Early life stress and blood pressure levels in late adulthood

Severe stress experienced in early life may have long-term consequences on adult physiological functions. We studied the long-term effects of separation on blood pressure levels in non-obese subjects who were separated temporarily in childhood from their parents during World War II (WWII). The original clinical study cohort consists of people born during 1934–1944 in Helsinki, Finland. This substudy includes 1361 non-obese subjects (body mass index <30?kg?m?2). Of these, 192 (14.1%) had been evacuated abroad during WWII. The remaining subjects served as controls. Blood pressure levels and use of blood pressure medication were studied. The separated subjects had significantly higher systolic blood pressure values than the non-separated (148.6+21.5 vs 142.2+19.6?mm?Hg, P<0.0001) in adult life. Those subjects separated in early childhood had markedly higher systolic and diastolic blood pressure values in adult life compared with the non-separated (154.6 vs 142.5?mm?Hg; 95% confidence interval (CI) 2.6–14.7; P<0.005 and 90.8 vs 87.7?mm?Hg; 95% CI 1.0–7.3; P<0.02, respectively). Systolic blood pressure was also higher in the group separated for a duration of <1 year (151.7 vs 142.2?mm?Hg; 95% CI 0.0–12.4; P<0.05) compared with the non-separated. Besides being separated, age at separation and duration of separation also influenced blood pressure levels in adult life. This could be due to early hormonal and metabolic programming, during plastic periods in early life, influencing blood pressure levels in adult life

Glucose tolerance at age 58 and the decline of glucose tolerance in comparison with age 50 in people prenatally exposed to the Dutch famine

AIMS/HYPOTHESIS: People who were small at birth have an increased risk of type 2 diabetes in later life. People who were in utero during the Dutch famine had decreased glucose tolerance and raised insulin concentrations at age 50. We aimed to evaluate whether prenatal famine exposure leads to more rapid progression of impaired glucose/insulin homeostasis with increasing age. METHODS: We performed an OGTT in 702 men and women at age 50 and in 699 men and women at age 58, all born as term singletons immediately before, during or after the 1944-1945 Dutch famine. RESULTS: People who had been exposed to famine in utero had significantly higher 120-min glucose concentrations at age 58 compared with people who had not been exposed to famine (difference=0.4 mmol/l, 95% CI 0.1 to 0.7, adjusted for sex and BMI). Glucose tolerance deteriorated between the age of 50 and 58. The unadjusted 120-min glucose concentrations rose by 0.2 mmol/l (95% CI 0.0 to 0.4), while 120-min insulin concentrations had increased by 64 pmol/l (95% CI 48 to 82). There were no differences in the rates of glucose and insulin level increase between the famine-exposed group and the unexposed group (p=0.28 for the difference in increase in glucose concentrations and p=0.09 for insulin concentrations). CONCLUSIONS/INTERPRETATION: Although we confirmed that undernutrition during gestation is linked to decreased glucose tolerance, the effect does not seem to become more pronounced at age 58 as compared with age 50

Maternal adaptations and inheritance in the transgenerational programming of adult disease

Adverse exposures in utero have long been linked with an increased susceptibility to adult cardio-renal and metabolic diseases. Clear gender differences exist, whereby growth-restricted females, although exhibiting some phenotypic modifications, are often protected from overt disease outcomes. One of the greatest physiological challenges facing the female gender, however, is that of pregnancy; yet little research has focused on the outcomes associated with this, as a potential ‘second-hit’ for those who were small at birth. We review the limited evidence suggesting that pregnancy may unmask cardio-renal and metabolic disease states and the consequences for long-term maternal health in females who were born small. Additionally, a growing area of research in this programming field is in the transgenerational transmission of low birth weight and disease susceptibility. Pathways for transmission might include an abnormal adaptation to pregnancy by the growth-restricted mother and/or inheritance via the parental germline. Strategies to optimise the pregnancy environment and/or prevent the consequences of inheritance of programmed deficits and dysfunction are of critical importance for future generations