Annals of Medicine, 2015; 47: 34–39 © 2014 Informa UK, Ltd. ISSN 0785-3890 print/ISSN 1365-2060 online DOI: 10.3109/07853890.2014.963664
ORIGINAL ARTICLE
Early life body mass trajectories and mortality in older age: Findings from the Helsinki Birth Cohort Study Mikaela B. von Bonsdorff1, Timo Törmäkangas1, Taina Rantanen1, Minna K. Salonen2,3, Clive Osmond4, Eero Kajantie2,5,6 & Johan G. Eriksson2,3,7,8,9
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1Gerontology Research Center and Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland, 2Division of Welfare and
Health Promotion, Department of Chronic Disease Prevention, Diabetes Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland, 3Folkhälsan Research Centre, Helsinki, Finland, 4MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, United Kingdom, 5Hospital for Children and Adolescents, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland, 6Department of Obstetrics and Gynaecology, Oulu University Hospital and University of Oulu, Oulu, Finland, 7Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland, 8Unit of General Practice, Helsinki University Central Hospital, Helsinki, Finland, and 9Vasa Central Hospital, Vasa, Finland
Background. Overweight and obesity in childhood have been linked to an increased risk of adult mortality, but evidence is still scarce. Methods. We identified trajectories of body mass index (BMI) development in early life and investigated their mortality risk. Data come from the Helsinki Birth Cohort Study, in which 4943 individuals, born 1934–1944, had serial measures of weight and height from birth to 11 years extracted from health care records, weight and height data in adulthood, and register-based mortality data for 2000–2010. Results. Three early BMI trajectories (increasing, average, and average-to-low for men and increasing, average, and low-to-high BMI for women) were identified. Women with an increasing or low-to-high BMI (BMI lower in early childhood, later exceeded average) trajectory had an increased risk of all-cause mortality compared to those with an average BMI trajectory (HR 1.55, 95% CI 1.07–2.23; and HR 1.57, 95% CI 1.04–2.37, respectively). Similar associations were observed for cancer mortality. Among men, BMI trajectories were not associated with all-cause mortality, but those with average-to-low BMI (BMI first similar then dropped below average) had an increased risk of cancer mortality. Conclusions. An increasing BMI in early life may shorten the lifespan of maturing cohorts as they age, particularly among women. Key words: Aging, birth size, body mass index, developmental origins of adult health and disease, growth mixture models, life-course epidemiology, mortality
Introduction Overweight and obesity in childhood (1,2) as well as thinness at birth followed by compensatory increase in body size in childhood (3–5) have been linked to an increased prevalence of
Key messages • Three early body mass trajectories were identified in which the majority of the participants had a similar BMI development pattern in infancy and childhood (average BMI), but two atypical patterns were identified (for men, increasing BMI, and average-to-low BMI; and for women increasing BMI, and low-to-high BMI). • The early BMI trajectories were differently associated with the risk for all-cause and cancer mortality among women and for cancer mortality among men in early old age. • Adult body size did not mediate, nor did socio-economic status in childhood or adulthood or lifestyle factors explain the association between early BMI development and mortality in early old age.
morbidity in later life. However, the association between body size in early life and mortality in later life has been little studied, and it is unclear whether the association is driven by adult body size. Using a single measure of body mass index (BMI weight/[height2]) in childhood, the studies that are available have shown that overweight and obesity were associated with an increased risk of premature mortality in adulthood (6–8). A number of studies have found that overweight and obesity in adolescence and early adulthood increased the risk of mortality (9–12). A recent study in the British 1946 birth cohort (13) found that both high and low compared to normal BMI measured in early adulthood were related to mortality. The same U-shaped association was found for women for body size measured in
Correspondence: Mikaela B. von Bonsdorff, Researcher, PhD, Gerontology Research Center and Department of Health Sciences, University of Jyväskylä, PO Box 35, FI-40014, Finland. E-mail: mikaela.vonbonsdorff@jyu.fi (Received 4 June 2014; accepted 3 September 2014)
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Early body mass index trajectories and mortality 35 childhood and adolescence. The associations between body size in early life and mortality in adulthood were partly explained by adult BMI in some (10,12), but not all (9,13) of the aforementioned studies. In these studies, the risk for subsequent health decline has been reported using predetermined categorization of body size, but so far no study has investigated whether different observed patterns of BMI development in early life predispose an individual to premature mortality in later life. Drawing on the original life-course epidemiology models (14), we will test the ‘critical period model’, where BMI development in early life is associated with later mortality risk and the ‘critical period with later effect modifiers model’, where the association between early BMI development and later mortality is attenuated by adult BMI. We have previously shown in a Finnish birth cohort that individuals who later develop major chronic diseases such as diabetes and coronary heart disease were born thin, they grew more slowly during infancy, and later in childhood they increased in body size compared to the healthy cohort members (4,15). Using these data, the aim of this study was to identify different trajectories of BMI development observed in data spanning from birth to age 11 years, examining whether the risk of all-cause, cardiovascular (CVD), and cancer mortality in early old age was different for these early life BMI trajectories and whether adult body size explained the potential association.
Late adulthood measures Information on weight and height were obtained from postal questionnaires which were sent to the participants at a mean age of 60 years (range 56 to 67 years). Participants’ living habits included information on smoking status (never smoked, former smoker, current smoker), alcohol consumption (does not use, uses at most 2 times per month, uses 3 or more times per month), and physical activity (at least 3 times per week, 2 times per week at most, sedentary). Register data from Statistics Finland was used to indicate adult socio-economic status. The highest occupational status at 5-year intervals between 1970 and 2000 was coded as upper middle class, lower middle class, self-employed, and manual workers (19).
Mortality Dates and causes of death from 11 November 2000 to 31 December 2010 were obtained from the Finnish National Death Register. Survival time was calculated as the number of days between date of birth and death or end of the follow-up in December 2010, whichever happened first. International Classification of Disease (ICD) codes for cardiovascular mortality included 400–499 in the ICD 9th revision and I00–I99 in the ICD 10th revision, and for cancer mortality the codes 140–239 in the ICD 9th revision and C00–C97 ICD 10th revision.
Statistical analyses
Materials and methods Study population The Helsinki Birth Cohort Study (HBCS) comprises 13,345 individuals born in Helsinki, Finland, at Helsinki University Central Hospital or Helsinki City Maternity Hospital between 1934 and 1944 for whom data on body anthropometrics in childhood have been retrieved from several health care records (5,16). There were on average 17 measurements on body size available for each individual from birth to school age (17). In the year 2000, a postal questionnaire was sent to 10,530 members of the cohort who were alive and living in Finland at that time, and, of these, 6874 (65.6%) answered. In the present paper, analyses were restricted to the 4943 (71.9%) individuals who had weight and height data available at birth, at age 11 years, and in late adulthood. These members of the cohort were similar to the other people in the original HBCS cohort in body size at birth, length of gestation, maternal BMI, and father’s socio-economic position. The study was approved by the Ethics Committee of Epidemiology and Public Health of the Hospital District of Helsinki and Uusimaa and that of the National Public Health Institute, Helsinki.
