Physical Fitness and Pregnancy - DiVA portaluu.diva-portal.org/smash/get/diva2:637104/FULLTEXT01.pdf · 2013. 8. 13. · Relaxin Relaxin is a pleiotropic peptide hormone of the insulin-like

ACTAUNIVERSITATIS

UPSALIENSISUPPSALA

2013

Digital Comprehensive Summaries of Uppsala Dissertationsfrom the Faculty of Medicine 913

Physical Fitness and Pregnancy

EVA THORELL

ISSN 1651-6206ISBN 978-91-554-8699-0urn:nbn:se:uu:diva-203630

Dissertation presented at Uppsala University to be publicly examined in Rudbecksalen, Dag Hammarskjölds väg 20, Uppsala, Friday, September 6, 2013 at 13:15 for the degree of Doctor of Philosophy (Faculty of Medicine). The examination will be conducted in Swedish. Abstract Thorell, E. 2013. Physical Fitness and Pregnancy. Acta Universitatis Upsaliensis. Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 913. 62 pp. Uppsala. ISBN 978-91-554-8699-0. Objectives To assess physical fitness in pregnancy and to evaluate its effect on perceived health, back pain, blood pressure and duration of gestation. Also, to evaluate the effect of serum relaxin levels on blood pressure and duration of gestation. Material and methods A prospective cohort of 520 pregnant women were examined in early pregnancy and five months postpartum with regard to socio-demographic characteristics and estimated peak oxygen uptake (V̇O2 peak, est.). Serum concentrations of relaxin were carried out in early pregnancy. Physical exercise, possible back pain and blood pressure were measured repeatedly throughout pregnancy. Results Absolute V̇O2 peak, est. in early pregnancy was positively correlated to perceived health, which was lower during than after pregnancy. The average absolute V̇O2 peak, est. in early preg-nancy of 2.4 l/minute was 0.02 l/minute less than the V̇O2 peak, est. postpartum, while regular physical exercise decreased throughout pregnancy. Absolute V̇O2 peak, est. in early pregnancy was not associated to the incidence of any low back pain location in pregnancy or postpartum, but inversely to intensity of back pain and diastolic blood pressure and positively with dura-tion of gestation. Elevated serum relaxin levels were associated with decreased diastolic blood pressure and higher duration of gestation among women with miscarriage. Conclusions Perceived health, diastolic blood pressure and duration of gestation were posi-tively affected by physical fitness while no effect was shown on the incidence of back pain. The effect of physical fitness on duration of gestation and diastolic blood pressure might have clinical implications as well as the increased serum relaxin levels on miscarriages. Keywords: Physical fitness, oxygen uptake, pregnancy, back pain, blood pressure, duration of gestation, relaxin, cycle ergometer test, physical exercise, perceived health Eva Thorell, Uppsala University, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, BMC, Husargatan 3, SE-752 37 Uppsala, Sweden. © Eva Thorell 2013 ISSN 1651-6206 ISBN 978-91-554-8699-0 urn:nbn:se:uu:diva-203630 (http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-203630)

Dedication To my daughter Sofia who is the future and to my 8th great grand uncle David Herlitz who was first after his thesison epilepsy 1597

List of Papers

This thesis is based on the following papers, which are referred to in the text by their Roman numerals.

I Thorell E, Svärdsudd K, Andersson K, Kristiansson P.

Moderate impact of full-term pregnancy on estimated peak oxygen uptake, physical activity and perceived health. Acta Obstetricia Gynecologica Scandinavica 2010;89:1140-48.

II Thorell E, Kristiansson P. Pregnancy related back pain, is it related to aerobic fitness? A longitudinal cohort study. BMC Pregnancy and Childbirth 2012;12(Apr 17):30.

III Thorell E, Goldsmith L, Weiss G, Kristiansson P. Physical fitness, serum relaxin levels and blood pressure in pregnancy. In manuscript.

IV Thorell E, Goldsmith L, Weiss G, Kristiansson P. Physical fitness, serum relaxin levels and duration of gestation. In manuscript.

Reprint was made with permission from the publisher.

Prologue

Attending a lecture about fitness levels in the Swedish population I heard about a report which revealed that one twenty-year old woman in five had such limited abdominal muscle strength that she could not manage a sixth sit-ups, a level of fitness which was considered necessary for the woman to be able to carry anything other than the weight of her own body 36. For several years I had worked as a doctor at the maternal health care centre in Kumla caring for pregnant women so I was aware of the pain my patients experienced, as well as other symptoms. So I started the first study to find out if low level of fitness was one reason for their pain.

Contents

Prologue .......................................................................................................... 7 Abbreviations ................................................................................................ 11 Definitions .................................................................................................... 12 Introduction ................................................................................................... 13

Maternal cardiovascular physiology in pregnancy ................................... 13 Oxygen uptake .......................................................................................... 13 Physical exercise and duration of gestation ............................................. 14 Back pain in pregnancy ............................................................................ 14 Relaxin ..................................................................................................... 15 Antenatal care ........................................................................................... 15

Aims .............................................................................................................. 16 Study population and methods ...................................................................... 17

Statistical considerations .......................................................................... 24 Results ........................................................................................................... 25

Characteristics .......................................................................................... 25 Perceived health ................................................................................... 27 Physical exercise .................................................................................. 28 Muscle strength .................................................................................... 29 Physical fitness .................................................................................... 29 Back pain ............................................................................................. 31 Blood pressure ..................................................................................... 34 Duration of gestation ........................................................................... 38

Discussion ..................................................................................................... 43 Physical fitness ......................................................................................... 44 Perceived health ....................................................................................... 45 Physical exercise ...................................................................................... 46 Back pain .................................................................................................. 46 Blood pressure .......................................................................................... 47 Duration of gestation ................................................................................ 48

Conclusions ................................................................................................... 49 Summary in Swedish (svensk sammanfattning) ........................................... 50 Acknowledgments......................................................................................... 52 References ..................................................................................................... 54

Abbreviations

SF-36 Short Form 36 C.I. 95% confidence interval BMI Body mass index V̇O2 peak, est. Estimated peak oxygen uptake

Definitions

In this study, the following definitions are used: • Early pregnancy: before the end of thirteen completed gestational weeks

(<91 days). • Physical activity: activities in daily life without the intention of

becoming physically fit. • Physical exercise: time spent on activities performed in order to increase

or maintain fitness. • Absolute V̇O2 peak, est.: absolute estimated peak oxygen uptake (l/minute). • Relative V̇O2 peak, est.: absolute V̇O2 peak, est. relative to bodyweight

(l -3/minute·kg). • Physical fitness: the result of physical activity and physical exercise,

measured in the present study by absolute V̇O2 peak, est.

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Introduction

Sedentary lifestyle is a potential negative risk factor of health 19. Women are at increased risk of having more sedentary lifestyles and lower physical exercise levels than men 101. During pregnancy a further decline in women’s physical exercise across the trimesters has been documented 27. However, women who exercise regularly while not pregnant continue to do so during pregnancy 82.

Physical exercise before and during pregnancy has been showed to reduce risk of prenatal complications such as excessive weight gain, abnormal glucose tolerance, gestational diabetes and musculoskeletal problems 15, 71, 79,

81, 97, 106, 112, 118.

Maternal cardiovascular physiology in pregnancy During pregnancy several anatomical, physiological, hormonal, and emotional changes take place in order to permit necessary maternal and foetal adaptations and optimise foetal growth and development. Most cardiovascular changes take place early in pregnancy 70.

Early vascular changes include increased blood volume, heart rate and cardiac output as well as decreased vascular resistance secondary to marked peripheral vasodilation 31. The mechanisms involved are uncertain but include several different vasodilator systems 109.

A decrease of both systolic and diastolic blood pressure has been seen in very early pregnancy 70 and it has also been seen until 18th gestational week 68, thereafter there is an increase of the blood pressure during the rest of pregnancy 48, 67.

Oxygen uptake The oxygen uptake is defined as the amount of oxygen consumed by the body in any work and measured as the difference in the amount of oxygen in exhaled and inhaled air and when oxygen uptake do not increase further, despite of the workload increases, the individual has reached their maximal oxygen uptake 2. Maximal oxygen uptake is widely considered to be the gold

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standard by which one can measure the cardiorespiratory level 88. Maximal oxygen uptake is reduced with age, partly due to the maximum pulse rate drop, which regulates cardiac output, and the maximal oxygen uptake is also dependent on body size and composition, blood volume, hemoglobin content, lung diffusion, stroke volume, muscular factors (fiber type, capillary density and mitochondria rate), heredity and fitness 78.

Oxygen uptake is generally lower in women than in men. The mean maximal oxygen uptake for women and men of 20-40 years of age are 2.0-2.4 l/minute and 3.1-3.4 l/minute and very high maximal oxygen uptake are 2.8 l/minute and 4.0 l/minute, respectively 5.

Maximal oxygen uptake can be estimated by submaximal cycle ergometer test 5, which have shown good agreement with maximal oxygen uptake measured with gas analyses as gold standard 66, 77, 90. The submaximal test is much easier to perform, since there is no need for sophisticated equipment and the risk for participants are low.

Physical exercise and duration of gestation Women are recommended regular physical exercise during pregnancy 1. A positive association between physical exercise and duration of gestation with protection against preterm delivery has been suggested in some studies 44, 55,

56, 64 although disputed by others 4, 29, 43. However, the impact of physical exercise on duration of gestation

including miscarriage is inconsistent. An increased risk of early miscarriages was found in women with higher levels of physical exercise 34, 38, 69 whereas no compromise of foetal growth and development, or increased risk of miscarriage were shown in healthy athletes 20, 46, 57, 63. During established pregnancy, it seems useful to improve physical fitness without affecting fetal growth 37, 57, 98, 99, 102, 114.

