BACKGROUND: Highly active antiretroviral therapy(HAART) is used in pregnancy to suppress viral load(pVL) before delivery, reducing risk of vertical HIV-transmission. Nelfinavir(NFV) containing HAART has been highly used in pregnancy, but dosages may be inadequate due to the physiologic changes that occur. Given concerns regarding optimal viral suppression in pregnancy, drug toxicity and resistance development, NFV levels need to be evaluated in this population to guide dosing recommendations. METHODS: As part of a prospective cohort study maternal blood was collected at 18-28wks, 32-37wks and at delivery. Times of last medication dose and blood sampling were recorded and drug levels were measured using HPLC MS-MS. NFV concentration-ratios(NFV-CRs) were calculated by dividing individual levels by a time-adjusted population value. Plasma NFV concentrations and NFV-CRs were compared across gestational age and correlated to variables of interest. Rate and maintenance of viral suppression were analyzed in relation to NFV concentrations and CRs. Statistical tests included ANOVA, χ2, linear regression, and Kaplan Meier estimates. RESULTS: 113 samples were collected from 32 subjects. Samples were eliminated if not in steady state (n=20); 93 samples from 32 subjects were analyzed. Mean NFV-CR at 18-28wks (1.1±0.73) and 32-37wks (0.86±0.73) were not significantly different but were both significantly higher by ANOVA (p=0.049) than the mean NFV-CR at delivery (0.44±0.50). CRs were highly variable. Of 49 antepartum samples, 49%(24) had a CR<0.90 (clinically relevant threshold). Four women reached a pVL <50 copies/mL by 34wks but had a detectable pVL at delivery. One woman never reached an undetectable pVL in pregnancy. Minimum and mean NFV-CRs in these 5 women were not significantly different than those who achieved and maintained virologic suppression. Vertical HIV transmission rate was 0%. CONCLUSIONS: There were no HIV transmissions but 16% (5/32) of women were inadequately suppressed at delivery, which is of concern. Factors associated with inadequate suppression and NFV-CRs need to be explored in conjunction with patient/physician reported adherence and viral resistance profiles. Extreme variability in CRs may limit the potential usefulness of random timed drug levels in all pregnant women. / Medicine, Faculty of / Obstetrics and Gynaecology, Department of / Graduate

Background: Pregnancy is a trigger point for the development of obesity with maternal obesity being associated with significant adverse effects in the mother and child. Nigeria is experiencing a double burden of under- and over-nutrition with rising levels of obesity particularly in women. However, there is scarcity of data on maternal obesity in Nigeria and other African countries. Aims and Objectives: This thesis aimed at identifying crucial components of potential interventions for maternal obesity in Nigeria. The objectives were to assess the prevalence, effects and distribution of maternal obesity; assess the knowledge, attitude and practice (KAP) of pregnant women and maternal healthcare providers and identify existing interventions for maternal obesity in Nigeria. Methodology: A systematic review and meta-analysis was initially conducted. Following this, a quantitative questionnaire survey of the KAP of pregnant women and a qualitative interview study of the KAP of Health Care Workers (HCW) were conducted in seven secondary and tertiary hospitals across Nigeria. Quantitative data was analysed with SPSS statistical software, while thematic analysis was conducted for qualitative data. Results: Twenty-nine studies included in the systematic review showed significant prevalence, socio-demographic associations, and adverse effects of maternal obesity on labour, maternal, and child outcomes in Africa. The questionnaire survey of 435 mothers revealed a maternal obesity prevalence of 17.9% among mothers who registered for antenatal care in the first trimester. Mothers had insufficient knowledge of the causes, complications, and safe ways to manage maternal obesity. However, majority felt that excess gestational weight gain be avoided and some practiced weight management during pregnancy. For the qualitative study, four main themes were identified: 'Concerns about obesity in pregnancy', 'Barriers to care for obese pregnant women', 'Practice of care for obese pregnant women', and 'Improving care for obese pregnant women'. Conclusions: Culturally adaptable/sensitive interventions should be developed for the management of obese pregnant women in Africa. Education and training of mothers and health care workers, and provision of guidelines are some of the components of potential interventions in Nigeria.

