Maternal activity restriction and the prevention of preterm birth

Clinical Opinion

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OBSTETRICS

Maternal activity restriction and the prevention of preterm birth Anthony C. Sciscione, DO

T

he prescription of maternal activity restriction is one of the most widely used interventions in obstetrics, with as many as 95% of obstetricians reporting having used it in their practice.1,2 Approximately 18% of pregnant women are placed on activity restriction sometime during their pregnancy.3 Whereas maternal activity restriction is prescribed to pregnant women for a variety of reasons, such as vaginal bleeding, fetal growth restriction, and hypertension during pregnancy, the focus of this review will be on the evidence to support its use to prevent preterm birth in those at risk. In the Cochrane database, the authors observed that bed rest is the customary initial therapy for women at risk for preterm birth.4 The American College of Obstetricians and Gynecologists recommend that a physically active woman at risk for preterm labor should be advised to reduce her activity.5 In a recent survey of members of the American College of Obstetricians and Gynecologists 34%, 37%, and 39% of obstetricians prescribed bed rest for a shortened cervical length (⬍2.5 cm), cervical funneling, and vaginal fetal fibronectin positivity, respectively. A 2007 survey of Canadian obstetricians, family practitioners, and midwives found that 72.3%, 77.2%, and 67.1% used activity restriction in their practices, despite apFrom the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Christiana Hospital, Newark, DE. Received Jan. 7, 2009; revised May 12, 2009; accepted July 1, 2009. Reprints: Anthony C. Sciscione, DO, Christiana Hospital, Division of Maternal Fetal-Medicine, 4755 Ogletown Stanton Rd., Suite 1905, Newark, DE 19718. 0002-9378/$36.00 © 2010 Published by Mosby, Inc. doi: 10.1016/j.ajog.2009.07.005

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Activity restriction is 1 of the most common interventions used in obstetrics. Although it is used for many reasons, 1 of the most common is to prevent preterm birth in those at risk. This review of the literature describes the potential advantages, disadvantages, and efficacy of activity restriction for the prevention of preterm birth. Key words: activity restriction, obstetrics, preterm birth Cite this article as: Sciscione AC. Maternal activity restriction and the prevention of preterm birth. Am J Obstet Gynecol 2010;202:232.e1-5.

proximately two-thirds of respondents answering that the evidence that activity restriction prevents preterm birth was in the fair to poor range.6 Lastly, in a 2007 survey of members of the Society of Maternal-Fetal Medicine, more than 80% of the members prescribed bed rest for women at risk for preterm birth.7 It is clear that maternal activity restriction is 1 of if not the most common interventions used to prevent preterm birth in women at risk. The frequency of its use is likely based on the perception that there is little harm in placing a woman on activity restriction and that uterine contractions, cervical effacement, and dilatation are related to maternal activity levels. Furthermore, there is likely a “do as my colleagues do” approach when using activity restriction. One of the often overlooked negative effects of activity restriction is the economic effects, with the majority of pregnant women in the United States employed; the financial burden alone from placing pregnant women on activity restriction was estimated at 5.7 billion dollars a year (1994). This has likely increased significantly using both current dollars and recognizing the increased number of women in the workplace.3

Defining activity restriction Bed rest is the most commonly used term when a woman is placed on activity restriction, yet there is no standard definition of bed rest. There are varying definitions listed in studies that have

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examined the effectiveness of bed rest including rest 3 times a day for an hour,8 no more than 1-2 hours a day out of bed,7 and bed confinement with the exception of bathroom use.9 Inconsistency in the definition of activity restriction in the literature undermines the ability to study the efficacy of activity restriction to decrease preterm birth. Furthermore, although the most common terms used in the literature are bed rest or activity restriction, other terms including lifestyle modification, rest, and hospital confinement are commonly used without definition. The lack of consistency in the terms and definitions of activity restriction is prevalent in the counseling and advising of pregnant women. To conduct meaningful research in this area and to provide consistent patient care and health care provider communication, it is important to be consistent in our terms and definitions. It seems most prudent to abandon other terms and solely use the term activity restriction. To create a meaningful intervention that can be used both clinically and for investigation, it must be generalizable and have a standard definition. The Table divides activity restriction into 3 increasing levels, which will allow standardization.

