the controversy of whether to use Korotkoff phase IV (muffling of sounds) vs phase V (disappearance of sounds) to record diastolic blood pressure. In the past, phase IV was accepted as more reproducible and a better estimate of diastolic pressure 11,12. However, more recent data support the use of Korotkoff phase V in pregnancy 13. The Report of the National High Blood Pressure Education Program Working Program on High Blood Pressure in Pregnancy recommends the use of phases I and V for determining systolic and diastolic pressures, respectively 1.
Ambulatory blood pressure monitoring in pregnancy
Ambulatory blood pressure monitoring (ABPM) allows multiple recordings of blood pressure in an out-of-office environment, thus providing a better estimate of actual blood pressure levels and variability. In addition, ABPM records blood pressure changes in response to physical and mental activity, which is not achieved by office blood pressure monitoring. These benefits are well documented in the non-pregnant patient, and the growing body of literature over the past 8 years indicates a heightened interest in ABPM among pregnant patients as well.
Several studies have been published on the patterns of ABPM in normal pregnancy (Table 2). Marguiles et al. were among the first to describe the 24-h blood pressure profile in 11 normotensive pregnant women in the third trimester 14. Although these women were hospitalized during the monitoring session, they described a similar pattern of 24-h blood pressure to that of nonpregnant patients, as well as a significant difference between awake and sleep blood pressures.
Since then, two larger studies have further evaluated the ambulatory blood pressure patterns in healthy normotensive women. Halligan et al. studied ABPM in 106 primigravid white women at three points during the pregnancy (9–16 weeks, 18–24 weeks, and 33–40 weeks) and 6 weeks postpartum 15. The study was strengthened by (1) a high compliance rate (over 90% of the patients studied had at least four monitoring sessions), (2) a homogeneous patient population, and (3) evaluation at 6 weeks postpartum serving as a control period. The results showed no difference in systolic blood pressure between 9 and 33 weeks, but a significant rise from 33 to 40 weeks. There was a decrease in diastolic blood pressure between 18 and 24 weeks, and a significant increase from 33 to 40 weeks. Postpartum blood pressures were significantly higher than the first trimester readings.
Contard et al. 16 performed ABPM on 48 patients at three points during the pregnancy (3, 6, and 9 months). This group of patients was less homogeneous than the group studied by Halligan et al. Additional limitations of the study included: (1) lack of a non-pregnant control group, and (2) the monitor used by some of the study patients had not been validated in pregnancy. Still, their results showed that blood pressures were lowest in the first trimester with significant increases in 24-h diastolic blood pressure, daytime diastolic blood pressure, night-time systolic and diastolic blood pressure between the second and third trimesters. All patients demonstrated a significant decrease in sleeping blood pressure when compared with the awake blood pressure.
Finally, Ferguson and coworkers published a cross-sectional study of ABPM in 150 women at different gestational ages 17. The women were equally divided so that 50 were monitored between 18–24 weeks, 50 between 30–32 weeks, and 50 between 36–38 weeks. Using a non-pregnant control group for comparison, the study patients had significantly higher ambulatory blood pressure at 36–38 weeks’ gestation as compared with the other two gestational groups.
ABPM as a predictor of perinatal outcome
Few researchers have studied the predictive value of ABPM as a screening tool for pre-eclampsia. In the British literature, two papers have been published addressing this issue. Kyle et al. studied 162 nulliparous women with no other risk factors for pre-eclampsia by performing ABPM at two points in the pregnancy (18 and 28 weeks’ gestation). Patients were followed until delivery to determine which ones developed pre-eclampsia 18. They obtained adequate results on 127 women and showed that awake and mean arterial pressures were significantly higher at 18 weeks in those patients who eventually developed pre-eclampsia compared to those who did not. However, the difference between the two groups was relatively small from a clinical standpoint (mean differences ranging between 2.3 and 6.9 mmHg). The sensitivity in predicting pre-eclampsia for a mean 24-h arterial pressure of ≥85 mmHg at 28 weeks’ gestation was 65% with a positive predictive value of 31%. One limitation of this study was the unusually high incidence of pre-eclampsia in the study group (13%). This may have occurred as a result of their non-traditional definition of pre-eclampsia (diastolic blood pressure ≥25 mmHg above baseline).
A larger study by Higgins and colleagues 19 evaluated ABPM as a tool to predict pre-eclampsia in 1102 nulliparous women. The definitions of pre-eclampsia and gestational hypertension were much more stringent than in the study of Kyle et al. 18, resulting in a smaller percentage of patients with these diagnoses (2.1 and 5.8%, respectively for pre-eclampsia and gestational hypertension). Again, both hypertensive groups had significantly higher ambulatory blood pressures than the normotensive group, but the differences were small. The best predictor of pre-eclampsia was a 24-h mean diastolic blood pressure ≥71 mmHg, which had an extremely low sensitivity of 22% and a positive predictive value of just 15%. The conclusion of the authors was that second trimester ABPM was not a clinically useful modality in predicting pre-eclampsia in a healthy primigravid population.
