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Decision analysis is a quantitative approach to decision-making that could bridge the gap between decisions based solely on evidence and the unique values and preferences of individual patients, a feature especially important when existing clinical evidence cannot support clear recommendations and there is a close balance between harms and benefits for the treatment options under consideration. Low molecular weight heparin for the prevention of venous thromboembolism (VTE) during pregnancy represents one such situation. The objective of this thesis is to explore the use of a decision analysis intervention for shared decision-making for thromboprophylaxis during pregnancy. This thesis begins with a scoping review that explores the ways in which decision analysis has been used to inform shared decision-making encounters, highlighting key challenges for implementing and evaluating this type of intervention. This is followed by a protocol that presents the methodology of an explanatory sequential mixed methods pilot study for the Decision Analysis in SHared decision making for Thromboprophylaxis during Pregnancy (DASH-TOP) tool. This tool was pilot tested through interviews of eligible women in Canada and Spain who were facing the treatment decision for the prevention of VTE in the antenatal period. While the tool was well received by patients, more effective ways of obtaining patient preferences and presenting the decision analysis results are required to enhance shared decision-making interactions. Finally, this thesis concludes with a reflection on the lessons learned from developing and evaluating a decision analysis intervention for shared decision-making. The insights from this research have informed the development of an integrated online shared decision-making tool for VTE in the antenatal period, which the DASH-TOP team plans to evaluate in a randomized controlled trial. It is hoped that this information will also provide guidance to researchers interested in developing or evaluating decision analysis interventions for other clinical decisions. / Dissertation / Doctor of Philosophy (PhD)

Incarceration and sacculation of a retroflexed gravid uterus is relatively benign, in contrast with pregnancy in a rudimentary uterine horn which can lead to perforation and hemorrhage. We report a case of pregnancy in an incarcerated sacculated non‐communicating rudimentary horn mimicking incarceration with sacculation of a retroflexed gravid uterus. Both physical and sonographic findings were unhelpful in the differential diagnosis. Therefore, decision for laparotomy in such cases should be based on severity of symptoms.

Objectives To define the magnitude of buprenorphine presence in the urine drug screens of pregnant women and to assess the presence of illicit buprenorphine use versus the presence of prescribed buprenorphine use. Methods Initial prenatal drug screen results for all pregnant patients in our practice for a 1-year period were analyzed and tabulated. Results Buprenorphine was found in the urine drug screens of 16% of pregnant patients. The presence of buprenorphine was by far the highest for any substance associated with neonatal abstinence syndrome (NAS). We estimate that the exposure to buprenorphine of approximately one-third of individuals in our population is associated with illicit buprenorphine use. Conclusions The high rate of NAS in our region is primarily associated with both illicit and prescribed buprenorphine rather than other substances. Buprenorphine usage at the time that prenatal care is initiated, rather than opiate use at the onset of prenatal care, is the underlying factor that must be addressed if our region is to successfully combat our high rates of NAS.

Gestational diabetes mellitus impacts between 3-10% of pregnancies, and increases the risk of pregnancy complications and lifelong health effects for mother and child (Bellamy, Casas, Hingorani, & Williams, 2009; Ross, 2006; Ryser Rüetschi et al., 2016). About half of cases occur without an evident risk factor (American College of Obstetricians and Gynecologists (ACOG), 1994; Dode & Santos, 2009). The present study was designed to examine possible psychophysiological connections linking psychological stress and stress reactivity, the magnitude of an individual’s response to stress, to blood sugar metabolization during mid-pregnancy between 24-28 weeks gestation. Participants were recruited from Sanford Health in Fargo, where patients underwent routine Oral Glucose Tolerance Testing (OGTT) a diagnostic assessment in which higher results indicate less blood sugar metabolization. They also completed a Virtual Trier Social Stress Task while psychological and physiological markers of stress reactivity were assessed. Additionally, maternal stress and stress reactivity were assessed using psychosocial questionnaires. There was support for proposed psychophysiological connections, including models in which positive associations between OGTT and maternal stress and anxiety were moderated by psychological stress reactivity. Results suggest that both the presence of stress and a women’s responses to that stress are influential over blood glucose metabolization during pregnancy. Continuing research in this area may have implications for improving outcomes of women at higher risk of GDM and other adverse pregnancy and perinatal outcomes.

Objective: To examine associations between in utero marijuana exposure and birth outcomes. Study design: In two separate cohorts (Appalachian, Rocky Mountain), data were collected from medical records. Marijuana exposure was positive based on urine drug screening at delivery, with nonexposed controls matched on multiple factors including other substance exposure. Result: Marijuana-exposed newborns (n = 531) had significantly worse birth outcomes than controls (n = 531), weighing 218 g less, 82%, 79%, and 43% more likely to be low birth weight, preterm, or admitted to the NICU, respectively, and significantly lower Apgar scores. Conclusion: Marijuana exposure in utero predicted newborn factors linked to longer-term health and development issues. Effects were not attributable to other comorbidities in this study due to rigorous matching and biochemical verification of marijuana and other drug use. Findings add to growing evidence linking marijuana exposure to adverse birth and longer-term outcomes. Women should be encouraged to avoid marijuana use during pregnancy.

Physical activity (PA) reduces the risk for deleterious outcomes in both mother and fetus during pregnancy and improves health across the lifespan. How these benefits are bestowed remains poorly understood but may involve the placenta, the critical interface responsible for fetal growth and survival during pregnancy. This thesis first aims to determine whether small extracellular vesicles (sEVs), potential biological mediators of cell-to-cell communication, are released into circulation after acute exercise during pregnancy and how this compares in the non-pregnant state. Pregnant women were found to have greater circulating sEVs levels compared to non-pregnant controls after a moderate-intensity treadmill walk. Since exercise-associated sEVs are proposed to mediate tissue cross talk in response to exercise, exercise-associated sEVs were examined for their ability to influence trophoblasts (specialized placental cells) in vitro using the BeWo choriocarcinoma cell line. Exercise-associated sEVs from pregnant and non-pregnant women interacted with trophoblast-like cells but did not alter their proliferation, gene expression of angiogenic growth factors, or production of the pregnancy hormone, human chorionic gonadotropin. Finally, the relationship between differing intensities of maternal PA and fetoplacental vascular density in a cohort of healthy pregnant women followed prospectively from 24 weeks of gestation until term delivery. Using traditional histopathological point-counting techniques, there was no difference in the fetoplacental vascular density of individuals meeting or exceeding recommended 150 min of moderate-to-vigorous intensity PA. However, the analysis revealed unexpected associations between fetoplacental vascular density and lower intensities of PA, and sedentary time. Together, the work presented in this thesis highlight the potential for exercise-associated sEVs to communicate the benefits of PA to mother and fetus and the need to investigate the effects of varying PA intensities on placental vascular development.