Includes bibliographic references. / 1 v. (various foliations) : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Details the results of in vivo and in vitro studies into the effects of zinc deficiency, hypervitaminosis A, alcohol, nicotine and salicyclic acid, at the morphological and ultrastructural levels in the developing embryo. / Thesis (Ph.D.)--University of Adelaide, Dept. of Anatomy and Histology, 1992

Research Doctorate - Doctor of Philosophy (PhD) / Maternal asthma is associated with low birth weight, a risk factor for disease in adult life. To determine the mechanisms involved, the relationships between mother, placenta and fetus were examined in asthmatic and non-asthmatic pregnancies. Maternal asthma and its treatment (no glucocorticoid or glucocorticoid) was monitored throughout pregnancy. Fetal growth was examined during gestation, and at birth, neonatal size and sex were determined. Placental 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) enzyme activity and umbilical vein plasma cortisol and estriol concentrations were measured. Placental cytokine, growth factor and glucocorticoid receptor (GR) mRNA were determined using quantitative RT-PCR. Birth weight of female neonates in the no glucocorticoid asthmatic group only, was significantly reduced compared to females of the non-asthmatic group. Male neonates were unaffected by asthma or its treatment. Asthmatic women pregnant with a female fetus showed a significant increase in circulating monocytes and glucocorticoid treatment as pregnancy progressed, while those pregnant with a male fetus did not, suggesting that maternal asthma worsens in the presence of a female fetus. 11beta-HSD2 activity was significantly reduced in placentae from female neonates of the no glucocorticoid group compared to other female neonates and was associated with a trend towards higher plasma cortisol, reduced fetal adrenal activity demonstrated by lower cord blood estriol, reduced placental GR expression, no alteration in placental or fetal insulin-like growth factors or their binding proteins and a significantly increased Th2:Th1 cytokine mRNA ratio, which was inversely correlated with 11beta-HSD2 activity in all females. Reduced placental 11beta-HSD2 activity may be an important component leading to decreased female fetal growth in pregnancies complicated by asthma. This study provides strong evidence for a fetal sex-specific effect on the maternal immune system which can have adverse effects on the female fetus. The female fetus alters maternal inflammatory pathways, which when not controlled by the use of inhaled glucocorticoids results in reduced placental 11beta-HSD2 activity, contributing to suppressed fetal adrenal function and a late gestation decrease in female fetal growth.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 5 uppsatser.

Thesis (Ph.D.)--University of Adelaide, Dept. of Obstetrics and Gynaecology, 1999? / Bibliography: p. 190-234.

Thesis (M. Phil.)--University of Hong Kong, 2009. / Includes bibliographical references (leaves 182-187) Also available in print.

Pregnancy complications such as fetal growth restriction (FGR) are often attributed to poor uteroplacental blood flow, but the risk of systemic side-effects hinders therapeutic intervention. We have utilised novel placental-specific homing peptides to overcome this and have conjugated these to biocompatible liposomes. Peptide-conjugated liposomes were found to selectively bind to the outer syncytiotrophoblast layer of the human placenta and to the uteroplacental vasculature and labyrinth region of the mouse placenta. The novel vasodilator SE175 was selected as a nitric oxide donor with a favourable stability and release profile, to encapsulate in peptide-conjugated liposomes in an attempt to restore impaired uteroplacental blood flow in a mouse model of FGR, the endothelial nitric oxide synthase knockout mouse. Liposomes containing SE175 or PBS were prepared by lipid film hydration and targeting peptides coupled to the liposomal surface. Vehicle control, free SE175, PBS- or SE175-containing liposomes were intravenously injected on embryonic (E) days 11.5, 13.5, 15.5 and 17.5. Animals were sacrificed at E18.5 and fetal and placental weights recorded. Targeted delivery of SE175 significantly increased fetal weight compared to vehicle control but no other treatment groups, whilst significantly decreasing placental weight, indicating improved placental efficiency. Treatment was well tolerated, having no impact on litter size or resorptions. Targeted delivery of SE175, but no other treatment group, reduced a marker of lipid peroxidation in the placenta, indicating a reduction in oxidative stress. These data suggest that selective delivery of SE175 to the uteroplacental vasculature in peptide decorated liposomes may represent a novel treatment for FGR.