Infant and childhood measures Birth date, weight, and length of the newborns were retrieved from the hospital birth records, and infancy and childhood weight and height from child welfare clinic and school health care records, described in detail previously (4,5,18). Date of the mothers’ last menstrual period prior to pregnancy was also extracted from the hospital birth records and used to calculate gestational age. Information on maternal weight and height during late pregnancy was also extracted from the birth records. Childhood socio-economic status was ascertained based on father’s highest occupation status extracted from birth, child welfare, and school health care records, coded as upper middle class, lower middle class, and manual workers based on the original social classification system issued by Statistics of Finland (19).
Analyses were conducted separately for men and women because of previous findings on gender differences in early growth and development and BMI in adulthood (13,20). Each BMI measure was converted to a Z score, and the successive Z scores were interpolated with a piecewise linear function for every month from birth to age 2 years and from 2 to 11 years for every birthday. The Z scores were back-transformed to obtain the corresponding BMI (4,5). Patterns of early body size development were determined by fitting latent class growth mixture models (GMM) to all available BMI data spanning from birth to school age using Mplus version 7.0 (21). In the analyses, the aim was to capture unobserved subpopulations (latent groups) with similar body size development but distinct across the latent groups over time, which each have their own growth parameters, intercept, and slope. We estimated the quadratic and cubic shapes of the trajectories, in order to identify all potential differences in early BMI development. We used several model fit indices to determine the optimal number of latent groups (21). In the Bayesian Information Criterion (BIC) and Akaike Information Criterion (AIC), lower values indicate a better fit of the model, and clarity of classification into trajectory classes was assessed with 1) high percentage of individuals falling into the latent class based on the posterior probabilities; and 2) high model entropy, which ranges between 0 and 1, with scores near 1 indicating clear classification (21). GMM yielded three early BMI trajectories for both men and women. These were named increasing BMI, average BMI, and average-to-low BMI for men; and increasing BMI, average BMI, and low-to-high BMI for women. Baseline characteristics of the participants were tested across the BMI trajectory classes using chi-square test for categorical variables and analysis of variance for continuous variables. Using Cox proportional hazards models we estimated mortality hazards and their 95% confidence intervals for early BMI trajectories and all-cause, CVD, and cancer mortality in early old age using the group ‘average BMI’ as the reference category. The proportional hazards assumption was assessed using a test based on scaled Schoenfeld residuals. We first made adjustment for age and then for socio-economic status
M. B. von Bonsdorff et al. Women 19 18 17 16 15 Average BMI 59.0% Increasing BMI 25.4% Low-to-high BMI 15.6%
14 13 0
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Years
Figure 2. Observed mean BMI values for early BMI development trajectories from growth mixture models for women in the Helsinki Birth Cohort Study, n 2574.
Results Altogether 52.1% of the study members were women, and the participants were on average 59.6 years (SD 2.7, range 56 to 67 years) when their BMI was assessed. During the 10-year follow-up, 460 (9.3%) individuals died, of whom 302 were men and 158 women. Of the cohort members, 174 died of cancer (main diagnoses were malignancies of digestive organs and lung cancer) and 142 of cardiovascular disease. Average age at death was 69.6 years (SD 2.9) for men and 69.2 years (SD 3.1) for women. We used the Bayesian Information Criterion (BIC) to define the best model fit for the data indicating the optimal number of latent classes, i.e. early BMI trajectories, in the study population. BIC was lowest for the three class solution indicating the optimal number of classes for both genders. Average membership probabilities in the three latent classes ranged between 0.69 and 0.91. Model entropy was 0.73 for men and 0.54 for women. The early BMI trajectories, presented in Figures 1 and 2, were named for men ‘increasing BMI’ (6.4% of men belonged to this class), ‘average BMI’ (66.7%), and ‘average-to-low BMI’ (26.9%); and for women ‘increasing BMI’ (25.4% of the women belonged to this class), ‘average BMI’ (59.0%), and ‘low-to-high BMI’ (15.6%).
Men 20 19 18 BMI (kg/m2)
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in childhood and adulthood and lifestyle factors (smoking, alcohol consumption, and physical activity). Finally we added adult BMI and the quadratic term (because of the known U-shaped association of BMI in adulthood and premature mortality (22)) into the analyses to test whether it mediated the association between early life BMI development and mortality in early old age. In order to obtain a data set with complete data on all main variables and covariates, we imputed values for covariates where data were missing using multiple imputations (childhood socio-economic status n 47, adult socio-economic status n 18, smoking status n 30, alcohol consumption n 21, physical activity n 34). A total of 20 imputed data sets were created using all variables in the analyses. Cox models were first performed using complete data available for all main variables and covariates and then using the multiply imputed data sets, with the effect estimates combined using Rubin’s rules. While the results were largely the same, we present findings on imputed data.
BMI (kg/m2)
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17 16 15 Average BMI 66.7% Increasing BMI 6.4% Average-to-low BMI 26.9%
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Figure 1. Observed mean BMI values for early BMI development trajectories from growth mixture models for men in the Helsinki Birth Cohort Study, n 2369.
