Skip main navigation

Impact of Exercise Training on Preeclampsia

Potential Preventive Mechanisms
Originally published 2012;60:1104–1109


Preeclampsia is characterized by hypertension and de novo proteinuria after 20 weeks of pregnancy. It is the leading cause of perinatal morbidity and mortality in the developed world, and to date, the only means of treating the disease is by inducing delivery. Many studies have shown the benefits of exercise training on normal pregnancy. Conversely, because the impact of exercise on reducing the risk of preeclampsia has long been debated, the American College of Obstetricians and Gynecologists has yet to support the prescription of exercise training to women at risk of developing the disease. There is, however, a significant body of evidence in support of the protective role of exercise training against preeclampsia. A recent animal study demonstrated that many preeclampsia features can be eliminated with prenatal followed by gestational exercise training. Hence, the present article reviews the literature on the impact of exercise training on preeclampsia risk, as well as the mechanisms that may be involved.


The benefits of exercise training (ExT) have been widely studied in healthy individuals, as well as in patients with cardiovascular diseases (CVD), such as hypertension and atherosclerosis.1 In addition, it has been shown to improve normal pregnancy outcomes.2 Preeclampsia, a gestational disease, complicates ≈5% to 10% of pregnancies and is the leading cause of maternal and fetal mortality/morbidity in developed countries.3 Given that, to date, the only treatment for this disease is fetal delivery, a simple intervention, such as ExT, may have a profound impact as an adjunctive and prophylactic treatment, if proven to be effective. Although many studies have investigated the potential beneficial impact of ExT on preeclampsia risk, there is still no clear consensus on its effectiveness. This article therefore reviews the literature on this subject and elaborates on the potential mechanisms involved.


A computer-based review was performed as described in the Methods section in the online-only Data Supplement.


The incidence of preeclampsia has risen in the past 20 years4 and will likely keep climbing as a result of the growing obesity pandemic5 and the increased incidence of hypertension and diabetes mellitus.6,7 Moreover, studies suggest that women who experience preeclampsia are more likely to develop cardiovascular diseases later in life.8 Although the development of the disease begins early in pregnancy, clinically, preeclampsia can only be diagnosed after 20 weeks of gestation with the onset of hypertension and proteinuria.9 Other manifestations of the disease include placental alterations, cerebral ischemia, liver abnormalities, cardiac hypertrophy, and impaired vascular reactivity; however, these features are not seen consistently in all women.10 In addition, severe cases of preeclampsia are associated with pulmonary edema, hemolysis, elevated liver enzymes and low platelets syndrome, severe central nervous system symptoms, renal failure, and intrauterine growth restriction.11

In the last decade, there has been an explosion of research on preeclampsia. Nonetheless, it remains a disease of theories, because a number of factors are proposed to be involved, but none have been clearly established to date. For instance, placental abnormalities, oxidative stress, endothelial dysfunction, inflammation, and immunity have all been suggested as being involved in disease progression.3 Epidemiological studies have been useful in shedding light on preeclampsia risk factors, such as type 2 diabetes mellitus, obesity, hypertension, and thrombophilia.3

Consequently, our limited understanding of the pathophysiology creates obstacles for those trying to treat patients affected by preeclampsia. A great deal of research has focused on identifying strategies to treat the disease. Preventive therapies, including the administration of antioxidants, calcium supplements, and antiplatelets, have been investigated without much success.1214 Given this, physicians must strive to control the progression of the disease to prolong gestation. Antihypertensive therapies are critical, because hypertension is known to have negative effects on other tissues, such as the heart, kidneys, and brain.15 The antihypertensive treatments available to preeclampsia include, methyldopa (an α-adrenergic agonist), labetalol (an α- and β-blocker), and nifedipine (a calcium channel antagonist), are considered relatively safe during pregnancy,16 although one study did find an association between labetalol and intrauterine growth restriction.17 More specifically, methyldopa has been shown to prevent the progression of moderate-to-severe preeclampsia.18 Conversely, some antihypertensive drugs are contraindicated because of their teratogenicity, such as inhibitors of the renin-angiotensin system, or physiologically unsuitable mechanism of action, such as diuretics, because of the hypovolemic state associated with preeclampsia.16 Although these agents have the potential to control the progression of disease, they are not always effective. In addition, when antihypertensive therapies can no longer control blood pressure, delivery is required to limit negative pregnancy outcomes.

Impact of ExT on Preeclampsia

ExT has been shown to lower blood pressure and improve cardiac function in both healthy and hypertensive men and women.19 In addition, it improves insulin sensitivity and reduces circulating levels of triglycerides and low-density lipoproteins.20 As such, ExT reduces the risks of cardiovascular diseases and type 2 diabetes mellitus21 and may improve pregnancy outcomes in patients at risk for preeclampsia by reducing the prevalence of these associated diseases. In addition, the incidence of gestational diseases is greatly increased in obese women,22 and ExT is well-known to promote weight loss by reducing fat stores and stimulating muscle mass development.20 Nonetheless, whereas ExT may play a role via its effect on other medical conditions (Figure), it is also proposed to directly alleviate preeclampsia features.


Figure. Potential mechanisms by which exercise training reduces preeclampsia risk. Preeclampsia is characterized by systemic endothelial dysfunction induced by inflammation, oxidative stress, and placental abnormalities. Gray box with solid lined arrows, preeclampsia-promoting entity; white box, effect of exercise training; dotted line arrows, reduction of identified preeclamptic pathway by exercise training. HTN indicates hypertension; CVD, cardiovascular disease; TLR, Toll-like receptor; TNF, tumor necrosis factor; IL, interleukin.

