Why Evidence for the Fetal Origins of Adult Disease Might Be a Statistical Artifact: The "Reversal Paradox" for the Relation between Birth Weight and Blood Pressure in Later Life

Tu, Yu–Kang; West, Robert; Ellison, George T. H.; Gilthorpe, Mark S.

doi:10.1093/aje/kwi002

Cited by 235 publications

(198 citation statements)

References 30 publications

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“…While adjusting associations between early feeding and later health outcomes for maternal factors such as education, adiposity and smoking, as well as individual/familial socio-economic markers is appropriate, this does not rule out that other factors known or as yet unknown may partly/wholly account for associations observed. In addition, over-adjustment for markers of body size at different stages of the life-course may lead to spurious associations (72) . Only evidence from wellconducted observational studies (which collect data on exclusivity and duration of feeding, as well as potential confounding factors), breast-feeding promotion trials (11,53) , and trials of infant formulae v. breast milk with adequate follow-up rates in adult life, will be able to establish whether beneficial associations between breast-feeding and cardiovascular risk factors and outcomes are truly causal, and if so, of public health importance.…”

Section: Discussionmentioning

confidence: 99%

Breast-feeding and cardiovascular risk factors and outcomes in later life: evidence from epidemiological studies

2011

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This paper considers the body of observational evidence examining the association of being breast-fed to cardiovascular risk factors and outcomes in later life, and whether any potentially advantageous findings are causal. Early cardiovascular consequences/correlates of breastfeeding, compared to being formula fed, include markedly higher levels of total blood cholesterol, lower levels of pre-prandial blood glucose and insulin and lower levels of adiposity. However, a key issue is whether these early differences at a period of rapid development programme/influence cardiovascular risk factors and outcomes in later life. Evidence of longterm effects of early feeding, largely from observational studies, has shown that those breastfed have lower levels of blood total cholesterol, lower risk of type-2 diabetes and marginally lower levels of adiposity and blood pressure in adult life. There is no strong evidence to suggest effects of early feeding on adult levels of blood glucose, blood insulin and CHD outcomes, although further data are needed. However, the influence of confounding factors, such as maternal body size, maternal smoking and socio-demographic factors, and exclusivity of early feeding on these potentially beneficial associations needs to be considered before inferring any causal effects. Moreover, fewer studies have examined whether duration of exclusive breastfeeding has a graded influence on these risk factors and outcomes; such data would help further in deciding upon causal associations. While strong observational evidence suggests nutritional programming of adult cholesterol levels, associations with other markers of cardiometabolic risk and their consequences in later life need to be confirmed in well-conducted observational and experimental studies.

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Section: Discussionmentioning

confidence: 99%

Breast-feeding and cardiovascular risk factors and outcomes in later life: evidence from epidemiological studies

2011

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“…If minimal attenuation is observed, it is assumed that the exposure is acting through pathways which are independent of the proposed intermediate, in this case adult BMI. However, there are potential issues with the use of statistical adjustment in this way, as demonstrated in a noteworthy statistical simulation experiment conducted by Tu et al (51) . Computer simulations of three hypothetical relations between birth-weight and adult blood pressure were used to investigate the effect of statistically adjusting for adult weight, as a potential mediator of the relationship.…”

Section: Statistical Considerations: the Reversal Paradoxmentioning

confidence: 99%

Childhood obesity: the impact on long-term risk of metabolic and CVD is not necessarily inevitable

McMullen

2014

Proc. Nutr. Soc.

