Objective: To study whether the effect of size at birth on the risk of ischaemic heart disease (IHD) death is modified by social circumstances in childhood or in adulthood.
Design: A cohort study. Data on circumstances at birth were retrieved from archived obstetric records, social characteristics in adulthood and mortality follow-up through routine registers.
Participants: 6159 men and 5663 women who were born in Uppsala University Hospital, Sweden (the Uppsala Birth Cohort) during 1915–1929, were singleton births with more than 30 weeks of gestational age and were alive in 1961. Follow-up time 1961–2002 (from age 31–46 to 73–88 years).
Main outcome measure: Death from IHD. Multivariate Cox regression with age as the time scale, controlling for year of birth and stratified by gender.
Results: The risk of IHD death was lower among men and women with higher weight for gestational age. Lower social class in adulthood was associated with a higher risk of IHD death. The effect of size at birth on IHD mortality did not appear to be modified by social class at birth but was only present in men of higher social class in adulthood (hazard ratio per 1 SD weight for gestational age 0.84, 95% CI 0.75 to 0.93).
Conclusions: Weight for gestational age was inversely associated with the risk of IHD death in men and women; this effect was present in men of non-manual adult social class only but did not appear to be modified by adult social class in women or by social class at birth in either men or women.
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There is now a body of evidence suggesting that early life growth and development have an effect on the risk of disease in adult life. A number of studies have found that impaired foetal growth is related to a higher risk of cardiovascular disease.1–6 The “developmental origins of health and disease” concept7 8 has major biological, medical and social implications and illustrates the importance of life-course and intergenerational influences in shaping people’s health.
Little information is available about how these biological mechanisms interact with social and economic circumstances. In particular, it is unclear how far early life influences can be moderated or ameliorated by, for example, upward social mobility and improved socioeconomic circumstances in adult life. It is also conceivable that changes in early growth may affect vulnerability to the effects of living standards in adult life.9 These questions are relevant for an understanding of the aetiology of health inequalities and can help to uncover possibilities for designing targeted prevention strategies conditional on individual and family histories. Longitudinal studies with prospective social and biological information collected in childhood and adulthood are needed to test these hypotheses.
Barker et al9 have examined the interplay between early growth and living conditions in a cohort of Finnish men born between 1934 and 1944. Their findings indicate that men of low social class or low household income in adult life had increased rates of coronary heart disease and that these effects were stronger in men who were thin at birth. The effects of low social class were also greater in those who had accelerated weight gain between the ages of one and 12 years.9 In another Finnish study, childhood growth had large effects on the risk of later hypertension in children living in poor social conditions, whereas living conditions in adult life did not affect the risk of hypertension.10
In our cohort of Swedish men and women born between 1915 and 1929 (the Uppsala Birth Cohort; UBCoS) we have previously demonstrated associations of size at birth and foetal growth rate, in particular with ischaemic heart disease (IHD).6 11 Impaired foetal growth rate was also associated with incident haemorrhagic stroke but not with occlusive stroke in UBCoS men.12 On the other hand, among UBCoS women, birth size adjusted for gestational age was positively associated with rates of breast cancer in premenopausal women13 and analyses of other cancer sites showed positive associations of birth weight for gestational age with digestive cancers and lymphatic cancers in both men and women.14 The associations of size at birth with circulatory disease or cancer incidence and mortality did not appear to be confounded by social characteristics.6 11–15
UBCoS men who were born outside marriage had an elevated risk of IHD mortality at 55–80 years of age, independent of social class of origin, with an extremely high mortality risk among those men born outside marriage who never married as adults.16 17 The strength of associations of social class at birth with mortality from stroke was greater than with mortality from IHD; the latter appeared to be more strongly influenced by adult social circumstances (car ownership and disposable income).18 The effects of social characteristics on circulatory disease appeared to be independent of size at birth.16–18
None of the earlier analyses of the UBCoS data explored how the socioeconomic environment during different stages of the life course of individuals interacts with adverse early life growth to determine disease risk in adult life. The aim of our current analysis was to explore whether the strength of the association of size at birth with mortality from IHD in men and women is modified by social circumstances at birth and in adulthood, or whether it is disproportionately affecting subjects who experienced social mobility.
MATERIALS AND METHODS
The analysis is based on a cohort born in the Uppsala University Hospital, Sweden during 1915–1929 (The Uppsala Birth Cohort; www.chess.su.se/ubcosmg). The original cohort consisted of 14 193 live births and was representative of the Uppsala region and Sweden in 1915–1929 in terms of infant mortality, with a slightly higher proportion of births to single mothers.19 20 Nearly all births have been successfully traced through parish archives and are being regularly linked to census, death and other registries.15 Our analysis is restricted to singletons born at 30 or more completed weeks of gestation and alive in 1961 when the Swedish mortality register was initiated (n = 11 827). The subjects were followed up from 1961 to 2002 (from ages 31–46 up to 73–88 years).
