Low birth weight is associated with an increased risk of impaired glucose tolerance and type 2 diabetes and with signs of increased hypothalamic pituitary adrenal axis activity in later life (1, 2). Low birth usually weight reflects a reduction in fetal growth, which largely depends on an adequate supply of nutrients and oxygen. Variations in supply modify the metabolic and neuroendocrine characteristics of the fetus, which in turn modulate the pattern of functional development as well as growth (3). An adverse fetal environment, evident as low birth weight, is therefore proposed to alter functional development with long term effects for the function and risk of disease in the individual later in life (4, 5). Increased HPAA impairs metabolic homeostasis and could therefore mediate effect of prenatal challenge on later metabolic control (6). It was therefore hypothesised that restriction of fetal growth, increases circulating cortisol and/or alters sensitivity to cortisol, which increases fasting blood glucose, and impairs glucose tolerance in the young adult. Large litter size in the guinea pig is characterised by reduced placental and fetal growth, reduced size at birth and insulin resistance in offspring in later life, providing a suitable model to test this hypothesis. Spontaneous restriction of fetal growth in the guinea pig, evident as small size at birth, was associated with increased salivary cortisol, in both sexes but at different stages of postnatal life. In males, salivary cortisol was increased with small size at birth in early and adult life, but reduced later with ageing. In females however, salivary cortisol was increased in juveniles and in aged adults, possibly reflecting the impact of the oestrus cycle on cortisol production in mature cycling females. Altered activity of the HPGA, which can influence that of the HPAA, has also been reported to be programmed by prenatal restriction. In the guinea pig, salivary testosterone in males increased with age and small size at birth in juveniles, young and aged adults. In females, salivary progesterone increased with age up to 300 days, and decreased with size at birth in the young guinea pig. Although testosterone inhibits HPAA activity, in males, mean salivary cortisol correlated positively with mean salivary testosterone at 100 and 300 days of age. In contrast, progesterone may enhance HPAA activity, and consistent with this, in females, mean salivary progesterone correlated with mean salivary cortisol at 400 days of age. Therefore, salivary testosterone in the male and salivary progesterone in the female guinea pig changes with maturation and has previously reported in this or other species, but small size at birth increases salivary testosterone in males with modest effects in early life in females. This together with the unexpected positive associations of salivary cortisol with testosterone in males, suggests that programming of the HPAA makes little contribution to that of the HPAA as indicated by salivary cortisol. Here we show that low birth weight is associated with increased fasting blood glucose and impaired glucose tolerance in both male and female young adult guinea pigs aged 100 days. Fasting and mean (during IVGTT) plasma cortisol was reduced in low birth weight female adult guinea pigs, and is not vary with size at birth at this age in males. This suggests that circulating cortisol does not contribute to the impaired glycaemia associated with small size at birth in the guinea pig. Glucose tolerance was increasingly impaired in males but not females, as mean plasma cortisol increased. This is consistent with cortisol impairing glycaemia in the guinea pig as in other species, in males at least. To assess the role of cortisol in prentally programmed impairment of glycaemia directly, metyrapone or vehicle containing 24% ethanol was administered to young adult guinea pigs for 3 days. Treatment with the latter impaired fasting blood glucose and glucose tolerance in females and the latter in males compared to a previous IVGTT and this was exacerbated in low birth weight females. Metyrapone prevented this impairment of fasting glycaemia and glucose tolerance in the low birth weight adult female guinea pig and in the male guinea pig regardless of birth weight class. Neither vehicle or metyrapone altered plasma cortisol, before or during a second IVGTT. Limited numbers of animals, particularly females, limited this study however and additional investigation is required. Nevertheless this shows for the first time that inhibition of glucocorticoid synthesis in the guinea pig improves glucose control. Furthermore this suggests that the low birth weight guinea pig may be more sensitive to cortisol, have increased cortisol synthesis or reduced inactivation of cortisol in peripheral tissues, leading to increased local cortisol action. In conclusion, alterations in peripheral HPAA activity in the guinea pig due to restricted fetal growth may contribute to their prenatally programmed development of impaired glucose tolerance as young adults, but the extent of that contribution may vary with age and gender. / Thesis (Ph.D.) -- University of Adelaide, School of Paediatrics and Reproductive Health, 2008