Epidemiological and clinical studies have shown that ExT may reduce the risk of several gestational diseases, such as gestational diabetes mellitus,23 gestational hypertension,24 and preeclampsia2433 (see Table S1 in the online-only Data Supplement). More specifically, most studies investigating the impact of physical activity in early pregnancy have demonstrated a significant decrease in preeclampsia risk compared with sedentary women.2426,28 Conversely, some studies have shown no protective role33,34 or a nonsignificant decreased risk32 with physical activity in pregnancy, although this may be attributable to the small number of cases32 or the short evaluation period33,34 in these studies. Indeed, the latter34 evaluated physical activity in pregnancy based on an assessment of the week before the first prenatal visit. However, studies that found a significant effect of training investigated all pregnancy weeks before this point. Curiously, 2 studies actually demonstrated a nonsignificant deleterious effect on preeclampsia risk either in the highest level of activity group35,36 or in women who initiated physical activity during pregnancy33 (see Table S2 in the online-only Data Supplement). However, unlike most of the other studies, they included severe cases of preeclampsia, as well as chronic hypertensive patients. Hence, it is possible that excluding these patients may mask this deleterious effect. Therefore, caution should be exerted regarding the intensity and frequency of exercise when it is initiated at the beginning of pregnancy, although additional studies will be required to further investigate this issue.

Regarding the impact of physical activity only before gestation, most studies have found either a significant25,27,33 or a nonsignificant30,31 decrease in preeclampsia risk. Of those who found a nonsignificant effect, the study by Tyldum et al31 evaluated physical activity on average 3.2 years before pregnancy (≤20 years before) and, as such, the women’s activity profile may have been different in the year immediately before gestation. In addition, their sedentary group included women who exercised less than once a week and as such were not completely inactive. Put together, these factors may have reduced the detectable effect of physical activity on pregnancy outcome. Moreover, 2 additional studies found no impact of physical activity before pregnancy on preeclampsia risk,26,32 but both of these included a very small number of cases (<50) and may not have had the statistical power to demonstrate this association. Finally, very few studies25,26,32,33 have investigated the effect of exercising both before and during pregnancy, but to date, there is little data to support the hypothesis that the effects are additive.

The first animal study to clearly demonstrate the benefits of ExT in the prevention of preeclampsia-like features has recently been published by our laboratory.37 This lends support to the many, albeit inconclusive, epidemiological findings present to date. Our study was carried out in a mouse model, where female mice overexpressing human angiotensinogen become spontaneously preeclamptic when mated with males overexpressing human renin.38 The use of animal models enables us to investigate the cause and effect relation between ExT and preeclampsia features, which is impossible to do in women given the many confounding factors present, such as environment and genetics. Sedentary human angiotensinogen mice had many hallmark features of the pathology38 because they presented with hypertension and proteinuria, as well as cardiac hypertrophy, placental alterations, and impaired vascular reactivity during pregnancy. In addition, placental alterations were associated with an increase in placental vascular endothelial growth factor (VEGF), which may be in response to the hypoxic state of the placenta or to counterbalance the increase in soluble fms-like tyrosine kinase-1 (sFlt-1), an antiangiogenic factor that is often increased in preeclampsia. This may seem to be contradictory to what has been published in the literature, where circulating proangiogenic factors, such as VEGF and the placental growth factor (PlGF), have been typically found to be decreased with preeclampsia.39 However, these reported decreases correspond to the free form of these factors and may result from the increased concentration of circulating sFlt-1, which binds to these angiogenic factors rather than a decrease in their production. Conversely, ExT before and during gestation prevented most of these preeclampsia-like features.37 Moreover, placental VEGF was normalized by ExT, although circulating angiogenic markers were not evaluated in our study. Indeed, Weissgerber et al40 demonstrated a decrease in free PlGF and an increase in antiangiogenic factors, such as sFlt-1, in sedentary pregnant women compared with active women. However, as explained previously, we cannot rule out the possibility that total PlGF levels may have been higher, because it is known to bind to sFlt-1.

Potential Mechanisms Involved in the Beneficial Impact of Exercise on Preeclampsia

Little is known concerning the mechanisms by which ExT may reduce the risk of preeclampsia. It has been proposed, however, to promote placental growth and vascular development, reduce oxidative stress, and improve endothelial function, as well as immune and inflammatory responses (Figure).41,42

