PhD, MS, FACSM Kelly R Evenson
email: kelly_evenson@unc.edu

PhD Ruben Barakat
email: barakatruben@gmail.com

PhD, MSc, FACSM Wendy J Brown
email: wbrown@hms.uq.edu.au

PhD Patricia Dargent-Molina
email: patricia.dargent@inserm.fr

Ph.D Megumi Haruna

RN, MPH Ellen M Mikkelsen

PhD Michelle F Mottola
email: mmottola@uwo.ca

PhD Katrine M Owe

PhD Emily K Rousham
email: e.k.rousham@lboro.ac.uk

PhD Seonae Yeo
email: syeo@email.unc.edu

Facsm R Samuel Mclaughlin

Guidelines for Physical Activity during Pregnancy: Comparisons From Around the World

Keywords: guidelines, exercise, global, leisure activities, pregnancy, prenatal

à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Introduction

Health benefits of physical activity during pregnancy include reduced risk of excessive gestational weight gain and conditions such as gestational diabetes, preeclampsia, preterm birth, varicose veins, and deep vein thrombosis [START_REF] Pivarnik | Impact of physical activity during pregnancy and postpartum on chronic disease risk[END_REF][START_REF]Physical Activity Guidelines for Americans[END_REF][START_REF] Davies | Joint SOGC/CSEP clinical practice guideline: Exercise in pregnancy and the postpartum period[END_REF][START_REF]Exercise in pregnancy[END_REF] . There is some evidence that physical activity during pregnancy is associated with a reduced length of labor and delivery complications 4 . However, vigorous leisure activity is associated with reduced birth weight [START_REF] Leet | Effect of exercise on birthweight[END_REF] . Psychological benefits to physical activity during pregnancy include reduced fatigue, stress, anxiety, and depression, as well as improved well-being [START_REF] Pivarnik | Impact of physical activity during pregnancy and postpartum on chronic disease risk[END_REF][START_REF]Physical Activity Guidelines for Americans[END_REF][START_REF] Davies | Joint SOGC/CSEP clinical practice guideline: Exercise in pregnancy and the postpartum period[END_REF][START_REF]Exercise in pregnancy[END_REF] . From a public health perspective, women who are active during pregnancy are more likely to continue physical activity during postpartum [START_REF]Exercise in pregnancy[END_REF] .

Physiologic responses to exercise, such as changes in heart rate, cardiac output, ventilation, and energy expenditure, are all greater during pregnancy than prepregnancy, and may become more pronounced as pregnancy progresses [START_REF] Mottola | Chapter 12: Performance in the pregnant woman: maternal and fetal considerations[END_REF][START_REF] O'toole | Physiologic aspects of exercise in pregnancy[END_REF] . Hormonal changes increase joint laxity that may place a woman at increased risk for injury [START_REF] Vladutiu | Physical activity and injuries during pregnancy[END_REF] . Adaptations to physical activity are needed to reduce the risk of injury for both the mother and baby.

Guidelines on physical activity during pregnancy provide recommendations for health professionals as to whether to prescribe physical activity and if so, in what manner. Guidelines from a variety of organizations help address questions about physical activity, such as how long, how far, how often, and at what intensity. The World Health Organization"s guideline on physical activity recommends that adults age 18 to 64 years should engage in at least 150 minutes of moderate intensity aerobic activity throughout the week (in bouts of at least 10 minutes), or at least 75 minutes of vigorous intensity aerobic activity, or an equivalent combination of the two [START_REF]Global Recommendations on Physical Activity for Health[END_REF] . Muscle strengthening should be done two or more days per week.

The guideline states that pregnant women may need extra precaution and should seek medical advice before striving to achieve the recommendations.

More detailed guidelines for physical activity during pregnancy are available from several countries, with some guidelines based on evidence and others based on expert consensus. As Evenson, page 5 these were produced by a range of professional bodies and government agencies, and were written for different target audiences, and at different times. The aim of this review was to summarize the different public health and clinical guidelines on physical activity during pregnancy from around the world. A summary of guidance across countries may stimulate national bodies to develop guidelines where they do not exist, share best practices, and update existing guidance. It could also facilitate the development of a global recommendation for physical activity during pregnancy.

Methods

For this review, we searched PubMed (MedLINE) for published guidelines on physical activity during pregnancy. The search was narrowed to peer-reviewed studies published between 1990 and 2012. We cross-referenced with articles that referred to country-specific guidelines and then identified an expert in that country to work with on the project. Thus, each country included in this review was represented by at least one scientist. To narrow the scope of the review, we included only the most recent country-specific or clinical guidelines. Laymanoriented guidelines and those from other societies (such as dietetics) were excluded. A single author reduced all extraction forms into tables that coauthors subsequently checked.

Results

Background

We identified 11 guidelines representing 9 countries, including Australia [START_REF] Sports | SMA statement: the benefits and risks of exercise during pregnancy[END_REF][START_REF]SMA Statement: The benefits and risks of exercise during pregnancy[END_REF] , Canada 3,12,13 , Denmark [START_REF] Damm | Physical activity and pregnancy [Motion og graviditet -Godkendt] -Sandbjerg 2008[END_REF][START_REF]Physical Activity -Handbook on Prevention and Treatment[END_REF] , France [START_REF]Comment meiux informer les femmes enceintes? Recommandations pour les professionnels de santé -Siant-Denis La Plaine: HAS[END_REF] , Japan [START_REF] Koshino | Management of regular exercise in pregnant women[END_REF][START_REF] Miyake | The guideline for safety sports during pregnancy[END_REF] , Norway [START_REF] Strømme | Physical activity and health -Guidelines [Fysisk aktivitet og helse -Anbefalinger[END_REF] , Spain [START_REF] Gurpegui | Chapter 11) Ejercicio fisico y deporte durante el embarazo[END_REF] , United Kingdom (UK) [START_REF]Exercise in pregnancy[END_REF] , and the United States (US) [START_REF]Physical Activity Guidelines for Americans[END_REF][START_REF] Acog | Exercise during pregnancy and the postpartum period[END_REF] (Table 1). The guidelines represented or were endorsed by obstetrics and gynecology (Australia, Canada, Denmark, Spain, UK, US), public health (Canada, Denmark, France, Norway, US), sports medicine (Australia, Japan), and exercise physiology (Canada). Since the two Danish guidelines were essentially identical in their recommendations, they were coded in the remaining tables as one guideline [START_REF] Damm | Physical activity and pregnancy [Motion og graviditet -Godkendt] -Sandbjerg 2008[END_REF][START_REF]Physical Activity -Handbook on Prevention and Treatment[END_REF] . The two US guidelines were Evenson, page 6 coded separately: American College (now Congress) of Obstetricians and Gynecologists (ACOG) [START_REF] Acog | Exercise during pregnancy and the postpartum period[END_REF] and the US Department of Health and Human Services (USDHHS) [START_REF]Physical Activity Guidelines for Americans[END_REF] .

