151 research outputs found
Long-term consequences of intrauterine growth retardation
No full textRecent studies in Europe, North America and the developing world have shown that low birth weight or other indices of abnormal fetal growth in babies born at term are linked with a higher prevalence of raised blood pressure, non-insulin-dependent diabetes and cardiovascular disease in late adult life. These findings have led to the 'fetal origins' hypothesis which proposes that fetal adaptations to an adverse intrauterine environment programme persistent physiological and metabolic changes which predispose to these diseases. The mechanisms are unknown, but evidence from animal studies and preliminary evidence in humans suggest that impaired fetal nutrient supply permanently alters neuroendocrine development in the offspring resulting in longterm changes in the set point of adrenocortical and sympathoadrenal hormonal activity.</p
Fetal origins of mental health: evidence and mechanisms
No full textThe concept of fetal programming states that changes in the fetal environment during sensitive periods of organ development may cause long-lasting changes in the structure and functioning of these organs later in life and influence the risk for chronic diseases such as coronary heart disease and type 2 diabetes. Fetal growth is a summary marker of the fetal environment and is reflected by relatively easy-to-obtain measures of size at birth such as birthweight. In the last two decades, a body of evidence emerged linking fetal growth with behavioural and mental health outcomes later in life. Cognitive functioning and behavioural problems in childhood, in particular inattention/hyperactivity, have been shown to be inversely related to fetal growth. Although results are mixed, risk for personality disorders and schizophrenia seems to be linked with fetal growth and adversity, while the evidence for mood disorders is weak. Vulnerability for psychopathology may also be influenced by prenatal adversity. There is evidence for associations of fetal growth with temperament in childhood as well as stress reactivity and distress. The associations of fetal growth with mental health later in life are potentially caused by specific prenatal factors such as maternal smoking, alcohol, toxins/drugs, nutrition, psychosocial stress and infection during pregnancy. The mechanisms likely involve changes in neurodevelopment and in the set point of neuroendocrine systems, and there is evidence that prenatal adversity interacts with genetic and postnatal environmental factors. Future studies should examine the effects of specific prenatal factors and attempt to disentangle genetic and prenatal environmental effects
Effortful control mediates associations of fetal growth with hyperactivity and behavioural problems in 7- to 9-year-old children
No full textBackground: Inverse associations of fetal growth with behavioural problems in childhood have been repeatedly reported, suggesting long-term effects of the prenatal developmental environment on behaviour later in life. However, no study so far has examined effects on temperament and potential developmental pathways. Temperamental traits may be particularly susceptible to neurodevelopmental alterations, and they are linked to behavioural problems. Therefore, we tested for associations of fetal growth with behavioural problems in children and tested if temperament mediated such effects. Methods: 139 mother-child pairs were recruited in early pregnancy. Weight, head circumference and gestational age were measured at birth, and the mother reported on their child’s behavioural problems and temperament at age 7 to 9 years. Results: Birth weight and head circumference at birth adjusted for gestational age (i.e. fetal growth) were inversely associated with hyperactivity and total behavioural problems, and positively associated with the temperamental trait Effortful Control. Path analyses showed that Effortful Control mediated the effects of fetal growth on hyperactivity and total behavioural problems. Conclusions: Our results suggest that an adverse fetal environment is associated with behavioural problems in childhood, in particular in those children that show a low capacity for attentional and behavioural regulation. An adverse fetal environment might induce vulnerability for behavioural problems, or it might induce changes in temperament and behavioural problems independently, representing a common cause. Pathways are likely to be based on long lasting neurodevelopmental alterations due to prenatal adversity
Fetal growth and the fetal origins hypothesis in twins-problems and perspectives
No full textAlthough there is substantial evidence from studies of singletons that small size at birth is linked with long-term adverse health effects, until recently little was known as to whether these associations extend to twins. A review of published studies suggests that at present there is little consistent evidence that birthsize in twins is associated with increased morbidity or morality. While, these findings may reflect methodological limitations, it is also argued that they arise as a consequence of the substantially different biology of fetal growth in twins
Increased glucocorticoid receptor expression in human skeletal muscle cells may contribute to the pathogenesis of the metabolic syndrome
No full textAltered glucocorticoid hormone action may contribute to the etiology of the metabolic syndrome, but the molecular mechanisms are poorly defined. Tissue sensitivity to glucocorticoid is regulated by expression of the glucocorticoid receptor (GR)-? and 11ß-hydroxysteroid dehydrogenase type I (11ß-HSD1)-mediated intracellular synthesis of active cortisol from inactive cortisone. We have analyzed GR? and 11ß-HSD1 expression in skeletal myoblasts from men (n = 14) with contrasting levels of insulin sensitivity (euglycemic clamp measurements of insulin-dependent glucose disposal rate), blood pressure, and adiposity. Positive associations were evident between myoblast expression of GR? under basal conditions and levels of insulin resistance (r^2 = 0.34, P < 0.05), BMI (r^2 = 0.49, P < 0.01), percent body fat (r^2 = 0.34, P < 0.02), and blood pressure (r2 = 0.86, P < 0.001). Similar associations were evident when myoblasts were incubated with physiological levels of cortisol (P < 0.01 for all). Importantly, GR? expression was unaffected by variations in in vivo concentrations of insulin, IGF-1, or glucose concentrations. In common with the GR, 11ß-HSD1 expression in myoblasts incubated with physiological concentrations of cortisol in vitro was positively associated with levels of insulin resistance (r^2 = 0.68, P < 0.001), BMI (r^2 = 0.63, P < 0.005), and blood pressure (r^2 = 0.27, P < 0.05). Regulation of GR? and 11ß-HSD1 by cortisol was abolished by the GR antagonist RU38486. In summary, our data suggest that raised skeletal muscle cell expression of GR? and 11ß -HSD1-mediated regulation of intracellular cortisol may play a fundamental role in mechanisms contributing to the pathogenesis of the metabolic syndrome
