Developmental Origins of Physical Fitness: The Helsinki Birth Cohort Study

Abstract

Background

Cardiorespiratory fitness (CRF) is a major factor influencing health and disease outcomes including all-cause mortality and cardiovascular disease. Importantly CRF is also modifiable and could therefore have a major public health impact. Early life exposures play a major role in chronic disease development. Our aim was to explore the potential prenatal and childhood origins of CRF in later life.

Methods/Principal Findings

This sub-study of the HBCS (Helsinki Birth Cohort Study) includes 606 men and women who underwent a thorough clinical examination and participated in the UKK 2-km walk test, which has been validated against a maximal exercise stress test as a measure of CRF in population studies. Data on body size at birth and growth during infancy and childhood were obtained from hospital, child welfare and school health records. Body size at birth was not associated with adult CRF. A 1 cm increase in height at 2 and 7 years was associated with 0.21 ml/kg/min (95% CI 0.02 to 0.40) and 0.16 ml/kg/min (95% CI 0.03 to 0.28) higher VO2max, respectively. Adjustment for adult lean body mass strengthened these findings. Weight at 2 and 7 years and height at 11 years became positively associated with CRF after adult lean body mass adjustment. However, a 1 kg/m2 higher BMI at 11 years was associated with −0.57 ml/kg/min (95% CI −0.91 to −0.24) lower adult VO2max, and remained so after adjustment for adult lean body mass.

Conclusion/Significance

We did not observe any significant associations between body size at birth and CRF in later life. However, childhood growth was associated with CRF in adulthood. These findings suggest, importantly from a public point of view, that early growth may play a role in predicting adult CRF.

About the Authors:

Minna K. Salonen

* E-mail: [email protected]

Affiliations Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland, Department of Public Health, University of Helsinki, Finland

Eero Kajantie

Affiliation: Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland

Clive Osmond

Affiliation: Epidemiology Resource Centre, Southampton, United Kingdom

Tom Forsén

Affiliations Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland, Vaasa Health Care Centre, Diabetes Unit, Vaasa, Finland, Developmental Origins of Health and Disease Division, University of Southampton, Southampton, United Kingdom

Hilkka Ylihärsilä

Affiliation: Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland

Maria Paile-Hyvärinen

Affiliation: Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland

D. J. P. Barker

Affiliation: Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland

Johan G. Eriksson

Affiliations Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland, Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland, Helsinki University Central Hospital, Unit of General Practice, Finland, Vaasa Central Hospital, Vaasa, Finland, Folkhälsan Research Center, Helsinki, Finland

Introduction

Cardiorespiratory fitness (CRF) is a good indicator of overall health. Physical activity and CRF are associated with the risk of all cause mortality, cardiovascular disease and several cancers [1]–[6]. It has been also suggested, that CRF is associated with brain structure and function [7] and that improvements in CRF brought about by exercise training are implicated in the restoration of neural and cognitive functioning in older adults [8]–[10]. Animal models and epidemiological studies in humans propose that physical activity and CRF may have a prenatal origin [11]–[16].

Babies who grow at slow rates in utero and thus end up being small or thin at birth, are at increased risk of developing cardiovascular disease (CVD), type 2 diabetes and components of the metabolic syndrome [17]–[21] in later life. Major influences of postnatal growth patterns on later health are also well established. While results of several studies suggest that slow gain in body size during the first two years of life is associated with cardiovascular disease and its risk factors [22]–[24], including type 2 diabetes [23] and dyslipidemia [25], [26], the others have shown the opposite effect of growth during infancy [27], [28] on these diseases and the risk factors. Postnatal conditions including dietary and exercise habits and other behavioral related aspects are mostly modifiable and hence important from a public health point of view.

Recent findings from the NordNet Study showed that the associations found between birth weight and leisure time physical activity (LTPA) are weak within the normal birth weight range. However, both low and high birth weights were associated with lower LTPA [12]. In a previous Finnish study, a low birth weight was associated with the metabolic syndrome, but not among those who were fit and active [13]. Our previous findings in a cohort of men and women born 1924–33 suggest that people born thin or with a low birth weight benefit most from physical activity and exercise in adult life by getting the biggest protective effect against diabetes [14]. More recent findings from Helsinki Birth Cohort Study on people born 1934–44 propose that those who were taller and heavier as children, tend to engage more in leisure time physical activity in adult life compared to their shorter and lighter peers [29].

While physical activity and CRF are tightly related to each other, associations of CRF with many health outcomes remain when physical activity levels are adjusted for. In addition, associations with health tend to be stronger for CRF than for physical activity [30]. However, whether CRF in adult life is associated with early growth has been little studied. Most previous publications focus on children, adolescents or young adults [15], [16], [31]. Our aim was to examine whether early growth during childhood, from birth to 11 years predicts CRF in later life. We hypothesized that small body size at birth, and slow growth during infancy and childhood would be associated with lower CRF levels in late middle aged men and women.

Methods

This study is part of the Helsinki Birth Cohort Study (HBCS) which in the epidemiological part included 8760 men and women born at Helsinki University Central Hospital. They were born between 1934 and 1944, attended child welfare clinics in the city and were living in Finland in 1971, when a unique identification number was assigned to all residents of Finland. The majority of the children (77%) also went to school in Helsinki. The birth records included data on weight and length at birth and gestational age. Records from child welfare clinics and school health care include serial measurements of weight and height. On average, the participants had 11 measurements between birth and two years, and 9 measurements between 2 and 11 years. Details of the birth, child welfare and school health records have been described in detail elsewhere [32].