Most guidelines included a comprehensive literature review, but not a quality assessment. However, Canada had a comprehensive rating of scientific evidence contributing to its guidelines, which included a quality assessment of the evidence (considering the study design in this process) to support each recommendation. The Danish Society of Obstetrics and Gynecologists guideline also rated the evidence for each issued recommendation.

Contraindications to Exercise During Pregnancy

Absolute contraindications refer to conditions where exercise is not recommended.

Relative contraindications refer to conditions where the risks of exercise may exceed the benefits. Guidelines from Canada, Japan, Spain, and the US ACOG described contraindications to exercise in absolute and relative terms; however, guidelines from Norway and the UK did not make these distinctions (Table 2). The guidelines from Australia, Denmark, France, and the USDHHS did not address contraindications, because they were intended for healthy women with normal pregnancies. Generally, where two or more countries identified contraindications, they agreed on whether it was an absolute or relative contraindication.

The six countries (Canada, Japan, Norway, Spain, UK, US ACOG) agreed on several contraindications to exercise including anemia, persistent bleeding, cardiovascular disease, cerclage or incompetent cervix, multiple gestation, preeclampsia or pregnancy induced hypertension, premature contractions or labor, and premature rupture of membranes. Five of the six guidelines identified contraindications for diabetes mellitus, eating disorder, morbid obesity, placenta previa, and thyroid disease.

Activities to Avoid During Pregnancy

For women who received physician clearance to exercise during pregnancy, all reviewed guidelines described specific characteristics of activities to avoid and specific sports to avoid (Table 3).

Evenson, page 7

Falls or Trauma: All guidelines generally ruled-out sports involving risks of either falls, trauma, or collisions. A sport"s safety was determined based on the movements required to participate in it. One concern was that the ligaments become relaxed due to increasing hormone levels, making joints more prone to injury (Australia, Canada). The Norwegian guideline was the only one to warn against high loads during strengthening exercises due to the risk of pressure reflex.

Position: All but two guidelines (France, Spain) warned against activities in the supine position (lying on one"s back) due to the chance of decreased cardiac output and orthostatic hypotension caused by the enlarged uterus, which may obstruct venous return or blood flow from the abdominal aorta. As a result, these guidelines recommended avoiding the supine position during physical activity after the first trimester or 16 weeks" gestation. Canada"s guideline suggested modifying the position of the exercise to instead be on one"s side, sitting, or standing. Denmark"s guidelines recommended a seated position during weight training.

Altitude and Depth: Four guidelines included recommendations about physical activity or exercise at altitude. Canada"s guideline accepted moderate exercise at altitudes up to 6000-8250 feet (1800-2500 meters). The US ACOG guideline stated that exercise up to 6000 feet (1800 meters) appeared safe, but exercise at higher altitudes carried risk. It also stated that women should be informed of the signs of altitude sickness and advised that if it develops, to stop exercising and descend from altitude to seek medical attention. Norway and the UK guideline suggested women at altitudes above 8250 feet (2500 meters) obtain 4 to 5 days of exposure at that altitude to avoid exertion and to regulate uterine blood flow. Seven guidelines specifically warned against scuba diving during pregnancy, because the fetus is not protected from decompression sickness and the fetal pulmonary circulation cannot filter bubble formation in the maternal bloodstream.

Heat and Cold: The Norwegian guideline warned of excessive body heat during exercise for pregnant women. Several guidelines (Australia, Canada, Japan, Spain, UK) warned of exercising in hot or humid weather.

Sedentary Behavior and Motionless Standing: The UK guideline specifically mentioned avoiding a sedentary lifestyle, stating that "women and care providers should consider the effects of a sedentary lifestyle during pregnancy" (page 3) because it can contribute to a number of adverse maternal outcomes. The Norwegian and US ACOG guidelines were the only ones to advise against motionless standing due to its association with decreased cardiac output.

Avoidance of Vigorous Intensity Activity: Regarding vigorous activity, the Canadian and Norwegian guidelines cautioned against athletic competition, while the Australian guideline advised close monitoring by a physician. For both Japan and Norway, the recommended rating of perceived exertion categories did not include the vigorous intensity range. The USDHHS guideline stated that women not already highly active or engaged in vigorous activity should focus on moderate intensity activity. The Denmark guidelines cautioned against vigorous activity for women not engaged in it prior to pregnancy. These guidelines also advised that pregnant women accustomed to high intensity physical activity during pre-pregnancy could continue this activity as long as they felt well. The Spanish guideline recommended no more than 15 minutes of vigorous activity and to decrease intensity by 20% to 30% for pregnant athletes. The French guideline mentioned that women engaged in jobs that involved hard or strenuous aspects or long travel time should refer to her occupational or family physician and consider specific adjustments to job tasks.

Activities to Perform During Pregnancy

Most guidelines recommended activities to engage in during pregnancy (Table 4). All but the French and Spanish guidelines indicated duration or total time and all but the Australian and French guidelines indicated frequency of physical activity. For all guidelines, intensity was Evenson, page 9 indicated as moderate or vigorous, or in absolute (e.g., heart rate) or relative (e.g., rating of perceived exertion) indicators.

Type: All but the French guidelines specified aerobic activities as an acceptable modality. Guidelines from Australia, Canada, Denmark, Norway, and the UK also recommended strengthening exercises. Other specific activities that were recommended are summarized in Table 4. Only Spain provided a list of activities to perform with caution. Preferably this activity should be spread throughout the week" (page 42).

