Abstract-With the aim to describe the daily pattern of blood pressure during the trimesters of pregnancy in clinically healthy women as well as in pregnant women who developed gestational hypertension or preeclampsia, we analyzed 1494 blood pressure series systematically sampled by ambulatory monitoring for 48 hours every 4 weeks after the first obstetric visit in 124 women with uncomplicated pregnancies, 55 with gestational hypertension, and 23 with a final diagnosis of preeclampsia. The circadian pattern of blood pressure variation for each group and trimester of gestation was established by population multiple-component analysis. A highly statistically significant circadian pattern represented by a linear model that includes components with periods of 24 and 12 hours is demonstrated for systolic and diastolic blood pressure for all groups of pregnant women in all trimesters (PϽ0.001 in all cases). The differences in circadian rhythm-adjusted mean between complicated and uncomplicated pregnancies are highly statistically significant in all trimesters (always PϽ0.001). There is also a statistically significant difference in circadian amplitude (extent of daily change) of blood pressure between healthy and complicated pregnancies in all trimesters (always PϽ0.004).Results further indicate similar circadian characteristics between women who later developed gestational hypertension or preeclampsia in the first trimester of pregnancy. The difference between these 2 groups in circadian mean is statistically significant in the second trimester for systolic (Pϭ0.022) but not for diastolic blood pressure (Pϭ0.986).In the third trimester, the difference in circadian mean is highly statistically significant for both variables (PϽ0.001).The differences in blood pressure between healthy and complicated pregnancies can be observed as early as in the first trimester of pregnancy. Those highly significant differences are found when both systolic and diastolic blood pressure for women with a later diagnosis of gestational hypertension or preeclampsia are well within the accepted normal physiological range of blood pressure variability. These differing changes in the circadian pattern of blood pressure with advancing gestational age between healthy and complicated pregnancies offer new end points that may lead to an early identification of hypertensive complications in pregnancy as well as to the establishment of prophylactic intervention. Key Words: blood pressure Ⅲ circadian rhythm Ⅲ pregnancy Ⅲ hypertension, gestational Ⅲ normotension Ⅲ preeclampsia B lood pressure (BP) assessment in pregnant women has relied mostly on a few measurements taken in the physician's office. These casual time-unspecified measurements perform poorly, even in the third trimester of pregnancy, in selection of a population for potential detection of preeclampsia. 1-6 Isolated BP measurement is, however, still the mainstay of the diagnosis of preeclampsia. The use of a reliable and accurate automated device for ambulatory BP monitoring (ABPM) is the l...

Preeclampsia and gestational hypertension are major contributors to perinatal morbidity and mortality. Several studies aimed to test the effects of low-dose aspirin (ASA) in the prevention of preeclampsia concluded that the beneficial effects of such treatment outweigh adverse ones. Such benefits have not been fully corroborated by larger randomized trials usually carried out in low-risk women, testing a dose of 60 mg/d ASA presumably ingested in the morning, and including women randomized as late as at 26-32 wks of gestation. The authors conducted a prospective, randomized, double-blind, placebo-controlled, chronotherapy trial on 350 high-risk pregnant women (183 nulliparous), 30.7 ± 5.3 (mean ± SD) yrs of age, and 13.5 ± 1.4 wks of gestation at the time of recruitment. Women were randomly assigned to one of six groups, defined according to treatment (placebo or ASA, 100 mg/d) and time of treatment: upon awakening, 8 h after awakening, or at bedtime. Intervention started at 12-16 wks of gestation and continued until delivery. Blood pressure (BP) was measured by ambulatory monitoring (ABPM) for 48-h at baseline, every 4 wks until the 7th month of gestation, every 2 wks thereafter until delivery, and at puerperium. The effects of ASA on ambulatory BP were markedly dependent on administration time: there was no effect on BP, compared with placebo, when ASA was ingested upon awakening, but the BP reduction was highly statistically significant when low-dose ASA was ingested 8 h after awakening and, to a greater extent, at bedtime (p < .001). At puerperium, 6-8 wks after discontinuation of treatment, there was no statistically significant difference in 24-h BP means between the groups of women who ingested ASA at different circadian times. Women ingesting low-dose ASA, compared with placebo, evidenced a significantly lower hazard ratio (HR) of serious adverse outcomes, a composite of preeclampsia, preterm delivery, intrauterine growth retardation (IUGR), and stillbirth (.35, 95% confidence interval [CI]: .22-.56; p < .001). The HR of individual outcome variables, i.e., preeclampsia, preterm delivery, IUGR, and gestational hypertension, were also significantly lower with ASA versus placebo (p always < .041). There were small and nonsignificant differences in outcomes between placebo and low-dose ASA ingested upon awakening. These four groups combined showed highly significant greater event rate of serious adverse outcomes than women ingesting ASA either in the evening or at bedtime (HR: .19, 95% CI: .10-.39; p < .001). There was no increased risk of hemorrhage, either before or after delivery, with low-dose ASA relative to placebo (HR: .57, 95% CI: .25-1.33; p = .194). Results indicate that (i) 100 mg/d ASA should be the recommended minimum dose for prevention of complications in pregnancy; (ii) ingestion of low-dose ASA should start at ≤16 wks of gestation; and (iii) low-dose ASA ingested at bedtime, but not upon awakening, significantly regulates ambulatory BP and reduces the incidence of preeclampsia, gestational hy...