Of the original cohort, 2003 randomly selected individuals participated in a detailed clinical examination between the years 2001–2004. The clinical study protocol was approved by the Ethics Committee of Epidemiology and Public Health of the Hospital District of Helsinki and Uusimaa. Written informed consent was obtained from each participant before any study procedure was initiated.

All measurements were taken by a team of trained research nurses. Height was measured in light indoor clothing without shoes to the nearest 0.1 cm and weight to the nearest 0.1 kg. Body mass index (BMI) was calculated as weight in kilograms divided by the square of height in meters. Waist circumference was measured midway between the lowest rib and the iliac crest. Lean body mass and body fat mass were measured by bioelectrical impedance analysis (BIA) using InBody 3.0 eight-polar tactile electrode system (Biospace Co. Ltd, Seoul, Korea) [33].

Using the occupations recorded on the birth, child welfare clinic and school health care records, we grouped fathers into three socioeconomic groups (manual workers, lower-middle and upper-middle classes), originally based on a nine-group social classification system by Statistics Finland. We used the highest group obtained from these three sets of records. Social class in adulthood, based on subjects' own occupation, was derived from Census data in 1980. Physical activity and smoking habits were obtained from a self-administered questionnaire. Being physically active was defined as taking at least moderate exercise three or more times per week. Subjects were defined as smokers if they smoked one or more cigarettes per day.

In the present study, we restricted our analyses to the 606 individuals who took part in the UKK 2-kilometer walk test, in order to examine the effects of fetal and childhood growth on cardiovascular performance among normally active men and women in later life. The UKK 2-km walk test is an indirect measurement of CRF, which can be used within a majority of the adult population without requirements of maximal physical efforts. It has been validated against maximal effort test by treadmill or bicycle ergometry in multiple populations including the obese and elderly [34], [35] During the test, subjects are directed to walk through a 2-km course on the flat ground as rapidly as possible. The test results are expressed as fitness index, or alternatively as VO2max, by using a formula in which subject's age, sex, BMI, time spent in walking and heart rate are taken in to account.

Several health status requirements for the UKK walk test were set. A subject was excluded if he/she had any of the following conditions affecting the walk test: myocardial infarction within the past year, unstable blood pressure, CHD with symptoms, active arthritis or other joint disorder with pain, arrhythmia, asthma or other breathing difficulties, and if the subject had other medical restrictions concerning physical activity. Subjects on drug therapy affecting pulse rate were also excluded from the analyses. Individuals (n = 25) whose test result indicated a VO2max status under 10 ml/kg/min were excluded from further analysis because those with the VO2max value of this low can not reach the intensity required in the UKK- test, and thus 581 individuals remained in the study.

Statistical analysis

A multiple linear regression was used to assess the associations of birth size, childhood height, weight and BMI with CRF. The basic models were adjusted for age and in the pooled analysis also for sex. Further analysis included the adjustments for gestational age, maternal BMI, socioeconomic factors (social class in childhood and adult life), exercise habits, smoking status, and current lean body mass. The regression models were also investigated using a quadratic term for each of the childhood body size variables (height and weight at birth, 2, 7 and 11 years); however, there was no evidence for nonlinear associations.

We calculated z-scores (SD-score) for height, weight and BMI for each child at birth and at each birthday until 12 years of age. The z-score is the number of standard deviations by which an observation differs from the mean for the whole study group. As the children were not measured exactly on their birthdays, we obtained the z-score for birthdays by interpolating the available measurements (if a measurement had been recorded within two years of the particular age) and used these estimated values. Most of the visits to child welfare clinics occurred before age two years; fewer measurements were made between ages two years and enrolment at school. We examined the effects of gains in height, weight and BMI after birth during three periods of growth (0–2, 2–7 and 7–11 years) on CRF. In these analyses, we used the residual from linear regression where current height, weight or BMI was regressed on previous corresponding measurements. By this construction, the residuals, which we refer to as “conditional growth” are uncorrelated with the earlier size measurements and enable the effects of changes in height, weight and BMI during different growth periods to be distinguished [36], [37].

The adult clinical as well as childhood growth characteristics are presented separately for men and women. Interaction terms were created to explore potential interactions between gender and growth measures in association to CRF. Since the effect of growth on CRF was similar in both, boys and girls, pooled analyses are presented.

Results

Comparison between the UKK 2-km walk test participants and non-participants

Childhood growth and adult characteristics are presented in the table 1. From the original cohort of 2003 individuals, those 606 who took part in the UKK 2-km walk test showed no difference in adult social class, exercise habits, birth size or growth during childhood, except for birth length in women, which was slightly higher for those who did attend in the walk test (p = 0.04). In adulthood the participants had a smaller BMI, smaller waist circumferences and lower body fat percentages than those who did not participate (p<0.001 for all). The results in relation to anthropometric characteristics were similar for both sexes. Men who did not attend in the walk test, were more often smokers compared to those who did attend (p = 0.02).

[Figure omitted. See PDF.]