Intensity: For absolute intensity, heart rate guidance was provided by Canada, Japan, Spain, and the UK. Guidelines from Canada and the UK specified heart rates accounting for age; however, Japan and Spain recommended heart rates less than 150 and 140 beats per minute, respectively. The Canadian guideline advised working in the lower ends of the heart rate zone if starting a new exercise program or in late pregnancy. The target heart rate zones provided by Canada represented 60% to 80% of maximal aerobic capacity. The UK guideline advocated for an "upper range of 60% to 90% maximal heart rate for women wishing to maintain fitness during pregnancy" (page 4), and 60% to 70% of maximal heart rate for women who were Evenson, page 10 sedentary prior to pregnancy. The Norwegian guideline recommended that aerobic exercise intensity should not exceed 70% to 75% of maximal oxygen uptake, instead advising use of a talk test (being able to talk while exercising) or the Borg"s rating of perceived exertion scale [START_REF] Borg | Perceived exertion and pulse rate during graded exercise in various age groups[END_REF] .

Canada and the UK also mentioned the usefulness of the "talk test". The lowest guidance on intensity was from Spain, which recommended not exceeding 50% of maximal oxygen consumption.

For relative intensity, Canada, Norway, and the UK recommended perceived exertion of 12 to 14, just above or below "somewhat hard", which generally coincided with moderate intensity. Japan recommended a perceived exertion less than 13 (somewhat hard) or 14, and for continuous exercise to be less than 11 (fairly light) or 12.

The French guideline recommended that beginning or continuing moderately intense sport physical activity during pregnancy was possible. The USDHHS guideline indicated that "pregnant women who habitually engage in vigorous-intensity aerobic activity or are highly active can continue physical activity during pregnancy and the postpartum period, provided that they remain healthy and discuss with their health-care provider how and when activity should be adjusted over time" (page 42). The Australian guideline condoned this: for healthy women not highly active or engaging in vigorous activity, then moderate intensity was recommended. The US ACOG stated that pregnant women should engage in regular, moderate intensity physical activity in the absence of contraindications.

Starting a New Exercise Program: All but the US ACOG guidelines included guidance for women starting a new exercise program during pregnancy. The Australian guideline suggested that women could begin a light to moderate exercise program in consultation with their doctor, and the Canadian guideline stated that for uncomplicated pregnancies "women with or without a previously sedentary lifestyle should be encouraged to participate in aerobic and strength-conditioning exercises as part of a healthy lifestyle" (page 517). It indicated this generally was "in the second trimester, when the nausea, vomiting, and profound fatigue of the first trimester have passed and before the physical limitations of the third trimester begin" (page 518). In Japan, the guideline indicated that if a pregnant woman started a sport during pregnancy, she should initiate it after 12 weeks" gestation and confirm a normal pregnancy.

In Norway and the UK, women engaging in new exercise programs during pregnancy were encouraged to begin gradually with shorter sessions of 15 minutes for 3 times per week, then increase gradually to 30 minute sessions 4 times a week, and eventually to daily sessions.

Spain recommended only initiating exercise slowly for previously sedentary women, but did not provide specifics. The US ACOG guideline indicated that previously inactive women should be evaluated before physical activity recommendations are made and to increase the amount of physical activity gradually over time. The USDHHS guideline also indicated that "when beginning physical activity during pregnancy, women should increase the amount gradually over time. The effects of vigorous-intensity aerobic activity during pregnancy have not been studied carefully, so there is no basis for recommending that women should begin vigorous-intensity activity during pregnancy" (page 42).

Other Exercise Guidance: The guidelines from Canada, Norway, and Spain suggested warming up and cooling down before and after exercise, respectively. Australia, Canada, Norway, and Spain also mentioned hydration during exercise. Norway"s guideline also suggested wearing light clothes during exercise. Japan"s guideline described environmental characteristics of the exercise, such as choosing a flat place and exercising between 10am and 2pm, supported by studies finding natural uterine contractions to be lower during that time period [START_REF] Murooka | Required conditions and contraindications Sports Medicine for Pregnant Women[END_REF][START_REF] Germain | Relationship of circadian rhythms of uterine activity with term and preterm delivery[END_REF] .

Signs and Symptoms to Stop Exercise

Six guidelines included indications for stopping exercise during pregnancy (Table 5), while Denmark, France, and the USDHHS did not. All six guidelines indicated ceasing exercise with dizziness or presyncope, dyspnea before exertion, or vaginal bleeding. Five of the six guidelines recommended ceasing exercise if there was indication of abdominal or back pain, Evenson, page 12 amniotic fluid leakage, or excessive shortness of breath. The remaining signs or symptoms in Table 5 were only indicated in one, two, three, or four of the guidelines.

Discussion

The earliest formal recommendations for physical activity during pregnancy can be documented from the 18 th century, which largely reflected the cultural and social norms of the times, rather than scientific evaluation [START_REF] Kerr | Historical Review of British Obstetrics and Gynaecology, 1800-1950[END_REF][START_REF] Downs | Physical activity and pregnancy: Past and present evidence and future recommendations[END_REF] . The earliest studies on maternal physical activity and birth outcomes were conducted in the late 19 th and early 20 th centuries [START_REF] Downs | Physical activity and pregnancy: Past and present evidence and future recommendations[END_REF][START_REF] Briend | Maternal physical activity, birth weight and perinatal mortality[END_REF] . Corresponding with the developing science, recommendations on physical activity during pregnancy continue to be created and updated to provide guidance to health professionals. In this review, we identified, summarized, and contrasted 11 clinical or public health guidelines for physical activity during pregnancy from around the world.

Generally, we found that the content of the guidelines varied depending on the date of publication and target audience (i.e., clinicians vs. public health professionals). There were commonalities as well. For example, almost all guidelines supported moderate intensity physical activity during pregnancy (Spain implied it through heart rate recommendations but not through oxygen consumption). Most guidelines also suggested that women should seek advice from their health care provider before starting or continuing an exercise program. All ruled-out sports involving either risks of falls, trauma, or collisions during pregnancy. The six more clinically focused guidelines included contraindications to exercise, including signs and symptoms that should indicate stopping. In terms of exercise prescription, most of the guidelines included specific type, frequency, and duration or time for physical activity or exercise during pregnancy.

