In this thesis I used Caenorhabitis elegans as a model of Fetal Alcohol Spectrum Disorder (FASD) to study the physical and behavioral effects of ethanol exposure during embryonic development. Davis et al. (2008) found that ethanol exposure during larval development in C. elegans produced physical/developmental and behavioral effects; however, whether exposure during embryonic development might produce similar outcomes remained to be elucidated. Because the type and degree of effects caused by developmental ethanol exposure was dependent on the pattern of ethanol treatment, in the first part of the thesis I investigated the physical/developmental effects of embryonic exposure to various ethanol doses, exposure durations, onsets and frequencies. I found that exposure to >30% ethanol for an hour during embryonic development was necessary to lower hatch rate, delay reproductive onset, and reduce body size in C. elegans. Furthermore, exposure during early embryonic development caused a larger effect than exposure during later stages, and multiple exposures produced a worse outcome than a single exposure for a comparable duration. In the second part of the thesis, I investigated locomotory activities and habituation of adult C. elegans exposed to various patterns of embryonic ethanol treatment. I found that the rate of locomotion was altered differently by chronic and acute embryonic ethanol exposure, but I did not find any effect in short- or long-term habituation. In summary, I have characterized the pattern of embryonic ethanol exposure necessary to produce physical/developmental effects in C. elegans, and identified the types of exposure conditions that would cause worse outcomes than others; in addition, I have found that embryonic ethanol exposure affects the rate of locomotion in C. elegans. In this thesis, I have established a foundation for the future investigation into the physical and motor defects caused by embryonic ethanol exposure in C. elegans.

No description available.

Con el objeto de determinar qué factores maternos que se asocian a la macrosomía fetal en las gestantes, se realizó una investigación no experimental, transversal tipo caso - control; la muestra estuvo formada por dos grupos: grupo de casos, recién nacidos con diagnóstico de macrosomía fetal y el grupo control, recién nacidos sin diagnóstico de macrosomía fetal. El estudio encontró que las variables asociadas significativamente fueron: civil: estado civil soltero (P: 0,002; OR: 5,851), la ocupación “estudiante (P: 0,002; OR: 5,851), la procedencia “Pocollay” (P: 0,007; OR: 1,910), la multiparidad (P:0,001; OR: 2,073), la edad gestacional postérmino (P:0,001 ; OR: 0,207). Los resultados sugieren brindar atención prenatal con calidad, realizar acciones y aplicar programas vigentes en el país para minimizar los factores que motivan el nacimiento de estos neonatos macrosómicos.

Hemoglobin is an oxygen binding protein in erythrocytes. Hemoglobin is composed of four polypeptide chains. During the fetal stage the type of hemoglobin called fetal hemoglobin (HbF) dominates. After birth HbF is replaced by adult hemoglobin (HbA). HbF persists in concentrations less than 1%. Elevated concentration of HbF in adults exists in different conditions, Talassemi for example. When the uterus is damaged and the fetus doesn’t feel well its blood can pass the placenta barrier and enter the blood stream of the mother. A venous blood sample from the mother is analyzed to determine the status of the fetus. Laboratory Medicine Västernorrland already has two methods for analyzing HbF, one routine and one on call. The routine method needed to be replaced and the possibility to use flow cytometry was investigated. In this study, results from flow cytometry using Fetal Cell Count™ kit was compared to the results from the presently used methods, Kleihauer-Betke and HPLC. Cord blood was diluted with venous blood from an adult with the same blood group in various concentrations. A number of tests were performed and showed a fairly good correlation between the different methods. However more tests will be necessary to draw any clear conclusion.

