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RAPID COMMUNICATION |
1 MRC Environmental Epidemiology Unit
2 University Geriatric Medicine, University of Southampton, United Kingdom.
Address correspondence to Dr. Avan Aihie Sayer, MRC Environmental Epidemiology Unit, Southampton General Hospital, Southampton SO16 6YD, U.K. E-mail: aas{at}mrc.soton.ac.uk
Abstract
Background. Sarcopenia is defined as the loss of skeletal muscle mass and strength with aging. Recent epidemiological studies have shown that men and women who grew less well in early life have lower muscle strength. Our objective was to investigate the relationship between birth weight, infant growth, and the development of sarcopenia.
Methods. We studied 730 men and 673 women, of known birth weight and weight at 1 year, who were born in Hertfordshire, U.K., between 1931 and 1939. Participants completed a health questionnaire, and we measured their height, weight, and grip strength. Standard deviation scores for birth weight, and for infant growth conditional on birth weight, were analyzed in relation to grip strength before and after adjustment for adult size.
Results. Grip strength was most strongly associated with birth weight in men (r = 0.19, p <.001) and women (r = 0.16, p <.001). These relationships remained significant after adjustment for adult height and weight. In contrast, the associations with infant growth were weakened after allowing for adult size. Adjustment for age, current social class, physical activity, smoking, and alcohol did not affect these results.
Conclusions. Birth weight is associated with sarcopenia in men and women, independently of adult height and weight. The influence of infant growth on long-term muscle strength appears to be mediated through adult size. Sarcopenia may have its origins in early life, and identifying influences operating across the whole life course may yield considerable advances in developing effective interventions.
Novel research suggests that early environmental influences may be important. A study of 717 men and women aged 64–74 years demonstrated that birth weight and weight at 1 year were significantly positively associated with adult grip strength (10). The findings for birth weight have been replicated in a U.K. national birth cohort of men and women born in 1946, which showed strong relationships between size at birth and grip strength in midlife (11). There is also evidence that muscle mass in older people is positively associated with their birth weight independent of current size (12,13). The findings are consistent with a growing body of work demonstrating that poor early growth has important long-term sequelae for human health including an increased risk of developing coronary heart disease, type 2 diabetes, and osteoporosis (14).
These associations have been explained by the phenomenon of programming, which is the persisting influence of exposures occurring at critical periods of early development on long-term organ structure, function, and regulation (15). Programming of muscle has been documented in animal models, for example, in the field of animal husbandry where prenatal nutritional manipulation of muscle growth and quality is of particular interest to the meat industry. Prenatal undernutrition has been associated with reduced neonatal muscle weight but not fiber number in the sheep (16) and a reduction in postnatal muscle fiber number in the pig (17), guinea pig (18), and rat (19). There is evidence that these effects persist (20,21). A recent review of the impact of manipulation of myogenesis in utero on the performance of adult skeletal muscle in animal models concluded that the effect was predominantly on secondary muscle fibers formed later in embryonic and fetal development (22). There is evidence that the muscle phenotype can also be influenced by postnatal nutrition (23).
The documented associations between size at birth, weight at 1 year, and adult muscle strength suggest that similar mechanisms may be operating in human muscle development but little is known about the relative importance of prenatal and postnatal size and growth. We have used a conditional statistical approach to investigate the relative contribution of birth weight, weight at 1 year, and growth in the first year of life independent of birth weight, to adult grip strength.
METHODS
Study Population
From 1911 to 1948, midwives collected detailed records, including information on birth weight and weight at 1 year, on infants born in the county of Hertfordshire, U.K. The records for people born 1911–1930 have been used in a series of studies linking early growth to health in later life. In 1998, a younger cohort was recruited to participate in studies examining the interactions between early life, diet, adult lifestyle, and genetic factors as determinants of adult disease. A total of 1760 men and 1447 women born in Hertfordshire between 1931 and 1939 and still living in East Hertfordshire were traced with the aid of the National Health Service (NHS) central registry in Southport and confirmed as currently registered with a general practitioner in Hertfordshire.
Permission to contact 1397 (79%) men and 1364 (94%) women was obtained from their general practitioners. A total of 768 (55%) men and 714 (52%) women agreed to take part in a home interview where trained nurses collected information on their medical and social histories. A total of 737 (96%) of the men and 675 (95%) of the women interviewed at home subsequently attended a clinic for a number of investigations. Anthropometry included measurement of height and weight. Grip strength was measured three times on each side using a Jamar handgrip dynamometer (Promedics, Blackburn, U.K.) (24). Grip strength and height measurements were obtained for 730 (99%) men and 673 (99%) women. Intraobserver and interobserver studies were carried out at regular intervals during the fieldwork to ensure comparability of measurements within and between observers. The study had ethical approval from the North and East Hertfordshire Local Research Ethics Committee, and all participants gave written informed consent.
Statistical Methods
Early size and growth were characterized by calculating sex-specific standard deviation (SD) scores for birth weight, weight at 1 year, and infant growth conditional on birth weight (25). The SD score for infant growth conditional on birth weight was free of the artefactual effects of regression to the mean, and could be included in a regression model simultaneously with birth weight without multicolinearity problems.
The best of the six grip measurements was used in analyses. The relationships between grip and adult lifestyle variables were explored using Pearson's correlations and analysis of variance. Adult determinants of grip were included as adjustment variables in subsequent analyses.