Adequate placental function is essential for the growth and development of a healthy fetus. A major cause of abnormal placental function is thought to occur from inadequate maternal spiral artery remodelling, leading to maternal vascular malperfusion (MVM) of the placenta and ultimately fetal growth restriction (FGR) and stillbirth due to uteroplacental hypoxia. Current methods of investigating a pregnancy at risk of FGR rely on ultrasound estimations of fetal size and Doppler studies. A more informative measure may be to quantify placental function in-vivo. Magnetic resonance imaging (MRI) has the ability to assess placental oxygen saturation (sO2), using Blood Oxygen-Level Dependent (BOLD), and the partial pressure of oxygen (pO2) using Oxygen-Enhanced MRI (OE MRI). These MRI techniques have been shown to correlate with gestation and poor pregnancy outcomes in cross sectional studies. MRI measures of placental oxygenation are hypothesised to be a potential antenatal tool for the identification and stratification of high risk pregnancies at risk of FGR related to uteroplacental hypoxia. To address this hypothesis changes in placental oxygenation, following maternal hyperoxia, were calculated in normal and FGR pregnancies in a cross sectional study. The change in placental oxygenation was reproduced longitudinally to determine if the rate of change differed between normal and FGR pregnancies. Baseline placental MRI parameters (R1 and R2*) and measures of the change in oxygenation were incorporated into a diagnostic model to identify FGR related to uteroplacental hypoxia, which was provisionally tested in a group of high risk pregnancies to demonstrate its potential clinical utility. Placental measures of baseline R1 and R2* were significantly increased in FGR pregnancies. The change in placental pO2 following hyperoxia was found to be significantly lower in FGR pregnancies. The change in pO2 declined similarly with gestation in both cross sectional and longitudinal studies, in normal and FGR pregnancies. There were no significant correlations in the change in placental sO2 with gestation or pregnancy outcome. The use of a diagnostic model combining baseline R1 and R2* and pO2 measures identified FGR with a high specificity, and provided additional information to aid in disease stratification and decision making in a significant proportion of the high risk pregnancies tested. In conclusion, MRI parameters of placental pO2 following hyperoxia are significantly lower in FGR pregnancies, in keeping with the concept of uteroplacental hypoxia. MRI techniques show promise in the identification of FGR pregnancies related to MVM through measures of placental function, irrespective of fetal size, and may aid in the disease stratification of high risk pregnancies.

Made available in DSpace on 2014-06-11T19:27:44Z (GMT). No. of bitstreams: 0 Previous issue date: 2006-12-21Bitstream added on 2014-06-13T19:56:27Z : No. of bitstreams: 1 vasconcellos_fc_me_botfm.pdf: 189391 bytes, checksum: 33e6d5f06fedd24bce2229365664f27c (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / A medida ultra-sonográfica seriada da circunferência da coxa fetal (CCx) tem se mostrado excelente parâmetro na identificação de desvios no crescimento e no desenvolvimento fetal após o segundo trimestre da gestação. Sua utilização como parâmetro biológico complementar em patologias como Diabete Mélito Gestacional (DMG) ou em patologias que ocasionem Restrição do Crescimento Intra-Uterino (RCIU), em especial nas de tipo assimétrico, está bem documentada. Baseia-se na capacidade inerente da coxa fetal em acumular tecidos moles e de seu crescimento linear do volume, área e circunferência. A mensuração da coxa fetal tem como principal objetivo identificar desvios no crescimento, pois sua relação com o comprimento do fêmur permanece inalterada após a vigésima semana de gestação. A introdução mais recente da ultrasonografia tridimensional agregou novos parâmetros de avaliação do crescimento fetal, como o volume da coxa, tornando mais precisas e simplificadas a medida e a avaliação da massa de tecidos moles fetais. / Fetal thigh circumference (CCx) serial ultrasound measurement has shown to be an excellent parameter in identifying fetal growth and development deviations following the second quarter of pregnancy. Its use as a supplementary biological parameter in pathologies such as Gestational Diabetes Mellitus (GDM) or in pathologies leading to Intrauterine Growth Restriction (IUGR), specially the asymmetric type, is well documented. It is based on the fetal thigh inherent ability to accumulate soft tissues, and its volume, area and circunference linear growth. Fetal thigh measurement primary objective is to identify growth deviations, because its relation to the femur length remains unaltered following the twentieth gestation week. The most recently introduced three-dimensional ultrasound added new fetal growth assessment parameters, such as thigh volume, leading to more precise and simplified fetal soft tissue measurement and assessment.