This study described the hospital morbidity of 194,persons with Fetal Alcohol Syndrome (FAS), born between 1973-1992, who were identified through a major referral center for Saskatchewan children with disabling conditions. Computerized provincial hospital separation data were obtained for 84% of 101 males and 77% of 93 females. Complete hospitalization histories were obtained for 128 patients, and partial histories for 29 patients. This data provided information on 1,556 hospitalizations from January 1, 1973 to November 30, 1992. At least 54% of study group members experienced morbidity as newborns, and 83% of all females and 91% of all males had experienced at least one other hospitalization (excluding the newborn stay) during their life (based on provincial data combined with information from patient follow-up and record reviews). By November 1992 (provincial data only), the mean number of hospitalizations (SD) for males and females age 15-19 years was 8.4 (7.0) and 10.2 (8.1), respectively. For children <5 years the mean (SD) was 6.0 (5.8) for males and 3.1 (4.7) for females. Age and sex-specific hospital separation rates for the FAS group (based only on provincial data pooled from fiscal years 1987-91) were compared to the 1989-90 Saskatchewan rates. The 95% confidence intervals for the rate ratios indicated significantly higher rates for both males and females with FAS <1 year, 1-4 years and 5-14 years of age, relative to children in general. Comparisons were made using Saskatchewan Registered Indian rates, since 88% of the study group was Aboriginal. The 95% confidence intervals indicated significantly higher rate ratios for males with FAS in all age groups, and for females with FAS age 5-14 years, relative to Registered Indians. The rate ratios for females <1 year and 1-4 years may not have achieved significance because of a possible bias toward underestimation, given the higher proportions of missing data in these groups. The results suggest the high rates of hospitalization in children with FAS are not explicable solely by factors associated with racial identity or ethnicity.

Vaccination has proven a cost-effective method of managing infectious diseases, but attempts to develop an effective fetal vaccine have proven difficult due to the immaturity of the immune system and the propensity of the developing immune system to induce tolerance to immunizing antigens. This thesis is concerned with the induction of specific immunity in the second trimester ovine fetus using the oral DNA immunization method. In utero oral delivery of naked DNA plasmid was selected as the method of immunization due to previous successes in the third trimester ovine fetus and the immunostimulatory properties of the bacterial DNA backbone, which may help overcome developmental tolerance. Transfection and expression studies in the third trimester ovine fetus revealed the oral mucosal epithelium as the primary site of transgene expression and functionally active antigen was also localized to lymph nodes draining the oral cavity. Efficient transfection and expression of plasmid following oral delivery was specific to the fetus and correlated with a lesser degree of epithelial differentiation. Oral DNA delivery in the second trimester resulted in detection of transgene activity in 100% of treated fetuses and the level of transgene activity was greater than in fetuses treated in the mid-third trimester. Using a plasmid encoding the gene for bovine herpesvirus-1 truncated glycoprotein D (tgD), immunization studies were then conducted in the second trimester fetus. A new lower age limit for fetal immunization was established at 55-60 days gestation (gestation period is 148 days), which coincides with the appearance of lymphocytes in peripheral tissues. Antigen-specific antibody, interferon-× responses and/or neonatal anamnestic responses were detected in 66% of fetuses immunized between 55 and 84 days gestation. The duration of fetal primary immune responses was equivalent to that achieved in young lambs following optimized DNA vaccination, but the magnitude of fetal immune responses was limited. The persistence of immune memory from the second trimester to birth was consistent with experimental data which showed that the duration of immune memory had a stronger correlation to the duration, as compared to the magnitude, of the primary antibody response. Overall, the experiments within showed that oral DNA immunization of the early second trimester fetus is feasible and not associated with the induction of tolerance. These findings suggest that it may be possible to protect against mother-to-child transmission of infectious pathogens by targeting protection at the level of the fetus.

This thesis examines the experiences of parents who are raising their adopted children who have Fetal Alcohol Effects (FAE). Four married couples, and one single mother, who married after she had raised her sons participated in this study. All are white and middle or upper-middle class. Five adoptive mothers and one adoptive father were interviewed, while their spouses contributed to the study by reviewing the interview transcripts, and discussing issues raised within them. Eight children with diagnosed or suspected FAE are discussed. They are Cree or Saulteaux, and are between the ages of nine and 23 . Through multiple in-depth interviews, and the demographic profile form, richly detailed information was recorded on these families' day-to-day lives: the children's school experiences, learning disabilities and behaviour problems, their strengths, their health and interactions with peers; parents' interactions with professionals, treatments and behaviour management strategies they sought or devised, their use of support groups and other forms of social support and encounters with the criminal justice and mental health systems. <p> Grounded theory methodology was used to analyse the data and a conceptual model was constructed to outline the process of redefining parenting which describes the practical and psychological tasks parents perform as the family evolves over time. A central role is taken by the mothers who become advocates for their children as they undertake a quest for the meaning of their children's behaviour, seek a diagnosis, and try to secure services for them. It was found that people with FAE are misunderstood and misdiagnosed because of their anomalous nature, which often leads to stigmatisation. This thesis attempts to dispel these misconceptions, document the parents' and children's struggles, and identify the types of services these families desperately need.