A difference across guidelines was the use of relative and absolute intensity to guide the exercise. Canada, Japan, and the UK all provided guidance for intensity using both heart rate (absolute intensity) and ratings of perceived exertion (relative intensity). In contrast, Denmark, France, US ACOG, and USDHHS indicated neither. However, the US ACOG prior guidelines from 1985 statement did include heart rate guidance [START_REF] Acog | Exercise during pregnancy and the postnatal period[END_REF] that was removed in 1994 [START_REF] Acog | Exercise during pregnancy and the postpartum period[END_REF] .

Only guidelines from Canada, Denmark, and USDHHS provided any recommendation on vigorous intensity physical activity. This reflects the lack of accumulated evidence from welldesigned studies on vigorous activity and pregnancy outcomes 30 . To date, most studies on vigorous intensity physical activity during pregnancy are laboratory based or observational, often with insufficient statistical power to detect findings on relatively rare outcomes. In addition, lack of recommendations about vigorous activity could be due to discrepancies in the definition for this level of intensity.

While most guidelines focused on aerobic exercise, five countries indicated strengthening exercises. Only a few studies have investigated the safety and efficacy of strength training during pregnancy [START_REF] O'connor | Safety and efficacy of supervised strength training adopted in pregnancy[END_REF][START_REF] Barakat | Resistance exercise training during pregnancy and newborn's birth size: a randomised controlled trial[END_REF] . Given the potential health-related benefits of strength training during pregnancy, more work is needed to clarify the safest prescription in terms of volume and intensity. The Canadian guideline suggest using lighter weights and more repetition, not lifting while lying flat on one"s back, and avoiding the valsalva maneuver.

Sedentary behavior is modifiable and comprises time spent in periods of little or no movement while awake, such as sitting, ranging from 1.0-1.5 metabolic equivalents (METS) 33- 35 . The concept that sedentary behavior is not equivalent to lack of physical activity has only recently emerged in the health literature, since one can be physically active and accumulate large amounts of sedentary time. Only the UK mentioned sedentary behavior in the context of reducing it. Future pregnancy guidelines could consider more specific recommendations on sedentary behavior, particularly as research evidence is accumulated around this topic for pregnant women. In addition, none of the guidelines discussed indications for bedrest, despite its prescription to many women [START_REF] Maloni | Antepartum bed rest: maternal weight change and infant birth weight[END_REF] . However, indication of bedrest implies a higher risk pregnancy, and these guidelines were usually geared towards women with normal pregnancies.

Evenson, page 14

A challenge across several guidelines was a lack of clarity in terminology used to describe exercise. For example, several guidelines (Denmark, Norway, UK, US ACOG) interchanged the terms "exercise" with "physical activity". Physical activity is a broad term that is defined as any bodily movement produced by contraction of skeletal muscles that results in increased energy expenditure above a basal level 37 . Exerciseis a subcategory of physical activity that is planned, structured, and purposive to maintain or improve one or more components of physical fitness. Some of the terminology issues arise from cultural differences.

For example, in the Danish guidelines "physical activity" and "exercise" are interchanged, and other terms are used as well (physical training, motion, fitness training), which are difficult to translate directly. Other terminology discrepancies reflect the differing target groups, for example athletes and sportswomen, who usually "exercise" and the general population, who are encouraged to "be active". -UK (cohort study in southwest England [START_REF] Liu | Physical activity during pregnancy in a prospective cohort of British women: results from the Avon longitudinal study of parents and children[END_REF] ), and -US (surveillance studies of the entire country [START_REF] Zhang | Exercise during pregnancy among US women[END_REF][START_REF] Evenson | Leisure-time physical activity among pregnant U.S. women[END_REF][START_REF] Petersen | Correlates of physical activity among pregnant women in the United States[END_REF][START_REF] Evenson | National trends in self-reported physical activity and sedentary behaviors among pregnant women: NHANES 1999-2006[END_REF] Evenson, page 15 Data from these countries indicate that a higher priority should be placed on promoting physical activity during pregnancy, including both education and addressing barriers to physical activity.

More work is needed to understand the advice offered to pregnant women by their health care providers and how that advice is received and used [START_REF] Evenson | Beliefs about exercise among pregnant women[END_REF] . Future studies across countries can elucidate the reasons behind the differences in beliefs, explore whether cultural reasons contribute to these differences, and determine whether tailored messages are more effective than general educational approaches.

Further work is also needed to enhance our understanding and use of pregnancy-related physical activity guidelines by health care providers. To facilitate the use of guidelines in practice, the Physical Activity Readiness Medical Examination (PARmed-X) for Pregnancy tool [START_REF] Wolfe | Physical activity readiness medical examination for pregnancy: PARmed-X for pregnancy[END_REF] was developed to open communication between the health care provider, fitness professional, and the pregnant woman. The 4-page form includes a pre-exercise checklist the woman can fill out, contraindications to exercise the health care provider completes, and a health evaluation form that can be used by the prenatal fitness professional. It also includes information on prescribing aerobic activity, muscular conditioning, and active living. This screening tool facilitates implementation of the guidelines by providing a convenient checklist and prescription for health care providers to use in evaluating pregnant women who want to start a prenatal fitness program. Use of this tool may increase adherence to the physical activity guidelines by both providers and their patients [START_REF] Warburton | Evidence-based risk assessment and recommendations for physical activity clearance: Consensus Document[END_REF][START_REF] Jamnik | Enhancing the effectiveness of clearance for physical activity participation: background and overall process[END_REF] .

Limitations

Several limitations of this review should be acknowledged. The review was narrowed in scope and not all inclusive; we hypothesize that there are other guidelines that met our review criteria were not captured with our search efforts, particularly those not found in PubMed. For example, the review did not include guidelines from lower income nations, indicating either the recommendations were not captured by our search procedures or do not exist. Another limitation was that one person was unable to review all the original guidelines, due to language Evenson, page 16 differences. This problem was diminished by using a standardized extraction form. It should also be noted that while the abstraction was based on the published guideline, many countries created supplemental documents geared towards laypersons and often available in print or on the web. While these materials may contain additional information, they were not reviewed herein. Despite these limitations, to our knowledge, this review is the first to summarize and compare current guidelines for physical activity during pregnancy from nine different countries around the world. This review can be expanded as guidelines are developed, updated, and better accessed.