<p><b>VLBW adolescents</b></p><p>We found that the VLBW adolescents had specific emotional and cognitive traits. Some of them fit with psychiatric concepts and others do not. They had an increased risk of developing psychiatric symptoms and disorders compared with controls, especially attention deficit, anxiety and relational problems affecting their social skills and overall functioning. Academic achievement was reduced. The attention problems were widespread, but only a minority fulfilled the diagnostic criteria of Attentiondeficit/ hyperactivity disorder. Increased prevalence of anxiety symptoms and disorders may be due to a number of factors, comprising both biological/neuroendocrine and psychosocial mechanisms. The peer problems and deficits in social skills may indicate specific difficulties in relating and adjusting to others, with deficits in comprehending the subtle cues of social relations. The implication of thought problems reported by teachers is unclear. Adolescents with birth weight ≤ 1000 g showed a tendency towards more psychiatric disorders than those with birth weight between 1000 and 1500 g. The lack of gender differences demonstrates that prematurity exceeds the usual effect of gender regarding vulnerability for developing psychiatric symptoms.</p><p>We found that the VLBW adolescents perceived self-esteem and quality of life as others did at the age of 14. However, parents reported functional disadvantages and reduced quality of life measures for their adolescents. The parents worried more for their children’s functioning and well-being, especially if the child had a psychiatric disorder or cerebral palsy. Still, being born VLBW did not influence the warmth in the parent-child relationship, nor did the parents have more mental health problems.</p><p>As the association between VLBW and psychiatric problems could not be explained by SES or the parents’ mental health, a biological cause-effect relationship seems plausible. The frequency of cerebral MRI abnormalities was higher in the VLBW group than in the control group. Furthermore, ADHD symptoms were associated with white matter reduction and thinning of the corpus callosum, while other psychiatric symptoms were not associated with MRI abnormalities. These results support the hypothesis of a specific (“pure”) type of ADHD with a dominant neurological aetiology, while interacting psychosocial experiences play a minor part. Our study indicates that being born VLBW involves a biological vulnerability with increased risk of psychiatric symptoms.</p><p><b>SGA adolescents</b></p><p>Although every fifth SGA adolescent had psychiatric symptoms, assessed by interview, the prevalence of symptoms and disorders did not differ significantly from controls. Yet, screening questionnaires displayed more behavioural problems, lowered social competence and a tendency towards attention deficit/hyperactivity. Teachers reported withdrawal and thought problems, while academic performance did not differ from controls. Boys had more attention and externalizing problems than girls.</p><p>Generally, on psychiatric measures, the term SGA group seemed to fall inbetween the VLBW and the control group, resembling the control group more than the VLBW group.</p><p>The SGA adolescents and their parents reported self-esteem and quality of life as in the control group. Being born SGA at term did not influence the warmth in the parent-child relationship, and the parents did not have more mental health problems than others. The frequency of cerebral MRI abnormalities in the SGA group did not differ from the control group, and no associations were found between psychiatric symptoms and MRI abnormalities.</p> / Paper V reprinted with kind permission of Elsevier, sciencedirect.com

<p>In this thesis, different aspects of the insulin resistance syndrome in relation to plasminogen activator inhibitor-1 (PAI-1) activity are investigated in a longitudinal population-based study. Participants were men investigated at ages 50 and 70 with follow-up data on mortality.</p><p>High PAI-1 activity was associated with low insulin sensitivity, high concentrations of serum triglycerides, high body mass index and high waist/hip ratio, independently of each other and of potential confounders. Low birth weight predicted high blood pressure, insulin resistance, truncal obesity and high PAI-1 activity but not the abdominal obesity or dyslipidaemia present in the insulin resistance syndrome. Increased physical activity level between 50 and 70 years of age, in the absence of active intervention, was associated with improved glucose, insulin, proinsulin and lipoprotein metabolism. Insulin and proinsulin seemed to be important factors that mediate much of the association between a sedentary lifestyle and increased risk of cardiovascular disease. The reported dietary intake of both mono- and polyunsaturated fatty acids was positively associated with PAI-1 activity, whereas saturated fatty acid intake displayed no association. The associations present between PAI-1 activity and the fatty acid proportions in serum cholesterol esters were partly influenced by factors related with the insulin resistance syndrome.</p><p>This thesis provides further knowledge to the epidemiological view of the interrelations of the insulin resistance syndrome, PAI-1, birth weight, and lifestyle factors as physical activity and dietary habits. PAI-1 is a part of the insulin resistance syndrome and is associated both with modifiable and non-modifiable factors related with this syndrome.</p>