Placental Development

Normal pregnancy necessitates proper invasion of trophoblasts into the uterine artery and myometrial spiral arteries, a step that is often defective in preeclampsia.43 It has been postulated that the stimulus for normal placental growth may be the periodic reductions in placental perfusion.44,45 Indeed, the proliferation of cytotrophoblasts is made possible by the low-oxygen environment present during early pregnancy. Upon invading maternal vessels, the cytotrophoblasts become exposed to higher oxygen levels,44,45 which inhibits proliferation and promotes differentiation. This results in the acquisition of an endothelial-like adhesion molecule phenotype of these cells.46 The low-oxygen environment may also produce placental hypoxia, which stimulates the hypoxia inducible factor-1α. This in turn activates VEGF and, in doing so, promotes angiogenesis.47 Consequently, maternal exercise is beneficial for placental and fetal growth because it diverts blood toward muscle and skin and thus creates a short-lived hypoxic environment.44 Indeed, trophoblastic, endothelial, and stromal cell proliferation has been shown to be enhanced in placentas from active women during normal pregnancy versus their sedentary counterparts (proliferation index: 45 ± 14 mitoses per 1000 nuclei versus 29 ± 10 mitoses per 1000 nuclei; P<0.008) (Figure).48 Moreover, placentas from trained mothers have a reduced nonfunctional tissue volume (28 ± 4 versus 45 ± 6 cm3; P=0.04) and an increased functional volume (434 ± 19 versus 367 ± 14 cm3; P=0.006) (Figure).49 Therefore, the placenta has an improved surface area available for gas and nutrient exchange.50 As a result, trained women have been reported to have a greater total placental (462 ± 18 versus 414 ± 14 cm3; P=0.05) and fetal (3.75 ± 0.08 versus 3.49 ± 0.07 kg; P=0.05) mass during normal pregnancy,51 along with a greater placental growth rate (26 ± 2 versus 21 ± 1 cm3/week; P=0.04).49 It is expected that these factors may contribute to reducing fetal complications associated with preeclampsia, such as intrauterine growth restriction.

This is in contrast to earlier studies that reported decreased fetal weight with ExT,52 likely a result of inadequate maternal caloric intake.50 Thus, with adequate nutritional intake, fetal development is not hindered but rather improved by ExT.

In addition, improved placentation may reduce the secretion of different mediators that are involved in preeclampsia development. For instance, endothelial dysfunction has been shown to be induced in vitro by combining endothelial cells with serum from preeclamptic women (Figure),53 supporting the premise that circulating mediators are implicated in the disease. Angiogenic factors have been proposed to be such mediators. Indeed, placental levels of VEGF and PlGF are initially high in normal pregnancy, whereas the level of sFlt-1 is low, which produces a proangiogenic environment.40 As placental development reaches completion, circulating levels of VEGF and PlGF begin to decline, whereas the level of sFlt-1 rises gradually until the end of pregnancy. Conversely, preeclampsia is characterized by an angiogenic shift, because circulating levels of soluble endoglin (sEng) and sFlt-1, both antiangiogenic factors, are elevated early in pregnancy and progressively more throughout gestation. Both sFlt-1 and sEng inhibit normal placental development by antagonizing circulating VEGF and PlGF, as well as transforming growth factor-β, respectively. It has been proposed that sEng may modulate trophoblastic invasion by affecting the ability of growth factor-β-3 to mediate trophoblastic differentiation.54 In addition, sEng inhibits endothelial tube formation in vitro, which may be playing a role in causing abnormal placentation.55 Interestingly, ExT has been reported to increase circulating PlGF (median [interquartile range]: 278 [221-647] versus 268 pg/mL [159-290 pg/mL]; P=0.014) and reduce circulating sFlt-1 (4217 [2014-5481] versus 5180 pg/mL [4549-5834 pg/mL]; P=0.005) and sEng (7.8 [6.5-10.1] versus 9.1 ng/mL [7.7-16.7 ng/mL]; P=0.025) in late gestation compared with the levels in sedentary pregnant women.40 This is further supported by data produced by our laboratory in a preeclampsia model, where improved placental development was associated with a normalization of placental VEGF levels in trained mice.37 Hence, ExT may restore angiogenic balance during preeclampsia and improve pregnancy outcome (Figure).

Oxidative Stress

Oxidative stress has also been implicated in promoting preeclampsia. The remodeling of uterine and placental vessels generates free radicals, which are normally controlled by appropriate antioxidant levels. In preeclampsia, lipid peroxide levels are elevated, which is associated with a decreased antioxidant defense, such as catalase, glutathione peroxidase, and superoxide dismutase activity.56,57

Interestingly, although acute exercise has been shown to promote oxidative stress, ExT stimulates antioxidant defenses (Figure). For instance, superoxide dismutase and glutathione peroxidase in skeletal muscle, plasma, and liver have been shown to be increased with ExT.58,59 Aerobic conditioning also increases the number of mitochondria in muscles and thus may enable the body to become more resistant to oxidative stress. Indeed, each mitochondrion has a reduced oxidative load, and, as such, more electrons are channeled to cytochrome oxidase rather than producing reactive oxygen species (Figure).60 In addition, exercise diminishes iron’s oxidative capabilities by increasing iron’s binding capacity to apotransferrin61 (Figure). This reduces the circulating ferrous iron61 that catalyzes the Fenton reaction that would otherwise generate reactive oxygen species (Figure). Moreover, lipid peroxidation, a marker of oxidative stress, in the circulation is reduced with ExT,62 providing further support that the body has an improved reactive oxygen species scavenging ability. Hence, by decreasing oxidative stress, ExT may reduce the risk of developing preeclampsia (Figure).

Endothelial Function

Endothelial dysfunction is a classic preeclampsia hallmark. For instance, it is thought that the placenta releases the tumor necrosis factor-α into the circulation and, as a result, damages the endothelium by reducing acetylcholine-induced vasodilatation and promoting the production of endothelin.63,64 ExT can, however, reverse this damage by reducing the formation of proinflammatory cytokines and reactive oxygen species, as noted above (Figure). For example, ExT has been shown to reduce the concentration of proinflammatory tumor necrosis factor-α in skeletal muscles65 and in the circulation.66 As a result, this causes a reduction in the levels of endothelin, and, as such, vasoconstriction is diminished.