Back pain in pregnancy Musculoskeletal pain is the most common cause of pregnancy related morbidity and there is a remarkably increased prevalence of back pain, as compared with the non-pregnant state. The prevalence of back pain with onset during pregnancy is reported to range between 61% and 88% 42, 75. This compares with a prevalence of back pain, irrespective of onset, among women of the same age of 20-40% of the general population 11, 12, 94. This means that a high proportion of women with previously healthy backs experience onset of back pain in pregnancy.

The cause of the development of pregnancy-related back pain remains uncertain. It is reported that patients with moderately to severely disabling

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back pain had lower physical fitness levels than healthy subjects matched for age, sex and physical activity. However low activity or fitness levels have not been identified as significant risk factors for developing chronic low back pain. Whether physical inactivity causes back pain or whether back pain causes patients to decrease their physical activity and become physically weaker is disputed 96, 111.

Relaxin Relaxin is a pleiotropic peptide hormone of the insulin-like growth factor family, and it has been known to be a pregnancy related hormone for over eighty years. The polypeptide hormone relaxin has been linked to miscarriage in early pregnancy 3, 87, 103.

Relaxin is involved in regulation of biochemical processes in remodelling the extracellular matrix of cervix and vagina during pregnancy and relaxin receptors have been found in fibroblasts in the cervix 85, 93. Relaxin also has growth effects on the uterus and placenta, influences vascular development and proliferation in the endometrium, and causes biochemical changes needed for rupture of the foetal membranes at term. Increased expression of endogenous decidual relaxin is seen in women with preterm rupture of membranes 17.

In very early pregnancy there is an initial increase of maternal serum concentrations of relaxin until a peak at about the 12th gestational week followed by a decline until the seventeenth week. Thereafter, serum relaxin levels remain stable for the duration of the pregnancy 3, 86.

Besides its well-known effects on the extracellular matrix of the female reproductive system, profound effects of relaxin on vasodilation have been shown in animal models 53, 115. Low serum relaxin levels have been associated with higher blood pressure during pregnancy and in hypertensive non-pregnant women and men 40, 62.

Antenatal care All women in Sweden are guaranteed by law the opportunity to attend a maternal health centre during pregnancy free of charge. More than 95% of women take up this offer. The centres are operated by Swedish county councils, or are subcontracted to the councils. The centres in this particular region were staffed by general practitioners, midwives and administrative staff, and they all follow the same general procedure with repeated appointments during pregnancy, and one appointment postpartum.

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Aims

The overall aim of this thesis was to evaluate the effect of physical fitness on health during and after pregnancy.

The specific aims were: • To study the effect of pregnancy on physical fitness, levels of physical

exercise and perceived health. • To examine the effect of physical fitness on back pain. • To assess the effect of physical fitness and serum relaxin on blood

pressure development during pregnancy. • To evaluate the effect of physical fitness and relaxin on duration of

gestation.

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Study population and methods

Between March 2001 and June 2003, 2085 women in the early stages of pregnancy attending eight maternal health centres in the city of Örebro (population 128,000), one maternal health centre in the community of Kumla (population 20,000) or one in the community of Hallsberg (population 15,000) were identified. Inclusion criteria were: pregnancy up to thirteen completed gestational weeks, no existing cardiovascular disease or on-going medication for hypertension, the ability to cycle, the ability to communicate in the Swedish language and the intention of living in the area for the following three months. According to these criteria 626 women were excluded. Furthermore, 76 women had a miscarriage before the end of the 13th gestational week and 230 women declined participation. 418 women were not invited to participate in the study since the degree of commitments varied across the maternal health care centres. Participation rate across the centres was 70–40%. In addition, 215 women could not be included because of acute infections, they were not tested in time, they miscarried or they changed their minds about participating. Consequently, 520 constituted the study population, Figure 1.

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Figure 1. Flow chart of participants and non-participants throughout the study

There were no significant differences in the basic characteristics of women in the study population and non-participants except that the non-participants reported more previous pregnancies and deliveries, and smoked significantly less, Table 1.

All pregnant women n=2085

Eligible for inclusion n=1383

Agreed to participate n=735

Excluded (n=626) because of: Gestational age ! 13

completed weeks n=396 Non-Swedish speaker n=166

Cardiovascular disease, unable to cycle or would move from the area n=64

Declined participation n=230 Not asked n=418

Visit 1 n=520 Gw 8-13

Visit 2 n=498 Gw 20-26

Included but not tested (n=215) because:

Disease n=68 Miscarriage n=16

Declined participation n=66 Gestational age >13

completed weeks n=62 Wrongly included n=3

Miscarriage n=20 Induced abortion n=2

Visit 3 n=498 Gw 28-32

Visit 4 n=456 Gw 36-38

Visit 5 n=488 4-6 month pp

Non-participants postpartum (n=10) because:

Stillborn n=3 Declined participation n=6

Psychosis n=1

Preterm delivery n=42

Miscarriage ! 13 completed weeks n=76

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Table 1. Characteristics in early pregnancy of women eligible to participate in the study according to participation or not (mean value (95% C.I.) and proportion (%))

Characteristic Participants Non-participants p= n n Age (year) 520 29.0 (28.5-29.3) 748 28.8 (28.4-29.1 0.52 Weight (kg) 520 68.1 (67.0-69.2) 782 67.4 (66.5-68.3) 0.33 Height (m) 520 1.67 (1.66-1.67) 793 1.66 (1.66-1.67) 0.61 BMI (kg/m2) 520 24.5 (24.2-24.9) 781 24.3 (24.0-24.6) 0.38 Number of pregnancies 520 2.0 (1.11.8-2.0) 799 2.2 (2.2-2.3) <0.001 Number of deliveries 520 0.7 (0.6-0.7) 808 0.8 (0.7-0.8) 0.035 Current smoker* (%) 38/520 7.3 30/836 3.6 0.002 Born abroad (%) 45/520 8.7 70/794 8.8 0.92

*) Reported to midwife

Among the study population two women had an induced abortion before gestational week 22, 23 women were delivered by elective caesarean section and 15 women were induced before 42 weeks of pregnancy, leaving 20 women with miscarriage and 460 women with spontaneous deliveries.

The duration of gestation was confirmed by ultrasound examination in the estimated gestational week 17 and registered as completed weeks of gestation. Information about the start of delivery and multiple pregnancies were retrieved from the medical records of the respective obstetric centre. The duration of gestation was categorised as miscarriage <22 completed weeks (<154 days), preterm birth 22-<37 weeks (154-258 days), birth at term 37-<42 weeks (259-293 days) and post term birth ≥42 weeks (>293 days).

Four study appointments were scheduled for each woman during preg-nancy and one appointment after delivery. The appointments were on aver-age at 10.9, 24.0, 29.7 and 36.5 completed gestational weeks, Table 2. The postnatal appointment was on average at 21.2 weeks after delivery.

Information about socio-demographic factors, obstetric history, physical exercise, physical activity, eating habits, and perceived health was sought by questionnaires and muscle strength, physical fitness by physical measurements at repeated time points, Table 2. Date of miscarriage and delivery were retrieved from the obstetric records as well as information on the non-participating women. The staff of the maternal health centres was blinded for the test results.

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Table 2. Schedule of appointments in the study and variables measured Appointment

Responsible

staff Gestational

week Variable

Mean (95% C.I.)

1 Test conductor Midwife

10.9 (10.8-11.1)

Height Weight Waist circumference Highest education Cigarette smoking habits Obstetric history Previous back pain Previous sick-leave due to back pain Eating habits Frequency of physical exercise before 20 years of age Physical exercise during the past four weeks Physical activity during the past four weeks Perceived health (Short Form-36) Muscle strength (sit-up test) Physical fitness (cycle ergometer test) Blood pressure Blood test (9.2 mean gestational week)

2 Midwife 24.0 (23.8-24.3)

Weight Physical exercise during the past four weeks Back pain during the past four weeks Pain intensity Blood pressure

3 Midwife 29.7 (29.6-29.9)


4 Midwife 36.5 (36.2-36.8)


5 Test conductor Midwife

Postpartum 21.2

(20.8-21.6)

Weight Waist circumference Physical exercise during the past four weeks Physical activity during the past four weeks Back pain during the past four weeks Obstetric history Perceived health (Short Form-36) Muscle strength (sit-up test) Physical fitness (cycle ergometer test) Blood pressure

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Height was measured without shoes using a wall-mounted tape measure, and was noted in meters to two decimal points. The women were weighted in indoor clothes and without shoes on a balance lever scale. Measurements were in kilogramme to one decimal point. BMI (kg/m2) was calculated. Waist was defined as the circumference between the twelfth rib and the iliac crest, and measured to the nearest centimetre.

Highest completed education was classified as compulsory school (=1), two years high school (=2) three years high school (=3), post-secondary education (=4), and university (=5). This classification was grouped into education on university or not (no/yes).

Cigarette smoking habits were recorded by a midwife, also regarding the non-participants, and by the test conductor, and classified as no smoking (=1), <1/day (=2,) 1-10 cigarettes/day (=3), 11-20 cigarettes/day (=4), respectively. Information was also available as to whether the woman had quit smoking in the previous six months. A variable was constructed as never smoked or quit >6 months ago (=0) and current smoker or quit <6 months ago (=1).

Previous back pain (before present pregnancy and irrespective of pregnancy) was classified as yes (=1) or no (=0). If the answer was yes, a question was asked regarding previous sick leave, yes (=1) or no (=0). Questions about eating habits (awareness of food intake) were classified as less then often (=0) and often or more often (=1).

The frequency of physical exercise before 20 years of age was classified as no sports (=0), sports without contest (=1) and sports with contest (=2).

Physical exercise during the past four weeks was classified as: never (=1), now and then (=2), once or twice a week (=3), three to five times a week (=4) and more than five times a week (=5). Infrequent physical exercise was defined as the sum of classification 1 and 2 and regular physical exercise as the sum of 3, 4 and 5.