Conclusion

This review contrasted pregnancy-related physical activity guidelines from around the world and may help to inform the creation of new guidelines, or updates of older ones. It could also facilitate the development of a worldwide guideline. The guidelines we reviewed were important sources of information at the national level for promoting physical activity and exercise during pregnancy. Recognizing contraindications to physical activity, the guidelines can be used to advise and encourage pregnant women to take part in physical activity either by maintaining their pre-pregnancy levels of activity or, for previously sedentary women, by starting a new exercise program during pregnancy.

  Frequency and Duration: Most guidelines (with the exception of those from France) included information on frequency and/or duration of exercise. Specifically, Canada and the UK indicated a minimum of 15 minute sessions for 3 times per week, progressing to 30 minutes, 4 times per week even if intensity was reduced. Denmark recommended at least 30 minutes of moderate intensity activity daily. Japan recommended aerobic exercise for up to 60 minutes, 2 to 3 times per week. Norway recommended 30 minutes per day of aerobic activity. Spain recommended a frequency of 3 times per week with no duration specified. The US ACOG recommended accumulating 30 minutes or more of moderate exercise on most if not all days of the week. The USDHHS indicated that "healthy women who are not already highly active or doing vigorous-intensity activity should get at least 150 minutes (2 hours and 30 minutes) of moderate-intensity aerobic activity per week during pregnancy and the postpartum period.

  Despite variations in the specific amount of physical activity recommended during pregnancy, pregnant women worldwide often do not meet the recommendations. Studies in each country represented in this review have shown that many pregnant women do not obtain as much physical activity or exercise as recommended in their country (examples of studies follow but are not exhaustive): -Australia (Australian Longitudinal Study on Women"s Health 38 ), -Canada (surveillance study of Ontario 39 ), -Denmark (Danish birth cohort study 40 ), -France 41 , -Japan (convenience sample of pregnant women from five facilities in Kanto, Tokyo 42 ), -Norway (pregnant women participating in a birth cohort study near Oslo 43 ), -Spain 44

Acknowledgment: The authors thank Margeaux Kiyoko Akazawa (Emory University) for assisting with translation between English and Japanese, and Sara Satinsky for review of earlier paper drafts. Funding: Kelly Evenson acknowledges support by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health (NIH, #UL1TR000083), and the University Research Council at the University of North Carolina -Chapel Hill. Ruben Barakat acknowledges funding from the Spanish Ministry of Science and Innovation (DEP2009-08990) and Technical University of Madrid, Spain (UPM AL12-P-I+D-14). Michelle Mottola acknowledges funding from the Canadian Institutes of Health Research, and endorsement from Health Canada and the Canadian Society of Exercise Physiologists. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.


Patricia Dargent-Molina
email: patricia.dargent@inserm.fr

Fabienne El Khoury

Bernard Cassou

The 'Ossébo' intervention for the prevention of injurious falls in elderly women: background and design

Keywords: 2013; 20 Supp. 2: 88-93) physical activity, prevention, elderly

This paper reviews the literature that contributed to the design of the 'Ossébo' intervention and describes the study that is underway. Background: Falls and fall-related injuries are a major cause of morbidity and mortality among older people. Extensive research into falls prevention has established physical exercise as an efficient method to reduce falls, but the effect of exercise on serious injuries caused by falls remains unclear. Moreover, populations that would benefit most from these interventions, as well as factors that determine adherence to exercise remain underreported. The Ossébo intervervention: 'Ossébo' is an on-going multicenter randomized controlled trial, aiming to assess the effect of a two-year community-based group physical exercise program on the prevention of falls among women aged 75-85 years old. The primary outcome examined is the rate of falls and injurious falls: secondary outcomes include functional capacities, fear of falling and quality of life. This study will help determine the effectiveness of a large scale falls prevention program and the factors that can potentially assist its success. (

Background

Falls and fall-induced injuries are among the most serious and common medical problems facing elderly persons [START_REF] Tinetti | Risk factors for falls among elderly persons living in the community[END_REF](2)[START_REF] Dargent-Molina | Epidemiology of falls and fall-related injuries in the aged][END_REF](4), and ageing of the population will further raise their burden and costs unless effective prevention measures are largely implemented. One in three people aged 65 years or older living in the community fall at least once a year: this proportion increases to one in two for those over 80 years [START_REF] Tinetti | Risk factors for falls among elderly persons living in the community[END_REF]. Falls can result in injuries, the most common of which are fractures, or loss of confidence which can progressively lead to decreased activity, functional deterioration, depression and social withdrawal [START_REF] Vellas | Fear of falling and restriction of mobility in elderly fallers[END_REF]. The reduction in mobility and independence are often serious enough to result in admission to a nursing home or even premature death (4,[START_REF] Tinetti | Falls, injuries due to falls, and the risk of admission to a nursing home[END_REF].

Up until recently, research into fracture prevention has mainly focused on the prevention and treatment of osteoporosis. Several clinical scores have been proposed to identify subjects at high risk of low bone mineral density and fracture who should be treated [START_REF] Black | An assessment tool for predicting fracture risk in postmenopausal women[END_REF][START_REF] Dargent-Molina | A comparison of different screening strategies to identify elderly women at high risk of hip fracture: results from the EPIDOS prospective study[END_REF][START_REF] Dargent-Molina | A triage strategy based on clinical risk factors for selecting elderly women for treatment or bone densitometry: the EPIDOS prospective study[END_REF][START_REF] Kanis | The use of clinical risk factors enhances the performance of BMD in the prediction of hip and osteoporotic fractures in men and women[END_REF][START_REF] Trémollieres | Fracture risk prediction using BMD and clinical risk factors in early postmenopausal women: sensitivity of the WHO FRAX tool[END_REF]. However, most fractures in the population occur in persons who are at moderate risk and do not have a very low bone mineral density for their age [START_REF] Stone | BMD at multiple sites and risk of fracture of multiple types: long -term results from the Study of Osteoporotic Fractures[END_REF][START_REF] Dargent-Molina | Fallrelated factors and risk of hip fracture: the EPIDOS prospective study[END_REF]. This implies that, although a 'high risk' prevention strategy based on bone-acting pharmaceutical treatments is important, it will not be sufficient to significantly reduce the population burden of fractures. Additional effective preventive measures more widely applicable in the population are needed (4,[START_REF] Järvinen | Shifting the focus in fracture prevention from osteoporosis to falls[END_REF][START_REF] Martin | Next steps for falls and fracture reduction[END_REF]. In this respect, an intervention aimed at preventing falls may be particularly useful. Indeed, most fractures in the elderly are the consequence of a fall, and fall-related factors have been shown to be significant predictors of the risk of fractures in the elderly [START_REF] Dargent-Molina | Fallrelated factors and risk of hip fracture: the EPIDOS prospective study[END_REF][START_REF] Nguyen | Prediction of osteoporotic fractures by postural instability and bone density[END_REF][START_REF] Cummings | Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group[END_REF].