Enhanced shear stress is likely to be another means by which endothelial dysfunction is reversed by ExT.67 This in turn induces endothelial cell proliferation and promotes the expression of endothelial nitric oxide (NO) synthase and antioxidants.6870 As a result, the increase in endothelial NO synthase leads to enhanced NO production,71 whereas improved antioxidant capacity reduces NO scavenging. This increased NO bioavailability thus enhances vasodilatory responses and contributes to improved endothelial function (Figure). The improved endothelium function observed after ExT could contribute to the blood pressure reduction observed with training72 and may thus contribute to the prevention of preeclampsia.

Immunity and Inflammation

During normal pregnancy, there is a diminished innate immune response to prevent fetal rejection with a shift away from cell-mediated immunity toward humoral immunity73 that modifies the expression pattern of proinflammatory cytokines. This equilibrium normally shifts back toward cell-mediated immunity toward the end of pregnancy. In preeclampsia, immunological responses against the fetus are proposed to have a causative pathophysiological role,74 leading to a cell-mediated dominant immunity that adversely affects the coagulation cascade and endothelial function.74 Levels of interferon-γ and proinflammatory factors, such as tumor necrosis factor-α and interleukins (ILs), have been shown to be increased in preeclampsia.73,74 Proinflammatory cytokines enhance the activity of neutrophils and monocytes, which in turn mediate an inflammatory response and promote endothelial cell damage. For instance, certain cytokines, such as IL-6, impair endothelium-dependent relaxation, thereby contributing to the preeclampsia-associated vasoconstriction.75 Furthermore, elevated levels of thromboxane, in conjunction with decreased prostacyclin, promote endothelial dysfunction and platelet aggregation in already damaged vessels and thus further contribute to the development of hypertension.76

Conversely, although acute exercise may evoke an inflammatory response, regular aerobic exercise has been shown to have anti-inflammatory effects (Figure).42 For instance, in heart-failure patients, ExT reduces circulating levels of proinflammatory mediators, such as IL-1β, IL-6, and tumor necrosis factor-α, whereas it increases circulating anti-inflammatory cytokines, such as IL-10. Platelet-related inflammatory mediators, like P-selectin and soluble CD40 ligand, are also reduced.77 In addition, inflammation-related endothelial damage can be reversed by ExT in patients with cardiovascular diseases. This is characterized by a reduction in peripheral inflammatory markers of endothelial dysfunction, such as granulocyte macrophage colony-stimulating factor, monocyte chemotactic protein-1, soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 (P<0.01).78 Furthermore, components of innate immunity, such as the Toll-like receptor-4, are decreased with ExT (Figure).65 Although the role of Toll-like receptors is not well understood, preeclampsia models have been discovered by infusing low doses of endotoxin, thereby stimulating Toll-like receptor-4.79 As such, this ExT decrease in Toll-like receptor-4 may contribute to promoting an adequate immune response during pregnancy. Put together, these data support the premise that ExT may promote a healthy immune response during pregnancy and, as such, may decrease the risk of preeclampsia by doing so.

Thus, as discussed in this section, ExT improves several pathways that have been implicated in the development of preeclampsia. Therefore, given the heterogeneity in the pathogenesis of preeclampsia, ExT may provide protection to a large population of women affected by this disease (Figure).


To date, ExT during pregnancy is not recommended by the American College of Obstetricians and Gynecologists for women at risk of certain gestational complications, such as gestational hypertension and preeclampsia,80 based on studies showing that ExT has deleterious effects on uteroplacental perfusion in at-risk pregnancies.81 Although several studies, as described above, have observed a beneficial effect of ExT on preeclampsia risk,2429,33 overall these are considered insufficient because they are not randomized studies and the mechanisms involved in these effects are unknown.82 Future observational studies will need to investigate not only the impact of exercise, per se, but also aerobic fitness to acquire a better understanding of the role of ExT in preeclampsia prevention. Indeed, a link has been observed between aerobic fitness and hypertension prevention.83 Conversely, the animal study conducted in our laboratory provides evidence that ExT, both before and during gestation, can alleviate preeclampsia-associated features.37 However, more animal studies are required to corroborate these results, in addition to evaluating the impact of ExT when initiated during gestation and at different exercise intensities.

Furthermore, animal models of the disease will be useful because more invasive studies will be essential to determine the specific pathways and tissues involved. Moreover, the type of ExT that seems to be beneficial to women at risk of preeclampsia requires further investigation. Indeed, determining which type of exercise, be it walking or low-impact aerobic training, provides the greatest benefit is necessary, because they produce different adaptations. Hence, much still remains to be done in this field to determine the best course of action in the prescription of ExT to women at risk of preeclampsia.