Table 1. Adult clinical and childhood growth characteristics of the 581 UKK 2-km walk test participants.

https://doi.org/10.1371/journal.pone.0022302.t001

A comparison of the associations of childhood body size measurements on potential components of adult CRF did not show differences between the participants and non-participants. Effect of childhood body size on adult BMI, body fat percentage, lean body mass and grip strength were similar in both groups.

Associations between adult anthropometric, socioeconomic and life style factors and CRF

Age in men (p = 0.01) and women (p<0.001), weight, BMI, waist circumference, body fat percentage and fat mass (p<0.001 for all) and lean body mass (p = 0.02 for men and p<0.001 for women) were all inversely associated with CRF. Adult social class in both men and women (p = 0.002 and p = 0.02) was also inversely associated with CRF. Mean VO2max in men was 32.5 ml/kg/min in the highest and 28.6 ml/kg/min in the lowest social class, and correspondingly 26.2 ml/kg/min in the highest and 23.4 ml/kg/min in the lowest social class in women. Again, height was positively associated with CRF in men (p = 0.005) and in women (p<0.001).

Men who took at least moderate exercise three or more times per week had higher CRF (mean VO2max being 32.15 ml/kg/min compared to the 28.15 ml/kg/min in the inactive group, p = 0.001). This finding was not observed in women. A positive smoking status was associated with lower CRF in both men (p = 0.008) and in women (p = 0.005). Age and sex adjusted correlations between childhood body size and adult VO2max are presented in figure 1.

[Figure omitted. See PDF.]

Figure 1. Age- and sex-adjusted correlations between VO2max and height, weight and BMI annually from birth to 12 years.

The horizontal dashed line indicates a correlation of 0.

https://doi.org/10.1371/journal.pone.0022302.g001

Impact of prenatal and childhood body size and socioeconomic factors on adult CRF

In the age and sex adjusted models birth length (table 2), birth weight (table 3), ponderal index, body mass index (table 4), gestational age and maternal BMI were not associated with CRF (VO2max) in adult life.

[Figure omitted. See PDF.]

Table 2. Adult cardiorespiratory fitness in relation to length at birth and height at 2, 7, 11 years of age.

https://doi.org/10.1371/journal.pone.0022302.t002

[Figure omitted. See PDF.]

Table 3. Adult cardiorespiratory fitness in relation to weight at birth, 2, 7 and 11 years of age.

https://doi.org/10.1371/journal.pone.0022302.t003

[Figure omitted. See PDF.]

Table 4. Adult cardiorespiratory fitness in relation to BMI at birth, 2, 7 and 11 years of age.

https://doi.org/10.1371/journal.pone.0022302.t004

Height at 2 and 7 years were positively associated with CRF in the age and gender adjusted models (table 2). Adjustment for adult lean body mass strengthened these findings and height at 11 years became associated with CRF. Additional adjustments for childhood and adult social class, exercise and smoking habits did not change these findings.

Weight at 2 and 7 years of age became positively associated with CRF after adjustment for lean body mass (table 3) and the other confounders, such as social circumstances, exercise and smoking. Higher BMI at 11 years, independently of the confounders, predicted lower adult CRF (table 4).

Lower childhood social class was negatively associated with adult CRF (p = 0.04), especially in men (p = 0.003). Mean VO2max was 33.3 ml/kg/min in the highest social class, 30.8 ml/kg/min in the second, and 29.3 ml/kg/min in the lowest group.

Gains in body size from birth to 11 years and adult CRF

Associations between childhood growth and adult CRF are presented in the table 5.

[Figure omitted. See PDF.]

Table 5. Association between childhood growth during the first 11years of life and adult cardiorespiratory fitness (VO2max).

https://doi.org/10.1371/journal.pone.0022302.t005

In the age and sex adjusted models gain in height during infancy predicted higher adult CRF while gain in weight and BMI between 7 and 11 years was associated with lower adult CRF. However, when adult lean body mass was additionally adjusted for, gains in height between birth and 2 years remained and between 2 and 7 years became associated with higher CRF. Again, after additional adjustment for adult lean body mass, gain in weight during infancy became positively associated with adult CRF while gain in weight and BMI between 7 and 11 years remained negatively associated with adult CRF.

Discussion

We hypothesized that non-optimal prenatal and childhood growth characterized by low birth weight and slow growth during childhood, predicts lower adult cardiorespiratory fitness (CRF). We did not find any significant associations between body size at birth and CRF in later life. However, childhood growth was associated with CRF in adulthood. We observed that children, who were taller at ages 2, 7 and 11 years, had higher CRF in their adult life, whereas higher BMI at 11 years of age predicted lower adult CRF. The positive association between childhood weight and adult CRF was largely explained by adult lean body mass.

An individual's CRF refers to ability of the body to supply oxygen to skeletal muscles during sustained physical activity. CRF is a physiological characteristic, commonly measured by a maximal or sub-maximal exercise test, whereas physical activity is a behavioral component, defined as any body movement that increases energy expenditure. Obviously, regular physical activity improves the cardiorespiratory system by increasing the amount of oxygen that is inhaled and distributed to body tissues and is thus a major determinant of CRF. As a behavioral component it is also a key target of interventions to reduce the risk of disease [38]–[40]. Both are important protective and modifiable factors when considering chronic diseases like type 2 diabetes, coronary heart disease and osteoporosis. In most studies associations with health outcomes tend to be stronger for CRF than for physical activity, although this may be in part explained by less accurate measurement of physical activity by self-report methods [30]. However, it has been proposed that CRF and physical activity may be differentially influenced by age, gender, social, environmental and behavioral factors as well as genotypes and subclinical disease [41]–[44].