Men with increasing BMI had lower BMI during the first three months of life, but after that it increased consistently compared to the ones with average BMI. Men with average-to-low BMI had similar BMI during infancy to those with average BMI, but at age 2 years it dropped below the average BMI. Women with increasing BMI had similar BMI to those with average BMI during the first 6 months, after which their BMI was consistently higher. Women with low-to-high BMI had lower BMI in infancy and early childhood, but around age 8 their BMI increased and was consistently higher compared to those with an average BMI. We identified differences in the characteristics of the participants according to early BMI trajectories, presented in Table I. Maternal BMI was lowest for men with average-to-low BMI (P 0.001). Men and women with an increasing BMI trajectory had the highest BMI in adulthood (P 0.049 and P 0.001, respectively). There were few differences in socio-economic or lifestyle factors in adulthood according to early BMI trajectories. Hazard ratios from the Cox models revealed that all-cause mortality did not differ according to early BMI trajectories among men. For women, compared to those with average BMI, the hazard was higher for those with increasing BMI and for those with low-to-high BMI (HR 1.67, 95% CI 1.15–2.41; and HR 1.58, 95% CI 1.03–2.41, respectively) (Table II). Adjustment for socio-economic status in childhood and adulthood and lifestyle factors did not attenuate this association. To test whether body mass in adulthood explained the association between early BMI development and mortality in early old age, we made adjustment for BMI at an average age of 60, but it did not attenuate the associations for women; the hazard was higher for those with increasing BMI and for those with low-to-high BMI (HR 1.61, 95% CI 1.12–2.31; and HR 1.58, 95% CI 1.05–2.37, respectively), compared to the average BMI trajectory. There were no differences in the hazards for cardiovascular mortality according to early BMI trajectories (results not shown). For cancer mortality, the hazards were higher among men with average-to-low BMI (HR 1.60, 95% CI 1.05–2.42) compared to those with average BMI. Among women the hazards were higher for those with increasing BMI and low-to-high BMI (HR 1.85, 95% CI 1.08–3.18; and HR 2.71, 95% CI 1.58–4.66, respectively). Adjustment for socio-economic and lifestyle confounders and adult BMI did not attenuate these associations (Table II). Furthermore, we adjusted the models for gestational age and found few differences in the associations.
Early body mass index trajectories and mortality 37 Table I. Characteristics of the study population (mean and standard deviation unless stated otherwise) according to early BMI trajectories.
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BMI trajectories for men
Birth and childhood characteristics Gestational age (weeks) Father’s highest occupational status, % Upper middle Lower middle Manual worker Adulthood characteristics Age at data collection in 2000 Body mass index Highest occupational status in adulthood, % Upper middle Lower middle Self-employed Manual worker Smoking status, % Never Former Current Alcohol consumption, % None 2 times per month at most 3 or more times per month Level of physical activity, % Sedentary Moderate 2 times/week at most Moderate 3 times/week or more aComparisons
Increasing BMI n 152
Average BMI n 1579
38.8 (2.0)
39.4 (1.8)
39.4 (1.8)
20.8 20.1 59.1
19.5 26.5 54.0
18.1 23.1 58.7
59.6 (2.4) 27.22 (3.84)
59.5 (2.6) 26.79 (4.06)
59.8 (2.8) 26.44 (3.84)
20.8 24.8 10.1 44.3
17.9 27.3 10.6 44.2
15.9 28.4 10.4 45.4
30.9 44.7 24.3
26.9 44.4 28.7
23.9 45.9 30.2
11.2 37.5 51.3
8.7 27.9 63.4
7.5 29.6 62.9
13.3 44.0 42.7
11.1 42.4 46.5
11.7 39.6 48.7
BMI trajectories for women
Average-to-low BMI n 638 P valuea 0.001 0.171
0.114 0.049 0.83
Increasing BMI n 653
Average BMI n 1520
Low-to-high BMI n 401 P valuea
39.5 (1.8)
39.4 (1.8)
39.3 (1.8)
14.3 25.9 59.8
16.9 23.6 59.5
14.9 24.2 60.9
59.4 (2.5) 27.78 (5.21)
59.7 (2.8) 60.2 (3.0) 0.001 26.12 (4.68) 26.78 (4.72) 0.001 0.126 10.4 8.3 56.9 56.6 7.5 9.3 25.2 25.8 0.403 52.7 50.9 25.5 28.6 21.8 20.6 0.588 8.9 8.2 50.1 51.6 41.0 40.1 0.331 13.4 11.3 42.8 42.4 43.8 46.4
11.1 50.8 9.4 28.7 0.337 51.2 24.4 24.4 0.044 10.8 50.3 38.9 0.604 12.0 39.7 48.3
0.178 0.501
for categorical variables performed with chi-square test and for continuous variables with analyses of variance.
Discussion To our knowledge this is the first study to investigate the association between early BMI development across infancy and childhood and all-cause and cause-specific mortality in early old age in a well-characterized birth cohort. The majority of the participants had a similar BMI development pattern in infancy and childhood which we named average BMI, but two atypical patterns were identified. For both men and women we found an early BMI trajectory which increased and, for men, one in which BMI was similar during infancy but later dropped below the average BMI trajectory and, for women, one in which BMI was lower in infancy and childhood but later exceeded the average trajectory. We found that the observed early BMI development patterns were associated with all-cause mortality about 70 years later among women but not men. The mortality rate was higher for cohort members who did not participate in data collection in the year 2000 than for those who did (27.4% versus 9.3%,
respectively) suggesting potentially that mortality related to atypical BMI development trajectories occurred at earlier ages and was not recorded. Given that mortality in early adulthood is higher among men than women this might partly account for the lack of association observed among men for all-cause mortality. Our findings among women are in line with those reported by Strand et al. (13) in the British 1946 birth cohort, where they found an association between BMI measured at the age of 4 years and mortality, which was not explained by adult body size. Other findings among women have shown that high BMI in adolescence increased the risk of mortality which was not explained by later BMI, supporting our findings (10). Our results, however, contrast those reporting that the increased risk of mortality in older age among those with high BMI in adolescence was mediated by adult BMI (12). Interestingly, we found that early BMI development was associated with cancer mortality among women and men which was not explained by socio-economic status and lifestyle factors or adult BMI. We did not find an
Table II. Hazard ratios (HR) and 95% CIs for all-cause and cancer mortality according to early BMI trajectories in the Helsinki Birth Cohort Study, n 4943. All-cause mortality
Men, Early BMI trajectories Average BMI Increasing BMI Average-to-low BMI Women, Early BMI trajectories Average BMI Increasing BMI Low-to-high BMI
Cancer mortality
Model 1 HR (95% CI)
Model 2 HR (95% CI)
Model 3 HR (95% CI)
Model 1 HR (95% CI)
Model 2 HR (95% CI)
Model 3 HR (95% CI)
ref. 0.86 (0.53–1.42) 0.98 (0.76–1.27)
ref. 0.87 (0.53–1.42) 0.95 (0.73–1.23)
ref. 0.87 (0.53–1.42) 0.95 (0.73–1.23)
ref. 0.73 (0.26–2.01) 1.60 (1.05–2.42)
ref. 0.73 (0.44–1.23) 1.55 (1.02–2.35)
ref. 0.73 (0.43–1.22) 1.55 (1.03–2.34)
ref. 1.61 (1.12–2.31) 1.58 (1.05–2.37)
ref. 1.55 (1.08–2.23) 1.57 (1.04–2.37)
ref. 1.55 (1.07–2.23) 1.57 (1.04–2.37)
ref. 1.85 (1.08–3.18) 2.71 (1.58–4.66)
ref. 1.79 (1.04–3.06) 2.72 (1.59–4.67)
ref. 1.73 (1.00–2.98) 2.70 (1.56–4.67)
Model 1 adjusted for age at data collection in 2000; Model 2 adjusted for Model 1 socio-economic status in childhood and adulthood, smoking, alcohol consumption, and physical activity; Model 3 adjusted for Model 2 BMI and quadratic term at average age of 60. BMI body mass index.