Objetivos. Avaliar os fatores prognÃsticos para o Ãbito neonatal em gestaÃÃes com diÃstole zero ou reversa na dopplervelocimetria da artÃria umbilical MÃtodos. Estudo transversal a partir dos prontuÃrios das gestantes com diagnÃstico de diÃstole zero (DZ) ou reversa (DR) em artÃria umbilical acompanhadas no ServiÃo de Medicina Materno Fetal da Maternidade-Escola Assis Chateaubriand â Universidade Federal do CearÃ. Foram analisadas 48 pacientes com gestaÃÃo Ãnica, sem anomalias estruturais ou cromossÃmicas, apresentando idade gestacional superior a 22 semanas e menor do que 34 semanas. Para a avaliaÃÃo estatÃstica, foram empregados os testes: t Student, Exato de Fisher, Qui-quadrado de Pearson e RegressÃo LogÃstica e Multinomial. Todos foram considerados estatisticamente significantes quando p<0,05. Resultados. As sÃndromes hipertensivas foram observadas na maioria (78,3 %) das gestantes. A maioria (52,1%) das gestaÃÃes foi resolvida nas primeiras 24 horas apÃs o diagnÃstico dopplervelocimÃtrico. Em uma semana, 81,3% dos casos tinham terminado em parto, preferencialmente (85,4%) pela via abdominal. Os maiores percentuais da idade gestacional no momento do diagnÃstico dopplervelocimÃtrico concentraram-se na faixa de 25 e 27 semanas. Os pesos do RN variaram entre 550g e 2600g, com mÃdia de 1021,7g. Os recÃm-nascidos foram classificados como pequenos para idade gestacional em 79,1% dos casos. Ao primeiro minuto de vida, 24 (57,1%) RN apresentaram Ãndices de Apgar menores do que 7. Ocorreram 26 Ãbitos neonatais. Do estudo estatÃstico univariado dos fatores de risco antenatais, a idade gestacional no momento do diagnÃstico dopplervelocimÃtrico revelou-se variÃvel significativamente relacionada com o Ãbito neonatal (RR; 2,1, 95% CI 1.152 â 4.008, p = 0.011). Do estudo estatÃstico univariado dos fatores de risco pÃs-natais peso do RN (RR; 2,6, 95% CI 1.329 - 5.238, p = 0.001) e Apgar ao primeiro minuto (RR; 1,9, 95% CI 1.03 â 3.588,p = 0.027) revelaram-se variÃveis significativamente relacionadas com o Ãbito neonatal, com peso do RN apresentando sensibilidade de 76,9%, especificidade de 73,6%, valor preditivo positivo de 80,0% e valor preditivo negativo de 30%, e Apgar ao primeiro minuto apresentando sensibilidade de 61,5%, especificidade de 61,1%, valor preditivo positivo de 69,5% e valor preditivo negativo de 47,6%. ConclusÃes. DiÃstole zero ou reversa estÃo relacionadas com resultados perinatais adversos, cujo risco para Ãbito neonatal està relacionado com a idade gestacional no momento do diagnÃstico dopplervelocimÃtrico e com o peso do RN e com Apgar ao primeiro minuto. / Objectives: evaluate the perinatal results in pregnancies with fetal brain sparing on the Doppler velocimetric study and identify the main prognostic factors associated with neonatal death. Methods: it is a transverse study from the charts of pregnant wowen with diagnosis of brain sparing, absent or reversed end-diastolic flow in the umbilical artery, followed at the Service of Maternal-Fetal Medicine of Maternidade-Escola Assis Chateaubrind â Universidade Federal do CearÃ. There were analyzed 143 patients with single pregnancies, without structural or chromosomal anomalies, presenting gestacional age above 22 weeks and fetal weight equal or above 500 grams. ROC curve was constructed for gestacional age and weight at birth (independent variables) and neonatal death (dependent variable). The perinatal results were evaluated on the general population and on each group (brain sparing, absent and reversed end-diastolic flow), later compared with each other. For the statistical analisys it was utilized the tests: Shapiro-Wilk, Levene, t Studente, Mann-Whitney, ANOVA, Kruskal Wallis, Fisher. Chi-square, Logistical and Multinomial Regression. All were considered statistically significant when p < 0.05. Results: the majority of pregnante wowen (78.3%) presented some hypertensive disturb associated to the pregnancy. The pregnancy was resolved in the first 24 hours after Doppler velocimetric diagnosis on most cases (74.8%), being the abdominal acess utilized in 96.5% of the times. At the moment of delivers, the average gestational age was 33.6 weeks and the weight was 1684g. The newborns were classified as small for gestational age in 69.6% and needed ICU admission in 63% of the cases. The indexes of perinatal mortality for brain sparing, absent and reversed end-diastolic flow were respectively 11.1, 31.1 and 70.6%. The weight of the newborn (area bellow the ROC curve 0.934, p=0.000 and gestational age at birth (area 0.909, p=0.000) have shown to be good predictors of neonatal death. The cutoff point calculated for the weight was 1010g and for the gestational age as 32.5 weeks. The incidence of diminished amniotic fluid indez (AFI) in the pregnancies with lethal perinatal outcome was 41.2% and in those without lethality was 41.3%. Conclusions: fetuses with diagnosis of brain sparing, absent and reversed end-diastolic flow presented progressively worse and statistically different with each other prognosis. The gestational age and weight at birth showed excellent correlation with neonatal mortality. The AFI did not demonstrate association with lethality rate.

