In recent decades, rates of type 2 diabetes mellitus (T2DM) and diabetic complications have reached epidemic proportions among Canadian Aboriginal people. Evidence in several populations suggests that abnormal birth weight, particularly low birth weight (LBW) and possibly high birth weight (HBW) may be linked to the development of T2DM. LBW often reflects poor maternal health/ nutritional status which may interfere with normal pancreatic development. HBW is a frequent complication of diabetic pregnancies which are associated with obesity and carbohydrate intolerance in adulthood. Since Saskatchewan Aboriginal newborns historically had higher rates of LBW, and more recently have experienced higher HBW rates, it follows that sub-optimal maternal/ fetal health may be important in the epidemic of T2DM in this population.<p> This thesis describes a case-control study that used Saskatchewan Health databases to determine the relationship between birth weight and T2DM. A sample of 846 adult diabetic Registered Indians (RI) were age and sex matched to three control groups: 1) non-diabetic RI, 2) diabetic general population (GP) subjects, and 3) non-diabetic GP subjects. RI subjects were identified as such by the provincial Health Insurance Registration File.<p> The results of this study show a significant association between HBW (> 4000 grams) and T2DM for RI people [odds ratio (OR) 1.63; 95% confidence interval (CI) 1.20, 2.24]. This association increased in strength from the middle to the latter part of this century and was found to be stronger for RI females than RI males. The comparison of birth weights within the four study groups revealed that diabetic RI (16.2%) were significantly more likely (p<0.05) than controls (10.7%,10.0%, 7.5% respectively) to have HBW. An association between LBW and T2DM (< 2500 grams) was not evident within either RI or GP sample populations.<p> The findings of this study support the hypothesis that HBW and its causes may be risk factors for T2DM among RI people. Programs to prevent gestational diabetes, and to diagnose and optimally manage diabetes during pregnancy could help to reduce rates of diabetes in future generations of Aboriginal peoples.

Statistics Canada data indicates that between 2002 and 2006, the late stillbirth incidence (at or beyond 28 weeks gestation) was 3.0/1000 and 4.0/1000 among Canadian and Saskatchewan births respectively. This difference questions the characteristics and associations of late losses in our province; this work aims to assess late Saskatchewan stillbirths in regard to incidence, causes, characteristics, and area-level factors.<p> Accessing Vital Statistics cases (1987 to 2007, n=1119), descriptive statistics and incidence were examined utilizing Chi-square testing and Poisson regression. Associations between variables were evaluated by log-linear models. Area-level factors relating to incidence within census divisions were explored using Poisson regression.<p> Although some variation existed by time and region, women were most often less than 35 years, of moderate parity, non-Aboriginal, had no previous stillbirths, and were not carrying multiple fetuses. Approximately half of the losses were preterm and half were inadequately grown. Incidence per 1000 births differed significantly for Saskatchewan (3.86) and Canada (3.43) with only Canada declining. Several division values were also higher than Saskatoons Division 11. Associations were seen between characteristics; most notably the combination of Aboriginality, increased maternal age, and large-for-gestational-age appeared over-represented compared to live births. Regions with higher proportions of Aboriginal preschoolers or land area with herbicide application had higher incidence (RR = 1.53 and 1.55, p-value less than 0.001). Further work is required to understand Saskatchewans lack of decline, what can be done about areas where incidence is increased, the significance of the associated characteristics as actual risk factors, and how Aboriginality and herbicide influence risk at the individual level.

La macrosomía fetal es un problema de salud pública, definida por muchos autores como peso de nacimiento igual o superior 4000g, el cual, que afecta a diferentes países entre ellos Perú. El presente trabajo tiene como objetivo determinar factores asociados a la macrosomía fetal en el Hospital Hipólito Unanue de Tacna, en el periodo de 2007 – 2012. Se realizó un estudio retrospectivo, de corte transversal, de casos y controles, con datos obtenidos de las Historias Clínicas registradas en el Sistema Informático Perinatal. Durante el año 2007 al 2012, se atendieron 22251 gestantes, nuestra población fue de 2670 recién nacidos macrosómicos comparándose 335 casos con 1005 controles, utilizando Odds Ratio con IC 95%. Los resultados del estudio indican que la Tasa de incidencia de recién nacidos macrosómicos fue de 120 por cada 1000 recién nacidos (RN) vivos y los factores asociados son: Edad ≥ 35 años, Talla >1,60 m, procedencia: distrito Alto de la Alianza, madres casadas, con estudios superiores o comerciantes, la ganancia excesiva de Kg durante el embarazo, multíparas, antecedente de macrosomía, periodo Intergenésico prolongado, edad gestacional por examen físico de 40 y 41semanas. Así como R.N masculino, con longitud ≥ 541mm