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38
M. B. von Bonsdorff et al.
association between early BMI development trajectories and cardiovascular mortality, although other papers using this cohort have found that those who had been small at birth, thin in infancy, but gained thereafter weight had an increased risk of coronary events (4). The present lack of an association might be attributable to the small number of individuals who died of cardiovascular causes, e.g. 1.3% of the women in our analyses died of cardiovascular causes, and the fact that men who had a high risk of CVD might have died before reaching the average age of 60 years and were thus not included in this study. Most previous studies have used a single measure of BMI in childhood or adolescence with a-priori defined categories for BMI, whereas we identified observed patterns of BMI development from birth to childhood. A similar type of modeling has been used in younger cohorts with serial measures of body size to identify developmental patterns of body size in childhood and to study underlying factors (23), but the predictive value of these patterns on older age health outcomes cannot yet be investigated while those cohorts are too young. In the present study, boys on an average-to-low trajectory had an average BMI until age two but then became thinner compared to boys on the average BMI trajectory. Girls on the low-to-high BMI trajectory were thinner during infancy and early childhood but later increased in body mass exceeding the average BMI trajectory. The girls who had an increasing or low-to-high BMI trajectory had higher BMI in adulthood compared to those with an average BMI trajectory, whereas the same was true for boys with an increasing BMI trajectory. This is in line with findings on the increased risk of later obesity among those with larger body size in infancy or of those who were born thin but later grew fast (24). Early obesity predisposes individuals to chronic conditions such as atherosclerosis and impaired glucose tolerance which have their roots in childhood (25,26). Furthermore, childhood obesity coincides with physical inactivity (27) and an unhealthy diet (28), which together increase the risk of premature mortality (29). The women in our study with a low-to-high BMI trajectory were born thinner, but later their body mass increased. This may indicate that these girls suffered from prenatal malnutrition which has been suggested to program the fetus for developmental plasticity, meaning that a certain genotype can produce different phenotypes depending on the early growth environment in utero (30,31). Prenatal undernutrition causes the fetus to adapt its growth, but later, if faced with excessive nutrition, as observed in the low-to-high BMI trajectory, these adaptations increase the risk of health decline in later life (32). This has been confirmed in several population-based studies (4,5,33–35) and might in part underlie the increased risk of mortality. Cancer has been suggested to have its origins in the prenatal phase of life. Studies have mostly focused on cancers related to the reproductive system such as breast (36) and prostate cancer (37) and found fairly consistent evidence that higher birth weight is associated with a higher prevalence of those cancers in later life. A similar finding was reported for cancers related to the digestive system (38). In an earlier study in this cohort (39), we found that those with a higher ponderal index at birth born to a mother with height below the median were at greater risk of developing lung cancer. Early BMI development in relation to cause-specific cancer mortality has been little studied. In a large Danish study higher birth weight, higher stature at age 14, peak growth at an early age, and lower BMI at age 14 were all associated with an increased prevalence of breast cancer (40). In the present study, the risk of cancer mortality was increased for the women and men whose BMI exceeded the average BMI in childhood and for those women whose BMI was first below but later in childhood
exceeded the average BMI trajectory. The biological mechanisms suggested to be related to a larger size at birth and an increased cancer risk include higher hormonal levels altering the structure of the tissue thus making it more susceptible for later exposure to carcinogens and a greater number of cells at risk of carcinogenesis among those born larger (41). Programming of the insulin-like growth factor system resulting in increased cell proliferation rates which has been further linked to an increased cancer risk has been suggested as another plausible mechanism (42).
Strengths and limitations The strengths of our study include the well-characterized sample and serial measures of body size during infancy and childhood collected from reliable health care records. We were also able to use register-based data on socio-economic position in adulthood and on mortality. Some limitations of the study should be recognized. BMI is not the ideal measure of adiposity in children, but it has been found to be a valid and feasible indirect measure of body fatness (43). We used self-reported weight and height in late adulthood to assess BMI. Although overestimation of height and underestimation of weight has been reported to be likely when using self-reported BMI, it has been shown to be a valid measure in epidemiological studies (44). We were able to compare selfreported and measured weight and height for a random sample of 2000 participants in the cohort and found that the correlation was very high (Pearson correlation 0.97 and 0.99, respectively). In this historical cohort, most individuals were born or grew up during the Second World War (WWII), a time during which families might have suffered from food shortages in Finland. To address this concern, we stratified according to birth year into those born before (1934–1939) and during WWII (1940–1944). There were no differences in the BMI trajectories among men. Among women with an increasing BMI trajectory, more of them had been born during than before WWII (26.8% versus 22.0%). However, although birth weight and weight at age 1 year were comparable with measures in the Hertfordshire Cohort born between 1931 and 1939 in England (45), this should be considered when generalizing these results to younger cohorts.
Conclusion We identified distinct trajectories of early BMI development which were differently associated with the risk of all-cause mortality for women and cancer mortality for men and women in early old age. Among women, having an increased compared to average BMI from infancy to childhood or a lower BMI in infancy and childhood but which later exceeded average BMI was associated with an increased risk of premature mortality. Among men, having an average BMI which then dropped below average increased the risk of cancer mortality. These different findings among men and women warrant further investigation into the etiology of childhood growth and later mortality risk in other cohorts. In conclusion, this piece of information indicates that, particularly for women, a persistently increasing BMI in childhood or higher BMI accompanied by thinness in infancy is likely to shorten the lifespan of the maturing cohorts as they reach older age. Maintaining normal body size from childhood onwards is potentially an important way of tackling health decline in older age. Funding: HBCS was supported by Emil Aaltonen Foundation, Finnish Foundation for Diabetes Research, Novo Nordisk Foundation, Signe and Ane Gyllenberg Foundation, Samfundet Folkhälsan, Finska Läkaresällskapet, Liv och Hälsa, Sigrid
Early body mass index trajectories and mortality 39 Jusélius Foundation. The Academy of Finland supported M.B.v.B. (grant no. 257239); E.K. (grant no. 127437, 129306, 130326, 134791, and 2639249), and J.G.E. (grant no. 129369, 129907, 135072, 129255, and 126775). The research leading to these results has received funding from the European Commission within the 7th Framework Programme (DORIAN, grant agreement no. 278603). Declaration of interest: The authors report no conflicts of interest.