The online-only Data Supplement is available with this article at

Correspondence to Julie L. Lavoie, CRCHUM, Technopôle Angus, 2901 Rachel St East, Suite 310, Montreal, Quebec H1W 4A4, Canada. E-mail


  • 1. Peterson JA. Get moving! Physical activity counseling in primary care.J Am Acad Nurse Pract. 2007; 19:349–357.CrossrefMedlineGoogle Scholar
  • 2. Sternfeld B, Quesenberry CP, Eskenazi B, Newman LA. Exercise during pregnancy and pregnancy outcome.Med Sci Sports Exerc. 1995; 27:634–640.CrossrefMedlineGoogle Scholar
  • 3. Sibai B, Dekker G, Kupferminc M. Pre-eclampsia.Lancet. 2005; 365:785–799.CrossrefMedlineGoogle Scholar
  • 4. Roberts JM, Pearson GD, Cutler JA, Lindheimer MD; National Heart Lung and Blood Institute. Summary of the NHLBI Working Group on Research on Hypertension During Pregnancy.Hypertens Pregnancy. 2003; 22:109–127.CrossrefMedlineGoogle Scholar
  • 5. O’Brien TE, Ray JG, Chan WS. Maternal body mass index and the risk of preeclampsia: a systematic overview.Epidemiology. 2003; 14:368–374.CrossrefMedlineGoogle Scholar
  • 6. Hossain P, Kawar B, El Nahas M. Obesity and diabetes in the developing world–a growing challenge.N Engl J Med. 2007; 356:213–215.CrossrefMedlineGoogle Scholar
  • 7. Fields LE, Burt VL, Cutler JA, Hughes J, Roccella EJ, Sorlie P. The burden of adult hypertension in the United States 1999 to 2000: a rising tide.Hypertension. 2004; 44:398–404.LinkGoogle Scholar
  • 8. Bellamy L, Casas JP, Hingorani AD, Williams DJ. Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis.BMJ. 2007; 335:974.CrossrefMedlineGoogle Scholar
  • 9. Visser W, Wallenburg HC. Central hemodynamic observations in untreated preeclamptic patients.Hypertension. 1991; 17(6 pt 2):1072–1077.LinkGoogle Scholar
  • 10. Roberts JM, Redman CW. Pre-eclampsia: more than pregnancy-induced hypertension.Lancet. 1993; 341:1447–1451.CrossrefMedlineGoogle Scholar
  • 11. Sibai BM. Diagnosis and management of gestational hypertension and preeclampsia.Obstet Gynecol. 2003; 102:181–192.MedlineGoogle Scholar
  • 12. Poston L, Briley AL, Seed PT, Kelly FJ, Shennan AH; Vitamins in Pre-eclampsia (VIP) Trial Consortium. Vitamin C and vitamin E in pregnant women at risk for pre-eclampsia (VIP trial): randomised placebo-controlled trial.Lancet. 2006; 367:1145–1154.CrossrefMedlineGoogle Scholar
  • 13. Levine RJ, Hauth JC, Curet LB, Sibai BM, Catalano PM, Morris CD, DerSimonian R, Esterlitz JR, Raymond EG, Bild DE, Clemens JD, Cutler JA. Trial of calcium to prevent preeclampsia.N Engl J Med. 1997; 337:69–76.CrossrefMedlineGoogle Scholar
  • 14. Caritis S, Sibai B, Hauth J, Lindheimer MD, Klebanoff M, Thom E, VanDorsten P, Landon M, Paul R, Miodovnik M, Meis P, Thurnau G. Low-dose aspirin to prevent preeclampsia in women at high risk. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units.N Engl J Med. 1998; 338:701–705.CrossrefMedlineGoogle Scholar
  • 15. Carretero OA, Oparil S. Essential hypertension: part I–definition and etiology.Circulation. 2000; 101:329–335.LinkGoogle Scholar
  • 16. Podymow T, August P. Antihypertensive drugs in pregnancy.Semin Nephrol. 2011; 31:70–85.CrossrefMedlineGoogle Scholar
  • 17. Sibai BM, Gonzalez AR, Mabie WC, Moretti M. A comparison of labetalol plus hospitalization versus hospitalization alone in the management of preeclampsia remote from term.Obstet Gynecol. 1987; 70(3 pt 1):323–327.MedlineGoogle Scholar
  • 18. Redman CW, Beilin LJ, Bonnar J. Treatment of hypertension in pregnancy with methyldopa: blood pressure control and side effects.Br J Obstet Gynaecol. 1977; 84:419–426.CrossrefMedlineGoogle Scholar
  • 19. Whelton SP, Chin A, Xin X, He J. Effect of aerobic exercise on blood pressure: a meta-analysis of randomized, controlled trials.Ann Intern Med. 2002; 136:493–503.CrossrefMedlineGoogle Scholar
  • 20. Fletcher GF, Balady G, Blair SN, Blumenthal J, Caspersen C, Chaitman B, Epstein S, Sivarajan Froelicher ES, Froelicher VF, Pina IL, Pollock ML. Statement on exercise: benefits and recommendations for physical activity programs for all Americans–a statement for health professionals by the Committee on Exercise and Cardiac Rehabilitation of the Council on Clinical Cardiology, American Heart Association.Circulation. 1996; 94:857–862.LinkGoogle Scholar
  • 21. Warburton DE, Nicol CW, Bredin SS. Health benefits of physical activity: the evidence.CMAJ. 2006; 174:801–809.CrossrefMedlineGoogle Scholar
