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(Hypertension. 1997;30:611.)
© 1997 American Heart Association, Inc.
Articles |
Blood Pressure Variability During Gestation in Healthy and Complicated Pregnancies
From the Bioengineering and Chronobiology Laboratories, ETSI Telecomunicación, University of Vigo, Campus Universitario, Vigo (D.E.A., R.C.H., A.M., J.R.F.); and the Obstetrics and Gynecology Department, Hospital General Clínico Universitario de Galicia, Medical School, University of Santiago, Santiago de Compostela (I.S., R.U., M.I.), Spain.
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Abstract |
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Abstract 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.
Key Words: blood pressure • heart rate • pregnancy • hypertension, gestational • preeclampsia
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Introduction |
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Pregnancies complicated by an elevated BP and/or preeclampsia contribute markedly to maternal mortality.1 Hypertension in pregnancy is also a major cause of intrauterine growth retardation, abruptio placentae, and preterm delivery, thus significantly increasing perinatal morbidity and mortality.2 3 4 5 It also appears that a history of preeclampsia or at least of gestational hypertension in a prior pregnancy places the pregnant woman and her offspring at a high risk for a later development of high BP 7 to 12 years later.6 Thus far, BP and HR assessment in pregnant women has relied mostly on a few measurements taken in the physician’s office. Such conventional time-unspecified single measurements may be misleading because BP and HR vary according to a spectrum of rhythms with several frequencies (the circadian in particular) and because measurements may be influenced by external and internal stimuli, among other factors, by the patient’s sleeping or waking schedule, physical activity, diet, and emotional state.7 8 9 10 The use of automatic instrumentation for indirect noninvasive ABPM has provided a method of BP assessment that may compensate for some of the limitations of casual measurements.11 12
In a study based on casual BP measurements, MacGillivray et al13 showed that BP fell in the second trimester and rose again in the third. Following the traditional approach to BP there have also been a few systematic studies of healthy pregnant women.12 Conclusions have been confounded by the fact that as BP rises in pregnancy, it is increasingly associated with preeclampsia even in the absence of any other sign or symptom of the condition.14 Only a few works, however, have been published on the 24-hour monitoring of BP in pregnancy.15 16 17 18 19 For the study of BP, the use of presently available automatic, fully ambulatory recording systems greatly facilitates data collection and, in combination with proper software, the interpretation of results. This approach can be useful in assessing early cardiovascular disease risk in pregnancy.20
Ayala and Hermida21 22 quantified predictable changes in the circadian characteristics of BP and HR in two consecutive pregnancies of a clinically healthy woman. These changes could not be found for data sampled during nonpregnancy in the same woman and over an equivalent span of time to what could have been her third pregnancy.23 24 The results from this preliminary study on only one (extensively documented) case have been validated from data sampled by ABPM in 289 pregnant women that provided a total of 745 series of BP in a study aiming at the provision of reference standards for BP in the course of a healthy pregnancy.24
In the attempt to corroborate and extend conclusions from this preliminary retrospective study, we here report results from an ongoing prospective study of BP variability during pregnancy. In particular, we quantified changes in circadian characteristics of BP along gestational age in clinically healthy pregnant women, as well as in pregnant women with gestational hypertension or preeclampsia that were systematically studied by ABPM from the first obstetric visit to the hospital until delivery.
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Methods |
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Subjects
We studied 113 white pregnant women (79 primipara). Of these women, 71 had uncomplicated pregnancies; 28 developed gestational hypertension, diagnosed by conventional BP values above 140/90 mm Hg for SBP/DBP without clinical record of hypertension previous to pregnancy. The remaining 14 women developed preeclampsia, here defined as gestational hypertension and proteinuria, above 300 mg/24 h in urine, with or without edema. All women received obstetric care at the Obstetric Physiopathology (high risk) Unit, Hospital General Clínico Universitario de Galicia, Santiago de Compostela, Spain. Reasons for receiving medical care at this unit include, among others, family or personal history of either gestational hypertension; preeclampsia; chronic hypertension; cardiovascular, endocrine, bleeding, or metabolic disease; or a personal history of previous spontaneous abortion, multiple pregnancy, obesity, and nulliparous pregnancy at less than 18 or more than 35 years of age. The incidence of gestational hypertension and preeclampsia in this unit is about three times that of the general obstetric population in our setting. Inclusion criteria were absence of any condition requiring the use of antihypertensive medication, age (18 to 40 years), and gestational age (less than 16 weeks at the time of inclusion). Exclusion criteria were, among others, multiple pregnancy, chronic hypertension, chronic liver disease, any disease requiring the use of antiinflammatory medication, diabetes, and any other endocrine disease such as hyperthyroidism, as well as the inability to tolerate the use of an ambulatory BP monitor. Subjects providing less than four BP profiles were eliminated from the study. All issues related to ABPM, including handling and preparation of the monitors, individualized explanation about their use to each patient, and processing of the data provided by any given pregnant woman after monitoring, were always carried out by the same members of the research group in one room of the unit. Conventional obstetric examinations of the pregnant women, usually done on the same day just before starting ABPM, were carried out by other members of the research group in different rooms of the unit. Diagnosis of gestational hypertension or preeclampsia (as defined above) was made using information from the conventional obstetric examinations and routine analyses of urine. The Ethics Committee of Clinical Research from the Medical School approved the study. All volunteers signed consent forms before entering the study.