Physical activity in daily living during the past four weeks included the frequency of house cleaning, gardening, walking/cycling, dancing, and open air activities which were classified as less then often (=0) or often or more (=1). In addition, occupational activity/workload was stated as not physically demanding (=0) and physically demanding (=1), mode of travel as <20 minutes walk/cycle to work (=0) and >20 minutes walk/cycle to work (=1).

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Self-rated perceived health was measured by the generic multi-purpose Short Form 36 (SF-36) questionnaire 107. The questionnaire yields an 8-scale profile of functional health and well-being scores (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health). Physical and mental health summary measures were given for the past four weeks. Physical and mental health scores are added to the total health score. Higher scores are associated with higher levels of functioning. A top score of 100 means excellent, a score 84-99 is very good, 61-83 is good, 25-60 is reasonable and scores below 25 are bad.

Back pain during the past four weeks was recorded (no/yes) at gestational weeks 24, 30 and 36 and 21 weeks postpartum. If the women had experienced any back pain they marked the location of pain on a pain drawing and marked the pain intensity on a visual analogue scale (0 mm indicated no pain and 100 mm indicated intolerable pain). Pain locations (cervico-thoracic, lumbar, lumbosacral and sacral) were identified by a standardised reading of the pain drawings. More than one location could be indicated.

The country of birth was classified as born in Sweden or not (no/yes).

Muscle strength was measured with a sit-up test performed in the supine position on the floor with the knees at a 90° angle and the feet flat on the floor, at gestational week 11 and 21 weeks post partum. The women were asked to perform three sets of sit-ups with five sit-ups in each set with no rest in between. They stopped when they were unable to perform any more or had performed a maximum of 15 sets of sit-ups 36. The load was increased at each of the three sets of exercises (first - fingers to knees, second - arms crossed over chest and elbows to thighs, third - arms behind head elbows to thighs). The sit-up test results were recorded as 0 to 15.

Physical fitness was estimated by using the submaximal cycle ergometer heart rate method on a Monark Exercise Ergometer 828E bicycle, adjusted to the individual’s height at gestational week 11 and 21 weeks postpartum. Cycle tests were performed between 8 a.m. and 4.30 p.m. The mean time for the first cycle test was 12.15 p.m. and for the postpartum test 11.30 a.m. The heart rate was measured every minute using a wireless chest pulse belt. The pedalling rate of 50 revolutions per minute was kept constant by the use of a metronome. The initial workload, 50 W or 75 W, was based on the woman’s reported actual physical activity levels. The incremental load was 25 W at one-minute stages until a steady state heart rate of ≥125 beats minute-1 was reached. At this heart rate, the women cycled for at least six minutes and until two consecutive (one minute apart) heart rates differed by three or

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fewer beats minute-1. The heart rate values were used to obtain estimated peak oxygen uptake in l/minute (V̇O2 peak, est.) according to a nomogram, in absolute value and relative to body weigh 2, 5. At the end of the test the women evaluated the intensity of the exercise on Borg’s rating of perceived exertion scale 14. During the test the women wore light clothes and sport shoes, and the room temperature was 18-20º Celsius. The women were instructed not to eat a light meal 1 hour or a heavy meal 2 to 3 hours before the test, and to avoid strenuous physical activity for one day before the test. Nicotine use was not allowed for 1 hour prior to the test. In case of an on-going infectious disease the test was postponed for two weeks.

Blood pressure was taken and registered by a midwife at the study appointments and at regular visits to the midwife. Blood pressure was measured in the brachial artery by indirect means, using a mercury sphygmomanometer with a triple cuff. The triple cuff consists of three chambers, with three different widths on the traditional cuff (9, 12 and 15 cm). When the triple cuff is placed on the arm and the clasp is in place, the air supply is automatically shut off from not needed areas. The blood pressure measurements utilising the onset of the first (systolic) and fifth (diastolic) sounds of Korotkov were taken in the right arm of the seated women after approximately five minutes of rest and registered to the nearest five mmHg.

Blood tests were carried out in early pregnancy, in average at 9.2 (C.I. 9.0-9.4) gestational weeks. Among women who miscarried the blood samples were drawn at 9.1 gestational weeks (C.I. 8.2-10.0). The blood samples were separated by centrifugation and the serum was stored at -20° until analysis.

Concentrations of relaxin in each serum sample were determined using a homologous, human relaxin-specific radioimmunoassay previously described 52. The intraassay and interassay coefficients of variation were 8.9 % (n = 12 observations) and 9.8 % (n=14 assays), respectively. All serum samples were analysed blindly in duplicate. The lowest and highest detectable relaxin values were 80 ng/l and 3450 ng/l, respectively. Five samples with values below the lowest detectable assay point and four samples with values above the highest assay point were replaced by 80 ng/l and 3450 ng/l. For illustration purposes (Figure 7) type values of 500 ng/l, 2000 ng/l and 3500 ng/l were used.

The Research Ethics Committee of Örebro University, Sweden approved the study in 2001 and 2003. The reference number was 217/01. Participation in the study was approved of the women by informed consent.

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Statistical considerations Because there was a big enough sample size the central limit theorem was applied. Means and proportions were calculated using standard techniques. Non-parametric tests (Wilcoxon´s and Signed rank tests) were used for categorical or not normally distributed variables. Relationships between continuous data were tested with Pearson’s correlation coefficients and between continuous and ordinal data with Spearman’s correlation coefficients. For simple and multiple regression analyses the general linear model was used. No multicollinearity problem was found. Only two tailed tests were used. Statistical tests were considered significant if p<0.05. Very small p-values were indicated <0.0001.

The curve in Figure 3 was produced with the linear regression technique with age squared. Compared with raw data there was a good line fit adjusted for the women’s age, time during the day for cycle test and duration of gestation.

For the regression analyses data on reported back pain, or no back pain, from each visit and women’s estimates of pain intensity were concatenated to create a data set consisting of pain reports and the corresponding pain intensity estimates throughout pregnancy. Cox regression and general linear model were used for regression analyses, and the latter also to produce a model and figure of adjusted back pain intensity by absolute V̇O2 peak, est.. To illustrate the pain intensity scores during pregnancy the women were grouped by absolute V̇O2 peak, est. into tertiles as 1.3 to 2.1, 2.2 to 2.6 and 2.7 to 4.4 l/minute.

Relying on the central limit theorem the paired t-test was used when comparing repeated measures of blood pressure at the different time points. Because blood pressure was measured at several time points for each individual woman during pregnancy, the term “mean” is used for each woman´s blood pressure values within a certain time interval, and the term “average” is used for mean of the time intervals throughout pregnancy. The weekly intervals chosen were 5-14, 15-27, 28-34 and 35-42, respectively.

For the analysis shown as a regression surface in Figure 7, the general linear model was used to compute expected blood pressure values based on levels of absolute V̇O2 peak, est. and serum relaxin, adjusted by cigarette smoking habits (current smoker or quit <6 months) and weight.

The level of significance in the simple regression analyses in Table 11 and Table 12 was set at p<0.1. Statistical analyses were performed using the SAS program package, versions 9.1 to 9.3 (SAS Institute Inc., Cary, NC, USA).

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Results

Characteristics Characteristics of the 520 women are shown in Table 3. The women were in average 29 years of age with a mean height of 1.67 metres. The mean weight at gestational week 11 was 68.1 kg and the mean weight gain to gestational week 36 and 21 weeks post-partum were 12.5 kg and 0.9 kg, respectively. These changes were statistically significant as was the increase of average waist circumference from gestational week 11 to 21 weeks postpartum.

More than 40% of the women had completed university education and 3% compulsory school only. Almost one in five reported current cigarette smoking or had quit smoking less than six months ago. The proportion of women pregnant for the first time was 42% and 50% had at least one previous delivery.

As a result of the present pregnancy, 498 women gave birth with an average duration of gestation of 278 days, 20 women had miscarriage with 98 days of duration of gestation in average and 2 women had an induced abortion. Among the women who gave birth, 460 women had a spontaneous start of labour. Six women had a multiple pregnancy, Table 3.

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Table 3. Characteristics of the study population (520 women) in gestational week 11 and additional variables with other time point specified Characteristic n Mean or

proportion 95% C.I.

Age (year) 520 29.0 (28.5-29.3) Height (m) 520 1.67 (1.66-1.67) Weight (kg)

Gestational week 11 520 68.1 (67.0-69.2) Gestational week 24 498 73.6 (72.5-74.7) Gestational week 30 496 76.8 (75.7-77.9) Gestational week 36 455 80.6 (79.4-81.8) Postpartum week 21 488 68.9 (67.7-70.1)

Waist circumference (cm) Gestational week 11 318 81.3 (80.2-82.5) Postpartum week 21 479 82.5 (81.6-83.5)

Highest education (%) Compulsory school 16 3.1 High school 227 43.7 Post-secondary education 49 9.4 University 228 43.9

Cigarette smoking habits (%) Current smoker, reported to midwife 38 7.3 Current smoker, reported to test conductor 54 10.4 Current smoker or quit <6 months (%) 96 18.5

Previous back pain irrespective of pregnancy (%) 238 45.8 Sick-leave due to back pain before present pregnancy (%) 44 8.3

Number of previous pregnancies Gravidity 0 218 41.9 Gravidity >1 302 58.1

Number of previous deliveries (%) Parity 0 258 49.6 Parity > 1 262 50.4

Multiple pregnancy (%) 6/498 1.2 Labour

Labour, induced <42 weeks (%) 15/498 3.0 Non-laboured delivered by elective caesarean section (%) 23/498 4.6 Spontaneous labour delivered by caesarean section (%) 30/460 6.5

Duration of gestation (days) Women giving birth 498 278 (277-279) Women with spontaneous start of delivery 460 279 (278-280) Women who miscarried 20 98 (88-108)