In this thesis, different aspects of the insulin resistance syndrome in relation to plasminogen activator inhibitor-1 (PAI-1) activity are investigated in a longitudinal population-based study. Participants were men investigated at ages 50 and 70 with follow-up data on mortality. High PAI-1 activity was associated with low insulin sensitivity, high concentrations of serum triglycerides, high body mass index and high waist/hip ratio, independently of each other and of potential confounders. Low birth weight predicted high blood pressure, insulin resistance, truncal obesity and high PAI-1 activity but not the abdominal obesity or dyslipidaemia present in the insulin resistance syndrome. Increased physical activity level between 50 and 70 years of age, in the absence of active intervention, was associated with improved glucose, insulin, proinsulin and lipoprotein metabolism. Insulin and proinsulin seemed to be important factors that mediate much of the association between a sedentary lifestyle and increased risk of cardiovascular disease. The reported dietary intake of both mono- and polyunsaturated fatty acids was positively associated with PAI-1 activity, whereas saturated fatty acid intake displayed no association. The associations present between PAI-1 activity and the fatty acid proportions in serum cholesterol esters were partly influenced by factors related with the insulin resistance syndrome. This thesis provides further knowledge to the epidemiological view of the interrelations of the insulin resistance syndrome, PAI-1, birth weight, and lifestyle factors as physical activity and dietary habits. PAI-1 is a part of the insulin resistance syndrome and is associated both with modifiable and non-modifiable factors related with this syndrome.

<b>VLBW adolescents</b> We found that the VLBW adolescents had specific emotional and cognitive traits. Some of them fit with psychiatric concepts and others do not. They had an increased risk of developing psychiatric symptoms and disorders compared with controls, especially attention deficit, anxiety and relational problems affecting their social skills and overall functioning. Academic achievement was reduced. The attention problems were widespread, but only a minority fulfilled the diagnostic criteria of Attentiondeficit/ hyperactivity disorder. Increased prevalence of anxiety symptoms and disorders may be due to a number of factors, comprising both biological/neuroendocrine and psychosocial mechanisms. The peer problems and deficits in social skills may indicate specific difficulties in relating and adjusting to others, with deficits in comprehending the subtle cues of social relations. The implication of thought problems reported by teachers is unclear. Adolescents with birth weight ≤ 1000 g showed a tendency towards more psychiatric disorders than those with birth weight between 1000 and 1500 g. The lack of gender differences demonstrates that prematurity exceeds the usual effect of gender regarding vulnerability for developing psychiatric symptoms. We found that the VLBW adolescents perceived self-esteem and quality of life as others did at the age of 14. However, parents reported functional disadvantages and reduced quality of life measures for their adolescents. The parents worried more for their children’s functioning and well-being, especially if the child had a psychiatric disorder or cerebral palsy. Still, being born VLBW did not influence the warmth in the parent-child relationship, nor did the parents have more mental health problems. As the association between VLBW and psychiatric problems could not be explained by SES or the parents’ mental health, a biological cause-effect relationship seems plausible. The frequency of cerebral MRI abnormalities was higher in the VLBW group than in the control group. Furthermore, ADHD symptoms were associated with white matter reduction and thinning of the corpus callosum, while other psychiatric symptoms were not associated with MRI abnormalities. These results support the hypothesis of a specific (“pure”) type of ADHD with a dominant neurological aetiology, while interacting psychosocial experiences play a minor part. Our study indicates that being born VLBW involves a biological vulnerability with increased risk of psychiatric symptoms. <b>SGA adolescents</b> Although every fifth SGA adolescent had psychiatric symptoms, assessed by interview, the prevalence of symptoms and disorders did not differ significantly from controls. Yet, screening questionnaires displayed more behavioural problems, lowered social competence and a tendency towards attention deficit/hyperactivity. Teachers reported withdrawal and thought problems, while academic performance did not differ from controls. Boys had more attention and externalizing problems than girls. Generally, on psychiatric measures, the term SGA group seemed to fall inbetween the VLBW and the control group, resembling the control group more than the VLBW group. The SGA adolescents and their parents reported self-esteem and quality of life as in the control group. Being born SGA at term did not influence the warmth in the parent-child relationship, and the parents did not have more mental health problems than others. The frequency of cerebral MRI abnormalities in the SGA group did not differ from the control group, and no associations were found between psychiatric symptoms and MRI abnormalities. / Paper V reprinted with kind permission of Elsevier, sciencedirect.com

