Objectives The aims of this thesis were to (1) investigate the association of gestational exposure to environmental phthalates with maternal and perinatal outcomes, and (2) explore phthalate-induced changes to maternal inflammatory responses as potential mediators of possible health effects. Methods A systematic review was performed to summarize existing evidence on the association of gestational exposure to phthalates with obstetrical outcomes, including pre-eclampsia (PE), pregnancy-induced hypertension (PIH), gestational diabetes mellitus (GDM), intrauterine growth restriction (IUGR), birth weight (BW), head circumference (HC), gestational age (GA), preterm birth (PB), and Apgar scores (AS). Additionally, a secondary analysis of data from the MIREC Study was conducted to evaluate the association of phthalate metabolites with clinical outcomes in the mother and infant using multiple linear and logistic regression, and with inflammatory biomarkers using multinomial logistic regression. Results The systematic review identified a total of 24 articles, and observed inconsistent evidence on BW, HC, GA, and PB, a paucity of research on IUGR, PE, GDM, and AS, and a lack of studies on PIH. However, among studies with statistically significant (p<0.05) results, most suggest an association of phthalates with decreased BW and GA, and increased HC and PB. Findings from the MIREC Study indicate a significant (p<0.01) positive association between MBP and HC among female infants; however, null results were identified for BW, GA, PB, AS, and PIH. In relation to the exposure to phthalates, general trends among suggestive associations (p<0.05) for head circumference showed consistent increases in females and decreases in males, and for gestational age displayed decreases in both stratums. Additionally, a significant positive association of MBzP and ∑DEHP was observed with high MMP-2 and low VCAM levels, respectively. Results approaching statistical significance demonstrated a positive association of ∑DEHP with low MCP1 and ICAM levels, MCPP with low GMCSF levels, MBzP with low CRP and high ICAM levels, and MEP with high MMP-7 and IL-2 levels. Conclusion From the systematic review, the effects of phthalates on maternal and perinatal health remain unclear, possibly due to sources of heterogeneity and challenges in exposure assessment. In the MIREC Study cohort, phthalate levels were associated with GA and HC in infants in a sex-specific manner. Phthalates also appear to influence the circulating inflammatory marker levels, possibly explaining the observed adverse effects. Future research is needed to validate these findings.

Orientador: Jose Norberto Dachs / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Matematica, Estatistica e Ciencia da Computação / Made available in DSpace on 2018-07-16T10:57:38Z (GMT). No. of bitstreams: 1 Roveri_CreusaMaria_M.pdf: 3123789 bytes, checksum: e1a76821bb93561f3e8eb73448f803ef (MD5) Previous issue date: 1987 / Resumo: Não informado. / Abstract: Not informed. / Mestrado / Mestre em Estatística

Introducción: A nivel global, en el año 2019, la prevalencia en todas las edades de agudeza visual disminuida es de 2.2 billones de personas. En niños, el número estimado con discapacidad visual es de 19 millones. La disminución de agudeza visual se encuentra asociado a malnutrición, obesidad, deficiencia de la vitamina A, prematuridad, edad, nivel socioeconómico, entre otros. Young Lives es una cohorte que siguió niños durante 15 años y cuya data está disponible para el análisis. Objetivo: Evaluar qué factores perinatales, neonatales y de la infancia temprana se encuentran asociados al desarrollo de agudeza visual disminuida en una cohorte de niños peruanos seguida por siete años, del 2002 al 2009. Métodos: Estudio cuantitativo, observacional, longitudinal, tipo cohorte, basado en la revisión secundaria de la base de datos “Young Lives - Niños del milenio”, la cual fue una cohorte prospectiva realizada entre 2002 y 2016. La población fue de 1860 niños, lo que da una potencia mayor al 90% para las variables principales que es la agudeza visual disminuida Otras variables son prematuridad, sexo, obesidad, nivel socioeconómico y residencia rural. El análisis se hará con Regresión de Poisson corregida según el muestreo complejo de la cohorte. Valores ≤0.01 (Corrección Bonferroni) serán considerados significativos.

Perinatal stroke, which occurs before or shortly after birth, may result in both beneficial and maladaptive plasticity in surviving tissue. However, current preclinical and clinical work have an unclear understanding on the relationship between functional outcome and neurophysiology. This thesis aims to dually characterize and correlate behaviour with cortical motor representations in a mouse model of perinatal stroke. On postnatal day 7, a unilateral photothrombotic stroke was produced in the primary motor cortex of Thy1-ChR2 mice. Sensorimotor function was evaluated in adulthood with a battery of behavioural tests. Subsequently, a transcranial window was implanted, and motor maps were created through optogenetic point stimulation. To evaluate the impact of skilled motor training on cortical reorganization, mapping was conducted before and after training on the single pellet reaching task. P7 stroke caused functional impairments across a battery of motor tasks, while both motor map size and movement latency were bilaterally impacted. Spontaneous limb use was positively correlated with map size of both hemispheres, but single pellet performance was only positively correlated with map size in the injured hemisphere. Following skilled motor training, both map size reductions and delayed latency was partially restored. Additionally, significant correlations between map size expansion and movement latency reduction following skilled motor training not only demonstrate that training-induced plasticity was beneficial, but also primarily mediated by the uninjured hemisphere. As the first study to conduct within-animal optogenetic motor mapping following perinatal stroke, we show that 1) perinatal stroke bilaterally impacts both cortical and descending aspects of the motor system, 2) the remaining movement sites in both the uninjured and injured hemispheres have a positive impact on functional outcome, and 3) skilled forelimb training can partially restore cortical and descending motor neurophysiology.