Bellomo and Verdecchia 20 reported from Italy on a prospective cohort study in pregnant women with elevated blood pressures in the medical care environment using ambulatory monitoring to rule out a significant white-coat effect. Women with 24-h ambulatory blood pressures less than 125/74 mmHg but with office pressures >40/90 mmHg were classified as having ‘white-coat’ hypertension. Patients with white-coat hypertension had a significantly lower risk of developing pre-eclampsia than women with elevated ambulatory blood pressures or ‘true hypertension’ (7.1 vs 61.7%). In addition, the authors showed a higher cesarean rate, lower birthweight, and longer hospital stay for both mothers and neonates in the true hypertensive group compared to the normotensives and white-coat hypertensive groups.
While this study is quite an important contribution to the maternal–fetal medicine literature, it does have certain limitations. For example, the 24-h blood pressure monitoring was performed on just one fixed occasion during the pregnancy (at 35 weeks’ gestation) and the patients were admitted to the hospital for the entire recording period. By admitting patients to the hospital where physical and mental activities are substantially reduced compared with home and work environments, these blood pressure values may not have represented values that were representative of the average daily ambulatory blood pressure for most of the patients. In addition, 75% of the patients with hypertension in the study were started on antihypertensive therapy in the third trimester. As it is not routine practice to medically treat gestational hypertension or pre-eclampsia in many countries, including the USA, results of a similarly designed study in another population could have quite different outcomes. Finally, self (or home) blood pressure monitoring was not performed in the Italian study. This might be of relevance since self-monitoring is far easier to accomplish in clinical practice than ambulatory blood pressure monitoring for a variety of reasons and is less costly 21.
A few studies evaluating the association between ambulatory blood pressure and fetal growth have been published since 1996. Churchill et al. studied 209 healthy nulliparous pregnant women by monitoring ambulatory blood pressure at three different points during pregnancy 22. The results of this study showed a continuous inverse relationship between fetal growth and maternal blood pressure. A 5 mmHg increase in mean 24-h diastolic blood pressure at 28 weeks’ gestation was associated with a 68 g decrease in birthweight. A similar elevation of diastolic blood pressure at 36 weeks’ corresponded to a 76 g decrease in birthweight. These findings were independent of confounding variables such as maternal cigarette smoking, age, alcohol intake, and preterm delivery. Peek et al. 23 and Halligan et al. 24 found similar results in their studies: elevated ambulatory blood pressure correlated better with small-for-gestational age infants than conventional blood pressure assessment.
Finally, Benedetto et al. 25 evaluated a two-stage screening protocol for detecting pre-eclampsia and fetal growth restriction using ABPM and uterine Doppler ultrasound. The study population consisted of 180 pregnant women with at least one risk factor for pre-eclampsia. Each patient underwent uterine artery Doppler ultrasound and ABPM between 20 to 24 weeks’ gestation, and patients were followed until delivery. The rates of pre-eclampsia, gestational hypertension, and fetal growth restriction were assessed. Thirty-three (18%) patients developed pre-eclampsia with or without fetal growth restriction, and 20 (11%) developed fetal growth restriction alone. When both the uterine artery Doppler studies and results ABPM were abnormal, the sensitivity to predict pre-eclampsia was only 58% with a positive predictive value of 63%. Both sensitivity and predictive values were less in detecting fetal growth restriction without pre-eclampsia (30 and 20%, respectively). A summary of the reports on ABPM and pregnancy outcome is shown in Table 3
ABPM in pregnant patients with chronic hypertension
Patients with chronic hypertension who become pregnant are at increased risk for developing pre-eclampsia compared to those women without hypertension prior to the pregnancy. The American College of Obstetrics and Gynecology Technical Bulletin on Hypertension in Pregnancy reports a risk ratio for the development of pre-eclampsia of 10:1 in women with hypertension antedating the pregnancy 2. This risk ratio represents data from various studies evaluating the incidence of pre-eclampsia in these women (which ranges from 25 to 50%)6,7.
Studies of ABPM in pregnant women with pre-existing hypertension have been more promising in the detection of pre-eclampsia and poor perinatal outcome than studies in healthy normotensive women. Halligan et al. used a linear regression model to identify a significant correlation between day and night, systolic and diastolic blood pressure and 24-h urine protein levels 24. In contrast, no correlation was detected using the office or obstetric day unit blood pressure. Peek and coworkers 23 noted that a systolic blood pressure cut-off of 140 mmHg on ABPM showed a strong relationship with preterm delivery (relative risk (RR) 2.14, P = 0.025), small-for-gestational-age infants (RR 2.22, P = 0.02), and admission to the neonatal special care nursery (RR 2.67, P = 0.014). Although there was an association between elevated ambulatory systolic blood pressure and proteinuria, this did not reach statistical significance (RR 1.68, P = 0.068. A stronger association was made for elevated ambulatory diastolic blood pressure >90 mmHg and proteinuria (RR 1.82, P = 0.03). These data suggest that there is a promising role for ABPM in women with chronic hypertension or other significant risk factors in predicting worsening of disease and development of superimposed pre-eclampsia with its inherent perinatal morbidity.