BP Assessment
The SBP, MAP, DBP, and HR of each subject were
automatically monitored every 30 minutes during the day (9
AM to 10 PM) and hourly during the night for 48
hours with an ABPM-630 Colin device at the time of recruitment and then
every 4 weeks until delivery. BP series were eliminated from
analysis when they showed an irregular schedule during the days
of sampling, an odd sampling with spans of more than 3 hours without BP
measurement, or a night resting span shorter than 6 hours or longer
than 12 hours. The total number of BP series provided by the women
under investigation fulfilling all mentioned requirements set a
priori was 759. During sampling, all women were living on their usual
diurnal waking (
8 AM to 12 PM for most
subjects), nocturnal resting routine, following everyday life
conditions with minimal restrictions. They were told to follow a
similar schedule during the days of sampling and to avoid the use of
medication for the duration of the trial. The clinical evaluation of
the monitor according to the standards published by the Association for
Advancement of Medical Instrumentation25 has been
previously established.14 26 The BP cuff was worn on the
nondominant arm. ABPM was performed in addition to the woman’s routine
antenatal care, and no person was hospitalized during monitoring. Cuff
size was determined by upper arm circumference at the time of each
visit. ABPM always started between 10 AM and 1
PM. During monitoring, each subject maintained a diary
regarding information about their activity cycle, dietary consumption,
physical activity, emotional state, and other external or internal
stimuli possibly affecting BP.
The Colin instrument uses both an oscillometric and an auscultatory (Riva Rocci-Korotkoff) method to assess BP and HR. Since the oscillometric approach is usually more sensitive, there were fewer missing values (due to arm movement or environmental noise) with the oscillometric than auscultatory measurements. Moreover, when relying on the oscillometric measurements, the exact positioning of the cuff over the brachial artery is not critical. Consequently, a patient can take the cuff off, for example, to take a shower, exercise, or recharge the battery, and then replace it. The ability of the oscillometric technique to take accurate measurements in noisy environments and in the presence of a significant degree of respiration artifact are further advantages. Therefore, the results reported here focus on the oscillometric measurements.
Statistical Methods
Original oscillometric data were edited according to
commonly used criteria for the removal of outliers and measurement
errors.27 28 The remaining data were first
analyzed by the use of Chronolab,29 a software
package for biologic signal processing by linear and nonlinear
least-squares estimation that, among others, includes the single and
population-mean cosinor methods,30 as well as the
fit of multiple components.30 Each BP series was
analyzed by the least-squares fit of a multiple component
cosine curve with periods of 24 and 12 hours to determine the
rhythm-adjusted mean or MESOR (midline estimating statistic of rhythm)
and the amplitudes of both components. This model has been shown to
describe sufficiently well the circadian pattern of BP
variability,10 31 despite the fact that other ultradian
rhythms can be demonstrated as statistically significant in some but
not all individuals studied by 48-hour ABPM. Since the data were
obtained at an unequidistant sampling rate covering two cycles (48
hours), the MESOR provides a better estimation of the true 24-hour mean
than the average of all BP values (usually overestimating the true mean
due to the denser sampling during activity). The estimates of the
24-hour mean thus obtained for all BP series were used to establish
their pattern of variation along gestational age for groups of
uncomplicated and complicated pregnant women by polynomial regression
analysis.32
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Results |
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For the normotensive pregnant women, no difference was found between circadian BP characteristics obtained as a function of parity or age for any trimester of pregnancy. Data from the whole database were therefore pooled for subsequent analysis and only divided according to pregnancy outcome. Regression analysis of 24-hour means of BP obtained in 503 series sampled on clinically healthy pregnant women revealed a predictable pattern of variation with gestational age. The predictable variability in the circadian MESOR of BP can be approximated by a second-order polynomial model on gestational age (P<.001 for SBP, MAP, DBP, and pulse pressure computed at each sampling time as the difference between SBP and DBP). Results indicate a steady linear decrease in SBP (Fig 1, top), MAP (Fig 2, top), DBP (Fig 3, top), and pulse pressure (Fig 4, top) up to the 21st week of pregnancy, followed by an increase in BP up to the day of delivery, with final BP values similar to those found early in pregnancy for the same women. The top graphs on Figs 1 through 4 show this second-order pattern of variation. Each dot represents the circadian MESOR of BP values obtained by ABPM for 48 consecutive hours. The continuous line drawn in each graph represents the second-order model on gestational age obtained by polynomial regression analysis.