Animal models have suggested that life style and exercise habits may have a prenatal origin. Severe malnourishment of a pregnant rat leads to a smaller body size at birth and inactivity in the offspring. Sedentary behaviour is further exacerbated by postnatal hypercaloric nutrition [11]. Human studies, however, suggest that the associations between prenatal characteristics and physical activity may be limited to extreme groups. For example, an extensive NordNet Collaboration study showed that the association between birth weight and leisure time physical activity was weak within the normal birth weight range, although both very low and high birth weights were associated with lower leisure time physical activity [12]. Accordingly, a recent study showed much reduced levels of physical activity in young adults born preterm with birth weight below 1500 g [45]. In the present study we found no evidence for a u-shaped relationship between birth measurements and CRF. This may be because when the study subjects were born, infants with very low birth weights were less likely to survive, and the rates of gestational diabetes, a key cause of high birth weight, are likely to have been lower than today. Our findings suggest that CRF in late adult life is affected by factors that affect growth during childhood. This is consistent with our recent findings on leisure time physical activity, assessed by a detailed questionnaire in the same cohort [29].

Mechanisms behind the relationship between early growth and CRF are still poorly understood. Muscle fitness may play a role: we have previously shown that low birth weight is associated with lower adult lean mass whereas grip strength, an important predictor of frailty and functional capacity in elderly people, was positively associated with birth weight through its association with lean mass [46]. Ortega and co-workers have shown that those who had higher birth weight also had higher hand grip strength from ages 13 to 18.5 years. However, the associations were mostly explained by fat-free mass and birth weight was not associated with CRF [16]. A study of Lawlor's and co-workers showed that those born bigger had higher CRF- levels at the age of 9 years [15]. Motor development may also play a role: The Northern Finland Birth Cohort showed that higher birth weight, lower infant weight gain and earlier infant motor development predict higher levels of adult physical performance for muscle strength, muscle endurance and aerobic fitness at the age of 31 years [31].

Strengths and limitations of the study

We have unique data on both men and women with details on reliable birth and growth measurements and with a long follow up period. Body composition was measured with a validated BIA method [47] and CRF with the validated UKK 2-km walk test [34], [48], [49]. In addition to the present study, there are only a few studies examining strictly the relationship between early growth and CRF.

Limitations of our study have been discussed elsewhere [22], [32]. Our study was restricted to the men and women who were born in the Helsinki University Central Hospital, attended child welfare clinics which was voluntary, were still alive and living in Finland in the year 2003 and willing to participate to the clinical examination. They may not be representative of the population born in Helsinki. However, our analyses are based on internal comparisons within the cohort. Of the 2003 clinical participants 606 men and women attended the UKK 2-km walk test, which means that the power is lower than that in the original study. Despite the fairly large set of exclusion criteria, the childhood growth of those who participated in the walk test did not differ from those who did not. In addition to the childhood gains in growth, it would be valuable to evaluate other factors such as physical activity and dietary patterns during childhood, and their impact on adult body composition and CRF. Further more, early versus late puberty may well be part of the explanation for the mechanisms which play a role in the associations between childhood growth and adult CRF. Unfortunately such data are not available for our cohort.

Conclusion

Besides the long term effect of birth size on adult body composition and several diseases that has been demonstrated in a large number of studies [17]–[19], [46], [50] growth during infancy and in childhood has been shown to play important roles in the pathogenesis of several diseases [22]–[27], [51], [52]. However, previous studies provide a good basis for the present study. The results of the present study emphasize a role of childhood height from the age of two years onwards and in particular the gain in height during infancy on CRF-level later in life. However, childhood height is strongly and positively correlated with adult stature, which is positively associated with CRF-level, and therefore it is difficult to disentangle the two. The observed associations between childhood height and CRF were independent of confounders including childhood and adult socio-economic circumstances, adult physical activity, smoking habits and adult lean body mass.

Author Contributions

Critical revision of the manuscript: EK CO TF HY MP-H DJPH JGE. Final approval of the submitted version: MKS EK CO TF HY MP-H DJPB JGE. Conceived and designed the experiments: MKS EK CO TF HY MP-H DJPB JGE. Analyzed the data: MKS CO. Contributed reagents/materials/analysis tools: JGE TF HY DJPB. Wrote the paper: MKS EK JGE.

