The magnitude of associations between childhood BMI and central or brachial SBP was broadly similar with associations being slightly stronger for brachial SBP at all ages, but with overlapping confidence intervals (CIs) providing no statistical evidence of differences. Associations tended to be weaker with DBP. Whereas growth trajectories were similar by sex (Supplementary Table 1), from age 7 years onwards, associations between BMI and BP were markedly stronger in males than females; for example, a 1 SD (z-score) increase in BMI at age 10 was associated with 4.2 mmHg (95% CI 3.1–5.3) higher central SBP in males compared with 2.5 mmHg in females (95% CI 1.4–3.5) (P for gender interaction = 0.03; Table 2).
Associations between BMI across childhood and BP at age 17 were broadly similar in analyses adjusted only for age at BP assessment and in analyses further adjusted for potential confounders, including earlier BMI measures (Table 2 and Supplementary Table 4). After adjustment for BMI at age 17, associations between childhood BMI and BP were attenuated, suggesting that mediation by continued adiposity is an important pathway in associations between childhood BMI and later BP (Supplementary Table 4). A similar overall pattern of association was also seen when using observed measures of BMI instead of those predicted from the multilevel model (Supplementary Table 5).
When separating participants into eight mutually exclusive groups defined by being in the bottom versus middle or top-thirds of birth weight, and being overweight or obese versus normal or low BMI at ages 2 and 17 years, the groups with the highest observed BMI at age 17 were those who went from the middle or top-third of birth weight to being overweight or obese at both 2 and 17 years [group N-O-O in Table 3, N = 125, mean (SD) BMI 29.3 (4.4) kg/m2]. The mean (SD) central SBP in this group was 100.7 (10.5) mmHg. Despite having a slightly lower mean BMI at age 17 [28.3 (3.5) kg/m2], participants who moved from the lowest third of birth weights to being overweight or obese at both 2 and 17 years had a higher central SBP (group L-O-O in Table 3, N = 32, mean = 104.2 mmHg, SD = 11.0). Testing the various hypothesized ways in which the combination between size at birth and overweight/obesity at 2 and 17 years could influence BP, the data were most compatible (largest P value and closest agreement between observed and predicted central SBP) with the ‘persistent risk’ model; this model specifies that BMI at age 17 influences BP and that there is an additional effect on BP from being in the lowest third of birth weight and being overweight/obese at both 2 and 17 years. The RMSE, however, did not reveal substantial differences in model fit across the various models. Similar results were observed for brachial SBP and DBP; for these BP measures, larger P values supported other hypothesized models, but the closest match between observed and predicted BP measurements was for the ‘persistent risk’ model (Supplementary Tables 6 and 7).
We show that BMI at birth and BMI later in childhood have distinctive associations with central BP in young adulthood. Low BMI at birth was associated with higher central (and brachial) BP, whereas higher BMI from age 7 onwards was associated with higher BP; this latter relationship was stronger in males than in females. This finding mirrors a systematic review of studies examining BMI in childhood with coronary heart disease in adulthood, which found that the association did not emerge until age 7 . Those who had low birth weight and then became obese or overweight at age 2 and maintained this status throughout childhood had the highest BP, despite having lower BMI at age 17 than other obese or overweight young adults. We did not observe differences in BP between participants who were in the lowest versus middle/top third of birth weights, normal BMI at age 2 and overweight/obese at age 17. This may suggest that any detrimental effect of low birth weight combined with later obesity is most marked in to those who experience rapid weight gain in infancy and become obese at an early age.
Non-invasive estimates of central BP are more strongly associated with target organ damage  and there is some evidence that they are better predictors of future cardiovascular events than brachial BP . The association of BMI throughout childhood with central BP has not been studied. Despite differences between brachial and central BP, which may have important implications for the definition of hypertension in children, our analyses demonstrate similar associations between BMI in childhood and measures of brachial and central BP in early adulthood. Further research is now needed to determine whether brachial and SBP demonstrate differing associations with measures of cardiovascular structure and function in young adults. Our findings with regard to the relationship between birth weight and subsequent BMI in childhood and central and brachial BP are also consistent with previous studies that only measured brachial BP [37–40]. Similarly, previous longitudinal studies of the associations between change in BMI in childhood and brachial BP have also found that the highest levels of BP are observed in participants who move from low birth weight to being overweight/obese in childhood [41,42]. One previous cross-sectional clinic-based study of 149 adolescents aged 10–17  found that central SBP was highest in obese participants who had a history of low birth weight, which is also in keeping with our findings. Typically, brachial SBP is higher than central (aortic) SBP, although this difference tends to diminish with age . The difference between brachial and central SBP in our study was substantial (mean of the difference = 19.8 mmHg) and the difference was greater in young men than women. These observations are very similar to a previous report that measured central BP in a cross-sectional sample that included a relatively small number of people below the age of 20 years .