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ORIGINAL ARTICLE
Early life body mass trajectories and mortality in older age: Findings from the Helsinki Birth Cohort Study Mikaela B. von Bonsdorff1, Timo Törmäkangas1, Taina Rantanen1, Minna K. Salonen2,3, Clive Osmond4, Eero Kajantie2,5,6 & Johan G. Eriksson2,3,7,8,9
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1Gerontology Research Center and Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland, 2Division of Welfare and
Health Promotion, Department of Chronic Disease Prevention, Diabetes Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland, 3Folkhälsan Research Centre, Helsinki, Finland, 4MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, United Kingdom, 5Hospital for Children and Adolescents, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland, 6Department of Obstetrics and Gynaecology, Oulu University Hospital and University of Oulu, Oulu, Finland, 7Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland, 8Unit of General Practice, Helsinki University Central Hospital, Helsinki, Finland, and 9Vasa Central Hospital, Vasa, Finland
Background. Overweight and obesity in childhood have been linked to an increased risk of adult mortality, but evidence is still scarce. Methods. We identified trajectories of body mass index (BMI) development in early life and investigated their mortality risk. Data come from the Helsinki Birth Cohort Study, in which 4943 individuals, born 1934–1944, had serial measures of weight and height from birth to 11 years extracted from health care records, weight and height data in adulthood, and register-based mortality data for 2000–2010. Results. Three early BMI trajectories (increasing, average, and average-to-low for men and increasing, average, and low-to-high BMI for women) were identified. Women with an increasing or low-to-high BMI (BMI lower in early childhood, later exceeded average) trajectory had an increased risk of all-cause mortality compared to those with an average BMI trajectory (HR 1.55, 95% CI 1.07–2.23; and HR 1.57, 95% CI 1.04–2.37, respectively). Similar associations were observed for cancer mortality. Among men, BMI trajectories were not associated with all-cause mortality, but those with average-to-low BMI (BMI first similar then dropped below average) had an increased risk of cancer mortality. Conclusions. An increasing BMI in early life may shorten the lifespan of maturing cohorts as they age, particularly among women. Key words: Aging, birth size, body mass index, developmental origins of adult health and disease, growth mixture models, life-course epidemiology, mortality
Introduction Overweight and obesity in childhood (1,2) as well as thinness at birth followed by compensatory increase in body size in childhood (3–5) have been linked to an increased prevalence of
Key messages • Three early body mass trajectories were identified in which the majority of the participants had a similar BMI development pattern in infancy and childhood (average BMI), but two atypical patterns were identified (for men, increasing BMI, and average-to-low BMI; and for women increasing BMI, and low-to-high BMI). • The early BMI trajectories were differently associated with the risk for all-cause and cancer mortality among women and for cancer mortality among men in early old age. • Adult body size did not mediate, nor did socio-economic status in childhood or adulthood or lifestyle factors explain the association between early BMI development and mortality in early old age.
morbidity in later life. However, the association between body size in early life and mortality in later life has been little studied, and it is unclear whether the association is driven by adult body size. Using a single measure of body mass index (BMI weight/[height2]) in childhood, the studies that are available have shown that overweight and obesity were associated with an increased risk of premature mortality in adulthood (6–8). A number of studies have found that overweight and obesity in adolescence and early adulthood increased the risk of mortality (9–12). A recent study in the British 1946 birth cohort (13) found that both high and low compared to normal BMI measured in early adulthood were related to mortality. The same U-shaped association was found for women for body size measured in
Correspondence: Mikaela B. von Bonsdorff, Researcher, PhD, Gerontology Research Center and Department of Health Sciences, University of Jyväskylä, PO Box 35, FI-40014, Finland. E-mail: mikaela.vonbonsdorff@jyu.fi (Received 4 June 2014; accepted 3 September 2014)
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Early body mass index trajectories and mortality 35 childhood and adolescence. The associations between body size in early life and mortality in adulthood were partly explained by adult BMI in some (10,12), but not all (9,13) of the aforementioned studies. In these studies, the risk for subsequent health decline has been reported using predetermined categorization of body size, but so far no study has investigated whether different observed patterns of BMI development in early life predispose an individual to premature mortality in later life. Drawing on the original life-course epidemiology models (14), we will test the ‘critical period model’, where BMI development in early life is associated with later mortality risk and the ‘critical period with later effect modifiers model’, where the association between early BMI development and later mortality is attenuated by adult BMI. We have previously shown in a Finnish birth cohort that individuals who later develop major chronic diseases such as diabetes and coronary heart disease were born thin, they grew more slowly during infancy, and later in childhood they increased in body size compared to the healthy cohort members (4,15). Using these data, the aim of this study was to identify different trajectories of BMI development observed in data spanning from birth to age 11 years, examining whether the risk of all-cause, cardiovascular (CVD), and cancer mortality in early old age was different for these early life BMI trajectories and whether adult body size explained the potential association.
Late adulthood measures Information on weight and height were obtained from postal questionnaires which were sent to the participants at a mean age of 60 years (range 56 to 67 years). Participants’ living habits included information on smoking status (never smoked, former smoker, current smoker), alcohol consumption (does not use, uses at most 2 times per month, uses 3 or more times per month), and physical activity (at least 3 times per week, 2 times per week at most, sedentary). Register data from Statistics Finland was used to indicate adult socio-economic status. The highest occupational status at 5-year intervals between 1970 and 2000 was coded as upper middle class, lower middle class, self-employed, and manual workers (19).
Mortality Dates and causes of death from 11 November 2000 to 31 December 2010 were obtained from the Finnish National Death Register. Survival time was calculated as the number of days between date of birth and death or end of the follow-up in December 2010, whichever happened first. International Classification of Disease (ICD) codes for cardiovascular mortality included 400–499 in the ICD 9th revision and I00–I99 in the ICD 10th revision, and for cancer mortality the codes 140–239 in the ICD 9th revision and C00–C97 ICD 10th revision.
Statistical analyses
Materials and methods Study population The Helsinki Birth Cohort Study (HBCS) comprises 13,345 individuals born in Helsinki, Finland, at Helsinki University Central Hospital or Helsinki City Maternity Hospital between 1934 and 1944 for whom data on body anthropometrics in childhood have been retrieved from several health care records (5,16). There were on average 17 measurements on body size available for each individual from birth to school age (17). In the year 2000, a postal questionnaire was sent to 10,530 members of the cohort who were alive and living in Finland at that time, and, of these, 6874 (65.6%) answered. In the present paper, analyses were restricted to the 4943 (71.9%) individuals who had weight and height data available at birth, at age 11 years, and in late adulthood. These members of the cohort were similar to the other people in the original HBCS cohort in body size at birth, length of gestation, maternal BMI, and father’s socio-economic position. The study was approved by the Ethics Committee of Epidemiology and Public Health of the Hospital District of Helsinki and Uusimaa and that of the National Public Health Institute, Helsinki.