  • 22. Cedergren MI. Maternal morbid obesity and the risk of adverse pregnancy outcome.Obstet Gynecol. 2004; 103:219–224.CrossrefMedlineGoogle Scholar
  • 23. Hegaard HK, Pedersen BK, Nielsen BB, Damm P. Leisure time physical activity during pregnancy and impact on gestational diabetes mellitus, pre-eclampsia, preterm delivery and birth weight: a review.Acta Obstet Gynecol Scand. 2007; 86:1290–1296.CrossrefMedlineGoogle Scholar
  • 24. Marcoux S, Brisson J, Fabia J. The effect of leisure time physical activity on the risk of pre-eclampsia and gestational hypertension.J Epidemiol Community Health. 1989; 43:147–152.CrossrefMedlineGoogle Scholar
  • 25. Sorensen TK, Williams MA, Lee IM, Dashow EE, Thompson ML, Luthy DA. Recreational physical activity during pregnancy and risk of preeclampsia.Hypertension. 2003; 41:1273–1280.LinkGoogle Scholar
  • 26. Saftlas AF, Logsden-Sackett N, Wang W, Woolson R, Bracken MB. Work, leisure-time physical activity, and risk of preeclampsia and gestational hypertension.Am J Epidemiol. 2004; 160:758–765.CrossrefMedlineGoogle Scholar
  • 27. Rudra CB, Williams MA, Lee IM, Miller RS, Sorensen TK. Perceived exertion during prepregnancy physical activity and preeclampsia risk.Med Sci Sports Exerc. 2005; 37:1836–1841.CrossrefMedlineGoogle Scholar
  • 28. Magnus P, Trogstad L, Owe KM, Olsen SF, Nystad W. Recreational physical activity and the risk of preeclampsia: a prospective cohort of Norwegian women.Am J Epidemiol. 2008; 168:952–957.CrossrefMedlineGoogle Scholar
  • 29. Yeo S, Davidge S, Ronis DL, Antonakos CL, Hayashi R, O’Leary S. A comparison of walking versus stretching exercises to reduce the incidence of preeclampsia: a randomized clinical trial.Hypertens Pregnancy. 2008; 27:113–130.CrossrefMedlineGoogle Scholar
  • 30. Hegaard HK, Ottesen B, Hedegaard M, Petersson K, Henriksen TB, Damm P, Dykes AK. The association between leisure time physical activity in the year before pregnancy and pre-eclampsia.J Obstet Gynaecol. 2010; 30:21–24.CrossrefMedlineGoogle Scholar
  • 31. Tyldum EV, Romundstad PR, Slørdahl SA. Pre-pregnancy physical activity and preeclampsia risk: a prospective population-based cohort study.Acta Obstet Gynecol Scand. 2010; 89:315–320.CrossrefMedlineGoogle Scholar
  • 32. Fortner RT, Pekow PS, Whitcomb BW, Sievert LL, Markenson G, Chasan-Taber L. Physical activity and hypertensive disorders of pregnancy among Hispanic women.Med Sci Sports Exerc. 2011; 43:639–646.CrossrefMedlineGoogle Scholar
  • 33. Rudra CB, Sorensen TK, Luthy DA, Williams MA. A prospective analysis of recreational physical activity and preeclampsia risk.Med Sci Sports Exerc. 2008; 40:1581–1588.CrossrefMedlineGoogle Scholar
  • 34. Vollebregt KC, Wolf H, Boer K, van der Wal MF, Vrijkotte TG, Bonsel GJ. Does physical activity in leisure time early in pregnancy reduce the incidence of preeclampsia or gestational hypertension?Acta Obstet Gynecol Scand. 2010; 89:261–267.CrossrefMedlineGoogle Scholar
  • 35. Spinillo A, Capuzzo E, Colonna L, Piazzi G, Nicola S, Baltaro F. The effect of work activity in pregnancy on the risk of severe preeclampsia.Aust N Z J Obstet Gynaecol. 1995; 35:380–385.CrossrefMedlineGoogle Scholar
  • 36. østerdal ML, Strøm M, Klemmensen AK, Knudsen VK, Juhl M, Halldorsson TI, Nybo Andersen AM, Magnus P, Olsen SF. Does leisure time physical activity in early pregnancy protect against pre-eclampsia? Prospective cohort in Danish women.BJOG. 2009; 116:98–107.CrossrefMedlineGoogle Scholar
  • 37. Falcao S, Bisotto S, Michel C, Lacasse AA, Vaillancourt C, Gutkowska J, Lavoie JL. Exercise training can attenuate preeclampsia-like features in an animal model.J Hypertens. 2010; 28:2446–2453.CrossrefMedlineGoogle Scholar
  • 38. Takimoto E, Ishida J, Sugiyama F, Horiguchi H, Murakami K, Fukamizu A. Hypertension induced in pregnant mice by placental renin and maternal angiotensinogen.Science. 1996; 274:995–998.CrossrefMedlineGoogle Scholar
  • 39. Maynard SE, Karumanchi SA. Angiogenic factors and preeclampsia.Semin Nephrol. 2011; 31:33–46.CrossrefMedlineGoogle Scholar
  • 40. Weissgerber TL, Davies GA, Roberts JM. Modification of angiogenic factors by regular and acute exercise during pregnancy.J Appl Physiol. 2010; 108:1217–1223.CrossrefMedlineGoogle Scholar
  • 41. Weissgerber TL, Wolfe LA, Davies GA, Mottola MF. Exercise in the prevention and treatment of maternal-fetal disease: a review of the literature.Appl Physiol Nutr Metab. 2006; 31:661–674.CrossrefMedlineGoogle Scholar