Previous research has revealed that the experience of HIV-positive refugee women arriving from endemic countries is complicated by social, structural, and cultural issues. If and when they become pregnant, HIV-positive refugee women face a unique situation that is poorly understood by health care providers. The intersecting influences of HIV and refugee status in the context of pregnancy have been essentially unexplored in the Canadian context. The objective of this study was to describe the lived experience of pregnancy among HIV-positive refugee women; to explore the meaning of pregnancy from the perspective of HIV-positive women; and to understand the complexity of issues facing HIV-positive refugee women. An interpretive qualitative research design viewed through a critical post-colonial lens guided the study. Women were interviewed using a semi-structured in-depth approach. Four core themes emerged from the phenomenological analysis. The findings suggest that the experience of HIV and pregnancy among refugee women in Canada involves both disconnection and restoration. They must manage the dynamics of pregnancy, the impact of HIV and the cultural, political and geographic ‘newness’ of Canada. Noteworthy, are the efforts women take to conceal the HIV diagnosis. Additional insight was gained through an intersectional analysis of the data. The findings of this analysis suggest that women: 1) experienced alterations in identity 2) faced significant social disruption, and 3) are impacted by macro-level polices that influence both their initiation and access to the health care system. The lived experience of pregnancy among HIV-positive refugee women in Canada is analogous to moving through a liminal reality. HIV-positive refugee women work to restore a disrupted and “Othered” identity. Pregnancy is integral to that restoration. The results of the study have implications for nursing’s ability to support the transformative aspects of the liminal reality of pregnant HIV-positive refugee women. The potential for these transformations draw attention to nursing at practice, policy, education and research levels.

This study investigated the relationships among family environment, demographic measures, the decisions made by unintentionally pregnant adolescents regarding post-delivery plans (stay single, get married, adoption), and the certainty with which these decisions were made. The Information Sheet, Family Environment Scale (Moos & Moos, 1981), and Multiple Affect Adjective Check List (Zuckerman & Lubin, 1965a) were administered to 17 5 pregnant adolescents, ages 14 through 22, who intended to carry their pregnancies to term. Pearson product-moment correlations and multiple regression analyses were utilized to assess the relationships between family environment and certainty of decision and between family environment and negative affect. Greater uncertainty was associated with nonwhite racial status and living with both natural parents or mother only. Higher levels of negative affect were related to lower levels of perceived family cohesion, independence, expressiveness, and intellectualcultural orientation. The demographic variables of age, trimester of pregnancy, and family constellation were also found to be useful in predicting levels of negative affect. Subjects who were older, further along in their pregnancies, and living with both natural parents or mother only tended to report greater negative affect. Findings of greater uncertainty and negative affect associated with living with the natural mother are consistent with previous reports of disturbed mother-daughter relationships among this population. Discriminant analysis revealed that subjects choosing adoption were more likely to be older and to be white than those choosing to keep the child. They also tended to perceive higher levels of expressiveness and independence in their families. Comparisons between the present sample and "normal" families revealed differences which were statistically significant, but quite small in terms of raw score units. Indeed, these groups may be more similar than has often been assumed. The implications of these findings for the delivery of services and for future research efforts in this area were discussed. More intensive assessment of family functioning is needed. Based upon present results, further investigation of the family constellation variable is warranted.