Researchers on falls prevention have been very active in the past two decades. Trials and systematic reviews [START_REF] Gillespie | Interventions for preventing falls in older people living in the community[END_REF][START_REF] Sherrington | Effective exercise for the prevention of falls: a systematic review and metaanalysis[END_REF][START_REF] Chang | Interventions for the prevention of falls in older adults: systematic review and meta-analysis of randomised clinical trials[END_REF][START_REF] Rose | The role of exercise in fall prevention for older adults[END_REF][START_REF] Province | The effects of exercise on falls in elderly patients. A preplanned meta-analysis of the FICSIT Trials. Frailty and injuries: cooperative studies of intervention techniques[END_REF][START_REF] Campbell | Comprehensive approach to fall prevention on a national level: New Zealand[END_REF] now provide clear evidence that falls in older people can be prevented with appropriately-designed intervention programs. The recently-updated Cochrane systematic review [START_REF] Gillespie | Interventions for preventing falls in older people living in the community[END_REF] concluded that exercise interventions reduce the rate of falls (i.e. number of falls per person-years) and risk of falling (i.e. number of people who fall) by up to 35-37%. Although many risk factors for falls have been identified [START_REF] Tinetti | Risk factors for falls among elderly persons living in the community[END_REF][START_REF] Dargent-Molina | Epidemiology of falls and fall-related injuries in the aged][END_REF], intervention trials have found that the size of falls prevention effects from exercise as a single intervention are comparable to those from multifaceted interventions [START_REF] Gillespie | Interventions for preventing falls in older people living in the community[END_REF][START_REF] Campbell | Rethinking individual and community fall prevention strategies: a metaregression comparing single and multifactorial interventions[END_REF]. Therefore, widespread implementation of exercise as a single intervention seems to be the best approach to falls prevention at a population level.

However, not all types of exercise programs are effective. Current evidence indicates that for exercise programs to successfully prevent falls they should target balance and gait [START_REF] Gillespie | Interventions for preventing falls in older people living in the community[END_REF][START_REF] Sherrington | Effective exercise for the prevention of falls: a systematic review and metaanalysis[END_REF][START_REF] Province | The effects of exercise on falls in elderly patients. A preplanned meta-analysis of the FICSIT Trials. Frailty and injuries: cooperative studies of intervention techniques[END_REF] and include progressively challenging balance exercises that are performed while standing and with minimal upper body support [START_REF] Sherrington | Effective exercise for the prevention of falls: a systematic review and metaanalysis[END_REF]. The Cochrane review indicates that multiple component programs that include other activities (e.g. muscle strength/resistance, flexibility) in addition to balance/gait training are the most effective. Tai chi interventions have also been shown to be an effective exercise intervention when delivered to community-residing older adults. However, more general physical activities, such as walking, have not demonstrated any significant efficacy in reducing fall rates or risk [START_REF] Gillespie | Interventions for preventing falls in older people living in the community[END_REF][START_REF] Sherrington | Effective exercise for the prevention of falls: a systematic review and metaanalysis[END_REF].

Both home-based and group-based programs have been shown to prevent falls. Home exercises are most suitable for a frail and less mobile population without easy access to transport, such as people aged over 80. These exercises are safe if properly established by a trained therapist. For instance, the home-based Otago Exercise Programme has been shown to reduce rates of falls by 35% in older women aged 80 years or older [START_REF] Campbell | Randomised controlled trial of a general practice programme of home based exercise to prevent falls in elderly women[END_REF]. It involves five home visits from a physiotherapist or trained nurse to teach exercises to be undertaken at home and monthly phone calls to encourage on-going adherence. Group-based training, on the other hand, has several advantages, including social interaction, peer reinforcement and encouragement, and efficient use of the instructor's time.

The frequency and intensity of the exercise program are also important to consider. A recent meta-analysis of 44 randomized controlled trials [START_REF] Sherrington | Effective exercise for the prevention of falls: a systematic review and metaanalysis[END_REF] showed a greater effect for programs that included a higher dose of exercise, i.e. more than 50 hours of exercise over the trial period which would equate to training classes twice weekly for six months or once weekly for one year. This finding has important implications for service delivery, because many 'balance/fall prevention' group-based programs are offered for shorter periods than this, typically for 10 weeks.

Further research is needed to determine which subgroups of the elderly population will benefit most from a fall exercise intervention [START_REF] Rose | The role of exercise in fall prevention for older adults[END_REF][START_REF] Gardner | Exercise in preventing falls and fall related injuries in older people: a review of randomised controlled trials[END_REF]. Is it the older adult who is at higher or lower level of fall risk? In the case of exercise interventions that include multiple categories of exercise, the Cochrane review indicates that fall rates can be lowered whether the older adults are at higher or lower risk for falls at baseline [START_REF] Gillespie | Interventions for preventing falls in older people living in the community[END_REF]. To our knowledge, only one research group examined the effect of the same exercise intervention, the Otago home-based program, in different subgroups with different falling risk levels [START_REF] Robertson | Preventing injuries in older people by preventing falls: a meta-analysis of individual-level data[END_REF]. The authors reported that the program was significantly more effective in those aged 80 and older than in younger trial participants (aged 65-79 years). The program was equally effective in reducing fall rates in those with and without a previous fall. However, since participants reporting a fall in previous year had a higher fall rate, the program resulted in a higher absolute reduction of falls and injuries when offered to those with a history of a previous fall. In a communitybased public health approach, the selection of the target population must be based on simple criteria (age, sex, a history of fall or decreased performances as measured by simple functional tests easily usable by GPs) and allow the program to be offered to a large number of the 'at risk' population [START_REF] Gardner | Exercise in preventing falls and fall related injuries in older people: a review of randomised controlled trials[END_REF][START_REF] Skelton | Exercise and injury prevention in older people[END_REF].