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This pattern of variation is not found in pregnancies complicated with gestational hypertension or even preeclampsia. In complicated pregnancies, the 24-hour mean of BP is stable until the 22nd week of pregnancy and then correlated with gestational age, indicating a significant linear increase of BP in the second half of pregnancy (linear correlation coefficient r=.591, P<.001 for SBP, bottom graph of Fig 1; r=.626, P<.001 for MAP, bottom graph of Fig 2; r=.572, P<.001 for DBP, bottom graph of Fig 3; r=.284, P<.001 for PP, bottom graph of Fig 4).
It is important to note that as represented in Figs 1 through 4, the 24-hour mean of BP at the beginning of gestation was similar for complicated and uncomplicated pregnancies. By the 14th week of gestation (end of the first trimester), the predictable trend of BP for women with gestational hypertension and preeclampsia reaches 113/65 mm Hg for SBP/DBP, whereas the second-order model of variation found for healthy pregnant women situates the level of mean BP on 102/59 mm Hg at the end of the first trimester of pregnancy. Differences in the 24-hour mean of BP between complicated and uncomplicated pregnancies can be observed, therefore, after the first few weeks of gestation, quite before the actual clinical diagnosis of gestational hypertension or preeclampsia took place for the women investigated.
For HR, Fig 5 shows a predictable pattern of slightly increasing values until the end of the second trimester and a stable HR thereafter. This predictable pattern of variation can be approximated by a second-order polynomial model on gestational age, equivalent for both complicated and uncomplicated pregnancies (P>.370 for the comparison of first- and second-order polynomial coefficients).
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Discussion |
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It is important to note that the total range of variation observed in the 24-hour mean (computed in each case from data representing about 48 hours of measurements) for clinically healthy pregnant women along gestation is of 25 and 21 mm Hg for SBP and DBP, respectively (Figs 1 and 3). For just one individual subject studied longitudinally along pregnancy, the range in daily average could be at least as wide as 27 and 22 mm Hg for SBP and DBP.22 24 This range is about three times larger if we consider individual observations instead of the 24-hour mean. The critical thresholds for BP of 140/90 SBP/DBP as recommended by the World Health Organization33 do not account for the large range of variation seen in these variables even within a single day. Usual tests for detecting gestational hypertension based on differences larger than 15 mm Hg in casual measurements of DBP34 are no longer valid in assessing gestational hypertension, since those differences can be found in the course of a healthy pregnancy (as indicated in Figs 1 through 3) not just for casual measurements but for the more stable and less noisy circadian MESOR.
The results agree with those found previously for a group of 189 normotensive pregnant women and another group of 100 women who developed gestational hypertension or preeclampsia providing 745 BP profiles in several stages of their pregnancies.24 These longitudinal results can also be compared with those of earlier studies35 on clinically healthy women monitored during at least two different stages of their pregnancies. Results showed, for SBP and DBP, a statistically significant decrease between the 12th and the 15th weeks and a statistically significant increase between the 30th and the 32nd weeks. The suggestion that the BP fall in clinically healthy pregnancies starts very early was also made by Halligan et al,17 in opposition to previous studies suggesting a BP fall only after the first half of pregnancy.36
In dealing with apparently healthy individuals, one important factor usually ignored when studying biological variables within conventional physiological normal ranges is the timing of a clinical measurement in relation to biological rhythms. Time-varying reference limits that adjust for the rhythmic behavior of BP have accordingly been suggested.9 10 37 These reference standards are derived from data provided by healthy peer groups, taking into consideration changes in mean and variance as a function of time. For the early diagnosis of gestational hypertension, those limits should be developed as a function of gestational age, taking into account the trends in BP dynamics throughout pregnancy shown in Figs 1 through 5. The next task is therefore to establish, for cardiovascular variables in a healthy pregnancy, proper reference limits from peer groups.37
This study represents an example of hybrid (transverse and longitudinal) monitoring in healthy and complicated pregnancies, keeping the everyday life conditions by the use of a fully ambulatory and noninvasive BP monitor. Limitations of this approach stem from the fact that instrumentation for automatic monitoring, although advanced, is not perfect and still quite expensive. This study confirms and extends to ambulatory everyday life conditions the predictable pregnancy-associated variability in BP and also allows the establishment of reference limits for cardiovascular parameters in a healthy pregnancy. Along these lines, the predictable variability of BP in human gestation offers new end points as reference standards for an early identification of gestational hypertension or even preeclampsia.20
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Selected Abbreviations and Acronyms |
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Acknowledgments |
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This research was supported in part by grants from Dirección General de Investigación Científica y Técnica (DGICYT), Ministerio de Educación y Ciencia (PB92-1111 and PB93-0372); Consellería de Educación e Ordenación Universitaria, Xunta de Galicia (XUGA-32203B93, 32205B95 and 32201B95); and Vicerrectorado de Investigación, University of Vigo.
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Footnotes |
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Reprint requests to Prof Ramón C. Hermida, PhD, Director, Bioengineering and Chronobiology Labs, ETSI Telecomunicación, Campus Universitario, Vigo (Pontevedra) 36200, Spain.
Received April 15, 1997; first decision May 19, 1997; accepted June 2, 1997.
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