Serum relaxin, gestational week 9 (ng/l) 510 767 (730-804) Regular physical exercise <20 years of age (%)

Sports with contest 235 44.9 Sports without contest 185 35.8 No sports 100 19.3

Regular physical exercise ≥once a week, past four weeks (%) Gestational week 11 259 49.8 Gestational week 24 237/498 47.6 Gestational week 30 227/498 45.6 Gestational week 36 154/456 33.7 Post partum week 21 243/488 49.7

Physical fitness Absolute V̇O2 peak, est., gestational week 11 (l/minute) 520 2.44 (2.40-2.49)

Absolute V̇O2 peak, est., post partum week 21 (l/minute) 466 2.42 (2.37-2.46)

Relative V̇O2 peak, est., gestational week 11 (l-3/minute·kg) 520 36.6 (35.9-37.3)

Relative V̇O2 peak, est., postpartum week 21 (l-3/minute·kg) 466 35.9 (35.2-36.7)

Muscle strength, sit-up test (number) Gestational week 11

15 442 85 10-14 31 6 <10 47 9

Postpartum week 21 15 325/464 70 10-14 46/464 10 <10 93/464 20

Perceived health (Short Form-36 score) Mean physical health, gestational week 11 520 79.7 (78.3–81.2)

27

V̇O2 peak, est. = Estimated peak oxygen uptake

Perceived health On SF-36 in gestational week 11, the women scored their mean mental health to 72.0 (C.I. 70.4-73.5) and their mean physical health to 79.7 (C.I. 78.3-81.2), Table 3. Among the mental health subscales, social function was scored highest (80.9) and vitality lowest (48.2). Among the physical health subscales, physical function was scored highest (90.8) and role physical lowest (67.5). In 21 weeks postpartum the SF-36 mean scores and all the subscales, except for bodily pain, were significantly higher than those of gestational week 11, Figure 2.

Figure 2. Short Form 36 (SF-36) subscale scores at gestational week 11 and 21 weeks postpartum Note: PF, physical functioning; RP, role physical; BP, bodily pain; GH, general health; VT, vitality; SF, social functioning; RE, role emotional; MH, mental health

0102030405060708090

100

PF RP BP GH VT SF RE MH

Scale score

SF-36 subscales

Postpartum

Early pregnancy

Mean mental health, gestational week 11 520 72.0 (70.4-73.5) Mean total health, gestational week 11 520 75.8 (74.5-77.29 Mean physical health, postpartum week 21 488 87.3 (86.0-88.6) Mean mental health, postpartum week 21 488 81.3 (80.0-82.7) Mean total health, postpartum week 21 488 84.3 (83.2-85.5)

Back pain location (%) Cervico-thoracic during pregnancy 69/459 15.0 Lumbar during pregnancy 67/459 14.6 Lumbosacral during pregnancy 274/471 58.2 Sacral during pregnancy 253/469 53.9 Any back pain during pregnancy 373/479 77.9 Any back pain postpartum week 21 179/488 36.7

Back pain intensity (mm) Gestational week 24 498 33.7 (30.9-36.4) Gestational week 30 497 38.0 (35.3-40.8) Gestational week 36 455 39.2 (36.2-42.1) Postpartum week 21 488 18.3 (15.9-20.6)

28

Physical exercise Before 20 years of age more than 81% of the women had engaged in sports with or without contest while 19% had not, Table 3.

Almost one of two women reported that they took regular physical exercise in gestational week 11 but as their pregnancies advanced a successively lower proportion reported regular physical exercise (p <0.0001) and in the third trimester one of three took regular physical exercise. At 21 weeks postpartum the proportion reporting regular physical exercise was back to early pregnancy levels, although 35% of the women who reported physical exercise in early pregnancy reported not doing so at the postpartum appointment, and vice versa.

Women who reported regular physical exercise in early pregnancy achieved a significantly higher absolute and relative V̇O2 peak, est., a higher number of sit-ups, a higher physical, mental and total score on SF-36, and were more aware of their food intake than women who reported infrequent regular physical exercise, Table 4. Height, weight, waist circumference and BMI were not statistically different between these groups.

Table 4. Physical characteristics, reported activities and Short Form 36 (SF-36) health profiles among women who reported infrequent physical exercise (less than once a week) or regular physical exercise (more than once a week) during the past four weeks, in gestational week 11 (mean values (95% C.I.) and proportions (%)) Characteristic Infrequent

physical exercise Regular physical

exercise p<

N 261 259 Age (year) 28.7 (28.2–29.3) 29.2 (28.6–29.7) n.s. Current smoker* (%) 11 7 0.05 Absolute V̇O2 peak, est. (l/minute) 2.35 (2.29–2.41) 2.53 (2.47–2.60) 0.0001

Relative V̇O2 peak, est. (l-3/minute·kg) 33.6 (32.6–34.5) 36.5 (35.5–37.4) 0.0001

Sit-ups (number) 13.5 (13.1–13.9) 14.3 (14.0–14.6) 0.01 Height (m) 1.66 (1.66–1.67) 1.67 (1.66–1.68) n.s. Weight (kg) 68.8 (67.2–70.4) 67.4 (66.0–68.8) n.s. Waist circumference (cm) 82.5 (80.8–84.1) 80.2 (78.7–81.6) n.s. BMI (kg/m2) 24.9 (24.3–25.4) 24.2 (23.7–24.7) n.s. Awareness of food intake, ≥often (%) 42 63 0.0001 Physical exercise <20 years of age (%) 39 52 0.001 Physically demanding work (%) 28 25 n.s. Walk or cycle >20 minutes to work (%) 10 14 0.05 Walk/cycle in daily life ≥often (%) 43 76 0.0001 Open air activity ≥often (%) 15 28 0.0001 House cleaning ≥often (%) 56 56 n.s. Dancing ≥often (%) 4 6 0.05 Gardening ≥often (%) 19 19 n.s. Mean physical health, SF-36 (score) 77.8 (75.7–79.9) 81.6 (79.7–83.6) 0.05 Mean mental health, SF-36 (score) 69.9 (67.6–72.2) 74.1 (72.0–76.1) 0.05 Mean total health, SF-36 (score) 73.9 (71.9–75.8) 77.8 (76.0–79.6) 0.01

* = reported to test conductor V̇O2 peak, est. = estimated peak oxygen uptake n.s. = not significant

29

Muscle strength In gestational week 11, 85% of the women performed 15 sit-ups, 6% performed 10-14 and 9% less than 10, Table 3. The women performed on average 1.5 fewer (C.I. -1.8 to -1.2) sit-ups (p<0.0001) at 21 weeks postpartum and the percentages changed to 70%, 10% and 20% respectively. Women who reported regular physical exercise performed in average 14.3 sit-ups in gestational week 11 as compared to 13.5 sit-ups in women who reported infrequent physical exercise (p<0.01), Table 4. In addition, the number of sit-ups showed no correlation to absolute V̇O2 peak, est. (p=0.37), Table 5.

Table 5. Correlation and multiple regression analysis of absolute estimated peak oxygen uptake (V�O2 peak, est.), at gestational week 11, and possible determinants Variable

r

p

Partial r2

Cumulative r2

Model p

Age (year) 0.29 <0.0001 0.05 0.05 <0.0001 Physical exercise <20 years of age

0.19 <0.0001 0.04 0.09 0.0002

Weight (kg) 0.23 <0.0001 0.03 0.12 0.0016 Physical exercise past four weeks 0.20 <0.0001 0.02 0.14 0.0049 Duration of gestation (week) -0.07 0.09 0.01 0.15 0.0416 BMI (kg/m2) 0.14 0.001 0.01 0.16 0.0292 Height (m) 0.21 <0.0001 Waist circumference (cm) 0.18 0.001 Mode of travel to work 0.16 0.0002 Open air activity 0.12 0.006 Awareness of food intake 0.10 0.02 Mean physical health (SF-36 score)

0.09 0.03

Walking/cycling in daily life 0.09 0.04 Occupational activity/workload 0.05 0.23 Gardening 0.05 0.26 Sit-ups (number) 0.04 0.37 Dancing 0.03 0.45 Mean mental health (SF-36 score) -0.02 0.67 House cleaning -0.03 0.45 Current smoker, reported to test conductor

-0.09 0.037

Physical fitness The 95 % C.I. for the intercept and the slope of the regression line of V̇O2 peak, est. by heart rate, during and after pregnancy, were for the intercept (6.2-7.1) and (6.1-7.0), respectively, and were for the slope (-0.027 to -0.034) and (-0.029 to -0.032), respectively.

30

The average absolute V̇O2 peak, est. in gestational week 11 was 2.442 l/minute (C.I. 2.399-2.486) and 2.418 l/minute (C.I. 2.372-2.463) 21 weeks postpartum. The difference of -0.024 l/minute (C.I. -0.057 to 0.010) was not significant (p=0.23). The average relative V̇O2 peak, est. in gestational week 11 and 21 weeks postpartum was 36.62 l-3/kg·minute (C.I. 35.90-37.35) and 35.94 l-3/kg·minute (C.I. 35.20-36.67), respectively and this decrease of 0.79 l-3/kg·minute (C.I. -1.3 to -0.30) was significant (p<0.01). There was also a significant positive correlation between both absolute and relative V̇O2 peak, est.

in gestational week 11 and 21 weeks postpartum (p<0.0001).

Relative V̇O2 peak, est. in gestational week 11 was positively correlated to the variation of SF-36 mean physical health (r=0.15, 0<0.0001) and the subscales physical function (r=0.18, p<0.0001) and general health (r=0.21, p<0.0001) in gestational week 11 (data not shown). The absolute V̇O2 peak, est. displayed weaker positive correlations to the same SF-36 scores. At 21 weeks postpartum, relative V̇O2 peak, est. showed a positive correlation to the SF-36 subscales physical function (r=0.22, p<0.0001), general health (r=0.17, p<0.0002) and mean physical health (r=0.016, p<0.0001). The absolute V̇O2 peak, est. in 21 weeks postpartum was correlated to physical health only (r=0.13, p<0.01). The other SF-36 subscales showed no such correlations with relative or absolute V̇O2 peak, est. in early pregnancy or at postpartum appointment.