Cytomegalovirus (CMV) is an important antenatal infection that is prevalent in the developing world. The disabling and potentially fatal effects of CMV acquisition or reactivation during pregnancy on the developing foetus and or neonate are known but, factors predisposing pregnant women to CMV are not well studied. CMV has a wide host cell tropism that includes gut epithelial cells. CMV infection in the gut epithelial cells results in a leaky gut and potential gut microbial dysbiosis. In this study, we set out to determine the prevalence of CMV infection as well as factors associated with CMV reactivation in a cohort of pregnant Zimbabwean women. We also aimed to determine the role of CMV infection and CMV susceptibility host genetics on gut bacterial profiles. Seroprevalence of CMV was determined using the enzyme-linked immunosorbent assay. A high prevalence of previous exposure to CMV, as denoted by the presence of anti-CMV IgG antibodies in participants' sera, was observed. Anti-CMV IgM antibodies that denote active CMV infection were detected in the sera of 4.6% (n=35/524) study participants. Prevalence of CMV was also determined using real time PCR, CMV reactivation was higher (6.7%) when using PCR than when using immunological assays (4.6%). The presence of CMV DNA was significantly associated with HIV positivity (p=0.04). PCR is the gold standard for CMV diagnosis, thus, CMV DNA positivity was used to denote CMV infection status in this thesis. The second objective was to determine if the differential effect of CMV acquisition or reactivation among HIV infected participants was due to variability in plasma efavirenz containing antiretroviral therapy (ART) exposure. Efavirenz (EFV) plasma concentrations were determined using high performance liquid chromatography (HPLC). Single nucleotide polymorphisms (SNPs) in the CYP2B6 gene, which encodes the main EFV metabolizing enzyme were genotyped. Carriers of CYP2B6 poor metaboliser (PM) genotypes (c.516T/T and c.983T/C) had significantly higher mean plasma EFV concentration compared to carriers of CYP2B6 fast metabolizer genotypes (i.e., c.516G/G and c.983T/T). CYP2B6 PM genotype carriers were significantly less likely to be positive for CMV DNA when compared with fast metabolizer genotype carriers (pC (p=0.002), TLR7 rs179008A>C (pC (p=0.003). In contrast, presence of the IL6 rs10499563T>C polymorphism was inversely correlated with CMV infection (p=0.002). The reported genetic variants are reported to modulate proteins involved in immune responses against viral infections, thus, their association with susceptibility to CMV infection. Such findings may assist in the designing of a muchneeded candidate CMV vaccine. Lastly, we set out to determine the possible role of CMV infection in shaping gut microbiota profiles. We report on a significant difference (p=0.001) in the beta diversity of gut bacterial profiles between HIV- and age-matched CMV-infected (cases) and CMVuninfected (controls) participants. Using linear discriminant analysis (LDA) effect size (LefSe), significant differences in the relative abundance of specific bacterial taxa were observed between cases and controls (p2). Significantly lower abundance of Lactobacillus reuteri and Roseburia, genera associated with lower microbial translocation was observed in cases than controls. Lower relative abundance of Lactobacillus and Roseburia, is consistent with microbial translocation and heightened inflammation, respectively, hence higher likelihood of microbial translocation and inflammation occurring in cases than controls. Furthermore, Prevotella copri, a species that has been association with cytokine release and chronic inflammation was significantly more abundant in cases than controls. CMV is a known chronic inflammatory condition, and this study provides further confirmation through the higher relative abundance of P.copri in cases than controls. Biomarker identification has proven to be a successful means of translating molecular data into clinical practice, such as vaccine development in the case of CMV infection. Overall, this study reports the possible interaction of various host factors in facilitating CMV acquisition or reactivation during pregnancy. In the setting of HIV-CMV coinfection, our findings emphasise on the need for genotype guided drug dosage to achieve therapeutic EFV so as to maintain the balance between host and coinfecting microbes in HIV management. Comprehensive genotype guided drug dosage, if taken as a once-off test should be affordable especially in resource-limited settings. This is particularly important in pregnant women who are at a risk of vertically transmitting infection to the immunologically immature foetus and or neonate. Data from this study may assist in curbing the host associated challenges in designing an effective CMV vaccine. Moreover, the biomarkers reported may assist in diagnosis and management of potential CMV acquisition or reactivation during pregnancy. However, bigger prospective, functional studies would be needed to confirm the exact roles of the biomarkers identified in this study in the diagnosis, prognosis and therapeutics of CMV infection.

This literature-based thesis aimed to evaluate the relationship between gestational diabetes mellitus (GDM) and the Latinx community. The Latinx community is one of the groups most affected by GDM in the United States of America. Latinx patients have higher prepregnancy body mass index (BMI) and excessive gestational weight gain (GWG), the two main risk factors for developing GDM. The occurrence of GDM increases the risk for adverse pregnancy outcomes and early onset type II diabetes mellitus (T2DM) postpartum. For the fetus, GDM increases the risk of hypoglycemia and hyperinsulinemia, both of which can affect the long-term metabolic health. Current treatments of GDM in Latinx patients focus on lifestyle intervention through diet and exercise, an action that proves to be effective in this population. Enhanced GDM care that includes pregnancy health education in a group setting significantly improves birth outcomes. Advanced screening utilizing biomarkers and more accessible diagnostic tools is recommended for improving GDM treatment in Latinx patients. Finally, pregnancy studies on GDM should adequately represent the Latinx population among participants. Although this thesis analyzed GDM in the Latinx community and offered solutions for the disproportionate adverse pregnancy outcomes, these results may also be applicable to other racially and ethnically diverse populations.