The thesis contends that holistic, community-based treatment is preferable to carceral options for offenders with fetal alcohol conditions, presents emerging support for this contention, identifies barriers to the implementation of community-based treatment, and culminates with analyses of ways of influencing policy reform or of legally mandating non-carceral treatment options. Potential avenues that will be examined include:<P> &bull;&#x00A0;&#x00A0; Charter of Rights and Freedoms, s. 15, including an analysis from Eldridge, Law, and Auton, based on the duty to accommodate disabilities;<BR> &bull;&#x00A0;&#x00A0; Constitution Act, 1982, s. 35 and its recognition and affirmation of such relevant treaty right as the alcohol ban, particularly as the ban operates as a contextual factor in a s. 15 Charter analysis as applied to affected treaty beneficiaries; and<BR> &bull;&#x00A0;&#x00A0; Articles 23, 24 and 40 of the Convention on the Rights of the Child, and Article 12(1) of the International Covenant on Economic, Social and Cultural Rights, particularly as they influence the s. 1 analysis under the Charter. <P> A remedy mandating a positive state obligation to provide community-based treatment likely would require favourable cost-benefit analyses, as well as evidence of effectiveness of the treatment (the latter to be studied in a subsequent interdisciplinary Ph.D. program using qualitative research techniques). The implications of a finding of disability and mental disorder related to fetal alcohol conditions will be examined. The present research topic is at the interface of health and justice, and indeed is multidisciplinary in nature as fetal alcohol influences every aspect of affected individuals' lives. Moreover, the problem is situated in its historical, ideological, global, and trans-disciplinary context.

In recent decades, rates of type 2 diabetes mellitus (T2DM) and diabetic complications have reached epidemic proportions among Canadian Aboriginal people. Evidence in several populations suggests that abnormal birth weight, particularly low birth weight (LBW) and possibly high birth weight (HBW) may be linked to the development of T2DM. LBW often reflects poor maternal health/ nutritional status which may interfere with normal pancreatic development. HBW is a frequent complication of diabetic pregnancies which are associated with obesity and carbohydrate intolerance in adulthood. Since Saskatchewan Aboriginal newborns historically had higher rates of LBW, and more recently have experienced higher HBW rates, it follows that sub-optimal maternal/ fetal health may be important in the epidemic of T2DM in this population.<p> This thesis describes a case-control study that used Saskatchewan Health databases to determine the relationship between birth weight and T2DM. A sample of 846 adult diabetic Registered Indians (RI) were age and sex matched to three control groups: 1) non-diabetic RI, 2) diabetic general population (GP) subjects, and 3) non-diabetic GP subjects. RI subjects were identified as such by the provincial Health Insurance Registration File.<p> The results of this study show a significant association between HBW (> 4000 grams) and T2DM for RI people [odds ratio (OR) 1.63; 95% confidence interval (CI) 1.20, 2.24]. This association increased in strength from the middle to the latter part of this century and was found to be stronger for RI females than RI males. The comparison of birth weights within the four study groups revealed that diabetic RI (16.2%) were significantly more likely (p<0.05) than controls (10.7%,10.0%, 7.5% respectively) to have HBW. An association between LBW and T2DM (< 2500 grams) was not evident within either RI or GP sample populations.<p> The findings of this study support the hypothesis that HBW and its causes may be risk factors for T2DM among RI people. Programs to prevent gestational diabetes, and to diagnose and optimally manage diabetes during pregnancy could help to reduce rates of diabetes in future generations of Aboriginal peoples.

Statistics Canada data indicates that between 2002 and 2006, the late stillbirth incidence (at or beyond 28 weeks gestation) was 3.0/1000 and 4.0/1000 among Canadian and Saskatchewan births respectively. This difference questions the characteristics and associations of late losses in our province; this work aims to assess late Saskatchewan stillbirths in regard to incidence, causes, characteristics, and area-level factors.<p> Accessing Vital Statistics cases (1987 to 2007, n=1119), descriptive statistics and incidence were examined utilizing Chi-square testing and Poisson regression. Associations between variables were evaluated by log-linear models. Area-level factors relating to incidence within census divisions were explored using Poisson regression.<p> Although some variation existed by time and region, women were most often less than 35 years, of moderate parity, non-Aboriginal, had no previous stillbirths, and were not carrying multiple fetuses. Approximately half of the losses were preterm and half were inadequately grown. Incidence per 1000 births differed significantly for Saskatchewan (3.86) and Canada (3.43) with only Canada declining. Several division values were also higher than Saskatoons Division 11. Associations were seen between characteristics; most notably the combination of Aboriginality, increased maternal age, and large-for-gestational-age appeared over-represented compared to live births. Regions with higher proportions of Aboriginal preschoolers or land area with herbicide application had higher incidence (RR = 1.53 and 1.55, p-value less than 0.001). Further work is required to understand Saskatchewans lack of decline, what can be done about areas where incidence is increased, the significance of the associated characteristics as actual risk factors, and how Aboriginality and herbicide influence risk at the individual level.