Citation: Salonen MK, Kajantie E, Osmond C, Forsén T, Ylihärsilä H, Paile-Hyvärinen M, et al. (2011) Developmental Origins of Physical Fitness: The Helsinki Birth Cohort Study. PLoS ONE6(7): e22302. https://doi.org/10.1371/journal.pone.0022302

References

1. Lakka TA, Venalainen JM, Rauramaa R, Salonen R, Tuomilehto J, et al. (1994) Relation of leisure-time physical activity and cardiorespiratory fitness to the risk of acute myocardial infarction. N Engl J Med 330: 1549–1554.TA LakkaJM VenalainenR. RauramaaR. SalonenJ. Tuomilehto1994Relation of leisure-time physical activity and cardiorespiratory fitness to the risk of acute myocardial infarction.N Engl J Med33015491554

2. Kodama S, Saito K, Tanaka S, Maki M, Yachi Y, et al. (2009) Cardiorespiratory fitness as a quantitative predictor of all-cause mortality and cardiovascular events in healthy men and women: a meta-analysis. Jama 301: 2024–2035.S. KodamaK. SaitoS. TanakaM. MakiY. Yachi2009Cardiorespiratory fitness as a quantitative predictor of all-cause mortality and cardiovascular events in healthy men and women: a meta-analysis.Jama30120242035

3. Sillanpaa E, Hakkinen A, Punnonen K, Hakkinen K, Laaksonen DE (2008) Effects of strength and endurance training on metabolic risk factors in healthy 40–65-year-old men. Scand J Med Sci Sports 19(6): 885–895.E. SillanpaaA. HakkinenK. PunnonenK. HakkinenDE Laaksonen2008Effects of strength and endurance training on metabolic risk factors in healthy 40–65-year-old men.Scand J Med Sci Sports196885895

4. Farrell SW, Fitzgerald SJ, McAuley P, Barlow CE (2010) Cardiorespiratory Fitness, Adiposity, and All-Cause Mortality in Women. Med Sci Sports Exerc 42: 2006–2010.SW FarrellSJ FitzgeraldP. McAuleyCE Barlow2010Cardiorespiratory Fitness, Adiposity, and All-Cause Mortality in Women.Med Sci Sports Exerc4220062010

5. Lee CD, Sui X, Blair SN (2009) Combined effects of cardiorespiratory fitness, not smoking, and normal waist girth on morbidity and mortality in men. Arch Intern Med 169: 2096–2101.CD LeeX. SuiSN Blair2009Combined effects of cardiorespiratory fitness, not smoking, and normal waist girth on morbidity and mortality in men.Arch Intern Med16920962101

6. Laaksonen DE, Lakka HM, Salonen JT, Niskanen LK, Rauramaa R, et al. (2002) Low levels of leisure-time physical activity and cardiorespiratory fitness predict development of the metabolic syndrome. Diabetes Care 25: 1612–1618.DE LaaksonenHM LakkaJT SalonenLK NiskanenR. Rauramaa2002Low levels of leisure-time physical activity and cardiorespiratory fitness predict development of the metabolic syndrome.Diabetes Care2516121618

7. Colcombe SJ, Erickson KI, Raz N, Webb AG, Cohen NJ, et al. (2003) Aerobic fitness reduces brain tissue loss in aging humans. J Gerontol A Biol Sci Med Sci 58: 176–180.SJ ColcombeKI EricksonN. RazAG WebbNJ Cohen2003Aerobic fitness reduces brain tissue loss in aging humans.J Gerontol A Biol Sci Med Sci58176180

8. Colcombe SJ, Erickson KI, Scalf PE, Kim JS, Prakash R, et al. (2006) Aerobic exercise training increases brain volume in aging humans. J Gerontol A Biol Sci Med Sci 61: 1166–1170.SJ ColcombeKI EricksonPE ScalfJS KimR. Prakash2006Aerobic exercise training increases brain volume in aging humans.J Gerontol A Biol Sci Med Sci6111661170

9. Colcombe SJ, Kramer AF, Erickson KI, Scalf P, McAuley E, et al. (2004) Cardiovascular fitness, cortical plasticity, and aging. Proc Natl Acad Sci U S A 101: 3316–3321.SJ ColcombeAF KramerKI EricksonP. ScalfE. McAuley2004Cardiovascular fitness, cortical plasticity, and aging.Proc Natl Acad Sci U S A10133163321

10. Kramer AF, Hahn S, Cohen NJ, Banich MT, McAuley E, et al. (1999) Ageing, fitness and neurocognitive function. Nature 400: 418–419.AF KramerS. HahnNJ CohenMT BanichE. McAuley1999Ageing, fitness and neurocognitive function.Nature400418419

11. Vickers MH, Breier BH, McCarthy D, Gluckman PD (2003) Sedentary behavior during postnatal life is determined by the prenatal environment and exacerbated by postnatal hypercaloric nutrition. Am J Physiol Regul Integr Comp Physiol 285: R271–273.MH VickersBH BreierD. McCarthyPD Gluckman2003Sedentary behavior during postnatal life is determined by the prenatal environment and exacerbated by postnatal hypercaloric nutrition.Am J Physiol Regul Integr Comp Physiol285R271273

12. Andersen LG, Angquist L, Gamborg M, Byberg L, Bengtsson C, et al. (2009) Birth weight in relation to leisure time physical activity in adolescence and adulthood: meta-analysis of results from 13 nordic cohorts. PLoS One 4: e8192.LG AndersenL. AngquistM. GamborgL. BybergC. Bengtsson2009Birth weight in relation to leisure time physical activity in adolescence and adulthood: meta-analysis of results from 13 nordic cohorts.PLoS One4e8192

13. Laaksonen DE, Lakka HM, Lynch J, Lakka TA, Niskanen L, et al. (2003) Cardiorespiratory fitness and vigorous leisure-time physical activity modify the association of small size at birth with the metabolic syndrome. Diabetes Care 26: 2156–2164.DE LaaksonenHM LakkaJ. LynchTA LakkaL. Niskanen2003Cardiorespiratory fitness and vigorous leisure-time physical activity modify the association of small size at birth with the metabolic syndrome.Diabetes Care2621562164