  • 42. Kasapis C, Thompson PD. The effects of physical activity on serum C-reactive protein and inflammatory markers: a systematic review.J Am Coll Cardiol. 2005; 45:1563–1569.CrossrefMedlineGoogle Scholar
  • 43. Roberts JM, Cooper DW. Pathogenesis and genetics of pre-eclampsia.Lancet. 2001; 357:53–56.CrossrefMedlineGoogle Scholar
  • 44. Clapp JF. The effects of maternal exercise on fetal oxygenation and feto-placental growth.Eur J Obstet Gynecol Reprod Biol. 2003; 110(suppl 1):S80–S85.CrossrefMedlineGoogle Scholar
  • 45. Genbacev O, Zhou Y, Ludlow JW, Fisher SJ. Regulation of human placental development by oxygen tension.Science. 1997; 277:1669–1672.CrossrefMedlineGoogle Scholar
  • 46. Kaufmann P, Black S, Huppertz B. Endovascular trophoblast invasion: implications for the pathogenesis of intrauterine growth retardation and preeclampsia.Biol Reprod. 2003; 69:1–7.CrossrefMedlineGoogle Scholar
  • 47. Patel J, Landers K, Mortimer RH, Richard K. Regulation of hypoxia inducible factors (HIF) in hypoxia and normoxia during placental development.Placenta. 2010; 31:951–957.CrossrefMedlineGoogle Scholar
  • 48. Bergmann A, Zygmunt M, Clapp JF. Running throughout pregnancy: effect on placental villous vascular volume and cell proliferation.Placenta. 2004; 25:694–698.CrossrefMedlineGoogle Scholar
  • 49. Clapp JF, Kim H, Burciu B, Lopez B. Beginning regular exercise in early pregnancy: effect on fetoplacental growth.Am J Obstet Gynecol. 2000; 183:1484–1488.CrossrefMedlineGoogle Scholar
  • 50. Jackson MR, Gott P, Lye SJ, Ritchie JW, Clapp JF. The effects of maternal aerobic exercise on human placental development: placental volumetric composition and surface areas.Placenta. 1995; 16:179–191.CrossrefMedlineGoogle Scholar
  • 51. Clapp JF. Influence of endurance exercise and diet on human placental development and fetal growth.Placenta. 2006; 27:527–534.CrossrefMedlineGoogle Scholar
  • 52. Clapp JF. Exercising Through Your Pregnancy. Omaha, NE: Addicus Books Inc; 2002.Google Scholar
  • 53. Roberts JM, Taylor RN, Musci TJ, Rodgers GM, Hubel CA, McLaughlin MK. Preeclampsia: an endothelial cell disorder.Am J Obstet Gynecol. 1989; 161:1200–1204.CrossrefMedlineGoogle Scholar
  • 54. Nishi H, Nakada T, Hokamura M, Osakabe Y, Itokazu O, Huang LE, Isaka K. Hypoxia-inducible factor-1 transactivates transforming growth factor-beta3 in trophoblast.Endocrinology. 2004; 145:4113–4118.CrossrefMedlineGoogle Scholar
  • 55. Venkatesha S, Toporsian M, Lam C, Hanai J, Mammoto T, Kim YM, Bdolah Y, Lim KH, Yuan HT, Libermann TA, Stillman IE, Roberts D, D’Amore PA, Epstein FH, Sellke FW, Romero R, Sukhatme VP, Letarte M, Karumanchi SA. Soluble endoglin contributes to the pathogenesis of preeclampsia.Nat Med. 2006; 12:642–649.CrossrefMedlineGoogle Scholar
  • 56. Hubel CA. Oxidative stress in the pathogenesis of preeclampsia.Proc Soc Exp Biol Med. 1999; 222:222–235.CrossrefMedlineGoogle Scholar
  • 57. Loverro G, Greco P, Capuano F, Carone D, Cormio G, Selvaggi L. Lipoperoxidation and antioxidant enzymes activity in pregnancy complicated with hypertension.Eur J Obstet Gynecol Reprod Biol. 1996; 70:123–127.CrossrefMedlineGoogle Scholar
  • 58. Sen CK, Marin E, Kretzschmar M, Hänninen O. Skeletal muscle and liver glutathione homeostasis in response to training, exercise, and immobilization.J Appl Physiol. 1992; 73:1265–1272.CrossrefMedlineGoogle Scholar
  • 59. Urso ML, Clarkson PM. Oxidative stress, exercise, and antioxidant supplementation.Toxicology. 2003; 189:41–54.CrossrefMedlineGoogle Scholar
  • 60. Møller P, Wallin H, Knudsen LE. Oxidative stress associated with exercise, psychological stress and life-style factors.Chem Biol Interact. 1996; 102:17–36.CrossrefMedlineGoogle Scholar
  • 61. Hubel CA, Kozlov AV, Kagan VE, Evans RW, Davidge ST, McLaughlin MK, Roberts JM. Decreased transferrin and increased transferrin saturation in sera of women with preeclampsia: implications for oxidative stress.Am J Obstet Gynecol. 1996; 175(3 pt 1):692–700.CrossrefMedlineGoogle Scholar
  • 62. Alessio HM, Goldfarb AH. Lipid peroxidation and scavenger enzymes during exercise: adaptive response to training.J Appl Physiol. 1988; 64:1333–1336.CrossrefMedlineGoogle Scholar
  • 63. Khalil RA, Granger JP. Vascular mechanisms of increased arterial pressure in preeclampsia: lessons from animal models.Am J Physiol Regul Integr Comp Physiol. 2002; 283:R29–R45.CrossrefMedlineGoogle Scholar
