Blood pressure patterns in normal pregnancy, gestational hypertension, and preeclampsia.

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 (P:<0.001 in all cases). The differences in circadian rhythm-adjusted mean between complicated and uncomplicated pregnancies are highly statistically significant in all trimesters (always P:<0.001). 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 P:<0.004). 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 (P:=0.022) but not for diastolic blood pressure (P:=0.986). In the third trimester, the difference in circadian mean is highly statistically significant for both variables (P:<0.001). 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.

Administration time-dependent effects of aspirin in women at differing risk for preeclampsia.

This study extends previous results on the effects of low-dose aspirin on blood pressure in pregnant women at differing risk of developing hypertension in pregnancy and who received aspirin at different times according to their rest-activity cycle. A double-blind, randomized, placebo-controlled trial was conducted in 240 pregnant women randomly assigned to 1 of 6 groups according to treatment (placebo or aspirin, 100 mg/d, starting at 12 to 16 weeks of gestation) and the time of treatment: on awakening (time 1), 8 hours after awakening (time 2), or before bedtime (time 3). Blood pressure and heart rate for each subject were automatically monitored for 2 days every 4 weeks from the day of recruitment until delivery, as well as at puerperium (6 to 8 weeks after delivery). Subjects were further divided for comparative purposes according to the results of the tolerance-hyperbaric test for early identification of those with a higher risk for developing hypertensive complications in pregnancy. Results indicated that there was no effect of aspirin on blood pressure at time 1 (compared with placebo). A blood pressure reduction was, however, highly statistically significant at time 2 and, to a greater extent, at time 3 (mean reductions of 14.2 and 9.6 mm Hg in 24-hour means for systolic and diastolic blood pressure, respectively, at the time of delivery compared with placebo given at the same time). Effects of aspirin on blood pressure were significantly larger for women with a positive test at the time of recruitment (P<0.001). Differences in blood pressure among pregnant women receiving aspirin at different times in the circadian cycle disappeared at puerperium (P>0.212). There was no effect of aspirin or placebo on heart rate. This study corroborates the statistically significant, time-dependent effect of low-dose aspirin on blood pressure in pregnant women with differing risk of developing hypertensive complications in pregnancy. Although the mechanism involved in the administration-time-dependent responsiveness of blood pressure to aspirin still remains uncertain, the use of doses of aspirin <80 mg/d that do not affect placental thromboxane, initiation of the use of aspirin after 16 weeks' gestation, and the lack of circadian timing for aspirin administration could all explain the lack of positive results in previous clinical trials.

Blood pressure excess for the early identification of gestational hypertension and preeclampsia.

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.

Time-dependent effects of low-dose aspirin administration on blood pressure in pregnant women.

This study investigated the effects of low-dose acetylsalicylic acid (aspirin) on blood pressure in pregnant women who were at risk of developing gestational hypertension or preeclampsia and who received aspirin at different times of the day according to their rest-activity cycle. A double-blind, randomized, controlled trial was conducted in 100 pregnant women. Blood pressure for each subject was automatically monitored for 2 days every 4 weeks from the day of recruitment until delivery. Women were randomly assigned to one of six groups according to treatment (placebo, 50 subjects or aspirin, 100 mg/d, starting at 12 to 16 weeks of gestation) and the time of treatment: on awakening (time 1), 8 hours after awakening (time 2), or before bedtime (time 3). Results indicated that there was (1) no effect on blood pressure from placebo at any time (P>.212) and (2) a highly statistically significant (P<.001) time-dependent effect on blood pressure from aspirin. There was no effect of aspirin on blood pressure at time 1 (compared with placebo), but the blood pressure reduction was highly statistically significant after time 2 and, to a greater extent, after time 3 (mean reduction of 12 and 8 mm Hg in 24 hours for systolic and diastolic blood pressure, respectively, at the time of delivery compared with placebo given at the same time). These time-dependent effects of aspirin on blood pressure should be taken into account for the optimization of long-term aspirin administration at low doses for prevention of preeclampsia. In any meta-analysis of aspirin effects, inquiries about the time when the subjects took the drug are indicated and may account for discrepancies in the literature.