From the birth records we have extracted birth weight, birth length and gestational age based on the last menstrual period, mother’s marital status, age and parity and occupational status of the head of the household. Gender-specific z-scores of birth weight for each week of gestation were calculated using the whole cohort as a reference. The ponderal index (birth weight/birth length3, mean = 26.2 kg/m3 and SD 2.6 kg/m3 in the cohort) was used as an alternative measure of size at birth (studied as a continuous variable and later grouped as <26 kg/m3 versus 26+ kg/m3). Size at birth for gestational age is a marker of the growth rate of the foetus in utero, the ponderal index measures the thinness of the infant at birth. Social class at birth, defined by the occupational status of the head of the household was grouped as non-manual, self-employed (including farmers), manual and other (no occupation or occupation could not be coded).
Social class based on occupation recorded in the 1960 census was classified into four categories similar to childhood social class: non-manual; self-employed (including farmers); manual and other (no occupation or occupation could not be coded). As the self-employed and other categories represent small and heterogeneous groups, analyses concerning social mobility were restricted to the non-manual and manual class: 8813 individuals at birth and 9312 in the 1960 census; 7196 individuals if combined. Income was not recorded in the 1960 census.
Personal earned gross income and household total gross income from the 1970 census were used in the analysis and grouped into gender-specific quartiles; those with zero personal income were treated as a separate group (1671 individuals; 25.8% women and 4.5% men); 138 individuals with zero household income were excluded from the analysis. Occupational social class was not recorded in the 1970 census.
Data on deaths and emigrations were obtained by linkage to the population and death registers. We studied the associations of foetal growth rate and length of gestation with the risk of death from IHD (International Classification of Diseases 7: 420–422; 8 and 9: 410–414; 10: I20–25) as the underlying or immediate cause of death. The results of analyses restricted to IHD as the underlying cause of death were consistent with those presented here.
Cox’s proportional hazards models with age as the time scale, controlling for year of birth (5-year intervals), were run in Stata/SE 9.2 for Windows (Stata Corp, College Station, Texas, USA). First we examined separately the effect of size at birth measured as standardised birth weight or ponderal index on IHD mortality and the effect of childhood and adulthood social class on IHD mortality. Second, we explored whether the association of size at birth and IHD death is modified by social class either in childhood or adulthood or by social mobility. Finally, we attempted to replicate findings by Barker et al9 and explored a potential interaction between the ponderal index at birth and adult income. The follow-up period was from 1961 to 2002, except for the analyses including income for which the follow-up was from 1970 to 2002.
The proportion of missing data was small; gestational age was the variable with the largest number of missing observations (n = 328). The sample size available for analysis including both birth information and social characteristics from the census was 11 147 (nearly 95% of those eligible for the study). Those with missing information did not differ significantly from the rest of the cohort with respect to social characteristics at birth, birth weight or IHD mortality.
There were 1531 IHD deaths (1111 men and 420 women) in the cohort between 1961 and 2002. The mean age at death from IHD was 68.8 (SD 9.2) years for men and 72.5 (SD 8.4) years for women.
Size at birth
The risk of IHD death was lower among men and women with higher birth weight for gestational age: age and cohort adjusted hazard ratios were 0.91 (95% confidence interval (CI) 0.85 to 0.96) per SD increase in standardised birth weight for men and 0.88 (95% CI 0.80 to 0.98) for women. The relationship was well approximated by a linear model. Controlling for parity, mother’s age and marital status changed the results only slightly (hazard ratios 0.90 with 95% CI 0.85 to 0.96 and 0.87 with 95% CI 0.78 to 0.96, respectively). The ponderal index was not associated with IHD mortality. Age and period-adjusted hazard ratios for mortality from IHD in subjects with a ponderal index of 26+ kg/m3 compared with those with a ponderal index less than 26 kg/m3 were 0.95 (95% CI 0.84 to 1.07) in men and 0.90 (95% CI 0.74 to 1.09) in women.
Childhood social class
Mean birth weight was highest in those born to the self-employed class among both men and women (3639 g (SD 521) and 3475 g (SD 529), respectively) and was lowest in the group of “others” (3395 g (SD 480) and 3277 g (SD 477)). The means were virtually equal for the non-manual and manual class (3505 g (SD 495) and 3508 g (SD 504), respectively, for men and 3364 g (SD 490) and 3402 g (SD 494) for women). The groups differed in the distribution of maternal age and parity; after adjusting for these factors, mean birth weight was highest in those born into the non-manual class, followed by self-employed, manual and other. Similar results were observed for the association between social class at birth and ponderal index (data not shown). There was a slight, statistically not significant, tendency in both men and women towards the manual class and others having a higher risk of IHD (table 1).