14. Eriksson JG, Yliharsila H, Forsen T, Osmond C, Barker DJ (2004) Exercise protects against glucose intolerance in individuals with a small body size at birth. Prev Med 39: 164–167.JG ErikssonH. YliharsilaT. ForsenC. OsmondDJ Barker2004Exercise protects against glucose intolerance in individuals with a small body size at birth.Prev Med39164167

15. Lawlor DA, Cooper AR, Bain C, Davey Smith G, Irwin A, et al. (2008) Associations of birth size and duration of breast feeding with cardiorespiratory fitness in childhood: findings from the Avon Longitudinal Study of Parents and Children (ALSPAC). Eur J Epidemiol 23: 411–422.DA LawlorAR CooperC. BainG. Davey SmithA. Irwin2008Associations of birth size and duration of breast feeding with cardiorespiratory fitness in childhood: findings from the Avon Longitudinal Study of Parents and Children (ALSPAC).Eur J Epidemiol23411422

16. Ortega FB, Labayen I, Ruiz JR, Martin-Matillas M, Vicente-Rodriguez G, et al. (2009) Are muscular and cardiovascular fitness partially programmed at birth? Role of body composition. J Pediatr 154: 61–66 e61.FB OrtegaI. LabayenJR RuizM. Martin-MatillasG. Vicente-Rodriguez2009Are muscular and cardiovascular fitness partially programmed at birth? Role of body composition.J Pediatr1546166 e61

17. Barker DJ (1998) Programming the baby. Mothers, babies and health in later life, 2nd ed. Edinburgh: Churchill Livingstone. pp. 13–41.DJ Barker1998Programming the baby.Mothers, babies and health in later life, 2nd edEdinburghChurchill Livingstone1341

18. Eriksson JG, Forsen TJ, Kajantie E, Osmond C, Barker DJ (2007) Childhood growth and hypertension in later life. Hypertension 49: 1415–1421.JG ErikssonTJ ForsenE. KajantieC. OsmondDJ Barker2007Childhood growth and hypertension in later life.Hypertension4914151421

19. McMillen IC, Robinson JS (2005) Developmental origins of the metabolic syndrome: prediction, plasticity, and programming. Physiol Rev 85: 571–633.IC McMillenJS Robinson2005Developmental origins of the metabolic syndrome: prediction, plasticity, and programming.Physiol Rev85571633

20. Whincup PH, Kaye SJ, Owen CG, Huxley R, Cook DG, et al. (2008) Birth weight and risk of type 2 diabetes: a systematic review. Jama 300: 2886–2897.PH WhincupSJ KayeCG OwenR. HuxleyDG Cook2008Birth weight and risk of type 2 diabetes: a systematic review.Jama30028862897

21. Huxley R, Owen CG, Whincup PH, Cook DG, Rich-Edwards J, et al. (2007) Is birth weight a risk factor for ischemic heart disease in later life? Am J Clin Nutr 85: 1244–1250.R. HuxleyCG OwenPH WhincupDG CookJ. Rich-Edwards2007Is birth weight a risk factor for ischemic heart disease in later life?Am J Clin Nutr8512441250

22. Barker DJP, Osmond C, Forsen TJ, Kajantie E, Eriksson JG (2005) Trajectories of Growth among Children Who Have Coronary Events as Adults. New England Journal of Medicine 353: 1802–1809.DJP BarkerC. OsmondTJ ForsenE. KajantieJG Eriksson2005Trajectories of Growth among Children Who Have Coronary Events as Adults.New England Journal of Medicine35318021809

23. Eriksson JG, Osmond C, Kajantie E, Forsen TJ, Barker DJ (2006) Patterns of growth among children who later develop type 2 diabetes or its risk factors. Diabetologia 49: 2853–2858.JG ErikssonC. OsmondE. KajantieTJ ForsenDJ Barker2006Patterns of growth among children who later develop type 2 diabetes or its risk factors.Diabetologia4928532858

24. Salonen MK, Kajantie E, Osmond C, Forsen T, Yliharsila H, et al. (2009) Childhood growth and future risk of the metabolic syndrome in normal-weight men and women. Diabetes Metab 35: 143–150.MK SalonenE. KajantieC. OsmondT. ForsenH. Yliharsila2009Childhood growth and future risk of the metabolic syndrome in normal-weight men and women.Diabetes Metab35143150

25. Kajantie E, Barker DJ, Osmond C, Forsen T, Eriksson JG (2008) Growth before 2 years of age and serum lipids 60 years later: the Helsinki Birth Cohort study. Int J Epidemiol 37: 280–289.E. KajantieDJ BarkerC. OsmondT. ForsenJG Eriksson2008Growth before 2 years of age and serum lipids 60 years later: the Helsinki Birth Cohort study.Int J Epidemiol37280289

26. Skidmore PM, Hardy RJ, Kuh DJ, Langenberg C, Wadsworth ME (2007) Life course body size and lipid levels at 53 years in a British birth cohort. J Epidemiol Community Health 61: 215–220.PM SkidmoreRJ HardyDJ KuhC. LangenbergME Wadsworth2007Life course body size and lipid levels at 53 years in a British birth cohort.J Epidemiol Community Health61215220