Blood pressure variability during gestation in healthy and complicated pregnancies.

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.

High sensitivity test for the early diagnosis of gestational hypertension and preeclampsia. IV. Early detection of gestational hypertension and preeclampsia by the computation of a hyperbaric index.

UNLABELLED: The aims of this study were to examine whether the combined approach of 1) establishing tolerance intervals for the circadian variability of blood pressure as a function of gestational age, and 2) computing the hyperbaric index by comparison of any patient's blood pressure profile (obtained by ambulatory monitoring) with the tolerance limits, provides a new highly sensitive test for the early detection of gestational hypertension and preeclampsia. We analyzed a total of 745 blood pressure series sampled by ambulatory monitoring for about 48 hours in each of several occasions in 189 women with uncomplicated pregnancies, 71 with gestational hypertension, and 29 with preeclampsia. After synchronization of all data by expressing times of sampling in hours from bed-time, circadian tolerance limits were first computed from the normotensive subjects as a function of trimester of pregnancy. The hyperbaric index and the percentage time of excess were then computed for each individual blood pressure series. The maximum hyperbaric index was below 15 mmHg X hour for normotensive pregnant women in all trimesters of pregnancy, and mostly above that value for women who subsequently developed gestational hypertension or preeclampsia. Sensitivity of the test based on the maximum hyperbaric index was 97% for women sampled during the first trimester of gestation, and increased up to 100% in the third trimester. The positive predictive value was 100% in all trimesters. Moreover, the computation of the hyperbaric index provided, on the average, an early identification of gestational hypertension or preeclampsia 20 weeks prior to the clinical confirmation of the disease. CONCLUSIONS: Ambulatory monitoring of blood pressure during gestation provides sensitive endpoints for use in early risk assessment and as a guide for establishing preventive interventions. The approach presented here represents a simple, reproducible, non-invasive, and highly sensitive test for the very early identification of gestational hypertension and preeclampsia.

High sensitivity test for the early diagnosis of gestational hypertension and preeclampsia. I. Predictable variability of cardiovascular characteristics during gestation in healthy and hypertensive pregnant women.

The evaluation of predictable variability in blood pressure and heart rate by (a) the use of fully ambulatory devices, and (b) the proper processing of the time series thus obtained, can be useful in assessing early cardiovascular disease risk in pregnancy. We have used this approach to quantify a predictable time structure of blood pressure throughout pregnancy in clinically healthy women as well as in pregnant women who developed gestational hypertension of preeclampsia. We analyzed a total of 745 blood pressure series sampled by ambulatory monitoring for about 48 hours in each of several occasions in 189 women with uncomplicated pregnancies, 71 with gestational hypertension, and 29 with preeclampsia. 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. Regression analysis 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 20th week of pregnancy, followed by an increase in blood pressure up to the day of delivery. Women with gestational hypertension or preeclampsia are characterized, however, by a continuous linear increase of blood pressure with gestational age, starting from the beginning of pregnancy. 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 endpoints for an early identification of gestational hypertension and preeclampsia.

[Use of diazepam during labor]. / Considérations sur l'emploi du diazépam au cours de l'accouchement

The effect of diazepam has been watched and studied by continuing monitoring of the heart rate of the mother, the fetus and the newborn, as well as by studying the acid-base balance of the mother and the fetus and the newborn after doses of 20 mg of diazepam had been given to 40 normal labouring women. A good calming effect was found in 87 p. % of women and the remainder had an acceptable result. Both in the mother and in the fetus tachycardia resulted from injection of diazepam as well as a lessening in the frequency of changes in the heart rate. These two alterations were statistically significant (p less than 0.01) and appeared very soon after the administration of the diazepam. Later, no other effects could be found in the mother, the fetus or the newborn.