1 Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA.
2 Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA.
3 Department of Biometry and Epidemiology, Medical University of South Carolina, Charleston, SC.
4 Yale Center for Perinatal, Pediatric, and Environmental Epidemiology, Yale School of Public Health, New Haven, CT.
Received for publication October 15, 2003; accepted for publication May 11, 2004.
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ABSTRACT |
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employment; exercise; hypertension; motor activity; pre-eclampsia; pregnancy
Abbreviations: Abbreviations: aOR, adjusted odds ratio; CI, confidence interval; LTPA, leisure-time physical activity.
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INTRODUCTION |
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Findings from the epidemiologic literature provide rational support for this mechanistic model. Factors consistent with an immune-based etiology include the higher risk after partner change among multiparous women with no prior preeclampsia (58), a short duration of sexual activity with the babys father at the time of conception (9), and conception aided by donor insemination or embryos (10, 11), as well as a protective effect of abortion among nulliparous women who conceive again with the same father (12). Numerous lines of evidence implicate oxidative stress as a causal mechanism. Cardiovascular disease and preeclampsia share both a common disease pathway (i.e., endothelial activation) and many of the same constitutional risk factors, including hypertension, dyslipidemia, insulin resistance, and obesity (1). Also suggestive are recent reports of reduced second trimester serum levels of vitamins C and E among women destined to develop preeclampsia (13).
Because regular physical activity has a beneficial effect on cardiovascular disease risk and insulin resistance, it is reasonable to hypothesize that regular physical activity might also decrease a womans risk of preeclampsia (14). We are aware of two studies that have examined an effect of leisure-time physical activity (LTPA) on risk of pre-eclampsia, both of which reported a protective effect (15, 16). Several other studies have found that employment in general or physically demanding work in particular was associated with increased risk of preeclampsia (1721). To our knowledge, just one study (15) examined the simultaneous effects of leisure-time activity and occupational physical activity on preeclampsia risk. The present study contributes to this very small body of literature with a comprehensive analysis of the independent and combined effects of LTPA and work activity on preeclampsia risk, based on prospectively collected exposure information.
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MATERIALS AND METHODS |
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Among the 415 subjects whose medical charts were reviewed a second time, 72 were excluded because of chronic hypertension, and 29 were excluded because they had some indication of hypertension but did not fully meet strict study criteria for preeclampsia or gestational hypertension. Of these women, 98 were found to be normotensive throughout pregnancy so they were included in the control group. Thus, 2,638 subjects were analyzed: 2,422 normotensive controls, 172 subjects with gestational hypertension, and 44 subjects with preeclampsia.
The study protocol and informed consent process were evaluated and approved by the Yale Human Investigations Committee.
Variables assessing work and leisure-time activity levels
We developed two different approaches to examine work activity using interview responses about the number of work hours per day spent standing, walking, and sitting: 1) sedentary versus nonsedentary work and 2) proportion of time on the job spent sitting (three levels). Women who spent more work time sitting than standing or walking were classified as "sedentary," while those who walked or stood more than they sat were "nonsedentary." The "proportional sitting" method involved calculating the fraction of each subjects work day spent sitting and then assigning those who spent less than one third of their day sitting to the "least sitting" group, those who spent between one third and two thirds of their day sitting to the "moderate sitting" group, and those who spent more than two thirds of their day sitting to the "highest sitting" group.
During the interview, subjects were asked if they engaged in exercise or sports at least once per week for the 12 months before pregnancy, as well as for early pregnancy up until the first interview (<16 weeks gestation). Those reporting exercise or sports were asked to indicate the types, average frequency each week, and average duration per exercise session. LTPA was evaluated as a dichotomous variable and as a cross-stratified variable with four levels (no LTPA before or during pregnancy; no LTPA before pregnancy/yes LTPA during pregnancy; yes LTPA before pregnancy/no LTPA during pregnancy; and yes LTPA before and during pregnancy). By definition, women who did not report regular physical activity expended zero calories per week in analyses of LTPA.
The number of calories expended on LTPA each week was derived by assigning a standardized energy expenditure value, a metabolic equivalent, to each reported activity, representing the intensity level of that activity (23). This metabolic equivalent value was then multiplied by prepregnancy weight (kg) and the weekly frequency and duration (hours) for each reported activity; then, scores were summed across all reported activities for each subject. LTPA calorie expenditure per week was analyzed in tertiles. Specifically, we divided control subjects whose calorie expenditures exceeded zero into three equal groups and applied the same tertile cutpoints to case subjects.
To account for work activity level while assessing LTPA level and vice versa, we created a cross-stratified variable consisting of four levels: 1) sedentary work/no LTPA (referent category); 2) sedentary work/some LTPA; 3) nonsedentary work/no LTPA; and 4) nonsedentary work/some LTPA. A second cross-stratification variable consisted of six levels, using the proportional sitting variable to represent work activity in place of the dichotomous variable for sedentary work: 1) least sitting/some LTPA; 2) least sitting/no LTPA; 3) moderate sitting/some LTPA; 4) moderate sitting/no LTPA; 5) highest sitting/some LTPA; and 6) highest sitting/no LTPA (referent group).