27. Tzoulaki I, Sovio U, Pillas D, Hartikainen AL, Pouta A, et al. Relation of immediate postnatal growth with obesity and related metabolic risk factors in adulthood: the northern Finland birth cohort 1966 study. Am J Epidemiol 171: 989–998.I. TzoulakiU. SovioD. PillasAL HartikainenA. PoutaRelation of immediate postnatal growth with obesity and related metabolic risk factors in adulthood: the northern Finland birth cohort 1966 study.Am J Epidemiol171989998

28. Ekelund U, Ong KK, Linne Y, Neovius M, Brage S, et al. (2007) Association of weight gain in infancy and early childhood with metabolic risk in young adults. J Clin Endocrinol Metab 92: 98–103.U. EkelundKK OngY. LinneM. NeoviusS. Brage2007Association of weight gain in infancy and early childhood with metabolic risk in young adults.J Clin Endocrinol Metab9298103

29. Salonen MK, Kajantie E, Osmond C, Forsen T, Ylihärsilä H, et al. (2010) Prenatal and childhood growth and leisure time physical activity in adult life. European Journal of Public Health. MK SalonenE. KajantieC. OsmondT. ForsenH. Ylihärsilä2010Prenatal and childhood growth and leisure time physical activity in adult life.European Journal of Public Health

30. Blair SN, Cheng Y, Holder JS (2001) Is physical activity or physical fitness more important in defining health benefits? Med Sci Sports Exerc 33: S379–399; discussion S419–320.SN BlairY. ChengJS Holder2001Is physical activity or physical fitness more important in defining health benefits?Med Sci Sports Exerc33S379399; discussion S419–320

31. Ridgway CL, Ong KK, Tammelin T, Sharp SJ, Ekelund U, et al. (2009) Birth size, infant weight gain, and motor development influence adult physical performance. Med Sci Sports Exerc 41: 1212–1221.CL RidgwayKK OngT. TammelinSJ SharpU. Ekelund2009Birth size, infant weight gain, and motor development influence adult physical performance.Med Sci Sports Exerc4112121221

32. Eriksson JG, Forsen T, Tuomilehto J, Osmond C, Barker DJ (2001) Early growth and coronary heart disease in later life: longitudinal study. Bmj 322: 949–953.JG ErikssonT. ForsenJ. TuomilehtoC. OsmondDJ Barker2001Early growth and coronary heart disease in later life: longitudinal study.Bmj322949953

33. Yliharsila H, Kajantie E, Osmond C, Forsen T, Barker DJ, et al. (2008) Body mass index during childhood and adult body composition in men and women aged 56–70 y. Am J Clin Nutr 87: 1769–1775.H. YliharsilaE. KajantieC. OsmondT. ForsenDJ Barker2008Body mass index during childhood and adult body composition in men and women aged 56–70 y.Am J Clin Nutr8717691775

34. Laukkanen R, Oja P, Pasanen M, Vuori I (1992) Validity of a two kilometre walking test for estimating maximal aerobic power in overweight adults. Int J Obes Relat Metab Disord 16: 263–268.R. LaukkanenP. OjaM. PasanenI. Vuori1992Validity of a two kilometre walking test for estimating maximal aerobic power in overweight adults.Int J Obes Relat Metab Disord16263268

35. Rance M, Boussuge PY, Lazaar N, Bedu M, Van Praagh E, et al. (2005) Validity of a V.O2 max prediction equation of the 2-km walk test in female seniors. Int J Sports Med 26: 453–456.M. RancePY BoussugeN. LazaarM. BeduE. Van Praagh2005Validity of a V.O2 max prediction equation of the 2-km walk test in female seniors.Int J Sports Med26453456

36. Gale CR, O'Callaghan FJ, Bredow M, Martyn CN, the Avon Longitudinal Study of Parents and Children Study T (2006) The Influence of Head Growth in Fetal Life, Infancy, and Childhood on Intelligence at the Ages of 4 and 8 Years. Pediatrics 118: 1486–1492.CR GaleFJ O'CallaghanM. BredowCN Martynthe Avon Longitudinal Study of Parents and Children Study T2006The Influence of Head Growth in Fetal Life, Infancy, and Childhood on Intelligence at the Ages of 4 and 8 Years.Pediatrics11814861492

37. De Stavola BL, Nitsch D, dos Santos Silva I, McCormack V, Hardy R, et al. (2006) Statistical issues in life course epidemiology. Am J Epidemiol 163: 84–96.BL De StavolaD. NitschI. dos Santos SilvaV. McCormackR. Hardy2006Statistical issues in life course epidemiology.Am J Epidemiol1638496

38. Pescatello LS, Franklin BA, Fagard R, Farquhar WB, Kelley GA, et al. (2004) American College of Sports Medicine position stand. Exercise and hypertension. Med Sci Sports Exerc 36: 533–553.LS PescatelloBA FranklinR. FagardWB FarquharGA Kelley2004American College of Sports Medicine position stand. Exercise and hypertension.Med Sci Sports Exerc36533553

39. Orozco LJ, Buchleitner AM, Gimenez-Perez G, Roque IFM, Richter B, et al. (2008) Exercise or exercise and diet for preventing type 2 diabetes mellitus. Cochrane Database Syst Rev CD003054.LJ OrozcoAM BuchleitnerG. Gimenez-PerezIFM RoqueB. Richter2008Exercise or exercise and diet for preventing type 2 diabetes mellitus.Cochrane Database Syst RevCD003054