Efficacy of activity restriction in preventing preterm birth The use of activity restriction as a therapeutic modality dates back to Hip-

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TABLE Type of activity restriction Light

Definition One hour or less of continuous rest, in bed or in the sitting position during waking hours, and no lifting of ⬎10 lb.

..............................................................................................................................................................................................................................................

Moderate

More than 1 hour but ⬍8 hours of continuous rest during waking hours with no household chores and no lifting. Health-related visits are allowed.

..............................................................................................................................................................................................................................................

Strict

Confinement to their dwelling except for health care-related visits. Rest in the sitting or supine position the entire day. No household chores or lifting.

..............................................................................................................................................................................................................................................

Sciscione. Activity restriction and prevention of preterm birth. Am J Obstet Gynecol 2010.

pocrates: “Rest as soon as there is pain, it is a great restorative in all disturbances of the body.”10 In the late 1800s, Hinton published the first book on activity restriction as a therapeutic option.11 However, in the modern era, sick people rarely went to bed for fear of loss of income. The effectiveness of dictated activity restriction as a therapy has been debated since the 1800s, and the beginning of its application to the obstetrical population is unclear. There have been few studies examining the potential benefit of activity restriction for the prevention of preterm labor.12-17 In 1983, Berkowitz et al13 performed a postpartum survey on 175 women who had a preterm delivery and compared it with 313 women who delivered at term. There was no difference in standing or moving periods, child care, occupational activities, or number of household chores between the groups. However, women who participated in sports or physical activity had a decreased rate of preterm birth. This led the authors to the conclusion that employment, housework, child care, and leisure time exercise during pregnancy did not increase the risk of preterm birth. In contrast, at least moderate forms of exercise may be beneficial, perhaps decreasing the risk of preterm birth. These findings are consistent with a recent population-based study, which found a decrease risk of preterm birth in women who participated in strenuous physical activity and competitive sports or vigorous leisure activity.13,18 The Europop study was a large population-based study of deliveries occurring in several European centers. They

compared work conditions in more than 5000 women who had a preterm birth vs almost 8000 women who had a term birth and found that women who had a preterm birth were more likely to perform manual labor, have more than a 42 hour work week, report prolonged standing, and have poor job satisfaction.14 However, these findings are not universal, with some population-based studies finding no difference in work-related conditions and preterm birth.15 In a recent metaanalysis examining work conditions and adverse pregnancy outcomes, Mozurkewich et al17 reported an increased risk of preterm birth in women who engaged in prolonged standing, shift work, and physically demanding work and had an increased fatigue score. In a randomized trial, Hobel et al19 sought to evaluate a preterm prevention program including education, increased clinic visits, and selected prophylactic interventions to reduce preterm birth. The authors randomized 8 west Los Angeles prenatal clinics. Five clinics were placed in the experimental clinics grouping and 3 were used as controls. Women in the 5 experimental clinics received increased frequency in prenatal visits, preterm birth prevention education, psychosocial and nutritional screening, and crisis intervention. The experimental clinics were randomized again to 1 of the following interventions: bed rest, defined as resting for 3 times a day for an hour; psychosocial support and an oral progestin group in which they were randomized again to either 20 mg of medroxyprogesterone acetate (MPA, Provera; Pfizer, New York, NY) or to placebo.

