Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 5 uppsatser.

Diss. (sammanfattning) Linköping : Linköpings universitet, 2007. / Härtill 4 uppsatser.

Objectif : Établir le profil psychosocial des femmes enceintes de l'Estrie et évaluer de façon préliminaire si ce profil diffère parmi les grossesses avec issues défavorables. Méthode. Cohorte prospective de 120 femmes enceintes, rencontrées à deux reprises (10-20 et 25-30 semaines), entre août 2004 et mars 2006. Il s'agit d'un questionnaire auto-administré des données démographiques, anthropométriques, des facteurs de risques biomédicaux, ainsi qu'un profil psychosocial comportant 6 dimensions: stress psychologique perçu, ennuis quotidiens, détresse psychologique, locus de contrôle, soutien social, traumatismes dans l'enfance. Les paramètres psychosociaux sont présentés en moyennes ou pourcentages. Le profil psychosocial est comparé entre les grossesses normales et anormales avec les tests t de Student ou le test de Mann Whitney, lorsque approprié. Résultats. Trente trois grossesses (27,5%) ont présenté des issues défavorables (prématurité, restriction de croissance intra-utérine, hypertension gestationnelle, diabète gestationnel). L'analyse du profil psychosocial révèle un score de stress psychologique perçu plus élevé entre 10-20 semaines chez les femmes avec issues défavorables de grossesse (score : 34,2 « 12,3 ; P < 0,01) et chez les femmes avec prématurité (score : 36,1 « 11,2 ; P < 0,02) comparativement à celui des femmes avec grossesses normales (score : 28,6 « 9,6). Par ailleurs, les 5 autres dimensions ne semblaient pas différentes selon les issues de grossesse. Conclusion. Ces résultats préliminaires suggèrent une piste possible reliant la perception de stress maternel durant la grossesse et certaines issues défavorables de grossesse, dont l'accouchement prématuré.

O objetivo deste estudo foi comparar a morbidade e a mortalidade entre prematuros tardios (34 a 36 semanas e 6 dias de idade gestacional ao nascimento) com e sem restrição do crescimento fetal (RCF). O estudo foi desenvolvido longitudinalmente, envolvendo gestantes que apresentaram parto prematuro, sendo 50 com RCF (Grupo I) e 36, sem RCF (Grupo II), no período de outubro de 2004 a outubro de 2006. Foram avaliados os seguintes resultados pós-natais: peso e idade gestacional (IG) ao nascimento, cesárea, Apgar de quinto minuto, pH do sangue da artéria umbilical ao nascimento, necessidade e tempo de intubação orotraqueal (IOT) e de internação na unidade de terapia intensiva neonatal (UTI). Foram também avaliados: síndrome do desconforto respiratório (SDR), sepse, plaquetopenia, hipoglicemia, hemorragia intracraniana (HIC), icterícia e necessidade de fototerapia, tempo de internação e ocorrência de óbito. Para análise estatística foram utilizados os testes de Qui-Quadrado, exato de Fisher e teste não paramétrico de Kruskal Wallis, adotado nível de significância de 5%. As idades gestacionais avaliadas foram semelhantes nos dois grupos, com média de 35,5 semanas. Observou-se, no grupo I, maior freqüência dos seguintes resultados pós-natais adversos: menor peso ao nascimento (p<0,001), maior incidência de cesárea (92% versus 25% do grupo II; p<0,0001), maior necessidade de internação em UTI (58% versus 33%; p=0,041), maior tempo de internação (p<0,001) e de internação em UTI neonatal (p<0,001), maior ocorrência de HIC (12% versus 0; p=0,037), maior ocorrência de hipoglicemia (p= 24% versus 6%; 0,047) e maior tempo de fototerapia (p=0,005). Os grupos não apresentaram diferenças nos índices de Apgar, pH de cordão, IOT, SDR, plaquetopenia, sepse e icterícia. Não houve casos de doença de membrana hialina, displasia broncopulmonar, hemorragia pulmonar ou óbito neonatal. Pode-se concluir que o grupo de prematuros tardios com RCF apresentou mais complicações neonatais do que o grupo sem RCF / The objective of this study was to compare neonatal morbidity and mortality between late-preterm infants (gestational age at birth: 34 to 36 weeks and 6 days) with and without fetal growth restriction (FGR). A longitudinal study was conducted between October 2004 and October 2006 involving 50 pregnant women with pre-term delivery associated with FGR (group I) and 36 women with spontaneous preterm delivery not associated with FGR (group II). The following postnatal outcomes were evaluated: weight and gestational age at birth, cesarean section rate, 5-minute Apgar score, umbilical artery pH at birth, and need for and duration of orotracheal intubation and hospitalization in the neonatal intensive care unit (NICU), as well as the presence of respiratory distress syndrome (RDS), sepsis, thrombocytopenia, hypoglycemia, intracranial hemorrhage (ICH) and jaundice, need for phototherapy, length of hospital stay, and occurrence of death. The chi-square test, Fishers exact test and nonparametric Kruskal-Wallis test were used for statistical analysis, adopting a level of significance of 5%. Gestational age was similar in groups I and II, with a mean of 35.5 weeks in both groups. A higher frequency of the following adverse postnatal outcomes was observed in group I: lower birth weight (p<0.001), higher incidence of cesarean section (92% versus 25% in group II; p<0.0001), greater need for NICU treatment (58% versus 33%; p=0.041), longer hospital (p<0.001) and NICU stay (p<0.001), higher frequency of ICH (12% versus 0; p=0.037) and hypoglycemia (24% versus 6%; p=0.047), and longer duration of phototherapy (p=0.005). No differences in Apgar scores, cord pH, orotracheal intubation, RDS, thrombocytopenia, sepsis, or jaundice were observed between groups. There were no cases of hyaline membrane disease, bronchopulmonary dysplasia, pulmonary hemorrhage, or neonatal death. In conclusion, the group of late-preterm infants with FGR presented more neonatal complications than the group without FGR