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The worldwide prevalence of overweight and obesity in the adult population is estimated to be 35 %. These trends are reflected in childhood obesity prevalence, and the potential impact of early-onset obesity is of great concern. The aim of this review was to investigate the long-term implications of childhood obesity for metabolic and cardiovascular health, focusing on the independent contribution of childhood obesity to adult disease risk, as distinct from associations mediated by tracking of obesity across the lifespan. The data systematically reviewed provide little evidence to suggest that childhood overweight and obesity are independent risk factors for metabolic and cardiovascular risk during adulthood. Instead, the data demonstrate that the relationships observed are dependent on tracking of BMI between childhood and adulthood, alongside persistence of dietary patterns and physical activity. Adjustment for adult BMI uncovers unexpected negative associations between childhood BMI and adult disease, suggesting a protective effect of childhood obesity at any given level of adult BMI. Further work is required to explain these findings, both in terms of pathways and statistical artefacts. To conclude, it must be stressed that it is not suggested that childhood obesity is without negative consequence. Childhood obesity is clearly associated with a range of adverse physical and psychological outcomes. However, the data are important in supporting a positive message that the long-term consequences of childhood obesity are avoidable; and that there remains opportunity for intervention across the lifespan. This nuance in understanding long-term risk is important when considering the effectiveness of interventions at different stages of the lifespan. Childhood: Obesity: Metabolic syndrome: Cardiovascular disease: Blood pressureThe worldwide prevalence of overweight and obesity in the adult population is currently estimated to be 35 %, rising to over 70 % in some population groups, with rates of obesity nearly doubling between 1980 and 2008 (1) . This is a global phenomenon, with the prevalence of overweight and obesity in low-and middleincome countries on the rise, mirroring their transition to the obesogenic environments more commonly associated with 'Western' living. The relationship between obesity and risk of non-communicable disease in adulthood has long been established, with a wealth of evidence demonstrating the considerable impact of excess adiposity on the health and wellbeing of populations (2) . The trends in adult overweight and obesity are reflected in childhood obesity prevalence, and the potential impact of early-onset obesity is of great concern. It has been estimated that 200 million school-aged children were overweight or obese in 2010 worldwide, with a prevalence of >20 % in European states and >30 % in regions of North America (3) . In the UK, the 2007 Foresight report showed that about 8-10 % of girls and boys were obese in 2004, and this was projected to rise to an estimated 25 % by 2050 (4)...

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“…Alternative models were constructed with and without adjustment for BMI because of recent concerns of overinterpretation of BMI-adjusted relationships with perinatal variables. 33 Proportional differences were evaluated with Pearson's w 2 -test.…”

Section: Experimental Stress Protocolmentioning

confidence: 99%

Cardiovascular reactivity to psychological stressors in late adulthood is predicted by gestational age at birth

Feldt

Räikkönen

Eriksson³

et al. 2007

J Hum Hypertens

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The relationships of body size and gestational age at birth with adult blood pressure (BP) are relatively modest compared to their stronger associations with cardiovascular disease. BP reactivity is a strong predictor of cardiovascular morbidity, and it is possible that reactivity, rather than resting level, is determined in utero. We investigated whether body size and gestational age at birth predict BP reactivity during experimentally induced psychosocial stress in late adulthood. A total of 73 men and 80 women born after 36 weeks' gestation in Helsinki, Finland, during 1934-1944 underwent the Trier Social Stress Test (TSST); a standardized psychosocial stress test consisting of a public speech and an arithmetic task. Changes in BP were monitored continuously by a non-invasive finger photoplethysmography (Finometer, FMS, Amsterdam, The Netherlands). The results showed that the most robust early determinant of BP reactivity was gestational age; however, with opposite relationships between the sexes (P for interaction o0.001). A 1-week increase in gestational age was associated with a 3.1 mm Hg (95% confidence interval (CI), 0.2 to 6.0) and 1.2 mm Hg (95% CI, À0.1 to 2.6) decreases in systolic and diastolic BP reactivity in women, but with 5.2 mm Hg (95% CI, 1.9 to 8.4) and 2.3 mm Hg (95% CI, 0.9 to 3.8) increases in men. In conclusion, normal variation in gestational age at birth predicts cardiovascular stress reactivity in later adulthood. Given that hypothalamic-pituitary-adrenal axis contributes to the regulation of autonomic nervous system function and the timing of parturition, and shows well-established sex differences, we speculate a role for early programming of this axis in explaining the findings.

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Why Evidence for the Fetal Origins of Adult Disease Might Be a Statistical Artifact: The "Reversal Paradox" for the Relation between Birth Weight and Blood Pressure in Later Life

Cited by 235 publications

References 30 publications

Breast-feeding and cardiovascular risk factors and outcomes in later life: evidence from epidemiological studies

Breast-feeding and cardiovascular risk factors and outcomes in later life: evidence from epidemiological studies

Childhood obesity: the impact on long-term risk of metabolic and CVD is not necessarily inevitable

Cardiovascular reactivity to psychological stressors in late adulthood is predicted by gestational age at birth

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