The greater impact of childhood adiposity gain on BP in males compared with females is supported by the findings in adults [43,44]. One potential explanation for our finding is that equivalent adiposity gain, as measured by BMI, may mask sex differences in ectopic fat deposition, particularly visceral fat, which may in turn be a stronger determinant of BP than BMI . However, previous longitudinal analysis in ALSPAC do not show that directly assessed fat mass measured at 9–12 years is more strongly associated with BP at age 15–16 than BMI, although this study examined whole-body fat mass, and not the regional fat patterning . An alternative explanation is that female sex hormones buffer adverse effects of stressors, such as weight gain, on BP. Animal studies show that oestrogen acts on the central oestrogen receptor to protect against renin–angiotensin–aldosterone system over-activation, autonomic dysfunction and hypertension [46,47]. Given the lower rates of hypertension in premenopausal, but not in postmenopausal women compared to men, it is plausible that such a mechanism may also operate in humans.
Key strengths of our study include the availability of brachial and central SBP and DBP on a large population-based birth cohort of 17-year-olds, in contrast to most previous studies that only have brachial BP measurements. We had sufficient numbers to observe sex differences in the impact of BMI change on BP. We were also able to examine the associations of BMI throughout childhood with BP in young adulthood, in contrast to most previous studies that have few measures of childhood BMI. Our statistical methods allowed us to exploit detailed data on childhood BMI to construct growth trajectories, which enable the prediction of BMI measures at the same ages for all children, regardless of when and how often they were measured. This methodology enables all available measures to be included in analyses and therefore reduces the problem of missing data, whilst also taking account of the differential measurement error between measured and parent-reported growth measurements. The models had good fit to the observed data. The pattern of results using raw BMI measurements was similar to those using measurements predicted by our growth trajectory models, providing further reassurance that the use of our growth trajectories was appropriate. In our main analyses, we adjusted each BMI measure for all previous BMI measurements, but not future measures; for example, BMI at 1 year was adjusted for BMI at birth and 3 months, but not for BMI measures after 1 year. This approach is intended to remove the confounding by earlier BMI and shed light on the role of BMI at different ages. In unadjusted models, children with a higher BMI at age 7 are likely also to have had a higher BMI at earlier ages; therefore an unadjusted regression coefficient for BMI at age 7 encompasses all BMI changes prior to age 7. In contrast, when adjusting for previous BMI measurements, the two hypothetical people being compared have the same BMI at birth, 3 months, and 1 and 3 years, and only differ in their BMI change between 3 and 7 years. We use BMI as a measure of adiposity; the appropriateness of BMI in young children has been questioned, but at least from age 9 onwards, it shows similar associations with cardiovascular risk factors to other adiposity measures . Despite our results being consistent with other studies [41,42], our conclusions with respect to the interplay of low birth weight and subsequent adiposity should be tempered by the fact that there were only 32 participants in the group who had low birth weight and were overweight or obese at 2 and 17 years, meaning that statistical power for this comparison was low and we cannot exclude the possibility that this is a chance finding.
Our results provide further evidence for the hypothesis that adiposity gain in childhood is detrimental for later BP. Importantly, we show this influence is evident for central BP, the pressure to which the heart is exposed and which shows a closer correlation with target organ damage and cardiovascular events in later life. We also show that this adverse effect of adiposity gain is worse for boys than girls. The magnitude of the associations we observe is large: the difference in central SBP observed between our lowest risk category (low birth weight, overweight at 2 years, not overweight at 17 years) and our highest risk category (low birth weight, overweight and obese at both 2 and 17 years) is 10 mmHg. In adults, a 20 mmHg difference in SBP is associated with a doubling in cardiovascular disease risk . There is now evidence that overweight children who return to a healthy BMI in later life can, at least to some extent, normalize their cardiovascular risk [45,48], highlighting the importance of interventions to prevent and reverse overweight and obesity in children and young people.
We are extremely grateful to the families who took part in the study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses.
Funding sources: This work was supported by a UK Medical Research Fellowship (G1002375) to L.D.H. and by a Wellcome Trust grant to A.D.H., D.A.L., G.D.S. and N.C. L.D.H., A.F., G.D.S. and D.A.L. work in a unit that receives funding from the University of Bristol and the UK Medical Research Council (MC_UU_12013/5 and MC_UU_12013/9). The UK Medical Research Council, the Wellcome Trust and the University of Bristol provide core support for ALSPAC. AF is supported by a UK Medical Research Council Fellowship (G0701594).
There are no conflicts of interest.
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