  • 64. Young BC, Levine RJ, Karumanchi SA. Pathogenesis of preeclampsia.Annu Rev Pathol. 2010; 5:173–192.CrossrefMedlineGoogle Scholar
  • 65. Flynn MG, McFarlin BK. Toll-like receptor 4: link to the anti-inflammatory effects of exercise?Exerc Sport Sci Rev. 2006; 34:176–181.CrossrefMedlineGoogle Scholar
  • 66. Clapp JF, Kiess W. Effects of pregnancy and exercise on concentrations of the metabolic markers tumor necrosis factor alpha and leptin.Am J Obstet Gynecol. 2000; 182:300–306.CrossrefMedlineGoogle Scholar
  • 67. Varin R, Mulder P, Richard V, Tamion F, Devaux C, Henry JP, Lallemand F, Lerebours G, Thuillez C. Exercise improves flow-mediated vasodilatation of skeletal muscle arteries in rats with chronic heart failure: role of nitric oxide, prostanoids, and oxidant stress.Circulation. 1999; 99:2951–2957.LinkGoogle Scholar
  • 68. Inoue N, Ramasamy S, Fukai T, Nerem RM, Harrison DG. Shear stress modulates expression of Cu/Zn superoxide dismutase in human aortic endothelial cells.Circ Res. 1996; 79:32–37.LinkGoogle Scholar
  • 69. Kingwell BA. Nitric oxide-mediated metabolic regulation during exercise: effects of training in health and cardiovascular disease.FASEB J. 2000; 14:1685–1696.CrossrefMedlineGoogle Scholar
  • 70. Wasserman SM, Mehraban F, Komuves LG, Yang RB, Tomlinson JE, Zhang Y, Spriggs F, Topper JN. Gene expression profile of human endothelial cells exposed to sustained fluid shear stress.Physiol Genomics. 2002; 12:13–23.CrossrefMedlineGoogle Scholar
  • 71. Sessa WC, Pritchard K, Seyedi N, Wang J, Hintze TH. Chronic exercise in dogs increases coronary vascular nitric oxide production and endothelial cell nitric oxide synthase gene expression.Circ Res. 1994; 74:349–353.LinkGoogle Scholar
  • 72. Higashi Y, Sasaki S, Kurisu S, Yoshimizu A, Sasaki N, Matsuura H, Kajiyama G, Oshima T. Regular aerobic exercise augments endothelium-dependent vascular relaxation in normotensive as well as hypertensive subjects: role of endothelium-derived nitric oxide.Circulation. 1999; 100:1194–1202.LinkGoogle Scholar
  • 73. Challis JR, Lockwood CJ, Myatt L, Norman JE, Strauss JF, Petraglia F. Inflammation and pregnancy.Reprod Sci. 2009; 16:206–215.CrossrefMedlineGoogle Scholar
  • 74. Schiessl B. Inflammatory response in preeclampsia.Mol Aspects Med. 2007; 28:210–219.CrossrefMedlineGoogle Scholar
  • 75. Orshal JM, Khalil RA. Reduced endothelial NO-cGMP-mediated vascular relaxation and hypertension in IL-6-infused pregnant rats.Hypertension. 2004; 43:434–444.LinkGoogle Scholar
  • 76. Wang Y, Walsh SW, Kay HH. Placental lipid peroxides and thromboxane are increased and prostacyclin is decreased in women with preeclampsia.Am J Obstet Gynecol. 1992; 167(4 pt 1):946–949.CrossrefMedlineGoogle Scholar
  • 77. Bjørnstad HH, Bruvik J, Bjørnstad AB, Hjellestad BL, Damås JK, Aukrust P. Exercise training decreases plasma levels of soluble CD40 ligand and P-selectin in patients with chronic heart failure.Eur J Cardiovasc Prev Rehabil. 2008; 15:43–48.CrossrefMedlineGoogle Scholar
  • 78. Adamopoulos S, Parissis J, Kroupis C, Georgiadis M, Karatzas D, Karavolias G, Koniavitou K, Coats AJ, Kremastinos DT. Physical training reduces peripheral markers of inflammation in patients with chronic heart failure.Eur Heart J. 2001; 22:791–797.CrossrefMedlineGoogle Scholar
  • 79. Faas MM, Schuiling GA, Baller JF, Visscher CA, Bakker WW. A new animal model for human preeclampsia: ultra-low-dose endotoxin infusion in pregnant rats.Am J Obstet Gynecol. 1994; 171:158–164.CrossrefMedlineGoogle Scholar
  • 80. Artal R, O’Toole M. Guidelines of the American College of Obstetricians and Gynecologists for exercise during pregnancy and the postpartum period.Br J Sports Med. 2003; 37:6–12.CrossrefMedlineGoogle Scholar
  • 81. Hackett GA, Cohen-Overbeek T, Campbell S. The effect of exercise on uteroplacental Doppler waveforms in normal and complicated pregnancies.Obstet Gynecol. 1992; 79:919–923.MedlineGoogle Scholar
  • 82. Meher S, Duley L. Exercise or other physical activity for preventing pre-eclampsia and its complications. Cochrane Database Syst Rev. 2006; 2:CD005942.Google Scholar
  • 83. Frisoli TM, Schmieder RE, Grodzicki T, Messerli FH. Beyond salt: lifestyle modifications and blood pressure.Eur Heart J. 2011; 32:3081–3087.CrossrefMedlineGoogle Scholar


eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.

Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.