To find determinants for the absolute V̇O2 peak, est. in gestational week 11, multiple regression analysis was performed. Age, physical exercise before 20 years of age, weight, gestational week and BMI were significantly and independently associated to absolute V̇O2 peak, est., Table 5. Each partial R2 was low, with a cumulative R2 of 0.16 (p<0.0001).

The absolute V̇O2 peak, est. in gestational week 11 and 21 weeks postpartum by women’s age, adjusted for weight, completed gestational week and time during the day for cycle test in early pregnancy and postpartum, increased successively by age to a maximum at 35 years, after which it decreased successively, Figure 3. In the model, absolute V̇O2 peak, est. among women 20 years of age was 0.624 l/minute (23.7%) less than absolute V̇O2 peak, est. of 2.630 l/minute among the 35-year-old women who had the highest value and 0.125 l/minute (4.8%) higher than 42-year old women. Among women of the same age, the effect of pregnancy from 8 to 12 completed weeks lowered the adjusted mean absolute V̇O2 peak, est. by 0.013 l/minute. At the postpartum test there was an additional decrease by 0.034, 0.014 and 0.011 l/minute among women 20, 35 and 42 years of age, respectively.

31

Figure 3. Absolute estimated peak oxygen uptake (V̇O2 peak, est.), at first study visit in pregnancy (mean10.9 gestational weeks) and at mean 21.2 weeks postpartum, in relation to women’s age, adjusted for weight, completed gestational week and time of the day of cycle test (age is squared)

Back pain Previous back pain irrespective of pregnancy was reported by nearly half of the women and 8% reported sickness absence because of back pain before the present pregnancy, Table 3.

The number and proportion of women reporting back pain at each appointment during and after pregnancy are shown in Table 6. Back pain of any location at any point during the present pregnancy was reported by almost 8 out of 10 women, with lumbosacral and sacral pain as the most commonly reported locations. At 21 weeks postpartum, nearly four out of ten women still reported back pain.

1,5

1,7

1,9

2,1

2,3

2,5

2,7

2,9

18 20 22 24 26 28 30 32 34 36 38 40 42 44

VO2peak, est l/min

Age

Gest week 8

Gest week 10

Gest week 12

Postpartum

32

Table 6. Prevalence of back pain during and after pregnancy by back pain location Back pain location Cervico-

thoracic Lumbar Lumbo-

sacral Sacral Any back

location Time N

total n % n % n % n % n %

Gestational week 24 498 30 6 28 6 157 32 152 30 278 56 Gestational week 30 497 40 8 33 7 185 37 157 32 306 62 Gestational week 36 455 39 8 26 6 161 35 142 31 263 58 Postpartum week 21 488 52 11 36 7 120 24 53 11 179 37

During pregnancy the prevalence of cervico-thoracic and lumbar pain locations were <10%, without changes postpartum. The corresponding prevalence of lumbosacral and sacral pain were stable at about 30-37% during pregnancy and displayed a significant decrease (p<0.0001) at the postpartum appointment to 24% and 11%, respectively. The proportion of women with more than one back pain location were at the pregnancy visits between 14% and 17% and at the postpartum visit 11%.

The incidence of back pain in any back pain location during pregnancy or back pain location at the postpartum appointment showed no association to absolute V̇O2 peak, est., measured in gestational week 11, in the Cox regression analysis (data not shown). However, an inverse significant association was displayed with age and incidence of back pain during pregnancy (HR 0.96, p=0.0005) and with back pain during pregnancy and back pain postpartum (HR 0.96, p=0.0007), (data not shown). Analyses including possible confounding factors did not change these findings.

The mean intensity of back pain increased successively by duration of gestation to a maximum of 39 mm on the visual analogue scale in late pregnancy. It subsequently declined to 18 mm at 21 weeks postpartum, Table 3.

Possible determinants in early pregnancy of intensity of back pain during pregnancy are shown in Table 7. In the univariate regression analyses absolute V̇O2 peak, est., physical exercise past four weeks, age and university education were significantly inversely associated and previous back pain, previous deliveries, weight and current smoking were significantly positively associated with back pain intensity. In a multiple linear regression analysis all factors remained significant except university education and current smoking. The R2 of the full model was 0.12. A multiple linear regression analysis was similarly performed to find determinants for pain intensity at the postpartum appointment: back pain before pregnancy was significantly

33

and positively associated with pain intensity but neither of the other factors (data not shown). The R2 of that model was 0.07.

Table 7. Effects on back pain intensity of factors in gestational week 11 in linear regression analyses Crude Adjusted Covariates Estimate p Estimate p

Absolute V̇O2 peak, est. (l/min) -6.0 0.0003 -5.2 0.0019

Physical exercise past four weeks -4.8 <0.0001 -3.3 <0.0001 Previous back pain irrespective of pregnancy 13.3 <0.0001 12.6 <0.0001 Previous delivery 4.5 <0.0001 4.1 0.0006 Age (year) -0.9 <0.0001 -1.3 <0.0001 Weight (kg) 0.4 <0.0001 0.3 <0.0001 University education -3.1 <0.0001 -0.6 0.35 Current smoker or quit <6 months 3.4 0.019 -0.6 0.66 V̇O2 peak, est. = estimated peak oxygen uptake

To illustrate the effect of absolute V̇O2 peak, est. on reported back pain intensity, during and after pregnancy, the women were grouped by absolute V̇O2 peak, est. into tertials. The pain intensity scores during pregnancy (adjusted by the independently significant determinants physical exercise during the past four weeks, previous back pain, previous delivery, age and weight), by the absolute V̇O2 peak, est. are presented in Figure 4. From the group with the lowest to the group with the highest absolute V̇O2 peak, est., the mean back pain intensity scores decreased in a dose-response manner, from 40 mm to 32 mm with significant differences between the group with the lowest absolute V̇O2 peak, est. and the other two groups, p=0.0003 and p=0.004, respectively. After delivery the influence of absolute V̇O2 peak, est. was the opposite compared with during pregnancy, but no significant difference was shown.

34

Figure 4. Mean of back pain intensity scores during and after pregnancy, adjusted by physical exercise during past four weeks, previous back pain (before current pregnancy), previous delivery, age and weight, presented by groups of absolute estimated peak oxygen uptake (V̇O2 peak, est.) in gestational week 11

Blood pressure Mean diastolic and systolic blood pressures by gestational week are presented in Figure 5. The mean change of diastolic blood pressure across the four weekly intervals was -0.9 (C.I. -1.6 to -0.3), 2.2 (C.I. 1.6-2.7) and 4.2 (C.I. 3.7-4.6) mmHg, respectively (p<0.0001). The corresponding changes of systolic blood pressure were 0.24 (C.I. -0.6-1.1), 1.2 (C.I. 0.6-1.9) and 3.4 (2.7-4.0) mmHg, respectively (p<0.0001). Between the weekly intervals 5-14 and 35-42, the average diastolic and systolic blood pressure increased significantly by 5.2 (C.I. 4.5-6.0) and 4.6 mmHg (C.I. 3.7-5.4) (p<0.0001), respectively.

The mean individual number of measurements of blood pressure throughout pregnancy was 9.1 (C.I. 8.9-9.4) which was significantly and positively associated with the blood pressure results at all four weekly intervals (0.28≤r≤0.42, p<0.0001 for diastolic blood pressure and 0.22≤r≤0.36, p<0.0001 for systolic blood pressure).

05

1015202530354045

1.3 - 2.1 2.2 - 2.6 2.7 - 4.4

Mean pain intensity

score, mm

Groups of absolute estimated maximal oxygen uptake

Pregnancy

Postpartum

35

Figure 5. Systolic and diastolic blood pressure during pregnancy by gestational week. The error bars indicate 95% C.I.

In each woman there was a highly significant correlation between the individual diastolic (0.56≤r≤0.81) and systolic (0.58≤r≤0.78) blood pressure values (p<0.0001). This means that some women uniformly had high levels relative to other women, whereas others had low levels and women followed a blood pressure track throughout pregnancy. As a consequence, the blood pressure of an individual woman could be fairly accurately described by her average value, which will be used henceforth.

Serum relaxin concentrations showed a significant inverse correlation to the average diastolic blood pressure (r=-0.13, p=0.003), Table 8, but no correlation to the average systolic blood pressure (r=-0.08, p=0.06), Table 9. A scatter plot of the serum relaxin concentrations and average diastolic blood pressure values is displayed in Figure 6. Average diastolic blood pressure by serum relaxin concentrations.

Levels of absolute V̇O2 peak, est. showed no correlation to either the diastolic (r=-0.02, p=0.6) nor the systolic (r=0.02, p=0.7) average blood pressure values.