Infant and childhood measures Birth date, weight, and length of the newborns were retrieved from the hospital birth records, and infancy and childhood weight and height from child welfare clinic and school health care records, described in detail previously (4,5,18). Date of the mothers’ last menstrual period prior to pregnancy was also extracted from the hospital birth records and used to calculate gestational age. Information on maternal weight and height during late pregnancy was also extracted from the birth records. Childhood socio-economic status was ascertained based on father’s highest occupation status extracted from birth, child welfare, and school health care records, coded as upper middle class, lower middle class, and manual workers based on the original social classification system issued by Statistics of Finland (19).
Analyses were conducted separately for men and women because of previous findings on gender differences in early growth and development and BMI in adulthood (13,20). Each BMI measure was converted to a Z score, and the successive Z scores were interpolated with a piecewise linear function for every month from birth to age 2 years and from 2 to 11 years for every birthday. The Z scores were back-transformed to obtain the corresponding BMI (4,5). Patterns of early body size development were determined by fitting latent class growth mixture models (GMM) to all available BMI data spanning from birth to school age using Mplus version 7.0 (21). In the analyses, the aim was to capture unobserved subpopulations (latent groups) with similar body size development but distinct across the latent groups over time, which each have their own growth parameters, intercept, and slope. We estimated the quadratic and cubic shapes of the trajectories, in order to identify all potential differences in early BMI development. We used several model fit indices to determine the optimal number of latent groups (21). In the Bayesian Information Criterion (BIC) and Akaike Information Criterion (AIC), lower values indicate a better fit of the model, and clarity of classification into trajectory classes was assessed with 1) high percentage of individuals falling into the latent class based on the posterior probabilities; and 2) high model entropy, which ranges between 0 and 1, with scores near 1 indicating clear classification (21). GMM yielded three early BMI trajectories for both men and women. These were named increasing BMI, average BMI, and average-to-low BMI for men; and increasing BMI, average BMI, and low-to-high BMI for women. Baseline characteristics of the participants were tested across the BMI trajectory classes using chi-square test for categorical variables and analysis of variance for continuous variables. Using Cox proportional hazards models we estimated mortality hazards and their 95% confidence intervals for early BMI trajectories and all-cause, CVD, and cancer mortality in early old age using the group ‘average BMI’ as the reference category. The proportional hazards assumption was assessed using a test based on scaled Schoenfeld residuals. We first made adjustment for age and then for socio-economic status
M. B. von Bonsdorff et al. Women 19 18 17 16 15 Average BMI 59.0% Increasing BMI 25.4% Low-to-high BMI 15.6%
14 13 0
1
2
3
4
5
6
7
8
9
10
11
Years
Figure 2. Observed mean BMI values for early BMI development trajectories from growth mixture models for women in the Helsinki Birth Cohort Study, n 2574.
Results Altogether 52.1% of the study members were women, and the participants were on average 59.6 years (SD 2.7, range 56 to 67 years) when their BMI was assessed. During the 10-year follow-up, 460 (9.3%) individuals died, of whom 302 were men and 158 women. Of the cohort members, 174 died of cancer (main diagnoses were malignancies of digestive organs and lung cancer) and 142 of cardiovascular disease. Average age at death was 69.6 years (SD 2.9) for men and 69.2 years (SD 3.1) for women. We used the Bayesian Information Criterion (BIC) to define the best model fit for the data indicating the optimal number of latent classes, i.e. early BMI trajectories, in the study population. BIC was lowest for the three class solution indicating the optimal number of classes for both genders. Average membership probabilities in the three latent classes ranged between 0.69 and 0.91. Model entropy was 0.73 for men and 0.54 for women. The early BMI trajectories, presented in Figures 1 and 2, were named for men ‘increasing BMI’ (6.4% of men belonged to this class), ‘average BMI’ (66.7%), and ‘average-to-low BMI’ (26.9%); and for women ‘increasing BMI’ (25.4% of the women belonged to this class), ‘average BMI’ (59.0%), and ‘low-to-high BMI’ (15.6%).
Men 20 19 18 BMI (kg/m2)
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in childhood and adulthood and lifestyle factors (smoking, alcohol consumption, and physical activity). Finally we added adult BMI and the quadratic term (because of the known U-shaped association of BMI in adulthood and premature mortality (22)) into the analyses to test whether it mediated the association between early life BMI development and mortality in early old age. In order to obtain a data set with complete data on all main variables and covariates, we imputed values for covariates where data were missing using multiple imputations (childhood socio-economic status n 47, adult socio-economic status n 18, smoking status n 30, alcohol consumption n 21, physical activity n 34). A total of 20 imputed data sets were created using all variables in the analyses. Cox models were first performed using complete data available for all main variables and covariates and then using the multiply imputed data sets, with the effect estimates combined using Rubin’s rules. While the results were largely the same, we present findings on imputed data.
BMI (kg/m2)
36
17 16 15 Average BMI 66.7% Increasing BMI 6.4% Average-to-low BMI 26.9%
14 13 0
1
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5 6 Years
7
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Figure 1. Observed mean BMI values for early BMI development trajectories from growth mixture models for men in the Helsinki Birth Cohort Study, n 2369.
Men with increasing BMI had lower BMI during the first three months of life, but after that it increased consistently compared to the ones with average BMI. Men with average-to-low BMI had similar BMI during infancy to those with average BMI, but at age 2 years it dropped below the average BMI. Women with increasing BMI had similar BMI to those with average BMI during the first 6 months, after which their BMI was consistently higher. Women with low-to-high BMI had lower BMI in infancy and early childhood, but around age 8 their BMI increased and was consistently higher compared to those with an average BMI. We identified differences in the characteristics of the participants according to early BMI trajectories, presented in Table I. Maternal BMI was lowest for men with average-to-low BMI (P 0.001). Men and women with an increasing BMI trajectory had the highest BMI in adulthood (P 0.049 and P 0.001, respectively). There were few differences in socio-economic or lifestyle factors in adulthood according to early BMI trajectories. Hazard ratios from the Cox models revealed that all-cause mortality did not differ according to early BMI trajectories among men. For women, compared to those with average BMI, the hazard was higher for those with increasing BMI and for those with low-to-high BMI (HR 1.67, 95% CI 1.15–2.41; and HR 1.58, 95% CI 1.03–2.41, respectively) (Table II). Adjustment for socio-economic status in childhood and adulthood and lifestyle factors did not attenuate this association. To test whether body mass in adulthood explained the association between early BMI development and mortality in early old age, we made adjustment for BMI at an average age of 60, but it did not attenuate the associations for women; the hazard was higher for those with increasing BMI and for those with low-to-high BMI (HR 1.61, 95% CI 1.12–2.31; and HR 1.58, 95% CI 1.05–2.37, respectively), compared to the average BMI trajectory. There were no differences in the hazards for cardiovascular mortality according to early BMI trajectories (results not shown). For cancer mortality, the hazards were higher among men with average-to-low BMI (HR 1.60, 95% CI 1.05–2.42) compared to those with average BMI. Among women the hazards were higher for those with increasing BMI and low-to-high BMI (HR 1.85, 95% CI 1.08–3.18; and HR 2.71, 95% CI 1.58–4.66, respectively). Adjustment for socio-economic and lifestyle confounders and adult BMI did not attenuate these associations (Table II). Furthermore, we adjusted the models for gestational age and found few differences in the associations.