Wang, Xiao. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 32-37). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts also in Chinese.

Fetal growth restriction (FGR) is a common and potentially life-threatening complication that affects 5-10% of human pregnancies. Maternal genetic predisposition and fetal male sex are known risk factors, but the underlying mechanisms are unknown. To study a known maternal genetic risk factor and the impact of fetal sex, we employed a published transgenic (TG) mouse model, which was designed to mimic a common human angiotensinogen (AGT) promoter variant associated with a 20% increase in circulating AGT levels. We hypothesized that TG dams would deliver growth restricted pups and that the underlying mechanism would be related to differences in maternal uterine pregnancy-induced vascular remodeling, abnormal blood flow to the placenta, and placental damage. In addition, since growth restricted human males are at an increased risk of developing adult onset hypertension, which has been associated with reduced nephron development, we tested for developmental programming in our mouse model and the impact of fetal sex. Our results show that TG dams have reduced uterine and placental angiogenesis when their pups were males, but relatively normal angiogenesis in the female siblings compared with wild-type controls. The uterine placental bed in TG dams had abnormal pro-angiogenic/anti-angiogenic expression ratios that were related to differences in uterine natural killer cell activation and fetal sex. The abnormal phenotype could be rescued by delivering vascular endothelial growth factor (VEGF) to uterine endothelial cells. Male progeny from TG dams had abnormal kidney epigenetic changes, fewer nephrons as adults, and they developed stress-induced hypertension. We conclude that the combination of maternal genetic risk and fetal male sex affect uteroplacental angiogenesis leading to FGR and the programming of stress-induced hypertension.