The mechanisms by which physical exercise prevents falls need to be understood better so that we can define the most effective programs. Programs that have been successful in decreasing fall risk generally showed improvement in some components of physical fitness, in particular balance and reaction time. However, physical exercise could also act by restoring self-confidence (decreasing fear of falling), by improving mental health status and feeling of well-being or by increasing general activity level. The effect of successful interventions on these potential 'intermediate' variables has rarely been reported. Furthermore, the impact of a fall exercise intervention in terms of quality of life has been questioned [START_REF] Laybourne | Falls exercise interventions and reduced falls rate: always in the patient's interest?[END_REF].

For long-term benefit, it is important that subjects continue to practice regularly because the benefit wears off rapidly when exercise is discontinued. Low compliance rates may explain, at least partly, the absence of effect in some trials. There are limited data to understand what factors promote or check initial uptake of exercise as well as long-term compliance. It is evident that programs that place emphasis on pleasure, conviviality and social interaction and that foster a climate of confidence are more attractive and more likely to maintain subjects' motivation over time. Easy access to the exercise center is certainly another important factor for the elderly. A study aimed at determining the socio-demographic and health profile of those subjects who continue to exercise over the long run would also be useful not only to help design optimum programs but also to identify subgroups that deserve particular attention and efforts [START_REF] Gardner | Exercise in preventing falls and fall related injuries in older people: a review of randomised controlled trials[END_REF].

Yet, the essential question that remains today concerns the effectiveness of exercise in protecting against the most serious falls such as those accompanied by fractures (4,[START_REF] Gardner | Exercise in preventing falls and fall related injuries in older people: a review of randomised controlled trials[END_REF][START_REF] Karlsson | Does exercise reduce the burden of fractures? A review[END_REF]. Some observational data suggest that while the highest functioning and more active older people have the lowest fall risk, they are more likely to sustain serious injuries when they do fall [START_REF] Gregg | Physical activity, falls, and fractures among older adults: a review of the epidemiologic evidence[END_REF][START_REF] Speechley | Falls and injuries in frail and vigorous community elderly persons[END_REF], maybe because they engage in higher-risk activities and fall with a higher energy. Hence, the effect of exercise on injury prevention may be less than expected. On the other hand, it is likely that regular practice with structured exercises aimed at improving strength, reaction time and coordination in addition to balance, will improve the efficacy of a person's protective responses during a fall (such as extending the arm to break the impact of the fall) as well as the thickness of local shock absorbers (like muscles), two key determinants of fracture risk, particularly for hip fracture. Furthermore, adequately designed programs may help people become more conscious of their capacities and limits, and help them develop strategies to effectively compensate while avoiding dangerous situations, which should also contribute to decrease the risk of fall-related injury. Most randomized controlled trials are underpowered to detect a significant reduction in injurious fall rates owing to the relative infrequency of injurious fall events [START_REF] Province | The effects of exercise on falls in elderly patients. A preplanned meta-analysis of the FICSIT Trials. Frailty and injuries: cooperative studies of intervention techniques[END_REF][START_REF] Gardner | Exercise in preventing falls and fall related injuries in older people: a review of randomised controlled trials[END_REF][START_REF] Schwenk | Definitions and methods of measuring and reporting on injurious falls in randomised controlled fall prevention trials: a systematic review[END_REF]. Some studies suggest a reduction of falls causing injuries parallel to the reduction of overall falls [START_REF] Gardner | Exercise in preventing falls and fall related injuries in older people: a review of randomised controlled trials[END_REF][START_REF] Robertson | Preventing injuries in older people by preventing falls: a meta-analysis of individual-level data[END_REF][START_REF] Lin | Community-based tai chi and its effect on injurious falls, balance, gait, and fear of falling in older people[END_REF][START_REF] Barnet | Community-based group exercise improves balance and reduces falls in at-risk older people: a randomised controlled trial[END_REF]. However, definitions of injuries varied a lot from one study to another, and often included relatively mild injuries such as bruises or scratches.

The 'Ossébo' intervention trial

With the above issues in mind, we have set up a large-scale multicenter randomized controlled trial, the 'Ossébo' study, to assess the effect of a groupbased physical exercise program targeting balance, gait, strength and coordination on the prevention of injurious falls. Additional objectives of the study are to improve our understanding of the mechanisms by which physical training helps to reduce falls and injuries, and to identify the socio-demographic and health-related individual factors that are associated with uptake and long-term adherence to the program. The target population were women, aged 75-85 years old, who lived at home but had diminished balance and gait capacities, i.e. a subgroup of the elderly population at higher risk of fractures and other fall-related injuries.

A total of 706 participants were recruited between December 2007 and April 2011 in 20 study centers located in medium to large cities throughout France. Voter registration lists were used to invite all women aged 75-85 years who lived near study centers to a 'balance health examination' that included a battery of well-standardized tests of balance and motor capacities. Selection for the intervention trial was then based on gait speed and ability to do four steps with feet in tandem position (tandem walk). These two tests have been chosen because they have been validated with regard to the prediction of hip fracture (one of the most serious fall-induced injury) in the EPIDOS (Epidemiologie de l'Ostéoporose) French cohort of 7500 women aged 75 years or older that had been recruited from voter registration listings like the Ossébo cohort [START_REF] Dargent-Molina | Fallrelated factors and risk of hip fracture: the EPIDOS prospective study[END_REF]. However, in case the benefit of the intervention is demonstrated, we will be able to assess whether the same effect is observed in different subgroups defined using other tests and criteria recommended in clinical practice to identify older people at risk of falling (for example: previous fall, get-up-and-go test, one-leg stance, aged 80 or more).

Frailer women, i.e. women who had a particularly slow gait speed (below the 95 th percentile in the EPIDOS cohort) or who were unable to stand for 10 sec with feet together, were excluded from the trial because they are at high risk of falling and would probably require individualized exercises. In other words, we included into the trial women who were 'not too fit and not too frail'.

Women with a substantial alteration in cognitive function (as assessed with the Pfeiffer test), a degenerative condition such as Parkinson's disease, or a medical conditions involving the neuromuscular, skeletal or cardiovascular system that generally precludes exercising, and women who were already taking exercise classes have also been excluded from the trial.