0

20

40

60

80

100

120

140

0 5 10 15 20 25 30 35 40 45

Blood pressure, mmHg

Time, week

Diastolic

Systolic

36

Table 8. Effect of factors measured in gestational week 11 on average diastolic blood pressure in linear regression analyses (n=488) Simple linear regression Multiple linear

regression r2=0.15, p<0.0001

Variable Estimate r2 p= Estimate p= Age (year) 0.13 0.00 0.66 0.12 0.15 Height (m) 8.2 0.00 0.17 -2.39 0.69 Weight (kg) 0.18 0.09 <0.0001 0.20 <0.0001 University education -0.14 0.00 0.61 -0.19 0.52 Current smoker or quit <6 months

-1.53 0.01 0.009 -1.76 0.003

Number of previous pregnancies -0.07 0.01 0.02 -0.23 0.70 Number of previous deliveries -1.08 0.01 0.02 -1.74 0.02 Serum relaxin (ng/l) -0.002 0.02 0.003 -0.002 0.03 Physical exercise past four weeks 0.13 0.00 0.63 0.06 0.82 Absolute V̇O2 peak, est. (l/minute) -0.35 0.00 0.60 -1.53 0.03

V̇O2 peak, est. = estimated peak oxygen uptake

Table 9. Effect of factors measured in gestational week 11, on average systolic blood pressure in linear regression analyses (n=488) Simple linear regression Multiple linear

regression r2=0.11 Variable Estimate r2 p= Estimate p=

Age (year) 0.04 0.00 0.66 0.16 0.17 Height (m) 22.47 0.02 0.004 10.68 0.18 Weight (kg) 0.21 0.07 <0.0001 0.22 <0.0001 University education 0.01 0.00 0.98 -0.15 0.69 Current smoker or quit <6 months

-1.21 0.01 0.11 -1.36 0.08

Number of previous pregnancies -0.83 0.01 0.038 -0.13 0.85 Number of previous deliveries -1.38 0.01 0.018 -2.40 0.02 Serum relaxin (ng/l) -0.002 0.01 0.06 -0.001 0.29 Physical exercise past four weeks 0.25 0.00 0.50 0.21 0.57 Absolute V̇O2 peak, est. (l/minute) 0.38 0.00 0.66 -1.27 0.16

V̇O2 peak, est. = estimated peak oxygen uptake

37

Figure 6. Average diastolic blood pressure by serum relaxin concentrations.

Crude estimates of possible associations between other factors measured in early pregnancy and average diastolic and systolic blood pressures were calculated by simple regression analyses and are displayed in Table 8 and Table 9, respectively. The number of previous pregnancies, number of deliveries and cigarette smoking habits were significantly negatively and weight significantly positively associated to the average diastolic and systolic blood pressure. In addition, height was significantly positively associated to average systolic blood pressure.

In the multiple regression analysis, with all measured factors in Table 8 included in the model, absolute 2 peak, est. appeared inversely and independently associated to the average diastolic blood pressure as did serum relaxin, the number of deliveries and cigarette smoking habits. Weight remained positively and highly significantly associated to average diastolic blood pressure. The R2 of the full model was 0.15 (p<0.0001).

Similar associations were shown in the multiple regression analysis with the average systolic blood pressure as the dependent variable, except that cigarette smoking habits, serum relaxin and 2 peak, est., showed no association, Table 9.

0

20

40

60

80

100

120

0 500 1000 1500 2000 2500 3000 3500 4000

Serum relaxin concentration (ng/l)

Average diastolic blood pressure (mmHg)

38

To illustrate the relationship between serum relaxin and absolute 2 peak, est. and average diastolic blood pressure in pregnancy, adjusted by number of deliveries, cigarette smoking habits and weight, the linear regression model was used to compute expected mean diastolic blood pressure levels, Figure 7. Women with the highest serum relaxin concentrations and the highest absolute 2 peak, est. showed the lowest diastolic blood pressure levels and women with the lowest serum relaxin values and the lowest absolute

2 peak, est. displayed the highest. When the most extreme observed combinations of relaxin and absolute 2 peak, est. (relaxin 3,450 ng/l and absolute 2 peak, est. 4.4 l/minute, and relaxin 60 ng/l and absolute 2 peak, est. 1.3 l/minute) were used the lowest diastolic blood pressure was estimated to 66.9 mmHg and the highest 77.3 mmHg.

Figure 7. The effect of serum relaxin concentration and absolute estimated peak oxygen uptake ( 2 peak, est.), adjusted by number of deliveries, weight and current cigarette smoking habits or quit <6 months ago, on average diastolic blood pressure in pregnancy

Duration of gestation Characteristics in gestational week 11 of women with miscarriage and women with spontaneous start of labour with delivery preterm, term and post term, are shown in Table 10.

4.53

1.50

20

40

60

80

5002000

3500 V̇O2 peak, est l/min

Diastolic blood

pressure (mmHg)

Serum relaxin (ng/l)

39

Tab

le 1

0. C

hara

cter

istic

s of

wom

en w

ith m

isca

rria

ge a

nd s

pont

aneo

us s

tart

of l

abou

r (p

rete

rm, t

erm

and

pos

t ter

m)

M

isca

rria

ge

(<15

4 da

ys)

Pre

term

del

iver

y (1

54-2

58 d

ays)

T

erm

del

iver

y (2

59-2

93 d

ays)

P

ost t

erm

del

iver

y (>

293

days

) C

hara

cter

istic

n

Mea

n (9

5% C

.I.)

/ pr

opor

tion

(%

) n

Mea

n (9

5% C

.I.)

/ pr

opor

tion

(%

) n

Mea

n (9

5% C

.I.)

/ pr

opor

tion

(%

) n

Mea

n (9

5% C

.I.)

/ pr

opor

tion

(%

) A

ge (

year

) 20

30

.4 (

27.9

-32.

8)

28

28.8

(27

.1-3

0.5)

40

1 28

.7 (

28.3

-29.

1)

31

30.5

(28

.7-3

2.4)

W

eigh

t, ge

stat

iona

l wee

k 11

(kg

) 20

68

.1 (

63.8

-72.

5)

28

69.2

(64

.1-7

4.3)

40

1 67

.8 (

66.6

-69.

0)

31

68.6

(62

.6-7

4.6)

H

eigh

t (m

) 20

1.

66 (

1.63

-1.6

8)

28

1.65

(1.

63-1

.67)

40

1 1.

67 (

1.66

-1.6

7)

31

1.66

(1.

63-1

.68)

G

ravi

dity

0

3 15

10

35

.7

176

43.9

15

48

.4

Par

ity

0 5

25

11

39.3

20

6 51

.4

19

61.3

P

arity

> 1

4

20

1 3.

6 47

11

.7

3 9.

7 H

ighe

st e

duca

tion

, uni

vers

ity

8 40

10

35

.7

185

46.1

12

38

.7

Cur

rent

sm

oker

or

quit

<6

mon

ths

(%)

3 15

6

21.4

78

19

.4

3 9.

7

Abs

olut

e V̇O

2 pe

ak, e

st.,

gest

atio

nal

wee

k 11

(l/

min

ute)

20

2.61

(2.

35-2

.89)

28

2.

31 (

2.15

-2.4

7)

401

2.44

(2.

39-2

.48)

31

2.

49 (

2.28

-2.6

9)

Ser

um r

elax

in (

ng/l

) 20

64

0 (5

11-7

68)

28

792

(565

-102

0)

392

767(

728-

806)

31

68

7 (5

98-7

76)

Dur

atio

n of

ges

tati

on (

days

) 20

98

(88

-108

) 28

24

7 (2

44-2

50)

401

280

(279

-281

) 31

29

7 (2

96-2

97)

Mul

tipl

e pr

egna

ncy

- -

4 14

.3

2 0.

5 0

- C

aesa

rean

sec

tion

-

- 3

10.7

20

5.

0 7

22.6

V̇O2

peak

, est

.= e

stim

ated

pea

k ox

ygen

upt

ake

40

The highest level of absolute 2 peak, est. was displayed among women with miscarriage (2.61 l/minute) who also displayed the lowest serum relaxin levels (640 ng/l). Among the 460 women with spontaneous start of labour the absolute 2 peak, est. increased successively from the lowest level (2.31 l/minute) among those with preterm birth to 2.49 l/minute among women with post term birth. An opposite trend was shown regarding serum relaxin levels from women with miscarriage to those with post term birth.

Among the 20 women with miscarriage the mean duration of gestation was 98 days (C.I. 88-108), Table 3, which was significantly different (p<0.0001) from the mean time of blood sampling at 66 days of gestation (C.I. 60-72).

Absolute 2 peak, est. was inversely correlated to duration of gestation among women with miscarriage (r=-0.52, p=0.02) and positively to duration of gestation among women with spontaneous start of labour (r=0.12, p=0.01), Figure 8.

Figure 8. Duration of gestation, among 20 women with miscarriages and 460 women with spontaneous start of labour, by absolute 2 peak, est..

0

50

100

150

200

250

300

350

0,0 1,0 2,0 3,0 4,0 5,0Absolute VO2 peak, est (l/min)

Duration of gestation (days)

41

Serum levels of relaxin showed a positive association to duration of gestation among women with miscarriage (r=0.48, p=0.03) but no association to duration of gestation among women with spontaneous start of labour (r=0.07, p=0.11), Figure 9.

Figure 9. Duration of gestation, among 20 women with miscarriage and 460 women with spontaneous start of labour, by serum relaxin levels

Among women with miscarriage absolute 2 peak, est was inversely and serum relaxin positively associated with duration of gestation in simple regression analyses but none of the other measured factors, Table 11. In a multiple regression analysis with the significant variables included in the model, serum relaxin remained independently associated with duration of gestation. The R2 of the model was 0.47 (<0.0001). By use of this model, an increase of relaxin by 100 ng/l would increase duration of gestation by 4 days. In addition, to allow for an increased duration of gestation by 57 days (to let the pregnancy beyond miscarriage to preterm birth) would correspond to an increased serum relaxin level of 1425 ng/l in early pregnancy.