For presentational purposes, means and SDs of grip strength were derived according to sex-specific quintiles of birth weight, weight at 1 year, and infant growth conditional on birth weight. However, statistical tests of association with grip strength were based on continuously distributed early life variables. Pearson's pair-wise and partial correlation coefficients were used to describe the relationships between grip strength and early size and growth without, and with, adjustment for adult determinants of grip.
The sex-specific regression coefficients for grip on adult height were used to calculate grip strength adjusted to average adult height. Analyses were repeated using height-adjusted grip strength in order to assess the impact of adult anthropometry on the relationships between early size and growth and grip strength in later life. All analyses were carried out for men and women separately, using the Stata statistical software package, release 7.0 (Stata Corp, College Station, TX).
RESULTS
Subject Characteristics
The characteristics of the 1403 study subjects are shown in Table 1.
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We have demonstrated that a higher birth weight is associated with better grip strength in later life in men and women. Adjustment for adult height weakens, but does not remove, these relationships. Similar associations were seen for weight at 1 year, but this appeared to reflect the fact that size achieved at 1 year is a combination of both size at birth and infant growth. When conditional infant growth was examined, which is growth in the first year of life independent of size at birth, a relationship with muscle strength was only seen in the men, and this became insignificant after adjustment for adult height. This suggests that the effect of infant growth is largely mediated through adult size but that other factors are also operating in the relationship between birth weight and adult muscle strength.
There are a number of potential caveats to the interpretation of our findings. Losses to follow-up occurred during tracing and in gaining consent to participate, and response bias may have been introduced. However, we were able to characterize those who did not take part in the study in a number of ways. There were no substantial differences in birth weight or weight at 1 year between participants who were traced and eligible to participate in the study but did not, and those who had a home interview. Furthermore, there were no major differences in age, social class, alcohol consumption, or activity level between interviewed participants who did or did not attend the clinic. The proportion of current smokers was lower among interview participants who did come to the clinic (16.8% men, 10.5% women) than those who declined (32.3% men, 28.2% women). This suggests that there may have been a "healthy subject" effect in this study. However, our comparisons were internal; therefore, unless the relationship between early size and adult grip strength differed between those who did and did not come to the clinic, no bias should have been introduced.
Research into the etiology of sarcopenia has focused on the adult determinants of muscle loss in older people. However, factors operating earlier in life to determine peak muscle mass and strength, and subsequent rate of loss, have been largely overlooked. Our findings suggest that it is important to consider determinants of early muscle growth. Human muscle development begins between 6 and 8 weeks of gestation with the formation of primary fibers followed by the laying down of secondary fibers between weeks 8 and 18 (26). There are genetic influences on fetal growth, but the importance of maternal factors, particularly nutrition, have long been recognized (27). There is evidence that secondary muscle fibers are sensitive to the prenatal environment, including nutritional and hormonal influences. For example, prenatal undernutrition may be associated with permanent reduction in both fiber size and number (22).
Work on animal models suggests that this sensitivity may extend into the postnatal period (28). It has long been held that the number of muscle fibers is determined by the time of birth, and subsequent growth is achieved by an increase in size rather than in the number of fibers (29). However, there is now emerging evidence that postmitotic myonuclei lying within mature myofibers might be able to reform myoblasts or stem cells, and there is increasing recognition of the role that satellite cells play in postnatal muscle growth and regeneration (30). The relevance of these findings to the growth of human muscle is, as yet, unclear. However, the relationships we have demonstrated between birth weight, infant growth, and adult grip strength suggest that muscle growth in both the prenatal and postnatal periods, whether by an effect on fiber size or number, or an effect on satellite cell activity, may have long-term importance for muscle function.
Furthermore, the finding that the relationship between birth weight and grip strength remains after allowing for adult size provides evidence that early influences may affect more than muscle growth and final size. The mechanism is not known but may reflect altered muscle fiber type, proportion, and quality, and this may have consequences not only for peak strength attained but also for subsequent decline. The underlying mechanisms need to be explored. We would suggest that identifying factors operating across the life course to influence peak muscle mass and strength, as well as loss, may yield considerable advances in developing effective interventions for sarcopenia.
Acknowledgments
This work was supported by the Medical Research Council and the University of Southampton, U.K.
Received April 8, 2004
Accepted April 12, 2004
References
This article has been cited by other articles:
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  P. M. Costello, A. Rowlerson, N. A. Astaman, F. E. W. Anthony, A. A. Sayer, C. Cooper, M. A. Hanson, and L. R. Green Peri-implantation and late gestation maternal undernutrition differentially affect fetal sheep skeletal muscle development J. Physiol., May 1, 2008; 586(9): 2371 - 2379. [Abstract] [Full Text] [PDF]
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 C J Edwards, H Syddall, R Goswami, P Goswami, E M Dennison, N K Arden, C Cooper, and on behalf of the Hertfordshire Cohort Study Group The autoantibody rheumatoid factor may be an independent risk factor for ischaemic heart disease in men Heart, October 1, 2007; 93(10): 1263 - 1267. [Abstract] [Full Text] [PDF]
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 C. R Gale, C. N Martyn, C. Cooper, and A. A. Sayer Grip strength, body composition, and mortality Int. J. Epidemiol., February 1, 2007; 36(1): 228 - 235. [Abstract] [Full Text] [PDF]
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 A. A. Sayer, E. M. Dennison, H. E. Syddall, H. J. Gilbody, D. I.W. Phillips, and C. Cooper Type 2 Diabetes, Muscle Strength, and Impaired Physical Function: The tip of the iceberg? Diabetes Care, October 1, 2005; 28(10): 2541 - 2542. [Full Text] [PDF]
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