Clinical Opinion

One thousand seven hundred seventyfour patients were entered into the trial. The rate of preterm birth in the experimental clinics was 7.4% vs 9.1% in the control clinics (odds ratio, 0.78; 95% confidence interval, 0.58 –1.04; P ⫽ .045). Of note, women in the MPA-exposed group had a higher rate of preterm birth (17.6% vs 6.1%), although this was attributed to a lack of compliance. Power was limited in this trial, with a 77% chance of detecting a 30% difference in preterm birth with an alpha error of 0.05, leading the authors to conclude that there was insufficient sample size for definitive conclusions to be made based on trial results. In a more recent trial,9 women with symptoms of preterm labor, a negative vaginal fetal fibronectin and less than 3 cm dilatation were tocolyzed and randomized to either activity restriction or no restriction. Activity restriction was defined as bed confinement except for use of the bathroom and physician visits. Thirty-eight women were randomized to the activity restriction group and 41 to the nonactivity restriction group. There was no difference in the rate of preterm delivery between the groups.

The negative physiologic effects of activity restriction In 1994, Goldenberg et al3 proposed that the reason that activity restriction had become so widely used, with so little proof to document its effectiveness, was likely because of the perception of little untoward effects to the mother and fetus. However, there exists a growing body of literature addressing the potential of untoward effects of activity restriction in humans with perhaps an increased potential for harm in pregnant states. Nonpregnant adults Humans spend the majority of their life awake, with the bulk of that time in motion. However, activity restriction is a natural part of human existence, with prolonged periods of rest happening in the form of daily sleep. But even during times of resting in bed, the average healthy adult changes position or turns every 11.6 minutes.20 The physiology of

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the body has naturally adapted over the centuries and has become dependent on these processes so that when prolonged activity restriction, also known as hypokinesia, is applied to the human body, physiologic adaption or maladaption must occur. When standing and moving, there is natural contraction and relaxation of muscles and weight bearing by the skeleton. This facilitates fluid movement and bone strength. When forced to the supine position for long periods of time, there is muscle deconditioning and calcium resorption. Studies in nonpregnant subjects have shown that when placed on strict activity restriction, diuresis begins within the first day, with a loss of plasma volume within 3 days.21 Electrolyte loss is immediately evident, most prominently with sodium and chloride and less so with potassium. Blood pressure tends to rise at the brachial artery because of the shift in fluid to the head, neck, and trunk.22 Within 4 days of bed rest, osteoblasts decrease the laying down of new bone, and bone resorption increases, resulting in increased calcium excretion.23-27 After 8 days, more procoagulants are found, thromboplastin times shorten, and fibrinolytic activity increases.21 Increase in thromboembolism is likely the result of lower extremity compression from being supine. After weeks of strict activity restriction, there are significant shifts in the cycles of glucose, insulin, growth hormone, cortisol, thyroid hormones, and aldosterone.28,29 Catabolism of immunoglobulin G occurs, which likely weakens defenses and may increase the risk of infection.30

Pregnant adults There are many physiologic changes that occur in women as they make the transition from the nonpregnant state to gravidity and progression through pregnancy. There is the possibility that the adverse affects of activity restriction that have been reported in nonpregnant adults may be improved in pregnant women, but they are much more likely to be worsened. There have been few reports addressing the potential risks of 232.e3

placing a pregnant woman on activity restriction. The risk of deep venous thrombosis in the pregnant woman is increased up to 5 times over the nonpregnant state.31 The prevalence of all thromboembolic events during pregnancy is also increased and has been reported from 0.5 to 3.0 cases per 1000 women.32 Because of this increased risk, the addition of activity restriction would appear to be additive. In a recent report by Kovacevich et al,33 192 women were placed on activity restriction for preterm labor or preterm premature rupture of the membranes and were compared with women not on activity restriction for the risk of thromboembolic events. The risk of thromboembolic events in women who were placed at bed rest was significantly higher than women not on activity restriction, 0.8 per 1000 in a pregnant control population vs 15.6 per 1000 in women placed at bed rest. However, Carr et al34 studied 265 pregnant women who were placed on bed rest and concluded that the rate of deep venous thromboembolism in women placed at bed rest did not warrant heparin prophylaxis. Because of their low risk, many obstetricians have used sequential compression boots to the lower extremity in pregnant woman placed on strict activity restriction to potentially prevent thromboembolism. However, the efficacy of this preventive treatment in this population has not been studied. Women placed on strict activity restriction have prolonged immobilization, resulting in a significant decrease in weight bearing and skeletal load. Bone mineral density decreases in healthy nonpregnant volunteers when placed on bed rest.35,36 In a study by Promislow et al,37 the investigators performed a prospective study of bone mineral density among 181 pregnant women. Women who were placed on bed rest had a significant increase in bone loss compared with women on normal activity. Kaji et al38 studied markers of bone turnover in women placed on bed rest vs those who were not. They found that markers of bone turnover, specifically for bone resorption, were markedly increased in women placed on bed rest. It is