0

50

100

150

200

250

300

350

0 1000 2000 3000 4000Serum relaxin (ng/l)

Duration of gestation (days)

42

Table 11. Effect of factors measured in gestational week 11 on duration of gestation in linear regression analyses among women with miscarriage (n=20) Simple linear regression Multiple linear

regression r2=0.47, p<0.0001

Estimate r2 p= Estimate p= Age (year) -1.4 0.09 0.21 Height (m) -154 0.13 0.12 Weight (kg) -0.5 0.04 0.41 University education 3.1 0.03 0.46 Current smoker or quit <6 months ago 0.30 0.00 0.97 Number of previous deliveries -4.8 0.05 0.35 Number of previous pregnancies -4.0 0.05 0.32 Serum relaxin (ng/l) 0.05 0.28 0.02 0.04 0.04 Absolute V̇O2 peak, est. (l/min) -20.5 0.22 0.04 -15.7 0.09

V̇O2 peak, est.= estimated peak oxygen uptake

Among women with spontaneous start of labour absolute V̇O2 peak, est. and age were positively and multiple pregnancy was inversely associated to duration of gestation but none of the other measured factors, in simple regression analyses, Table 13. In a multiple regression analysis, multiple pregnancy and absolute V̇O2 peak, est. remained significantly and independently associated to duration of gestation. In this model an increase of absolute V̇O2 peak, est by one litre would increase duration of gestation by 2.3 days and multiple pregnancy would decrease duration of gestation by 24.5 days. The R2 of the model was 0.07 (p<0.0001).

Table 12. Effect of factors measured in gestational week 11 on duration of gestation in linear regression analyses among women with spontaneous start of labour (n=460) Simple linear regression Multiple linear

regression r2=0.07, p=0.0001

Variable Estimate r2 p= Estimate p= Age (year) 0.26 0.00 0.05 0.20 0.12 Height (m) 12.1 0.00 0.22 Weight (kg) 0.04 0.00 0.33 University education 0.01 0.00 0.98 Current smoker or quit <6 months (%) -0.80 0.00 0.40 Parity 0 -0.53 0.00 0.48 Gravidity 0 -0.30 0.00 0.56 Multiple pregnancy -25.2 0.06 <0.0001 -24.5 <0.0001 Serum relaxin (ng/l) 0.00 0.00 0.11 0.00 0.48 V̇O2 peak, est. (l/minute) 3.2 0.02 0.004 2.33 0.04

V̇O2 peak, est.= estimated maximal oxygen uptake

43

Discussion

In this prospective cohort study, 520 pregnant women from the general population performed weight supported cycle ergometer test in early pregnancy and half a year postpartum to evaluate the effect of physical fitness on health during and after pregnancy. Pregnancy had a moderate influence on well-being, physical fitness, and perceived health despite reported less regular physical activity during pregnancy. Physical fitness in early pregnancy was positively correlated to perceived health, which was lower during than after pregnancy.

Physical fitness in early pregnancy displayed no influence on the onset of subsequent back pain during or after pregnancy where the time sequence support the hypothesis that poorer physical deconditioning is not a cause but a consequence of the back pain condition. An attenuating effect of increased physical fitness on back pain intensity was shown during pregnancy but not postpartum.

Increased physical fitness and elevated serum relaxin levels displayed a significant reduction of diastolic blood pressure during pregnancy. The results give implication for non-pharmacological approach on lowering blood pressure during pregnancy in a public health perspective. In addition, diastolic and systolic blood pressures were inversely associated with parity and cigarette smoking and positively with weight.

Physical fitness was positively associated with increased duration of gestation among women with spontaneous start of labour but negatively associated with duration of gestation among women with miscarriage, although the latter not independently significant. Among women with miscarriage, increased duration of gestation was correlated with higher levels of serum relaxin although their levels were generally low.

The strengths of the study were the prospective approach, use of validated methods and more than 10-fold higher number of women included as compared with previous experimental studies of oxygen uptake in pregnancy. Use of a direct method of oxygen uptake would have further increased the accuracy of the physical fitness assessment, although this would have been difficult to realise.

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The number of non-participants was a limitation. However, there was no difference in the main variables between participants and non-participants. In addition, none of the main variables used in the present study showed a statistically significant association with the variations in recruitment across the Maternal Health Centres. Hence, the possibility of extrapolating the results to cardiovascular healthy pregnant women in general seems appropriate.

The lack of more precise information on the onset of back pain was another limitation. However, this was to some extent adjusted for by including reported back pain before pregnancy in the regression analysis.

The limitations also include the accuracy of blood pressure measurement. The blood pressure was measured to the nearest 5 mmHg instead of the recommended 2 mmHg 24, and no precaution was taken against digit preference or threshold avoidance 100. This probably reduced the sensitivity of the study to show only the strongest relationship to blood pressure, and suggest that the chance of a false positive in detecting this relationship was small.

Physical fitness In early pregnancy, resting heart rate increases more than oxygen consumption followed by further increase as pregnancy advances to about 15-20 beats minute-1 over non-pregnant values. Also, maximum heart rate is attenuated during maximal exercise testing 66, 91, 112, 113. These changes might affect the heart rate-based method or estimation of V̇O2 peak, est., such as by the Åstrand nomogram used in the present study. Validation of the heart rate submaximal incremental exercise methods has been done in both pregnant and non-pregnant (postpartum) women with V̇O2 peak, est. at volitional fatigue with gas analyses as gold standard with both cycle ergometer and treadmill exercise 65, 77, 91. Sady et al. suggested that pregnancy does not alter the relation between heart rate and V̇O2 peak, est. with cycle ergometer test. However, this is disputed by Lotgering et al., whereas Mottola et al. presented a reliable prediction equation of V̇O2 peak, est. for pregnant women on treadmill exercise test in gestational weeks 16 and 22 65, 77, 91. In the present study the intercepts and slopes of the regression line during early pregnancy and postpartum were not different speaking for only small influence of the pregnant state. In summary, we believe estimated V̇O2 peak, est. was an adequate method to investigate a possible change of peak O2 uptake between early pregnancy and postpartum within a large group of women with repeated measures. Also, the use of weight-supported exercise prevented an increase of workload due to higher maternal weight in early pregnancy as compared with the postpartum weight.

45

Estimated mean absolute V̇O2 peak, est. derived by cycle ergometer test, has been reported in previous studies in non-pregnant women of age groups 20-29 and 30-39 in one study 33 and 19-47 years in another 45 with presented V̇O2 peak, est. of 2.6, 2.5 and 2.4 l/minute, respectively. The slightly lower mean absolute V̇O2 peak, est., of 2.4 l/minute, in the present study, might be caused by both the pregnant state and methodology.

Previous studies have shown that the maximal oxygen consumption was not significantly affected by pregnancy, although there was a tendency toward lower values with advancing pregnancy 18, 66, 91. This is in agreement with observations in the present study where absolute V̇O2 peak, est. from gestational week 11 to 21 weeks postpartum displayed a non significant decrease of 0.02 l/minute. However, when pre-pregnant values of absolute V̇O2 peak, est. were used as start values, in a previous study, there was a significant decrease in oxygen consumption at week 6 postpartum, with some recovery by 27 weeks postpartum 108. This view is supported by the decrease of adjusted absolute V̇O2 peak, est. by gestational week in early pregnancy displayed in the present study.

When oxygen uptake was appropriately related to anthropometric measures, no difference was observed between young and adult women 89. However, when adjustment to body size was made in the present study, women at 35 years of age displayed higher V̇O2 peak, est. than women of other ages. An explanation might be those women who choose pregnancy after 30 years of age have been more physically active than 35-year old women in general, a conclusion that is supported by results from studies of Swedish non-pregnant women 23, 36.

The best way to assess women’s fitness by determinants measured in early pregnancy, with absolute V̇O2 peak, est. as the gold standard, was to consider age, previous and present physical exercise habits, weight and height. However, since the correlations were weak, the possibility of prediction was low, as was also shown when self-reported physical activity was compared with absolute V̇O2 peak, est. among non-pregnant women 95. Use of accelerometer might have improved the prognostic accuracy.

Perceived health Perceived health was scored higher among women who reported regular physical exercise in previous studies 13, 22, 105. This is in agreement with the positive correlation between V̇O2 peak, est. in early pregnancy and the variation of SF-36 mean physical health and general health scores as well as the higher SF-36 score among women reporting regular physical exercise, in the present study.

46

With SF-36 in the present study, women scored physical concepts higher during pregnancy as compared with pregnant women in England 54. However, after pregnancy, women in the present study did not differ from Swedish non-pregnant women 25-34 years of age 107. Because assessment of physical fitness and perceived health was performed at the same time, in the present study, no conclusions about cause and effect mechanisms can be drawn.

Physical exercise No change of self-reported physical exercise from before to after pregnancy was shown in a previous study 108, although the specific physical exercise activities had changed. The women in the present study also reported no change of reported frequency of physical exercise on group level from early pregnancy to postpartum, whereas on an individual level 35% of the women had changed physical exercise activity. The successive decline of physical exercise during pregnancy in the present study was also reported by Downs 27.

Back pain To the best of our knowledge, no previous study has investigated the influence of physical fitness on development of back pain in subsequent pregnancy and postpartum. However, there are studies of non-pregnant populations with back pain that imply an inverse association between aerobic fitness and back pain 30, 96 although these findings are disputed by others 51. In addition, physical fitness has been inversely correlated with facet degeneration, a significant problem in all chronic low back pain patients although not clearly related to pain 6. As regards a possible preventive effect of physical activity level on the development of pregnancy-related back pain, the results of a retrospective study with inherent problem regarding recall bias, indicate a decreased frequency of back pain in relation to the amount of regular physical activity before pregnancy 74. In addition, the cross-sectional methodology used in the above studies made it impossible to evaluate the cause and effect mechanism.

Regular physical exercise reduced pain among Iranian women but not the frequency of back pain 39. Lower back pain and neck/shoulder pain has also been found to be inversely associated with regular exercise during pregnancy in a Norwegian study 82. This is in accord with the results in the present study where pain intensity was influenced by physical fitness while the prevalence of back pain was similar to that found in previous studies 8, 9, 61, 72,

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80. These findings speak for the hypothesis that poorer physical condition is not a cause but a consequence of the back pain.