Abstract-We have examined prospectively whether the combined approach of establishing tolerance intervals for the circadian variability of blood pressure (BP) as a function of gestational age, and then determining the so-called hyperbaric index (area of BP excess above the upper limit of the tolerance interval) by comparison of any patient's BP profile (obtained by ambulatory monitoring) with those intervals provides a high sensitivity test for the early detection of pregnant women who subsequently will develop gestational hypertension or preeclampsia. We analyzed 657 BP series from 92 women with uncomplicated pregnancies and 378 series from 60 women who developed gestational hypertension or preeclampsia. BP was sampled for about 48 hours once every 4 weeks after the first obstetric consultation. Circadian 90% tolerance limits were determined as a function of trimester of gestation from 497 series previously sampled from a reference group of 189 normotensive pregnant women. The hyperbaric index was then determined for each individual BP series in the validation sample. Sensitivity of this test for diagnosing gestational hypertension was 93% for women sampled during the first trimester of gestation and increased up to 99% in the third trimester. The positive and negative predictive values were above 96% in all trimesters. Despite the limitations of ambulatory monitoring, the approach presented here, now validated prospectively, represents a reproducible, noninvasive, and high sensitivity test for the very early identification of subsequent gestational hypertension and preeclampsia, on the average, 23 weeks before the clinical confirmation of the disease. Key Words: Ⅲ blood pressure Ⅲ diagnostic test Ⅲ tolerance intervals Ⅲ hyperbaric index Ⅲ human pregnancy Ⅲ normotension Ⅲ hypertension, gestational Ⅲ preeclampsia I n order to predict the occurrence of gestational hypertension or even preeclampsia, several (clinical, biochemical, and biophysical) tests have been designed with various degrees of specificity and sensitivity.1 Gant et al 2 proposed the roll-over or supine pressor test for predicting the development of acute hypertension in pregnancy. The results of this test are highly variable among different investigators, and there is poor reproducibility in the same patient.1 Therefore, although the roll-over test has gained some popularity because of its simplicity, it is of little use clinically as a predictive test. Intravenous infusion of angiotensin II was reported to cause a smaller rise in BP in pregnant women than in nonpregnant women.3 These results were complemented by the finding that the relative refractoriness to the pressor effects of angiotensin II is lost to a marked extent in women who subsequently developed preeclampsia. [4][5][6] As for the roll-over test, sensitivity and specificity of the angiotensin II test varied greatly among different studies. Moreover, this test is too complicated and time consuming to be used as a clinical screening procedure. 1Because an elevated BP is the hallmark fo...

The evaluation of predictable variability in blood pressure by the use of ambulatory devices, and the proper processing of the time series thus obtained, can be useful for the early assessment of hypertensive complications in pregnancy. We have used this approach to quantify a predictable pattern of blood pressure and heart rate throughout pregnancy in clinically healthy women as well as in pregnant women who developed gestational hypertension or preeclampsia. We analyzed 503 blood pressure series from 71 healthy pregnant women and 256 series from 42 women who developed gestational hypertension or preeclampsia. Blood pressure monitoring (48-hour) was done once every 4 weeks after the first obstetric consultation. The pattern of variation along gestation of the 24-hour mean of blood pressure for groups of normotensive and hypertensive pregnant women was established by polynomial regression analysis. This method revealed predictable patterns of variation of 24-hour means with gestational age: for normotensive pregnant women, results indicate a steady decrease in blood pressure up to the 21st week of pregnancy, followed by an increase in blood pressure up to the day of delivery. This pattern of variation is not found in pregnancies complicated with gestational hypertension or even preeclampsia: the 24-hour mean of blood pressure is stable until the 22nd week of pregnancy and then correlated with gestational age, indicating a significant linear increase of blood pressure in the second half of pregnancy. For both healthy and complicated pregnancies, heart rate slightly increases until the end of the second trimester, and it is stable thereafter. This study confirms and extends to ambulatory everyday life conditions the predictable pregnancy-associated variability in blood pressure. The differences between uncomplicated and complicated pregnancies offer new end points for an early identification of gestational hypertension and preeclampsia.