ABPM in pregnant women with type 1 diabetes
Pregnant patients with type 1 diabetes have an increased incidence of developing pre-eclampsia, which has been reported to be as high as 20% compared to the baseline population of 6–7%26,27. Flores et al. reported on the ability of ABPM to predict the development of pre-eclampsia in this high-risk population 28. They studied 22 normotensive diabetic women and 10 normal controls by monitoring 24-h blood pressure in all three trimesters of pregnancy. Despite the small numbers, the authors showed that the incidence of pre-eclampsia was fourfold greater in the diabetic women versus controls. The diabetics had a higher mean 24-h diastolic blood pressure in the third trimester than controls, and those who developed pre-eclampsia had higher blood pressure profiles in all three trimesters. The best predictor of pre-eclampsia in this study was a night-time systolic blood pressure of >105 mmHg in the second trimester (85% sensitivity, 92% specificity).
Overall, ABPM has become a clinically useful modality in blood pressure assessment during pregnancy. The growing body of literature on ABPM in pregnancy indicates heightened interest in this area. Several ABPM devices have been validated in pregnancy 29. However, the role of ABPM in managing pregnant patients with hypertension and predicting perinatal outcome has yet to be determined in a well-controlled, prospective manner.
Home blood pressure monitoring in pregnancy
Automated self-monitoring blood pressure devices are currently commercially available and provide an inexpensive and non-invasive method of blood pressure assessment outside of the medical care environment. They provide a more realistic estimation of true blood pressure, and are especially useful in rural areas where frequent visits to a medical facility are difficult. While the use of these devices has been well-established in the non-pregnant population 30, there has been much less widespread use of home blood pressure monitoring in pregnancy. Unlike ABPM, there is a paucity of literature on the subject of home or self-blood pressure assessment in pregnancy. In a study by Naef et al. 30, a small number of patients with chronic hypertension were prospectively evaluated by recording their blood pressure at home four times a day using an electronic transtelephonic blood pressure monitor (VasoPlex home blood pressure monitor, American Medical Systems, Pittsburgh, PA, USA). The patients participated in the study for an average of 12.2 ± 5.8 weeks at gestational ages that were in the range 23–42 weeks. None of the patients had difficulty using the home monitor, and most found the device helpful in managing their hypertension and avoiding unnecessary visits to their care provider. Their data also showed that mean arterial pressure and heart rate were significantly higher in the office than at home. Although limited by its small sample size, this study represents one of the few published papers addressing home or self-blood pressure monitoring in pregnancy.
In 1997, Gupta et al. evaluated the accuracy of the Omron HEM 705 CP oscillometric home blood pressure device (Omron Healthcare Inc., Vernon Hills, IL, USA) in pregnancy and pre-eclampsia 31. After testing the device according to the British Hypertension Society protocol in 85 women with a wide variety of blood pressures and 43 women with pre-eclampsia, they found that the device did reach a ‘B’ grading for the pregnant population. However, in the pree-clamptic population, the device did not reach acceptable accuracy criteria, receiving a grade ‘C’ for systolic blood pressure and a grade ‘D’ for diastolic blood pressure. In addition, the device failed to meet the criteria for Association for the Advancement of Medical Instrumentation (AAMI) in both the pregnant and pre-eclamptic populations.
This study emphasizes the importance of device validation specifically in pregnancy and pre-eclampsia. It also suggests that validation guidelines should possibly be re-evaluated for pregnant patients. The hemodynamic changes that occur in healthy pregnant women are outlined in Table 4. Further changes occur in pre-eclampsia such as systemic vasospasm and reduced circulatory volume, thereby complicating the issue of device validation in these patients. To date, few studies have been performed to validate home blood pressure monitors in pregnancy. In addition, although several ambulatory blood pressure monitors have been validated in pregnancy, there is only one that has been assessed for precision in pre-eclampsia 29
Since the 1980s, the importance of ambulatory and home blood pressure monitoring in diagnosing and managing hypertensive patients has been well established. In pregnancy, there is a growing interest in these forms of out-of-office blood pressure assessment as evidenced by numerous publications in the obstetric and hypertension literature. However, further research is needed in order to better define the role of ambulatory and home blood pressure monitoring in both routine and high-risk obstetric practice.
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