Adulthood social class and income
IHD mortality showed a statistically significant association with adulthood social class in men (p<0.001) but not in women. Men in the manual class ran a 28% higher risk of IHD death than men in the non-manual class (table 1). There was a clear trend in IHD mortality according to personal earned gross income and household total gross income among men (both p values <0.001) with a higher income being associated with a lower risk of IHD death. Among women, a similar trend was seen only for household total gross income (p = 0.005; table 1).
What is already known on this subject
People who grow slowly in utero have an increased risk of coronary heart disease
Socioeconomic circumstances during both childhood and adulthood contribute to adult coronary heart disease mortality
It has been found that the effects of low household income in adult life on coronary heart disease mortality are stronger in men who were thin at birth
Interactions between size at birth and social characteristics
We found a significant interaction between the standardised birth weight for gestational age and social class in adulthood in their effect on IHD mortality among men (p = 0.031, fig 1). Birth weight had a strong effect on IHD mortality in men of the non-manual class (hazard ratio 0.84 with 95% CI 0.75 to 0.93 per SD increase in standardised birth weight) but no significant effect in men of the manual class. There was no interaction between birth weight and social class at birth for men and no interaction between birth weight and social class either at birth or in adulthood for women.
Having found that the effect of size at birth for gestational age among men was stronger in the non-manual than in the manual adult class, we continued to study a potential interaction between size at birth and social mobility. Four social trajectories were considered: stable high (non-manual in childhood and in adulthood); stable low (manual in childhood and in adulthood); upward mobile (manual in childhood and non-manual in adulthood) and downward mobile (non-manual in childhood and manual in adulthood). No evidence of an interaction between size at birth and social mobility was found in our data (table 2).
Analysis of personal or household income as an indicator of adulthood socioeconomic position and ponderal index as a measure of size at birth did not indicate a statistically significant interaction in their effect on IHD (table 3). In order to replicate the analysis performed by Barker et al,9 we also studied the effect of adult income on IHD mortality, stratified by ponderal index at birth (table 4). When comparing the linear trends in IHD mortality over categories of personal income, we noted a significant interaction: men with a lower ponderal index showed a steeper trend in IHD mortality by adult income than men with a higher ponderal index (p = 0.041). Although the linear trend in IHD mortality across categories of household income appeared slightly stronger among women with a high ponderal index, the difference in women was not statistically significant (table 4).
What this paper adds
The association between weight for gestational age and the risk of death from IHD was stronger in men of the non-manual adult social class but did not appear to be modified by adult social class in women or by social class at birth in either men or women
It is of importance to promote the health and nutrition of women of reproductive age in order to prevent IHD in the next generation
Weight for gestational age was inversely associated with the risk of death from IHD in men and women aged 31–88 years; this effect was present only in men of the non-manual adult social class but did not appear to be modified by adult social class in women or by social class at birth in either men or women. There was also a suggestion that the effect of adult income on IHD death in men may be stronger in those who had a lower ponderal index at birth.
The analysis was based on a large, well defined and representative cohort born in Sweden at the beginning of the 20th century, with an almost complete mortality follow-up. Birth records from the Uppsala Academic Hospital comprise a comprehensive record of all deliveries in the hospital since the 1870s. It is, however, plausible that a measurement of social class taken later during the childhood might have generated stronger associations of childhood social class with later IHD mortality. It is also likely that there was a degree of misclassification in the adult social characteristics of the study subjects, probably more so for women and older study subjects. The exclusion of a small proportion of men and women who did not participate in the census is unlikely to bias the results seriously.
We saw a strong association of standardised birth weight with IHD mortality, whereas there were no associations between the ponderal index and the risk of IHD death. Mean birth weight was similar in the manual and non-manual class, with a clear gradient from higher birth weight in more advantaged social classes to lower birth weight among the disadvantaged social classes apparent after adjustment for parity and mother’s age. Although it is plausible that mechanisms leading to low birth weight differ to some extent between social groups, controlling for parity, mother’s age and marital status in the analysis did not change our results. Whether the effect of small body size at birth on later cardiovascular disease is modified by the path of childhood growth,2–5 9 10 21 22 adult obesity23 24 or other cardiovascular risk factors, could not be investigated, as our data did not contain information on risk factors for cardiovascular disease or anthropometric measurements in childhood or adulthood.
An inverse association between childhood and adult socioeconomic conditions and cardiovascular disease mortality has been found in a number of studies.9 10 21 25–28 Recent systematic reviews concluded that the relative contribution of childhood and adult circumstances varies among specific circulatory outcomes. There was a suggestion of a particularly strong influence of childhood conditions on stroke, whereas coronary heart disease appeared to be associated with both childhood and adult socioeconomic circumstances.25 26 In our study, social class at birth showed only a weak, non-significant, inverse association with IHD mortality. There was an inverse association between adult social class and IHD risk for men, but no significant association for women.