Eligible women who agreed to participate into the trial were randomized into one of two groups: a group that received the intervention and a control group without intervention.

Women from both groups received a summary of their test results and general advice regarding the prevention of falls and fractures based on recommendations from Institut national de prévention et d'éducation pour la santé (Inpes, French National institute for prevention and health education) and Groupe de Recherche et d'Information sur les Ostéoporoses (GRIO).

Women allocated to the intervention group were invited to attend exercise sessions in small groups of 10-15 persons, supervised by an instructor specialized in physical training for the elderly and specifically trained for the study. The participants take one class a week, an hour per class, for two years.

After a 5-10-min warm-up period including stretching of the major muscle groups, the participants are given various types of exercises such as:

•

Exercises that help them become aware of the importance of the eye position, and of foot-eye coordination for balance and gait. • Exercises designed to relax the trunk and arms with the aim to become conscious of the importance of axial tonicity and of the arms role in maintaining balance.

• Exercises involving variations of the base of support under static and dynamic balance conditions. • Exercises designed to sharpen plantar sensations, and acquire a good foot unfolding movement on the ground.

•

Going through a circuit while dealing with interfering elements.

• Movements of transfer in various directions (front-back, lateral) as well as in rotation. • Muscle strength training exercises and improvement of muscle tonicity; use of repeated movements of short duration ensuring loading of major fracture sites (femur, spine, wrist, etc).

• Posture verticalization through lowering of the center of gravity, 'grounding', and straightening of the vertebral column.

Throughout the class, the instructor gives advice relevant to situations in everyday life (such as sitting or rising from a chair or bed, picking up an object on the floor, etc). The last phase of the class consists of a 10 min cool-down period involving gentle stretches, relaxation and controlled breathing. At the end of the class, an informal discussion time allows participants to talk about the problems they encountered during the session. Implementation of the program is progressive to avoid discomfort and pain, with priority given to long-term activity maintenance rather than intensity. Although following a core theme, the exercise classes are adapted to the functional capabilities of the participants (for instance, by adapting the number of movement repetitions).

To complete the group sessions, the participants are encouraged to practice regularly at home, with a simple routine based on the class exercises and adapted by the instructor to each participant's physical ability.

The intervention is implemented in partnership with the association Siel Bleu (www.sielbleu.org) that is specialized in training of older adults and is largely present in most regions of France. The content of the exercise program has been developed based on the extensive experience of the two managers of Siel Bleu in training older adults in diverse settings and populations, on the published description of successful programs and after direct contacts with some of the leader investigators in the field [START_REF] Campbell | Randomised controlled trial of a general practice programme of home based exercise to prevent falls in elderly women[END_REF][START_REF] Skelton | Exercise and injury prevention in older people[END_REF][START_REF] Barnet | Community-based group exercise improves balance and reduces falls in at-risk older people: a randomised controlled trial[END_REF].

Fall occurrence among all trial participants is monitored during two years by asking women to return monthly pre-paid pre-addressed calendar cards where they can mark the date of any falls. In case a fall is reported, a telephone interview is carried out to confirm the fall and to gather information on its circumstances and consequences (follow-up rates close to 90%). Falls are defined as 'unintentionally coming to rest on the ground, floor, or other lower level' [START_REF] Buchner | Development of the common data base for the FICSIT trials[END_REF]. There is currently no consensus on the definition of an injurious fall to be used as an outcome in randomized controlled fall prevention trials. We intend to use various falls classification schemes, in particular the one of Campbell (which has been used most frequently in past exercise trials) and the one recently proposed by Swenk and colleagues from the PROFANE (Prevention of Falls Network Europe) group [START_REF] Schwenk | Definitions and methods of measuring and reporting on injurious falls in randomised controlled fall prevention trials: a systematic review[END_REF]. Using the Campbell's definition, for instance, fall events are classified as resulting in (i) serious injury if the fall resulted in a fracture or admission to hospital with an injury or required stitches (sutures); (ii) moderate injury if bruising, sprains, cuts, abrasions, or reduction in physical function for at least three days resulted or if the participant sought medical help; and (iii) no injury. For our sample size calculation, we had used a slightly modified version of the Campbell classification where bruises, sprains, cuts and abrasion that did not lead to medical care or any functional limitation were classified in the 'minor or no injury' category. Using this classification, we have calculated that we will have a statistical power of 80% (risk alpha 5%) to detect a 25% reduction in serious and moderate injuries assuming a 30 per 100 incidence rate in the control group [START_REF] Dargent-Molina | Fallrelated factors and risk of hip fracture: the EPIDOS prospective study[END_REF][START_REF] Robertson | Preventing injuries in older people by preventing falls: a meta-analysis of individual-level data[END_REF] and a 10% drop out rate.

The investigator classifying fall events will be blind to group allocation. Serious injuries are confirmed from hospital and general practice records.

The main results regarding the effect of the intervention on serious falls are expected in 2013 (after all participants would have been followed for two years).To better understand how the intervention 'works', participants are reviewed at one and two years to assess changes in physical motor capacities, fear of falling, physical and social activity level, perceived health and well-being. As of today, 580 women have been reviewed at one year, and 379 at two years (response rates around 85%).

Expected results

The group intervention that we propose to assess is relatively simple to implement. It relies on a network of participants already established across France. In the case of a demonstrated benefit it could therefore be easily generalized as part of a population-based public health program of falls and fractures prevention in the elderly. Results of the Ossébo study should also contribute to better understand the determinants of compliance and to better define subjects who would benefit most from the intervention and, therefore, who should be targeted in priority. The intervention should enable elderly women to preserve two elements essential to their quality of life as they age, that is, their functional capacity and their independence. It may also lead to a global improvement in their health status since physical exercise can have beneficial effects on other aspects of health.

Funding

The Ossébo study is supported by the French National Research Agency (ANR), Hospital program of clinical research (PHRC, Ministry of Health), the National Institute of prevention and health education (Inpes), and the Council of the Ile-de-France region, Partenariat Institutions-Citoyens pour la Recherche et l'Innovation (PICRI). The intervention is implemented in partnership with the association Siel Bleu (Sport, Initiatives et Loisir).

Conflict of interest

None declared.