Early body mass index trajectories and mortality 37 Table I. Characteristics of the study population (mean and standard deviation unless stated otherwise) according to early BMI trajectories.
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BMI trajectories for men
Birth and childhood characteristics Gestational age (weeks) Father’s highest occupational status, % Upper middle Lower middle Manual worker Adulthood characteristics Age at data collection in 2000 Body mass index Highest occupational status in adulthood, % Upper middle Lower middle Self-employed Manual worker Smoking status, % Never Former Current Alcohol consumption, % None 2 times per month at most 3 or more times per month Level of physical activity, % Sedentary Moderate 2 times/week at most Moderate 3 times/week or more aComparisons
Increasing BMI n 152
Average BMI n 1579
38.8 (2.0)
39.4 (1.8)
39.4 (1.8)
20.8 20.1 59.1
19.5 26.5 54.0
18.1 23.1 58.7
59.6 (2.4) 27.22 (3.84)
59.5 (2.6) 26.79 (4.06)
59.8 (2.8) 26.44 (3.84)
20.8 24.8 10.1 44.3
17.9 27.3 10.6 44.2
15.9 28.4 10.4 45.4
30.9 44.7 24.3
26.9 44.4 28.7
23.9 45.9 30.2
11.2 37.5 51.3
8.7 27.9 63.4
7.5 29.6 62.9
13.3 44.0 42.7
11.1 42.4 46.5
11.7 39.6 48.7
BMI trajectories for women
Average-to-low BMI n 638 P valuea 0.001 0.171
0.114 0.049 0.83
Increasing BMI n 653
Average BMI n 1520
Low-to-high BMI n 401 P valuea
39.5 (1.8)
39.4 (1.8)
39.3 (1.8)
14.3 25.9 59.8
16.9 23.6 59.5
14.9 24.2 60.9
59.4 (2.5) 27.78 (5.21)
59.7 (2.8) 60.2 (3.0) 0.001 26.12 (4.68) 26.78 (4.72) 0.001 0.126 10.4 8.3 56.9 56.6 7.5 9.3 25.2 25.8 0.403 52.7 50.9 25.5 28.6 21.8 20.6 0.588 8.9 8.2 50.1 51.6 41.0 40.1 0.331 13.4 11.3 42.8 42.4 43.8 46.4
11.1 50.8 9.4 28.7 0.337 51.2 24.4 24.4 0.044 10.8 50.3 38.9 0.604 12.0 39.7 48.3
0.178 0.501
for categorical variables performed with chi-square test and for continuous variables with analyses of variance.
Discussion To our knowledge this is the first study to investigate the association between early BMI development across infancy and childhood and all-cause and cause-specific mortality in early old age in a well-characterized birth cohort. The majority of the participants had a similar BMI development pattern in infancy and childhood which we named average BMI, but two atypical patterns were identified. For both men and women we found an early BMI trajectory which increased and, for men, one in which BMI was similar during infancy but later dropped below the average BMI trajectory and, for women, one in which BMI was lower in infancy and childhood but later exceeded the average trajectory. We found that the observed early BMI development patterns were associated with all-cause mortality about 70 years later among women but not men. The mortality rate was higher for cohort members who did not participate in data collection in the year 2000 than for those who did (27.4% versus 9.3%,
respectively) suggesting potentially that mortality related to atypical BMI development trajectories occurred at earlier ages and was not recorded. Given that mortality in early adulthood is higher among men than women this might partly account for the lack of association observed among men for all-cause mortality. Our findings among women are in line with those reported by Strand et al. (13) in the British 1946 birth cohort, where they found an association between BMI measured at the age of 4 years and mortality, which was not explained by adult body size. Other findings among women have shown that high BMI in adolescence increased the risk of mortality which was not explained by later BMI, supporting our findings (10). Our results, however, contrast those reporting that the increased risk of mortality in older age among those with high BMI in adolescence was mediated by adult BMI (12). Interestingly, we found that early BMI development was associated with cancer mortality among women and men which was not explained by socio-economic status and lifestyle factors or adult BMI. We did not find an
Table II. Hazard ratios (HR) and 95% CIs for all-cause and cancer mortality according to early BMI trajectories in the Helsinki Birth Cohort Study, n 4943. All-cause mortality
Men, Early BMI trajectories Average BMI Increasing BMI Average-to-low BMI Women, Early BMI trajectories Average BMI Increasing BMI Low-to-high BMI
Cancer mortality
Model 1 HR (95% CI)
Model 2 HR (95% CI)
Model 3 HR (95% CI)
Model 1 HR (95% CI)
Model 2 HR (95% CI)
Model 3 HR (95% CI)
ref. 0.86 (0.53–1.42) 0.98 (0.76–1.27)
ref. 0.87 (0.53–1.42) 0.95 (0.73–1.23)
ref. 0.87 (0.53–1.42) 0.95 (0.73–1.23)
ref. 0.73 (0.26–2.01) 1.60 (1.05–2.42)
ref. 0.73 (0.44–1.23) 1.55 (1.02–2.35)
ref. 0.73 (0.43–1.22) 1.55 (1.03–2.34)
ref. 1.61 (1.12–2.31) 1.58 (1.05–2.37)
ref. 1.55 (1.08–2.23) 1.57 (1.04–2.37)
ref. 1.55 (1.07–2.23) 1.57 (1.04–2.37)
ref. 1.85 (1.08–3.18) 2.71 (1.58–4.66)
ref. 1.79 (1.04–3.06) 2.72 (1.59–4.67)
ref. 1.73 (1.00–2.98) 2.70 (1.56–4.67)
Model 1 adjusted for age at data collection in 2000; Model 2 adjusted for Model 1 socio-economic status in childhood and adulthood, smoking, alcohol consumption, and physical activity; Model 3 adjusted for Model 2 BMI and quadratic term at average age of 60. BMI body mass index.