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www.AJOG.org highly likely that there is bone resorption and loss in pregnant women placed on strict activity restriction. It is not clear whether bone mass returns to prepregnancy levels, peak bone mass is permanently reduced, or how fast equilibrium may occur once a woman is taken off activity restriction. Placing the pregnant woman on bed rest has been associated with loss of muscle strength,39 myalgias, weight loss,39 and muscle weakness.40 This has been compared with the side effects of space travel by astronauts. A recent report by Maloni et al41 studied the effects of bed rest on gastrocnemius muscle metabolism and postpartum muscle deconditioning in 65 pregnant women. They found that reoxygenation after exercise significantly increased in the antepartum period and significantly decreased postpartum with the relief from activity restriction. Postpartum muscle soreness, deconditioning, and difficulty with mobility were reported.41 In the postpartum period, 71% of women who were placed on activity restriction had difficulty ascending and descending stairs, 14% needed help walking, 71% needed assistance sitting, and 14% reported their knees buckling.39 Pregnant women who are placed on strict activity restriction often believe that the reduction in calorie expenditure will result in weight gain. But likely secondary to a loss in muscle mass from deconditioning, there is actually a significant decrease in weekly weight gain when compared with nonactivity-restricted pregnant women.42 In the first week of strict activity restriction, more than 75% of women will either lose weight or maintain weight. Furthermore, women placed on activity restriction have lower birth weights across all gestational ages than nonactivity-restricted pregnant women.42

The negative psychosocial affects of activity restriction There is little debate regarding the additional stressors placed on women who are prescribed activity restriction, especially when strict restriction is used. The majority of pregnant women in the United States work and represent a sig-

www.AJOG.org nificant contribution to household income. In a recent survey, 71% of women placed on activity restriction incurred financial difficulties.43 After a prolonged absence from work, there is also fear of losing one’s job or position. This decrease in family income is cited as 1 of the most prominent stressors to pregnant women placed on activity restriction.44 There have been many reports citing the negative psychosocial effects of placing women on strict activity restriction. These include an increase in negative feelings about the pregnancy, anxiety, rate of depression, hostility, emotional lability, sleep disturbances, feelings of loss of control, somatic complaints, and worry about children.38,45-52 The emotional toll on the family is also high, with a recent report finding an increased risk of emotional difficulty in children, children being frightened or confused, and family anxiety about maternal and fetal health. In summary, once a woman is placed on activity restriction, the negative effects on the mother and family are well documented and serious. The benefits of placing a woman on activity restriction should outweigh the psychosocial, financial, and maternal physical risks before being instituted.

Activity restriction in twin gestations Hospital admission for prophylactic bed rest became a common intervention for women with multiple gestations in the 1970s and 1980s. There were multiple reports of significantly increasing gestational age at delivery and birth weight with routine hospital admission.19,53-55 This lead Komaromy and Lampe56 to recommend that women with twins “be hospitalized from the 26th or 27th week of gestation.” However, reports in the 1980s and 1990s began to question the benefit of such a practice. Multiple studies did not find a significant benefit of routine hospital admission for twin gestations.56-59 The largest trial to examine the potential benefit of routine hospital admission of twin gestations was reported by Saunders et al.58 In this randomized trial, 212 women with twins were either admitted to the hospital at 32 weeks’ gestation or received routine care. Ironically, they