No description available.

Background: A multitude of studies suggest an association between periodontal disease and adverse birth outcomes. Although the evidence is controversial, it is biologically plausible, and the key link maybe inflammation. Purpose: To correlate levels of periodontal disease as measured by conventional methods with PMN counts from an oral rinse in pregnant women. Methods: Sixty-three pregnant women were recruited. Periodontal examinations were carried out. Fifteen-second saline rinses were collected. ABTS, a colour changing redox agent was added to each rinse. The intensity of the colour reaction was measured by absorbance to count the oral PMNs. Results: A statistically significant difference in oral PMN counts was observed between those with periodontal disease and the healthy patients (P < .05). The sensitivity and specificity using the bleeding index was 0.94 and 0.76 respectively. Conclusions: The rinse assay can be used as a screening tool for periodontal disease and oral inflammation in pregnant women.

Background: A multitude of studies suggest an association between periodontal disease and adverse birth outcomes. Although the evidence is controversial, it is biologically plausible, and the key link maybe inflammation. Purpose: To correlate levels of periodontal disease as measured by conventional methods with PMN counts from an oral rinse in pregnant women. Methods: Sixty-three pregnant women were recruited. Periodontal examinations were carried out. Fifteen-second saline rinses were collected. ABTS, a colour changing redox agent was added to each rinse. The intensity of the colour reaction was measured by absorbance to count the oral PMNs. Results: A statistically significant difference in oral PMN counts was observed between those with periodontal disease and the healthy patients (P < .05). The sensitivity and specificity using the bleeding index was 0.94 and 0.76 respectively. Conclusions: The rinse assay can be used as a screening tool for periodontal disease and oral inflammation in pregnant women.

Adverse birth outcomes have many causes but there is increasing awareness that air pollution is one of them. This study examines the effects of air pollution on infant health and mortality using data from the State of Georgia. The estimation methods control for potential endogenous variables such as the length of gestation and the demand for prenatal care. Moreover dummy-fixed effects are used to control for unobserved neighborhood characteristics using the place of residence of the mother. In addition, the model uses a comprehensive framework, which considers birth weight, length of gestation, and mortality, thus allowing pre and postnatal assessment of the impact of air pollution on health. The empirical results show moderate evidence of an effect of air pollution on low birth weight and length of gestation and found a more substantive effect on infant mortality.

SAIDA SHARAPOVA The role of stress in racial disparities of preterm and low birth weight births in Georgia (Under the direction of Richard Rothenberg, MD, MPH) Preterm birth (PTB) and low birth weight (LBW) are the leading causes of infant deaths in Georgia. Georgia PRAMS data (2004-2008) were analyzed for non-Hispanic White and non-Hispanic Black women with singleton births, using SAS 9.2 survey procedures. Thirteen stressful life events experienced in a year before delivery, socio-demographic, medical and behavioral risks were used as predictors of PTB and LBW. Significant racial disparity in birth outcomes and risks was found. In Whites stressful events were associated with adverse birth outcomes in bivariate logistic regression, but weakened when controlling for other factors (income, education, maternal age, maternal health, alcohol and tobacco use, infant’s gender and birth defects). In Blacks, association between stressful events and adverse birth outcomes adjusted for other risks was stronger. Socio-economic factors and mother’s health status were more significant in predicting birth outcome. Women’s health and SES improvement might increase favorable pregnancy outcomes and reduce racial disparities.