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38
M. B. von Bonsdorff et al.
association between early BMI development trajectories and cardiovascular mortality, although other papers using this cohort have found that those who had been small at birth, thin in infancy, but gained thereafter weight had an increased risk of coronary events (4). The present lack of an association might be attributable to the small number of individuals who died of cardiovascular causes, e.g. 1.3% of the women in our analyses died of cardiovascular causes, and the fact that men who had a high risk of CVD might have died before reaching the average age of 60 years and were thus not included in this study. Most previous studies have used a single measure of BMI in childhood or adolescence with a-priori defined categories for BMI, whereas we identified observed patterns of BMI development from birth to childhood. A similar type of modeling has been used in younger cohorts with serial measures of body size to identify developmental patterns of body size in childhood and to study underlying factors (23), but the predictive value of these patterns on older age health outcomes cannot yet be investigated while those cohorts are too young. In the present study, boys on an average-to-low trajectory had an average BMI until age two but then became thinner compared to boys on the average BMI trajectory. Girls on the low-to-high BMI trajectory were thinner during infancy and early childhood but later increased in body mass exceeding the average BMI trajectory. The girls who had an increasing or low-to-high BMI trajectory had higher BMI in adulthood compared to those with an average BMI trajectory, whereas the same was true for boys with an increasing BMI trajectory. This is in line with findings on the increased risk of later obesity among those with larger body size in infancy or of those who were born thin but later grew fast (24). Early obesity predisposes individuals to chronic conditions such as atherosclerosis and impaired glucose tolerance which have their roots in childhood (25,26). Furthermore, childhood obesity coincides with physical inactivity (27) and an unhealthy diet (28), which together increase the risk of premature mortality (29). The women in our study with a low-to-high BMI trajectory were born thinner, but later their body mass increased. This may indicate that these girls suffered from prenatal malnutrition which has been suggested to program the fetus for developmental plasticity, meaning that a certain genotype can produce different phenotypes depending on the early growth environment in utero (30,31). Prenatal undernutrition causes the fetus to adapt its growth, but later, if faced with excessive nutrition, as observed in the low-to-high BMI trajectory, these adaptations increase the risk of health decline in later life (32). This has been confirmed in several population-based studies (4,5,33–35) and might in part underlie the increased risk of mortality. Cancer has been suggested to have its origins in the prenatal phase of life. Studies have mostly focused on cancers related to the reproductive system such as breast (36) and prostate cancer (37) and found fairly consistent evidence that higher birth weight is associated with a higher prevalence of those cancers in later life. A similar finding was reported for cancers related to the digestive system (38). In an earlier study in this cohort (39), we found that those with a higher ponderal index at birth born to a mother with height below the median were at greater risk of developing lung cancer. Early BMI development in relation to cause-specific cancer mortality has been little studied. In a large Danish study higher birth weight, higher stature at age 14, peak growth at an early age, and lower BMI at age 14 were all associated with an increased prevalence of breast cancer (40). In the present study, the risk of cancer mortality was increased for the women and men whose BMI exceeded the average BMI in childhood and for those women whose BMI was first below but later in childhood
exceeded the average BMI trajectory. The biological mechanisms suggested to be related to a larger size at birth and an increased cancer risk include higher hormonal levels altering the structure of the tissue thus making it more susceptible for later exposure to carcinogens and a greater number of cells at risk of carcinogenesis among those born larger (41). Programming of the insulin-like growth factor system resulting in increased cell proliferation rates which has been further linked to an increased cancer risk has been suggested as another plausible mechanism (42).
Strengths and limitations The strengths of our study include the well-characterized sample and serial measures of body size during infancy and childhood collected from reliable health care records. We were also able to use register-based data on socio-economic position in adulthood and on mortality. Some limitations of the study should be recognized. BMI is not the ideal measure of adiposity in children, but it has been found to be a valid and feasible indirect measure of body fatness (43). We used self-reported weight and height in late adulthood to assess BMI. Although overestimation of height and underestimation of weight has been reported to be likely when using self-reported BMI, it has been shown to be a valid measure in epidemiological studies (44). We were able to compare selfreported and measured weight and height for a random sample of 2000 participants in the cohort and found that the correlation was very high (Pearson correlation 0.97 and 0.99, respectively). In this historical cohort, most individuals were born or grew up during the Second World War (WWII), a time during which families might have suffered from food shortages in Finland. To address this concern, we stratified according to birth year into those born before (1934–1939) and during WWII (1940–1944). There were no differences in the BMI trajectories among men. Among women with an increasing BMI trajectory, more of them had been born during than before WWII (26.8% versus 22.0%). However, although birth weight and weight at age 1 year were comparable with measures in the Hertfordshire Cohort born between 1931 and 1939 in England (45), this should be considered when generalizing these results to younger cohorts.
Conclusion We identified distinct trajectories of early BMI development which were differently associated with the risk of all-cause mortality for women and cancer mortality for men and women in early old age. Among women, having an increased compared to average BMI from infancy to childhood or a lower BMI in infancy and childhood but which later exceeded average BMI was associated with an increased risk of premature mortality. Among men, having an average BMI which then dropped below average increased the risk of cancer mortality. These different findings among men and women warrant further investigation into the etiology of childhood growth and later mortality risk in other cohorts. In conclusion, this piece of information indicates that, particularly for women, a persistently increasing BMI in childhood or higher BMI accompanied by thinness in infancy is likely to shorten the lifespan of the maturing cohorts as they reach older age. Maintaining normal body size from childhood onwards is potentially an important way of tackling health decline in older age. Funding: HBCS was supported by Emil Aaltonen Foundation, Finnish Foundation for Diabetes Research, Novo Nordisk Foundation, Signe and Ane Gyllenberg Foundation, Samfundet Folkhälsan, Finska Läkaresällskapet, Liv och Hälsa, Sigrid
Early body mass index trajectories and mortality 39 Jusélius Foundation. The Academy of Finland supported M.B.v.B. (grant no. 257239); E.K. (grant no. 127437, 129306, 130326, 134791, and 2639249), and J.G.E. (grant no. 129369, 129907, 135072, 129255, and 126775). The research leading to these results has received funding from the European Commission within the 7th Framework Programme (DORIAN, grant agreement no. 278603). Declaration of interest: The authors report no conflicts of interest.
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