Maternal alcohol abuse during pregnancy can result in a range of structural and functional abnormalities that include lifelong physical, mental, behavioral and learning disabilities, now collectively termed as Fetal Alcohol Spectrum Disorders (FASD). The incidence of FASD is now estimated be as high as 10 per 1000 live births. Each year, 40,000 babies are born with FASD in the United States at an estimated cost of $1.4 million per individual and total cost of $6 billion. Because of the magnitude of this problem and because the incidence has not decreased in spite intensive efforts to educate women to not abuse alcohol during pregnancy, ways to prevent or mitigate the effects of prenatal alcohol exposure must be explored in addition to education. Therefore, we wished to identify the precise mechanisms by which alcohol mediates the neurodevelopmental damage in order to develop intervention/amelioration strategies. The present study was conducted using an ovine model system. The large body mass of the ovine fetus, the longer gestation that is more similar to that of humans, and that all three trimester equivalents occur in utero, make the sheep an excellent model to study the effects of alcohol on the developing fetus. Our study establishes that maternal alcohol exposure does not result in fetal cerebral hypoxia. Instead, alcohol results in hypercapnea and acidemia leading to a cascade of events in the maternal and fetal compartments that include deficits in the levels of glutamine and glutamine-related amino acids, alterations in endocrine axes, oxidative stress, alteration in cardiovascular homeostasis and fetal neuronal loss. Further, we demonstrate that inhibiting the novel two-pore domain acid sensitive potassium channel (TASK) expressed in the cerebellar granule cells and the peripheral and central chemoreceptors may prove to a be potential therapeutic strategy. Preventive strategies that are safe to use in pregnant women and that involve glutamine-related pathways are also suggested. Finally, the study also establishes the beneficial effects of moderate alcohol consumption on the fetal skeletal system.

Bovine horns develop primarily after birth and the presence or absence of horns is due to a single gene. It has been reported that the horn bud appears in the bovine embryo at d 60 of gestation. Our hypothesis is that the gene that determines the presence of horns is expressed in osteoprogenitor cells of the early fetus and will affect the expression of RUNX2, MSX1, MSX2, and/or TWIST1. To test this hypothesis, bovine fetal samples were collected from commercial females at the Caviness Packing Company in Hereford, Texas. Fetuses ranged from d 28 to d 80 of gestation. A survey of the expression of genes from the region on bovine chromosome 1 known to contain the locus that causes horns (IFNAR1 to SOD1), was conducted using qualitative and quantitative RT-PCR, and in situ hybridization. Genes with known roles in osteogenesis and chrondrogenesis (MSX1, TWIST1, RUNX2 and SOX9) were included as positive controls. With the exception of OLIG1, which was only expressed in the brain, all of the genes investigated were expressed in fetal frontal and parietal bones by qualitative RT-PCR. The level of expression of C21orf59, C21orf66, IL10RB, and SFRS15 increased in the frontal bone of horned samples from d 55 to d 70 of gestation. At d 60 of gestation, a change in the shape of the frontal bone was observed, which has been reported to be the developmental stage when the horn bud appears. At this time point, MSX1, TWIST1, RUNX2 and SOX9 were detected in frontal bone, in cells from the osteoblast lineage, as expected. Furthermore, C21orf59, C21orf62, C21or66 and SFRS15 from the polled interval were localized to developing mesenchyme, osteoblasts and/or osteoclasts of the frontal bone, suggesting that each of these genes has a role in intramembranous bone formation. In addition, gradients of expressed C21orf66 and SFRS15 were detected in developing endochondral bone. There was evidence of an antisense transcript of C21orf66 expressed in the same cell types as the sense transcript. Further characterization of this antisense transcript demonstrated that it covered the entire sense transcript. Based on observed expression in the mesenchyme, rather than just in mature osteoblasts or osteoclasts, C21orf66 and/or its antisense transcript become the most likely candidates for the polled locus.