Obstetrics found that the rate of preterm birth was actually higher in the hospitalized group. The same year MacLennan et al60 reported on a population with routine admission at an earlier gestational age, between 26 and 30 weeks. In this trial, 141 women with twin gestations were randomized to routine hospital admission or routine care. The trial was halted in the interim analysis because of no benefit between the groups and a possible detrimental effect to the hospitalized group. There was a trend to greater frequency of preterm birth, admission to the neonatal intensive care unit, and higher morbidity and mortality in the hospital admission group. In a recent report examining the possible maternal effects of placing women with twin gestation on activity restriction,60 the investigators found similar findings as reported among singleton gestations including increased rates of maternal weight loss, stress, depression, and physiologic and psychosocial symptoms.

Conclusions There is scant evidence supporting the efficacy of activity restriction to decrease preterm birth in single or multiple gestations. However, there is adequate evidence that there are detrimental effects to the mother and her family when the gravid patient is placed on activity restriction. At this time the use of activity restriction as an intervention to decrease the risk of preterm birth cannot be supported until a large randomized trial can be performed to prove its benefit. Since 1978, there have been 4 reviews on the role of activity restriction in the prevention of preterm birth, including the most recent Cochrane database, that have all come to the same conclusions as in this review.61-63 The fact that multiple recent surveys have shown that the use of activity restriction to prevent preterm birth is still common among obstetricians gynecologists and maternal-fetal medicine specialists supports the urgent need for a trial to address this issue. In obstetrics, the ability to accept a donothing approach to potential interventions to pregnancies at risk has been difficult, especially when neonatal out-

Clinical Opinion

comes can be so devastating, like those associated with early preterm birth. So until a trial can be performed to support or disprove the role of activity restriction to decrease preterm birth in those at risk, any practitioner choosing to use activity restriction should consider having an informed consent discussion with a patient outlining the unknown benefit and f known detrimental effects. REFERENCES 1. Maloni JA. Bed rest and high-risk pregnancy. Differentiating the effects of diagnosis, setting, and treatment. Nurs Clin North Am 1996 31: 313-25. 2. Diddle AW, O’Connor KA, Jack R, Pearse RL. Evaluation of bed rest in threatened abortion. Obstet Gynecol 1953;2:63-7. 3. Goldenberg RL, Cliver SP, Bronstein J, Cutter GR, Andrews WW, Mennemeyer ST. Bed rest in pregnancy. Obstet Gynecol 1994;84: 131-6. 4. Sosa C, Althabe F, Belizan J, Bergel E. Bed rest in singleton pregnancies for preventing preterm birth. Cochrane Database Syst Rev 2004: CD003581. 5. American College of Obstetricians and Gynecologists. ACOG committee opinion no. 267. Exercise during pregnancy and the postpartum period. Washington, DC: January 2002. 6. Sprague AE, O’Brien B, Newburn-Cook C, Heaman M, Nimrod C. Bed rest and activity restriction for women at risk for preterm birth: a survey of Canadian prenatal care providers. J Obstet Gynecol Can 2008;30:317-26. 7. Fox NS, Gelber SE, Kalish RB, Chasen ST. The recommendation for bed rest in the setting of arrested preterm labor and premature rupture of membranes. Am J Obstet Gynecol 2009;200:165.e1-6. 8. Hobel CJ, Ross MG, Bemis RL, et al. The West Los Angeles Preterm Birth Prevention Project. I. Program impact on high-risk women. Am J Obstet Gynecol 1994;170(1 Pt 1):54-62. 9. Elliott JP, Miller HS, Coleman S, et al. A randomized multicenter study to determine the efficacy of activity restriction for preterm labor management in patients testing negative for fetal fibronectin. J Perinatol 2005;25:626-30. 10. Schroeder CA. Women’s experience of bed rest in high-risk pregnancy. Image J Nurs Sch 1996;28:253-8. 11. Saurel-Cubizolles MJ, Kaminski M. Work in pregnancy: its evolving relationship with perinatal outcome (a review). Soc Sci Med 1984;22:431-42. 12. Sprague AE. The evolution of bed rest as a clinical intervention. JOGNN J Obstet Gynecol Neonatal Nurs 2004;33:542-9. 13. Berkowitz GS, Kelsey JL, Holford TR, Berkowitz RL. Physical activity and the risk of spontaneous preterm delivery. J Reprod Med 1983;28:581-8.