Abstract not available

Intrauterine Growth Restriction (IUGR) is evident in infants born with a reduced weight or length, and/or increased thinness for gestational age. IUGR is associated with altered postnatal growth and regulation, due to unknown mechanisms. Much clinical IUGR results from the reduced delivery of essential substrates (oxygen and nutrients) to the fetus, due to either maternal or placental limitations. Catch-up growth (accelerated rate of growth in absolute or fractional terms) occurs in the majority of IUGR infants, and returns an infant to their predetermined growth curve. IUGR is associated with increased risks of morbidity and mortality in the perinatal period, and with a reduced final adult stature and increased risk of adult onset diseases, particularly diabetes and cardiovascular disease. Catch-up growth after IUGR predicts improved health in terms of reduced hospital visits in infants and children, and an increased final adult stature but also predicts an increased risk of developing obesity, as well as diabetes and cardiovascular disease. The underlying mechanisms for catch-up growth may contribute to this range of outcomes in later life, but are poorly understood. Studies in IUGR infants have demonstrated increased absolute and/or fractional growth rates following birth, termed catch-up growth, in the presence of reduced or normal plasma concentrations of the thyroid hormones and major anabolic hormones (insulin and/or IGF-I). This suggests that increased sensitivity to, rather than increased production of insulin, IGF-I and thyroid hormone, causes catch-up growth following IUGR. We therefore hypothesised that placental restriction of fetal growth would reduce size at birth and increase postnatal growth and adiposity in association with increased metabolic sensitivity to insulin, IGFs and thyroid hormones. This study has shown that the placentally restricted (PR) lamb has a reduced size at birth in terms of soft and skeletal tissues, has increased rates of growth postnatally, and has increased adiposity by six weeks of age. We have also shown that PR of fetal growth in the sheep did not alter gestational age at delivery, but reduced survival rate. PR lambs demonstrated catch-up growth in most parameters by 30 days of age and increased adiposity at six weeks of age compared to the control lambs. Placental restriction increased insulin and IGF sensitivity of circulating free fatty acids, which in turn, predicts increased adiposity. Neonatal catch-up growth after fetal growth restriction was substantially predicted by both abundance of, and metabolic sensitivity to insulin, suggesting increased insulin action as an underlying cause. Catch-up growth occurs in the neonate despite reduced concentrations of fasting plasma IGFs, along with increased IGF sensitivity of free fatty acid metabolism and adiposity. Plasma TH concentrations predicted growth of soft and skeletal tissue in lambs during early postnatal life, particularly in those undergoing catch-up growth following PR. Therefore neonatal catch-up growth after IUGR is associated with increased sensitivity to both insulin and IGFs, particularly of circulating free fatty acids, and appears to occur to the extent allowed by the prevailing abundance of these hormones and of thyroid hormones. If this altered endocrine state persists, increased adiposity and its subsequent amplification may contribute to the development of obesity, and related adverse metabolic and cardiovascular outcomes in adult life. / Thesis (Ph.D.)--School of Molecular and Biomedical Science, 2004.

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

The purpose of this study was to look at the genotoxic and cytotoxic effects of benzo-á-pyrene (BáP), a chemical mutagen that is present in cigarette smoke, on the insulin-like growth factor-I (IGF-I) gene. Women who smoke during pregnancy are more likely to have a growth-restricted baby. We hypothesized that BáP exerts its effects through genotoxic and cytotoxic avenues. The cytotoxicity is manifested by chromosomal abnormalities and a decrease in the rate of cell division. The genotoxicity is manifested by changes in certain genes known to be important in mammalian fetal development such as IGF-I. IGF-I is implicated in intrauterine growth restriction (IUGR), a problem that greatly increases the risk of perinatal morbidity and mortality. To futher understand the mechanism by which BáP influences the normal growth and development of human placental cells, human placental trophoblast cells from an established immortalized cell line were utilized. Cells were cultured in appropriate media, starved (using starvation "Serum Free Medium"), and treated with two doses of BáP, 1µM (dose 1) and 5µM (dose 2). Chromosomes were prepared for cytogenetic analysis and visualized using light microscopy after Giemsa staining. Chromosomal aberrations were identified and the rate of cell division was determined through the analysis of the mitotic index for treated cells compared to a control group. To further understand the influence of BáP on the IGF-I gene expression level, RNA was extracted from control and treated cells, from which cDNA was synthesized and used for further analysis using polymerized chain reaction (PCR). The PCR results were used to better understand the genotoxicity of BáP, while chromosomal aberration analysis was used to determine the cytotoxic effects of BáP on human placental cells. Our results indicate that many chromosomal abnormalities were present in the treated groups compared to the control group. In addition, there was a significant decrease in the mitotic index of the BáP-treated cells (MI=0.3%) verses the control group (MI=0.93%), p value 0.0447. Through the PCR assay, we speculate that there is a dose-related response to BáP of the IGF-I RNA expression level, with low levels in the treated groups compared to the control group. We conclude from these results that BáP influences placental cells at both the gene and chromosome level. It also affects the cell cycle of human placental cells. It is known that smoking is deleterious for fetal development. We believe that the current study brings us closer to understanding the mechanism by which smoking can lead to fetal growth restriction.