Statistical analyses
We evaluated selected risk factors as potential confounders of the associations of interest. Abortion and parity were evaluated using a cross-classified variable: 1) nulliparous/no abortions (referent group); 2) nulliparous/one or more abortions; and 3) multiparous, regardless of abortion history. Also evaluated for confounding were maternal age at delivery, body mass index (kg/m2), years of education, and cigarette smoking during pregnancy (up to the time of interview). Only those variables that produced at least a 10 percent change in the relative risk estimates for the leisure-time and work activity variables were retained in the final models for preeclampsia and gestational hypertension.
All statistical analyses were performed using SAS System for Windows, version 8 (SAS Institute, Inc., Cary, North Carolina). To compare the preeclamptic, gestational hypertensive, and control subjects, we conducted descriptive analyses using 2 tests to examine differences in frequency distributions and t tests for mean differences. Subjects who did not report LTPA and/or were among the most sedentary at work comprised the referent group for all analyses. The strength of the association between the primary exposure variables and the risk of preeclampsia and gestational hypertension was based on estimates of relative risk. Adjusted estimates of relative risk and the corresponding 95 percent confidence intervals were calculated from multivariate logistic regression models, which retained confounding variables.
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RESULTS |
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To examine the combined effects of LTPA during pregnancy (yes, no) and work activity (1: sitting time was less than the time spent walking and/or standing; 2: sitting time was greater than or equal to the time spent walking and/or standing), we cross-stratified these two variables in model 3 of table 2. Consistent with our previous findings, engaging in any work or LTPA during pregnancy was associated with a reduced risk of preeclampsia. More detailed cross-stratification of work activity (least, moderate, highest sitting) and LTPA during pregnancy (yes, no) further supported the observation that any regular physical activity at work or in leisure time confers protection against preeclampsia, relative to women who are both sedentary at work and do not engage in regular physical activity, as shown in model 4 of table 2.
In contrast to preeclampsia, analyses of gestational hypertension consistently showed no protective effect of work or LTPA, before or during pregnancy (table 3). When work activity was examined while controlling for LTPA, as shown in model 2 of table 3, the lowest risk of gestational hypertension was seen among women who sat the most at work. Increased risks were observed for unemployed women (aOR = 1.18, 95 percent CI: 0.70, 1.98) and those who were less sedentary on the job: moderate sitting (aOR = 1.21, 95 percent CI: 0.80, 1.85) or least sitting (aOR = 1.26, 95 percent CI: 0.83, 1.91). For LTPA during pregnancy, the only suggestion of a protective effect was seen among women engaged in moderate physical activity (aOR = 0.82, 95 percent CI: 0.51, 1.31).
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DISCUSSION |
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Two other studies of LTPA and preeclampsia conducted to date provide overall support for our findings. Marcoux et al. (15) controlled simultaneously for work activity and found a significantly reduced risk (aOR = 0.67, 95 percent CI: 0.46, 0.96) among recreational exercisers. Likewise, Sorensen et al. (16) found that any regular leisure-time exercise significantly decreased risk of preeclampsia (aOR = 0.65, 95 percent CI: 0.43, 0.99). The adjusted odds ratio of pre-eclampsia associated with any regular LTPA during pregnancy from our study (aOR = 0.66, 95 percent CI: 0.35, 1.22) is remarkably similar to the risk estimates reported by the other two studies (15, 16). Unlike our findings, both studies reported increased protection against preeclampsia with increasing levels of recreational exercise. While Sorenson et al. (16) did not assess work activity levels, they did account for "daily living" activities, such as walking and stair climbing, and found those activities to be protective against preeclampsia as well.
In contrast to our findings of LTPA and risk of gestational hypertension, Marcoux et al. (15) noted a nonsignificant protective effect. These same investigators reported no effect of work activity on the risk of gestational hypertension (15), assessed as frequent walking or standing during work hours. In contrast to one study (16), we found no direct association between preeclampsia and leisure-time activity before pregnancy; however, less than 6 percent of those who exercised during pregnancy did not exercise before pregnancy, suggesting that developing a pattern of activity before pregnancy may increase the likelihood of continuing that exercise during pregnancy, thus indirectly reducing preeclampsia risk.
Studies investigating the biochemical effects of physical activity have noted that regular exercise (as opposed to sporadic exercise) reduces oxidative stress by reducing lipid peroxidation (24) and increasing iron-binding capacity, antioxidant enzyme levels, and prostacyclin (a vasodilator), while reducing levels of thromboxane (a vasoconstrictor) (25, 26). These biochemical effects of regular exercise directly oppose those occurring in preeclampsia, suggesting that exercise could minimize or even prevent pathologic changes related to preeclampsia. Thus, there appears to be a clear biologic rationale to explain the protective effect of regular activity on the risk of preeclampsia. It is unclear why this protective effect did not generalize to gestational hypertension in our study, but it suggests that these two conditions have different or divergent pathologies.