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www.AJOG.org 45. Rosen EL. Concerns of an obstetric patient experiencing long-term hospitalization. J Obstet Gynecol Neonatal Nurs 1975;4:15-9. 46. Schroeder CA. Women’s experience of bed rest in high-risk pregnancy Image J Nurs Sch 1996;28:253-8. 47. Maloni JA, Chance B, Zhang C, Cohen AW, Betts D, Gange SJ. Physical and psychosocial side effects of antepartum hospital bed rest. Nurs Res 1993;42:197-203. 48. Maloni JA, Kutil RM. Antepartum support group for women hospitalized on bed rest. MCN Am J Matern Child Nurs 2000;25:204-10. 49. Maloni JA, Kasper CE. Physical and psychosocial effects of antepartum hospital bedrest: a review of the literature. Image J Nurs Sch 1991;23:187-92. 50. May KA. Impact of prescribed activity restriction during pregnancy on women and families. Health Care Women Int 2001;22:29-47. 51. Monaham PA, DeJoseph JF. The woman with preterm labor at home: a descriptive analysis. J Perinat Neonatal Nurs 1991;4:12-20. 52. Maloni JA, Brezinski-Tomasi JE, Johnson LA. Antepartum bed rest: effect upon the family. JOGNN J Obstet Gynecol Neonatal Nurs 2001;30:165-73. 53. Laursen B. Twin pregnancy. The value of prophylactic rest in bed and the risk involved. Acta Obstet Gynecol Scand 1973;52:367-71. 54. Persson PH, Grennert L, Gennser G, Kullander S. On improved outcome of twin pregnancies. Acta Obstet Gynecol Scand 1979;58:3-7. 55. Misenhimer HR, Kaltreider DF. Effects of decreased prenatal activity in patients with twin pregnancy. Obstet Gynecol 1978;51:692-4. 56. Komaromy B, Lampe L. The value of bed rest in twin pregnancies. Int J Gynaecol Obstet 1977;15:262-6. 57. Hartikainen-Sorri AL, Jouppila P. Is routine hospitalization needed in antenatal care of twin pregnancy? J Perinat Med 1984;12:31-4. 58. Saunders MC, Dick JS, Brown IM, McPherson K, Chalmers I. The effects of hospital admission for bed rest on the duration of twin pregnancy: a randomised trial. Lancet 1985; 2:793-5. 59. Crowther CA, Neilson JP, Verkuyl DAA, Bannerman C, Ashurst HM. Preterm labor in twin pregnancies: can it be prevented by hospital admission? Br J Obstet Gynaecol 1989; 96:850-3. 60. MacLennan AH, Green RC, O’Shea R, Brookes C, Morris D. Routine hospital admission in twin pregnancy between 26 and 30 weeks’ gestation. Lancet 1990:335:267-9. 61. Maloni JA, Margevicius SP, Damato EG. Multiple gestation: side effects of antepartum bed rest. Biol Res Nurs 2006;8:115-28. 62. Hemminki E, Starfield B. Prevention of low birth weight and pre-term birth: literature review and suggestions for research policy. Milbank Memorial Fund Q 1978;56:339-61. 63. Sosa C, Althabe F, Belizan J, Bergel E. Bed rest in singleton pregnancies for preventing preterm birth. Cochrane Database Sys Rev 2004: CD003581.