This study investigated the effect of chronic alcohol exposure on the responses of the maternal hypothalamus-pituitary adrenal axis (HPA-axis) and thyroid hormones throughout gestation using an ovine model. Maternal plasma concentrations of ACTH, cortisol and the thyroid hormones T3, free T4 and total T4 were determined in response to infusion of 0.75, 1.25 and 1.75 g/kg alcohol. Maternal endocrine responses to alcohol administration have been investigated before in rodent models. However, this is the first study using a large animal model (sheep), in which all three human trimester equivalents occur in utero. Different concentrations of alcohol were administered intermittently from gestational day 4 to 132 in a pattern that modeled human binge drinking during pregnancy. Maternal blood samples were collected on specific days (GD 6, 40, 90, 132) and at multiple time-points (0, 0.5, 1, 1.5, 2, 6, 24 hours) and were analyzed to determine blood alcohol concentrations (BACs) and ACTH, cortisol, free T4, total T4 and T3 plasma concentrations. Alcohol readily permeates the placenta and can directly affect fetal cells and tissues. Alcohol also causes endocrine imbalances in the mother and interferes with maternal-fetal hormonal interactions and the mother’s ability to maintain a healthy pregnancy, thus also indirectly affecting fetal development. Sheep receiving either 0.75, 1.25 or 1.75 g/kg alcohol achieved peak BAC values of 93 + 5, 126 + 5 and 183 + 5 respectively. Alcohol exposure resulted in increased plasma ACTH and cortisol concentrations peaking at 2 hours after beginning of the infusion and returning to baseline values at 6 hours after beginning of the infusion. There was no effect of alcohol on any of the plasma thyroid hormone concentrations. Thyroid hormone concentrations changed as a result of progressing pregnancy. Plasma concentrations of total T4 and free T4 were higher on gestational days 6 and 40 compared to GDs 90 and 132, and plasma T3 concentrations were highest on GD 6. The results of this study show that alcohol stimulates the HPA-axis in a dose dependent fashion in pregnant sheep. The response of the HPA-axis to repeated alcohol exposure throughout gestation remained unchanged. Alcohol exposure did not affect the release of thyroid hormones. Thyroid hormone concentrations changed during pregnancy in sheep in a manner similar to changes observed in pregnant women.

No description available.

Dos pacientes con valvulopatía mitral reumática fueron sometidas a comisurotomía mitral abierta con circulación extracorporea (CEC) durante el segundo trimestre de gestación. Ambas pacientes fueron hospitalizadas por presentar insuficiencia cardíaca congestiva, y se propuso cirugía cardíaca abierta para aliviar la sintomatología y prevenir las graves complicaciones de mortalidad maternal y fetal, debido a una severa estenosis mitral que las afectaba. El monitoreo cardíaco fetal (MCF) durante la cirugía cardíaca registró en los dos casos, bradicardia fetal durante el bypass cardiopulmonar. En un intento por mejorar la perfusión placentaria, se aumentó el flujo de perfusión de bomba, registrándose en un caso taquicardia fetal. La clase functional en ambas pacientes y segun la asociación del corazón de Nueva York (NYHA), fue IV en el pre-operatorio y I en el post-operatorio. La superficie del orificio mitral en cada una de ellas se incrementó de 1.0 y 1.1 a 3.0 y 3.3 cm2 respectivamente. El tratamiento produjo buenos resultados y los embarazos llegaron a término, realizándose operación cesarea por trabajo de parto disfuncional en un caso y cesarea electiva con ligadura tubaria en el otro, produciendo dos bebes normales. Ambas pacientes usaron anticoagulantes durante la gestación y no se encontró ningún tipo de malformación congénita en los neonatos. El seguimiento hasta los 2 años de edad demostró un buen desarrollo neurológico y psicomotriz en ambos bebes. Para una adecuada evaluación de nuestro estudio, se hace una revisión de la literatura mundial de todos los casos de CEC en gestantes con monitoreo cardíaco fetal, y nuestra conclusión es que la cirugía cardíaca es el mejor procedimiento alternativo para la mujer embarazada con valvulopatía complicada y resistente al tratamiento médico. Ademas, el uso del MCF durante la CEC nos ayuda a minimizar los riesgos para el feto. Revisada igualmente la literatura nacional, y a nuestro entender, estos son los primeros casos de monitoreo cardíaco fetal durante cirugía cardíaca con CEC en gestantes que se reportan en el Perú.