Hypoxia (decreased tissue oxygen levels) has long been considered as a possible mechanism of alcohol-induced developmental deficits, yet research has not conclusively disproved this hypothesis, nor has it provided substantial evidence for a mechanism of developmental alcohol insults involving hypoxia. Previous research has shown that moderate acute doses of alcohol does not induce hypoxemia (decreased arterial oxygen levels), yet these same studies have shown that this same alcohol exposure does transiently decrease cerebral blood flow (CBF). This is significant because although developmental alcohol exposure did not result in hypoxemia, the decreases in CBF seen in these previous studies may induce hypoxia within the brain. Unfortunately, these experiments were only performed after acute doses of alcohol, so it is unknown if a more chronic or repeated alcohol exposure paradigm would have similar effects. The present study examined blood flow in the sheep fetus after repeated alcohol exposure in a bingelike paradigm throughout the third trimester. Additionally, this study examined the fetal neurovascular response to a subsequent infusion of alcohol after the repeated alcohol exposure. This latter experiment was designed to examine the hypothesis that alcohol exposure throughout the third trimester affects the normal responsiveness of the neurovasculature to alcohol (compared to previous research demonstrating acute alcohol-induced decreases in CBF). The results from the present experiments indicate that although few regions were significant, the majority of the regions (especially the brain regions) exhibited a trend for increases in blood flows after alcohol exposure. This phenomenon was especially prominent in the group receiving the lower dose of alcohol. Additionally, the data from this study demonstrated that after repeated alcohol exposures the near-term sheep fetus did not respond to a subsequent dose of alcohol in a similar manner seen in previous experiments when the acute alcohol exposure was administered in alcohol naïve animals. After the final alcohol exposure the subjects in this study had either no effect in terms of blood flow or an increase in CBF. This is opposite to previous observations which demonstrated reduced blood flow in numerous brain regions. The present experiments suggest that alcohol does not induce fetal hypoxia, but does negatively affect the normal neurovascular response to alcohol. This latter phenomenon could have negative consequences on future development of the brain.

Se realizó un estudio prospectivo, cuasi experimental, transversal, comparativo, en 60 pacientes de riesgo obstétrico del Instituto Materno Perinatal (IMP), en la Unidad de Medicina Fetal, entre los meses de octubre y diciembre del 2002. Este estudio corresponde en realizar un Test Estresante o de esfuerzo fetal, considerado como, un tipo de monitoreo electrónico fetal que nos da la información neurológica y cardiovascular fetal; mediante la premisa de la oxigenación fetal provocando un estrés fisiológico de una contracción uterina. El Test Estresante se puede realizar de varias formas, pero las que más se utilizan en la Unidad de Monitoreo Fetal del IMP son: el Test estresante con Oxitocina exógena, que se da por la infusión endovenosa de oxitocina de 10UI diluída en 1000cc de suero salino o solución glucosada; y el Test Estresante con oxitocina endógena, que se da por la estimulación mamaria. Nuestro estudio compara estos dos tipos de estimulación para un Test Estresante, con la finalidad de dar a conocer que el estímulo mamario es el más eficaz. Para este estudio se dividió la muestra en dos grupos: El primer grupo con 30 pacientes, a quienes se les realizó un Test Estresante con estímulo mamario; y el segundo grupo de 30 pacientes a quienes se les realizó un Test Estresante con oxitocina exógena. En el Test Estresante con estímulo mamario se tomó como referencia la técnica de estimulación mamaria empleada por la doctora Ayllon Bulner, Dr. José Huamán y Dra. Nelly Lam. (23) Se obtuvo como resultado, que el Test Estresante con estímulo mamario es más eficaz, hallando un tiempo de latencia de 1 a 4 minutos en el 96.43% de la muestra; en comparación con el Test estresante con Oxitocina exógena en el que se obtuvo un tiempo de latencia de 1 a 4 minutos en el 23.3% de la muestra; mientras que el 76.67% de la muestra, tuvo un tiempo de latencia igual o mayor de 5 minutos. Por lo tanto se encuentra que el tiempo de latencia fue menor en el test estresante con estímulo mamario. También, el tiempo de obtención del patrón de contracciones uterinas va influir en la eficacia del Test Estresante con estímulo mamario, encontrando un tiempo de 1 a 5 minutos en el 82.14% de la muestra, en comparación con el Test Estresante con oxitocina exógena en el que se obtuvo un tiempo de obtención del patrón de contracciones uterinas, de 1 a 5 minutos, en el 13.33% de la muestra. Mientras que el 86.67% obtuvo un tiempo de obtención del patrón de contracciones uterinas en un tiempo mayor o igual a 6 minutos. Por lo tanto se encuentra que el tiempo de obtención del patrón de contracciones uterinas fue menor en el test estresante con estímulo mamario. En el 80.47% del total de la muestra (60 gestantes), el parto se desencadenó dentro de las 48 horas después de terminar el trazado del Test Estresante. El estímulo mamario no sólo puede ser aplicado en un Test Estresante, también se puede emplear en el trabajo de parto, estimulando la liberación de Oxitocina endógena; teniendo en consideración que debe ser indicado a la gestante previa capacitación adecuada en el empleo de la técnica de estimulación mamaria, por supuesto que con un control obstétrico necesario para evitar cualquier eventualidad.