Subjects in this study were categorized as engaging in LTPA only if they did so at least once per week (i.e., they are "regular" exercisers). It was not possible to assess the impact of sporadic exercise on the risk of preeclampsia. There is preliminary evidence indicating that intermittent exercise may increase oxidative stress, which could presumably increase the risk of preeclampsia (25). This complicates the assessment of physical activity, since it becomes essential to differentiate regular from irregular exercise. In studies relying on self-report for LTPA information, it is usually impossible to know to what extent sporadic exercise may be misreported as regular exercise.
Regarding work and preeclampsia, the findings of Marcoux et al. (15) agree with our results. Frequent walking or standing during work hours was associated with a decreased risk of preeclampsia, even after control for LTPA during pregnancy. However, most studies of work and pre-eclampsia did not directly examine the activity level at work, or they defined work activity differently, making comparisons with our study difficult. For example, Klebanoff et al. (18) found that female medical residents, who worked an average of 74 hours per week during their pregnancies, incurred more preeclampsia than did the wives of medical residents, who worked an average of 38 hours per week. It is difficult to discern whether the increased risk among female residents is due to the longer hours of physical activity or the psychosocial strain and other physical aspects of their jobs. Likewise, Mozurkewich et al. (17), in a meta-analysis, observed an increased risk of preeclampsia with physically demanding work. Physically demanding work was defined as heavy or repetitive lifting or load carrying, manual labor, or significant physical exertion and was not equivalent to our "nonsedentary work."
Spinillo et al. (21) directly assessed work activity levels but only in relation to severe preeclampsia outcomes. Like our study, their study found that "no work" was protective relative to work but, in contrast to our findings, their findings demonstrated that moderate- to high-activity work was associated with a twofold increased risk of preeclampsia relative to mild work activity (mostly sitting). Most of these studies did not consider LTPA (2729).
Most subjects in our study (82 percent) were employed, making it difficult to assess the effect of general employment status on preeclampsia risk. Our finding of a nonsignificant reduced risk of preeclampsia among unemployed women is supported by two other studies assessing blood pressure and preeclampsia in relation to work outside the home (30, 31). In both studies, an increase in blood pressure level was associated with work. One of these studies (30) found that work during pregnancy was also associated with later development of preeclampsia.
In our study, increasing activity levels in work and/or leisure time did not confer additional protection against preeclampsia. If replicated, these data suggest that interventions to prevent preeclampsia may not require strenuous exercise regimens. When interventions to reduce the risk of preeclampsia are prioritized, exercise may not be as important among patients who encounter physical activity at work.
Data collected via self-report are prone to misclassification. However, recall problems in this study were minimized because information on early pregnancy work and LTPA was collected in close temporal proximity to the reported behaviors and before diagnosis of preeclampsia or gestational hypertension. Another major strength is the use of medical chart review to apply consistent case definitions and to exclude subjects with preexisting hypertension. By including women with transient hypertension in our assessment, we are able to examine the specificity of the relation between activity level and preeclampsia.
Caution should be observed when generalizing these study findings to other populations. Women were recruited from private obstetric practices in the New Haven, Connecticut, area, reflecting predominantly White, well-educated women with middle-to-high socioeconomic status. In addition, our assessment did not consider physical activity in nonwork, nonstructured exercise situations, such as walking or biking to work, climbing stairs, caring for small children outside of work, and performing household chores. Ideally, we would have also followed subjects beyond delivery to exclude any whose hypertension persisted chronically, but this was beyond the scope of the parent study. Another study limitation is related to the effect that preeclampsia symptoms may have on activity level. By restricting our assessment to activity during early pregnancy (up to the time of the interview at less than 16 weeks gestation), we are presuming that preeclampsia symptoms have not yet manifested themselves and will not impact activity levels. However, it is theoretically possible that preeclampsia symptoms appear early in pregnancy but are not overtly recognized (an example of reverse causality). There are no data to address this possibility but, if true, the association between preeclampsia and activity level would be systematically biased toward detecting a protective effect of physical activity. By identifying early biochemical changes that occur with both preeclampsia and physical activity, it may be possible to overcome this limitation using a prospective study design.
Larger studies of preeclampsia and physical activity are needed, in which a more comprehensive measure of physical activity is used. Determining the nature of each physical activity may also be important (32). For example, the aerobic, continuous activity associated with many types of exercise may have a different effect than the intermittent and, thus, anaerobic activity associated with many work tasks or household chores. Ideally, future studies will prospectively collect biologic samples to examine markers of oxidative stress, to enable improved assessment of the association of physical activity and preeclampsia. Finally, such studies should also account for psychosocial stressors, which may help to explain the distinct risk patterns associated with gestational hypertension relative to preeclampsia, since stressors are likely to be related to both physical activity and risk of these diseases. Such potential confounders may account, in part, for conflicting results in the existing literature.
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ACKNOWLEDGMENTS |
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NOTES |
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REFERENCES |
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