The mechanism underpinning reduced back pain intensity in relation to increased physical fitness can only be speculated on. Firstly, incipient or present pregnancy-related back pain may have reduced the women’s ability to perform the ergometer cycle test in early pregnancy. This view is supported by the fact that a higher level of pain experienced before testing is associated with prematurely quitting the bicycle test 25, 96 and that maximal exertion in patients with low back pain was limited 30. An argument against this is that none of the women in this study complained about or stopped the ergometer cycle test because of back problems. Secondly, a direct effect of physical fitness on pain perception may be a possibility. Although, animal research strongly supports this hypothesis 41 it is disputed in human beings 16,

76 and has been shown to provide only temporary relief from pain in healthy individuals 58 and in people with low back pain 49. Thirdly, there may be co-variation between physical exercise and muscular strength, the latter a suggested protective factor for back pain in pregnancy 28, 42.

Blood pressure No study has investigated the influence of oxygen uptake on blood pressure in the pregnant or non-pregnant state, to the best of our knowledge. However, the short-term and accumulated effect of exercise on lowering systolic blood pressure has been established in both the non-pregnant 73, 84 and pregnant states 117.

The collective mechanism of the different significant variables which have been shown to be associated with lowering blood pressure in the present study may occur through several, partly redundant, interrelated vasodilatory systems involved in the extraordinary circulatory changes characteristic of pregnancy 59, 109.

It has been suggested that relaxin causes increased renal vasodilation and hyperfiltration in women during the luteal phase and pregnancy 21, 92. In addition, treatment of scleroderma patients exogenously by the daily administration of recombinant relaxin infusion for 24 weeks resulted in significantly lower diastolic blood pressure than that of a placebo group, although systolic blood pressure was not lowered 60. Among non-hypertensive controls, as compared with patients who had never been treated for hypertension, higher levels of circulating relaxin were detected 40. In a previous study of pregnant women, relaxin levels were positively and significantly related to lower systolic blood pressure during pregnancy 62. Probably because of wider dispersion in the present study, there was no association with systolic blood pressure, but with diastolic blood pressure

48

during pregnancy. The latter is further strengthened by the fact that no statistically significant association was disclosed when the study population was technically randomly increased twice.

A decreased risk of gestational hypertension among women reporting cigarette smoking has previously been reported in large epidemiologic studies, although partly disputed by others 7, 35, 104, 110, 119. The present study confirms some previous results by suggesting an inverse association between cigarette smoking and blood pressure during pregnancy. In addition the number of previous pregnancies and the woman´s weight have been demonstrated to be associated with decreased and increased blood pressure during pregnancy, respectively 10, 26, 50, 83, 104, 116. This was also confirmed by the results of the present study.

Duration of gestation To the best of our knowledge no previous study has investigated the influence of physical fitness assessed by absolute V̇O2 peak, est. on duration of gestation among women who miscarried or women who gave birth.

An increased risk of miscarriage among women with increased level of physical exercise has been shown in previous studies, although high frequencies of miscarriages were included 34, 38, 69. A similar trend was shown in the present study of physical fitness although not significant and without information on early miscarriages. In a previous experimental study no increase of miscarriages was found across fit women with different load of physical exercise during pregnancy 20.

A suggested protective effect of physical fitness on preterm births and an increased proportion of post-term birth, particularly by exercise between gestational weeks 17 to 30 has been reported and a decreased risk of up to 50% have been suggested 44, 56, 64. This is supported by the results of the present study and others 44, 56, 64, although disputed by others 4, 29, 43. However, the latter studies included women with a sedentary life-style, diabetes or concentrated on the effects of vigorous exercise.

Low serum relaxin levels in early pregnancy have been associated with increased risk of miscarriage 3, 103, which was shown also in the present study. No decrease of relaxin levels before miscarriage has been noted 87. Interestingly, among women with miscarriage, in the present study, those with higher relaxin level had a longer duration of gestation. With an otherwise viable foetus this might enable relaxin treatment to save an imminent miscarriage, especially when considering that serum relaxin is known to have an important role in implantation by remodelling and immunotolerance 32, 47.

49

Conclusions

1. Pregnancy had a moderate influence on well-being, physical fitness, and perceived health six months postpartum, although there were reports of less regular physical activity during pregnancy. Absolute V̇O2 peak, est. in early pregnancy was positively correlated to perceived physical health.

2. Oxygen uptake and physical exercise in early pregnancy had no influence on the onset of subsequent back pain during or after pregnancy. An examination of the time sequence supports the hypothesis that poorer physical condition is not a cause but a consequence of back pain. The mechanism by which increased oxygen levels attenuate the intensity of back pain is uncertain.

3. Increased oxygen uptake and increased levels of serum relaxin were associated with a significant reduction of diastolic blood pressure. The effect of oxygen uptake has not been reported previously. The results give clinical implications for lowering blood pressure during pregnancy.

4. Physical fitness appears to be a protective factor of an established pregnancy and not significantly involved in the risk of miscarriage. Increased serum relaxin level to prevent imminent miscarriage with a viable foetus is suggested a future research challenge.

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Summary in Swedish (svensk sammanfattning)

Stillasittande livsstil är en potentiell riskfaktor för hälsan. Kvinnor har ökad risk för fysisk inaktivitet och under en graviditet minskar kvinnor ofta sin träning. Kvinnor som motionerar regelbundet före graviditeten fortsätter dock i större utsträckning med det även under graviditeten.

Fysisk träning före och under graviditet har visat sig minska risken för många graviditetskomplikationer och kvinnor rekommenderas att träna un-der graviditeten även om det inte är fullständigt klarlagt att det är helt risk-fritt. Mestadels har positiva effekter setts men det finns även rapporter om en ökad risk för missfall.

Ryggsmärtor är vanligt och jämfört med icke-gravida är det en hög andel av kvinnor med tidigare friska ryggar som får besvär under graviditeten. Relaxin är ett insulinliknande hormon som ökar under graviditeten och låga nivåer har förknippats med både missfall och ökat blodtryck tidigare.

Avhandlingens syfte är att studera kvinnors fysiska kondition under gravidi-teten och utvärdera dess effekt på upplevd hälsa, ryggsmärta, blodtryck och graviditetslängd. Dessutom, att utvärdera effekten av serum relaxin nivåer på blodtryck och graviditetslängd.

Studien består av 520 gravida kvinnor som genomfört en konditionstest i tidig graviditet och fem månader efter förlossningen. Blodprov för relaxin togs i början av graviditeten. Fysisk träning, eventuellt ryggsmärta och blod-tryck följdes fortlöpande under graviditeten.

Första delarbetet antydde att graviditeten har ganska liten påverkan på fysisk kondition postpartum även om kvinnorna tränade mindre under graviditeten. Kvinnor med bättre fysisk kondition upplevde sin fysiska hälsa bättre.

Andra delarbetet antydde att kvinnor med god fysisk kondition fick rygg-smärta i lika stor utsträckning som kvinnor med sämre kondition men att kvinnorna med god kondition upplevde smärtans intensitet mindre under graviditeten.

Tredje delarbetet antydde att både bättre fysisk kondition och högre relaxin nivåer var förknippade med ett lägre diastoliskt blodtryck.

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Fjärde delarbetet antydde att bättre kondition kan minska risken för prematur förlossning och visade ingen ökad risk för missfall men gruppen kvinnor med missfall var liten och selekterad eftersom kvinnor med tidiga missfall inte var med i studien. I denna grupp kvinnor med missfall var relaxin nivå-erna högre ju senare missfallet inträffade.

Sammanfattningsvis antyder avhandlingen att upplevd hälsa, diastoliskt blodtryck och graviditetslängden påverkades positivt av fysisk kondition medan förekomsten av ryggsmärtor inte påverkades. Effekten av fysisk kondition på graviditetstid och diastoliskt blodtryck kan ha kliniska implikationer liksom ökade serumnivåer av relaxin på diastoliskt blodtryck och missfall.

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Acknowledgments

My thanks go to: • Docent Per Kristiansson, my supervisor, who without losing his

enthusiasm or showing fatigue, guided me through the whole process • Kjell Andersson, my husband and a physical exercise teacher, who

conducted all tests, shared his knowledge about physical exercise with me and was always prepared to discuss findings

• Professor Kurt Svärdsudd for his enthusiasm and invaluable advice on statistics

• Ph.D. Margareta Eriksson, for reading the manuscript and for all her advice.

• Professor Laura T. Goldsmith, for analysis of the blood samples, sharing her knowledge about relaxin and reviewing papers 3 and 4, and part of my thesis

• Adolfsberg maternal care center and midwives Mia Blomqvist, Carina Westergren and Annika Ekstedt

• Brickebacken maternal care center and midwives Gunilla Ekelund, Lilian Olander and Febe Zetterlund

• Hallsberg maternal care center and midwives Ina Henriksson and Monica Wärnelid

• Karla maternal care center and midwives Birgitta Olsson, Inger Lundqvist and Yvonne Tammert

• Kumla maternal care center and midwives Gunilla Ahlvin, Rigmor Hermansson, Catharina Sjöstedt and Yvonne Skogsdal

• Mikaeli maternal care center and midwives Eva Hedlund and Susanne Gärdefors

• Olaus Petri maternal care center and midwives Eva Karbring and Margaretha Kleberg

• Skebäck maternal care center and midwives Berit Liljeberg, Ann Katrin Forsberg, Rose-Marie Bromdal and Elisabeth Pino

• Varberga maternal care center and midwives Gunilla Östring and Inger Wätterbjörk

• Vivalla maternal care center and midwives Anne Nilsson, Eva Engvall and Eva Naess

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• All staff at the medical record archive at the Obstetric Clinic at Örebro University Hospital

• All midwives and other staff at the Obstetric Clinic at Örebro University Hospital

• The Family Research Centre in Örebro. • All my other colleagues and friends who have supported me

This research was supported by grants from Örebro County Council and the medical faculty, Uppsala University.

54

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