M.Tech. (Radiography) / Monitoring the growth and wellbeing of the foetus is a major purpose of antenatal care. The use of diagnostic ultrasound to assess foetal wellbeing has become an important part of prenatal care in both low and high risk pregnancies. Pre-eclampsia and foetal growth restriction (FGR) remains important causes of maternal and perinatal mortality and morbidity. Pre-eclampsia is characterised by an abnormal vascular response to placentation and is a multisystem disorder of unknown cause specific to pregnancy which affects the health of both mother and fetus. Prep-eclampsia complicates between 2 and B % of all pregnancies and is the second most common cause of maternal deaths in the developing world. The aim of this study was to assess the sensitivity of uterine artery spectral Doppler screening in the prediction of pregnancies with a high risk of developing pre-eclampsia or FGR before the clinical onset of the disease. The research objectives were to: 1) Determine the sensitivity of first and second trimester uterine artery spectral Doppler assessment in predicting pre-eclampsia or FGR Identify associations between normal and abnormal uterine artery Doppler waveforms and pregnancy outcomes. 2) Determine the most effective Doppler indices 3) Develop ultrasound management guidelines The data was statistically analyzed to determine the sensitivity of uterine artery Doppler screening. In this study uterine artery Doppler screening performed well. in the risk assessment of the most severe cases of pre-eclampsia and FGR. A larger prospective multicenter trial in South Africa is long overdue and therefore a follow-up study to assess Doppler as a screening tool in a high risk population, as per the guidelines formulated.