Early growth and adult health: focus on blood pressure, glucose tolerance status and body composition

Background. Theory of developmental origins of adult health and disease proposes that experiences during critical periods of early development may have consequences on health throughout a lifespan. Circumstances in utero or during infancy may induce changes in body size and structure, metabolism, hormone secretion and gene expression. These changes may serve as advantageous adaptations aiming at better survival if environmental conditions, such as nutrient availability, remain as predicted in early life. If the predictions, however, mismatch with reality, these adaptations may lead to increased susceptibility to disturbances in adult health. Low birth weight in subjects born at term is a widely used crude indicator of adjustments during fetal life that are unfavourable in an affluent society. The aim of these studies was to characterize the associations between early growth and some components of the metabolic syndrome cluster, and factors that may contribute to and interact with these associations. Subjects and methods. Participants of these studies belong to clinically examined subsets of two epidemiological cohorts with data on birth measurements and, for the younger cohort, on serial recordings of weight and height during childhood. They were born as singletons between 1924-33 and 1934-44 in the Helsinki University Central Hospital, and 500 and 2003 of them, respectively, attended clinical studies at the age of 65-75 and 56-70 years, respectively. Their clinical examinations included an oral glucose tolerance test, blood pressure (BP) measurements, an analysis of body composition by bioelectrical impedance, questionnaires on medication and exercise habits, and determination of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor2 (PPAR 2) gene. Results. In the 65-75 year old men and women, the inverse relationship between birth weight and systolic BP was confined to people who had established hypertension. Among them a 1-kg increase in birthweight was associated with a 6.4-mmHg (95% CI: 1.0 to 11.9) decrease in systolic BP. This inverse relationship was further confined to people with the prevailing Pro12Pro polymorphism of the PPAR 2 gene (9.3 mmHg/kg, 95% CI: 2.1-16.4). Low birth weight was related to the use of angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (ACEI/ARB, p=0.03). Again, this association interacted significantly with the PPAR 2 gene polymorphism, the carriers of the Pro12Pro with low birth weight being more likely to receive ACEI/ARB treatment (p=0.01 for interaction). A lower rate of glucose intolerance was related to habitual frequent or moderate leisuretime exercise. This effect was dependent on birth size, being strongest among those with a small body size at birth. Among subjects with birth weight 3000 g, the odds ratio (OR) for glucose intolerance was 5.2 (95% CI: 2.1 to 13) in those who exercised less than 3 times per week compared to regular exercisers; in those who scored their exercise light compared with moderate exercisers (defined as comparable to brisk walking) the OR was 3.5 (1.5 to 8.2). In the 56-70 year old men a 1 kg increase in birth weight corresponded to a 4.1 kg (95% CI: 3.1 to 5.1) and in women to a 2.9 kg (2.1 to 3.6) increase in adult lean mass. Heightnormalized indices of adult lean and fat body mass (LMI, lean mass/height squared and FMI, fat mass/ height squared) were used in the analyses of associations of body mass index (BMI) at birth and change in BMI during four periods of childhood growth with adult body composition. Adult LMI was positively associated with BMI at birth (0.24 and 0.20 kg/m higher for each 1 SD increase in BMI at birth in men and in women, respectively). Rapid growth, i.e. crossing from an original BMI percentile to a higher one, was positively related to adult LMI during all growth periods analysed: rapid gain in BMI between birth and 1 year of age, 1-2, 2-7 and 7-11 years resulted in men to a 0.17, 0.21, 0.44 and 0.32 kg/m and in women to a 0.22, 0.20, 0.46 and 0.26 kg/m higher adult LMI, respectively. FMI and percent body fat were positively associated with rapid gain in BMI between 2 and 11 years of age. Conclusions. These studies suggest that in the 65-75 year old subjects the well-known inverse association between birth weight and systolic BP becomes focused in hypertensive people because pathological features of BP regulation, associated with slow fetal growth, become self-perpetuating in adult life and are amplified by age. Insulin resistance of the Pro12Pro carriers with low birth weight may interact with the reninangiotensin-aldosterone system leading to raised BP levels. Subjects predisposed to type 2 diabetes due to their low birth weight are strongly protected from glucose intolerance by regular exercise at a moderate intensity. In the 56-70 year old subjects rapid gain in BMI before the age of 2 years increased adult lean body mass without excess fat accumulation whereas rapid gain in BMI during later childhood, despite the concurrent rise in lean mass, resulted in relatively higher increase in adult body fat mass. These findings illustrate how genes, the environment and their interactions, early growth patterns, and adult lifestyle modify adult health risks which originate from early life.