Size at birth and motor activity during stress in children aged 7-9 years
No full textObjective: Small size at birth is linked with metabolic and cardiovascular disease. There is increasing evidence that it is also linked with physiological stress responses and abnormal behaviour, in particular symptoms of hyperactivity. We therefore investigated associations between size at birth and motor activity during psychosocial stress.Methods: In 123 children aged 7-9 years, we examined the relations of birth weight, head circumference, length and ponderal index at birth with motor activity upon exposure to both stress and non-stress situations. Videos were recorded while the children performed a story and a maths task in front of an audience (stress) and watched a movie (non-stress); motor activity was defined as lifting or tilting of a foot.Results: Children who had had a smaller head circumference at birth demonstrated greater motor activity during the stress test. There were marked gender differences in the results. In boys, lower birth weight, head circumference and ponderal index were associated with greater motor activity during the stress test, but not associated with motor activity during the non-stress situation. The findings remained significant when potential confounding variables were controlled for. There were no associations in girls.Conclusions: The findings suggest long-term effects of an adverse fetal environment on the behavioural stress response in boys, and parallel similar sex-specific effects on different stress response systems in humans and animals. The results could reflect permanent alterations of dopaminergic neurotransmission and have implications for the etiology of clinical hyperactivity
Lower maternal folate status in early pregnancy is associated with childhood hyperactivity and peer problems in offspring
No full textBackground: Maternal nutrition during pregnancy has been linked with fetal brain development and psychopathology in the offspring. We examined for associations of maternal folate status and dietary intake during pregnancy with brain growth and childhood behavioural difficulties in the offspring.Methods: In a prospective cohort study, maternal red blood cell folate (RCF) was measured at 14 weeks of pregnancy and total folate intake (TFI) from food and supplements was assessed in early and late pregnancy. The offspring’s head circumference and body weight were measured at birth and in infancy, and 100 mothers reported on children’s behavioural difficulties at a mean age of 8.75 years using the Strengths and Difficulties Questionnaire.Results: Lower maternal RCF and TFI in early pregnancy were associated with higher childhood hyperactivity (RCF: beta = -.24; p = .013; TFI: beta = -.24; p = .022) and peer problems scores (RCF: beta = -.28; p = .004; TFI: beta = -.28; p = .009) in the offspring. Maternal gestational RCF was positively associated with head circumference at birth (adjusted for gestational age), and mediation analyses showed significant inverse indirect associations of RCF with hyperactivity/inattention and peer problems via fetal brain growth. Adjustment for mother’s smoking and drinking alcohol during pregnancy did not change the results. Conclusions: Although the associations are small and residual confounding is possible, our data provide preliminary support for the hypothesis that lower folate status in early pregnancy might impair fetal brain development and affect hyperactivity/inattention and peer problems in childhood
Size at birth and autonomic function during psychological stress
No full textSmall size at birth is associated with exaggerated blood pressure responses to psychological stressors, which increase the risk of developing sustained hypertension in adult life. Explanatory mechanisms for this association are not well characterized. We investigated the hypothesis that an adverse fetal environment, reflected by small size at birth, persistently alters autonomic nervous system and baroreflex control of cardiovascular function, resulting in exaggerated blood pressure and heart rate responses to stressors. Men and women from an Australian prospective cohort study underwent a series of 3 psychological stressors (Stroop, mirror-tracing, and speech) while their blood pressure was recorded continuously using a Portapres. Indices of autonomic function were derived using spectrum analysis (wavelet packet transform), and baroreflex function was estimated using an adaptive autoregressive model. We found that women who were small at birth demonstrated increased levels of low-frequency blood pressure variability at rest (r=-0.28; P<0.05) and during stress (r=-0.42; P<0.001), reduced levels of high-frequency heart period variability (r=0.22; P<0.05), and reduced baroreflex sensitivity (r=0.34; P<0.01). These findings were not present in the men. This study provides evidence that markers of impaired fetal growth are related to autonomic cardiovascular control involving modulation of both sympathetic and parasympathetic function but in a sex-specific manner. We also provide the first human evidence of a relationship between size at birth and baroreflex function
Mortality from birth to adult life: a longitudinal study of twins
No full textWe have examined mortality from birth through adult life in a cohort of 2562 twins born in Birmingham, UK, between 1950 and 1954. Their birthweights and obstetric details had been recorded as part of a longitudinal study of births in Birmingham. There were a total of 151 perinatal deaths (perinatal mortality rate = 116 per 1000 births) and 227 infant deaths (infant mortality rate = 94 per 1000 live births). 70 deaths occurred after the age of one year. In comparison with national mortality rates in the UK, overall mortality in the twins was high (standard mortality rate, SMR = 259, 95% CI 221-300). Mortality was highest in the first year of life and, although it then declined progressively, it remained significantly higher that that of the general population until age 5 years. The excess mortality was largely due to conditions originating in the perinatal period but there were excess rates of congenital abnormalities, diseases of the respiratory system, digestive system and nervous and sensory organs. A Cox proportional Hazards analysis showed that the risk of death was related to low birthweight, prematurity and male sex. Death of the co-twin was highly predictive of mortality throughout the period of follow up. These studies not only underline the excess mortality associated with twin birth but show for the first time that this excess mortality extends into childhood.</p
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