There are only a small number of published studies of interactions between size at birth and socioeconomic position, all based on data from Finland.9 10 22 Although we did not see a statistically significant effect of the ponderal index at birth on IHD mortality, there was some consistency in that both in our study and a Finnish cohort9 the effect of adult income on IHD death appeared stronger among men with a history of a lower ponderal index. On the other hand, the interaction effects of social class and size at birth on IHD mortality found in our Swedish cohort have not been reported previously. It is important to note that the two cohorts may not be directly comparable as living conditions in the two neighbouring countries differed during the 20th century. A large proportion of the Finnish cohort experienced the effects of World War II at a young age or were born during the war. Moreover, the follow-up time for the Swedish cohort was longer, with a higher mean age at the end of follow-up. Lawlor et al27 studied whether the effects of family socioeconomic position at birth on cardiovascular disease risk were mediated via intrauterine growth in a Scottish cohort but no results about effect modification were reported.
Despite the fact that evidence on the foetal and early postnatal origins of cardiovascular diseases is largely based on studies of men, there are other studies documenting gender differences in the strength and pattern of observed associations.2 4 22 Most recently, such differences have been interpreted as evidence for female foetuses being less vulnerable to undernutrition in utero and better able to sustain postnatal growth in adverse environments than male foetuses.5 On the other hand, Lawlor et al29 did not find any evidence of gender difference in the association between birth weight and systolic blood pressure in later life in their meta-analysis of published studies.
We found similar associations in men and women between birth weight standardised for gestational age and IHD mortality; however, the effect of adulthood social class was weaker among women than among men and the effect modification of size at birth by social class on IHD mortality was present in men only. Interestingly, greater socioeconomic variation in coronary events in women compared with men has been reported from studies using educational level30 and socioeconomic deprivation31 as a measure of socioeconomic position. On the other hand, no gender differences were seen in a study of social class and atherosclerosis.32 It is likely that changing social gradients in health behaviours have also affected our results. During the last 20–30 years of the 20th century, Sweden experienced decreasing gender differences in smoking prevalence,33 accompanied by growing inequality in smoking habits between those with high and low levels of education,34 as well as an equalisation and reversal of the social gradient in alcohol consumption.35 To what extent the effects of social class on IHD are mediated by smoking in our cohort is not known.
It is possible that size at birth conditional on anthropometric characteristics of the parental generation is a better predictor of the risk of disease in later life. If so, a stronger effect of size at birth in those of higher childhood (rather than adult) social class would be expected as body size tends to be greater among those in higher social classes and is positively correlated with the birth weight of the offspring. The stronger effect of standardised birth weight on IHD among men of the adult non-manual class was thus an unexpected finding. On the other hand, the effect of size at birth may be more pronounced in the higher adult social class if other cardiovascular risk factors are more prominent among the lower class, thus rendering the effect of size at birth relatively unimportant in that group. Based on the previously proposed theories of status incongruence and rapid cultural change,36 37 it is also possible that high social status might be associated with specific stresses and challenges that disproportionately affect subjects with a history of impaired early growth.
The consistency of findings on increased vulnerability to the effects of low adult income in men whose ponderal index at birth was low9 merits further exploration of the mechanisms behind this statistical interaction. In line with Barker et al,9 we would also like to propose that mechanisms involving programming of the hypothalamo–pituitary–adrenal axis in utero,38 combined with the psychosocial consequences of perceived low social status,39 might underlie this interaction.
We conclude that the effect of birth weight for gestational age on death from IHD in men was most pronounced among those of the non-manual social class in adulthood. Our findings do not support the hypothesis that the impact of impaired foetal growth on IHD is potentiated by lower social class in adulthood. Whether and how a low ponderal index at birth can increase men’s susceptibility to the effects of low income in adulthood needs to be elucidated further in other settings.
The authors would like to thank Rawya Mohsen and Bitte Modin for help with preparation of the dataset, Bianca De Stavola for advice on statistical analysis and Marie Reilly, Johan Hallqvist and Denny Vågerö for comments on an earlier version of this manuscript.
Funding: The UBCoS Multigen study is supported by grants from the Swedish Council for Working Life and Social Research (FAS project no 2003-0101) and the Swedish Research Council (VR project no 345-2003-2440 ). IK is currently funded by the Swedish Council for Working Life and Social Research. The funders were not involved in the study design or execution and the views and conclusions expressed in this paper are the responsibility of the authors.
Competing interests: None.
Ethics approval: The study was approved by the Regional Ethics Committee in Stockholm.