Postpartum depression is a serious mental illness with onset of symptoms appearing anytime within the first four months after delivery (e.g. irritability, severe sadness, profound feelings of hopelessness, etc.). Environmental toxicants are synthetic (i.e. manufactured) or naturally found chemicals that are not produced by organisms as a result of cellular metabolism (e.g. tobacco smoke, pesticides, etc.). There is limited consideration for how exposure to environmental toxicants can create adverse psychological health effects, specifically postpartum depression. The purpose of this systematic review was to determine if the literature supports a link between exposure to environmental toxicants during the prenatal/perinatal period and postpartum depression and if so, to identify whether there are specific classes of toxicants that provide a higher risk for postpartum depression. Several databases were used to search the online literature, with the following inclusion criteria: articles published in English, publication years between 1995-2018, and with women of reproductive age (15-49 years old). The article selection process comprised of screening each article by title/abstract, followed by screening those articles based on full-text. Six categories of toxicants were identified among the thirty included articles. Active/passive smoke exposure was largely found to increase the risk of developing postpartum depression; dietary supplements provided mixed results; antidepressants demonstrated preventative effects; particulate air pollution was found to be associated with postpartum depression; oral contraceptives (DMPA) exhibited an increase in postpartum depressive symptoms; and organochlorine pesticides had no associative risk. Quality assessments were performed for all of the included articles, with the majority being assessed as satisfactory. This systematic review presents as a foundation for encouraging future research to investigate the link between environment and mental health, in order to attain a greater perspective.

Background: The field of perinatal palliative care aims to support the unique needs of parents who choose to continue pregnancy following the diagnosis of a life-limiting fetal condition (LLFC). As parents navigate this challenging trajectory, the support they receive from healthcare providers is crucial in shaping parental experiences. Objective: to critically reflect on existing literature and to reveal a deeper understanding of the experience of continuing pregnancy in the presence of a LLFC Design: Qualitative meta-synthesis Methods: The primary search strategy consisted of multiple searches within four electronic databases. The analysis was guided by thematic analysis. Results: This meta-synthesis included 29 qualitative studies. Three main themes were identified; time, uncertainty and relationships. These concepts exist concurrently within this trajectory and continuously influence each other as well as the overall experiences of parents. Conclusion: Nurses are encouraged to acknowledge the significance of the interconnectedness between these key concepts and to critically reflect on how their everyday interactions become part of parents’ lived experiences.

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Regulatory T cells (TRegs) are stable markers of immune functioning, acting to suppress inflammation. TRegs are important during implantation and early pregnancy where they suppress immune-mediated rejection of the embryo. Given the role of TRegs in the maintenance of pregnancy, their depletion can be associated with obstetric complications. Through the completion of two studies, this thesis seeks to identify the role of TRegs in two forms of perinatal pathology: depression and arterial thickening. The first study examines whether decreased TReg levels during pregnancy are associated with an increase in depressive symptoms, and if this relationship is mediated by maternal stress. We predicted that the TReg-depression relationship would be unique to pregnancy, and not occur in the postpartum. In the second study we assessed if decreased TRegs were inversely correlated with carotid arterial thickness. TReg samples were obtained from women between 24 and 32 weeks gestation (N=16), and at 12 weeks postpartum (N=19). Depression was assessed using the Edinburgh Perinatal Depression Scale (EPDS) and the Mongomery-Asberg Depression Rating Scale (MADRS) , and stress with the Perceived Stress Scale (PSS). TRegs were measured using flow cytometry. In the first study, we showed that lower TRegs were associated with increased levels of depression in pregnancy, and that this association was mediated by perceived stress. In the postpartum period, TRegs were not associated with changes in mood. In the second study, we found no relationship between TRegs and carotid arterial thickness. Our results suggest that TReg changes in pregnancy may be associated with maternal mood in pregnancy, but not in the postpartum period. Despite the fact that we failed to find a correlation between TRegs and carotid arterial thickness during pregnancy, our limited sample size leads us to recommend that the presence of an inverse correlation between these two markers not be ruled out, but suggest that these links be further examined using a larger sample and more precise imaging. Together, these two studies may provide very early insights into the role of TRegs in perinatal mood disorders and cardiovascular health and highlight the need for further research. / Thesis / Master of Science (MSc)

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