40. Kohrt WM, Bloomfield SA, Little KD, Nelson ME, Yingling VR (2004) American College of Sports Medicine Position Stand: physical activity and bone health. Med Sci Sports Exerc 36: 1985–1996.WM KohrtSA BloomfieldKD LittleME NelsonVR Yingling2004American College of Sports Medicine Position Stand: physical activity and bone health.Med Sci Sports Exerc3619851996

41. Tager IB, Hollenberg M, Satariano WA (1998) Association between self-reported leisure-time physical activity and measures of cardiorespiratory fitness in an elderly population. Am J Epidemiol 147: 921–931.IB TagerM. HollenbergWA Satariano1998Association between self-reported leisure-time physical activity and measures of cardiorespiratory fitness in an elderly population.Am J Epidemiol147921931

42. Eaton CB, Lapane KL, Garber CE, Assaf AR, Lasater TM, et al. (1995) Physical activity, physical fitness, and coronary heart disease risk factors. Med Sci Sports Exerc 27: 340–346.CB EatonKL LapaneCE GarberAR AssafTM Lasater1995Physical activity, physical fitness, and coronary heart disease risk factors.Med Sci Sports Exerc27340346

43. Bouchard C, Rankinen T (2001) Individual differences in response to regular physical activity. Med Sci Sports Exerc 33: S446–451; discussion S452–443.C. BouchardT. Rankinen2001Individual differences in response to regular physical activity.Med Sci Sports Exerc33S446451; discussion S452–443

44. Lee DC, Sui X, Ortega FB, Kim YS, Church TS, et al. (2011) Comparisons of leisure-time physical activity and cardiorespiratory fitness as predictors of all-cause mortality in men and women. Br J Sports Med 45: 504–510.DC LeeX. SuiFB OrtegaYS KimTS Church2011Comparisons of leisure-time physical activity and cardiorespiratory fitness as predictors of all-cause mortality in men and women.Br J Sports Med45504510

45. Kajantie E, Strang-Karlsson S, Hovi P, Raikkonen K, Pesonen AK, et al. (2010) Adults born at very low birth weight exercise less than their peers born at term. J Pediatr 157: 610–616, 616 e611.E. KajantieS. Strang-KarlssonP. HoviK. RaikkonenAK Pesonen2010Adults born at very low birth weight exercise less than their peers born at term.J Pediatr157610616, 616 e611

46. Yliharsila H, Kajantie E, Osmond C, Forsen T, Barker DJ, et al. (2007) Birth size, adult body composition and muscle strength in later life. Int J Obes (Lond) 31: 1392–1399.H. YliharsilaE. KajantieC. OsmondT. ForsenDJ Barker2007Birth size, adult body composition and muscle strength in later life.Int J Obes (Lond)3113921399

47. Bedogni G, Malavolti M, Severi S, Poli M, Mussi C, et al. (2002) Accuracy of an eight-point tactile-electrode impedance method in the assessment of total body water. Eur J Clin Nutr 56: 1143–1148.G. BedogniM. MalavoltiS. SeveriM. PoliC. Mussi2002Accuracy of an eight-point tactile-electrode impedance method in the assessment of total body water.Eur J Clin Nutr5611431148

48. Laukkanen RM, Oja P, Ojala KH, Pasanen ME, Vuori IM (1992) Feasibility of a 2-km walking test for fitness assessment in a population study. Scand J Soc Med 20: 119–126.RM LaukkanenP. OjaKH OjalaME PasanenIM Vuori1992Feasibility of a 2-km walking test for fitness assessment in a population study.Scand J Soc Med20119126

49. Laukkanen RM, Kukkonen-Harjula TK, Oja P, Pasanen ME, Vuori IM (2000) Prediction of change in maximal aerobic power by the 2-km walk test after walking training in middle-aged adults. Int J Sports Med 21: 113–116.RM LaukkanenTK Kukkonen-HarjulaP. OjaME PasanenIM Vuori2000Prediction of change in maximal aerobic power by the 2-km walk test after walking training in middle-aged adults.Int J Sports Med21113116

50. Barker DJ (1995) Fetal origins of coronary heart disease. Bmj 311: 171–174.DJ Barker1995Fetal origins of coronary heart disease.Bmj311171174

51. Salonen MK, Kajantie E, Osmond C, Forsen T, Yliharsila H, et al. (2009) Role of childhood growth on the risk of metabolic syndrome in obese men and women. Diabetes Metab 35: 94–100.MK SalonenE. KajantieC. OsmondT. ForsenH. Yliharsila2009Role of childhood growth on the risk of metabolic syndrome in obese men and women.Diabetes Metab3594100

52. Ekelund U, Ong K, Linne Y, Neovius M, Brage S, et al. (2006) Upward weight percentile crossing in infancy and early childhood independently predicts fat mass in young adults: the Stockholm Weight Development Study (SWEDES). Am J Clin Nutr 83: 324–330.U. EkelundK. OngY. LinneM. NeoviusS. Brage2006Upward weight percentile crossing in infancy and early childhood independently predicts fat mass in young adults: the Stockholm Weight Development Study (SWEDES).Am J Clin Nutr83324330