The clinical practice guideline (CPG) is the implementation of a depression screening tool to be used in the early perinatal period. The practice change occurred in a rural Obstetrical and Gynecological (OBGYN) practice in the southern United States. The CPG change has been guided by recommendations from both the American Congress of Obstetrics and Gynecology and the American College of Nurse Midwives. Implementation of this CPG change addresses the gap in practice of not doing depression screening during the perinatal period, and only screening during the postpartum period, which was being done at the OBGYN office. Theorist Lewin’s ‘change theory’ guided the implementation of the project. In order to apply this project, a process of changing practice guidelines was needed at the OBGYN office. The DNP project presented the practice change guideline of implementing the Edinburgh Postpartum Depression Screening (EPDS) tool. The need for the CPG development was evaluated by 3 nurse leaders using the AGREE II tool and was recommended 100% without modifications by all 3 evaluators. The CPG, with the results, was presented and discussed with the practice site’s practitioners. The practitioners implemented the EPDS to be given at the 12- week checkup appointment versus the confirmation of pregnancy appointment, which was suggested through the DNP project’s CPG. The implementation of this CPG has the potential to provide a safer environment for pregnant women, their newborns, and their families.

BACKGROUND: Suicide is a leading cause of maternal death globally, and suicide prevalence rates have been shown to be increased in those with migraine. No previous study has examined the association between migraine and suicidal ideation during pregnancy. OBJECTIVE: To examine the association between migraine and suicidal ideation among a cohort of pregnant women. METHODS: A cross-sectional study was conducted among 3372 pregnant women attending prenatal care clinics in Lima, Peru. Suicidal ideation and depression were assessed using the Patient Health Questionnaire-9 (PHQ-9) scale during early pregnancy. Migraine classification (including migraine and probable migraine) was based on International Classification of Headache Disorders-III beta criteria. Multivariable logistic regression analyses were performed to estimate odds ratios (OR) and 95% confidence intervals (95%CI). RESULTS: Suicidal ideation was more common among those with migraine (25.6%) as compared to those with probable migraine (22.1%, P < .001) or non-migraineurs (12.3%, P < .001). After adjusting for confounders, including depression, those with migraine or probable migraine had a 78% increased odds of suicidal ideation (OR = 1.78; 95% CI: 1.46-2.17), as compared with non-migraineurs. Women with both migraine and depression had a 4.14-fold increased odds of suicidal ideation (OR = 4.14; 95% CI: 3.17-5.42) compared to those with neither condition. CONCLUSION: Migraine is associated with increased odds of suicidal ideation in pregnant women even when controlling for depression. These findings support the consideration of screening women with comorbid migraine and depression for suicidal behavior during pregnancy. / Revisión por pares

El texto completo de este trabajo no está disponible en el Repositorio Académico UPC por restricciones de la casa editorial donde ha sido publicado. / Women have a higher prevalence of post-traumatic stress disorder (PTSD) than men, with a peak during the reproductive years. PTSD during pregnancy adversely impacts maternal and infant health outcomes. The objectives of this study were to estimate the prevalence of antepartum PTSD symptoms in a population of pregnant Peruvian women and to examine the impact of number of traumatic events and type of trauma experienced. The Traumatic Events Questionnaire was used to collect data about traumatic exposures. The Post-traumatic Stress Disorder Checklist-Civilian Version (PCL-C) was used to assess PTSD. Multivariable logistic regression procedures were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (95% CI). Three thousand three hundred seventy-two pregnant women were interviewed. Of the 2920 who reported experiencing one or more traumatic events, 41.8% met criteria for PTSD (PCL-C score ≥ 26). A quarter of participants had experienced four or more traumas, and 60.5% of those women had PTSD. Interpersonal trauma was most strongly associated with PTSD (aOR, 3.20; 95% CI, 2.74-3.74), followed by unspeakable trauma (aOR, 2.87; 95% CI, 2.35-3.50), and structural trauma (aOR, 1.39; 95% CI, 1.15-1.67). These findings indicate the high prevalence of PTSD during pregnancy in the Peruvian population, which is relevant to other countries suffering from terrorism, war, or high rates of violence. This underscores the importance of screening for PTSD in pregnancy. / Revisión por pares

Fibrinogen-like protein 2 (FGL2) is a known immunomodulator and prothrombinase, expressed by several subsets of immune cells. This thesis explores its potential role during the establishment of pregnancy, in mice, as well as in trophoblast function and in an immune-mediated subtype of preeclampsia (PE), in humans. We first noticed a marked subfertility in Fgl2 knockout (ko) and Fgl2 overexpressing (tg) colonies, where litters were fewer and smaller. To explain this, we mapped spatiotemporal patterns of FGL2 expression in the female reproductive tract and through the estrous cycle. FGL2 is expressed in the ovarian stroma and theca cell layer, peaking shortly before ovulation. Fgl2 ko and tg mice do not show a defect in natural or induced ovulation. FGL2 is expressed in secretory cells of the oviductal epithelium, and Fgl2 ko mice have reduced fertilization efficiency. Fgl2 tg pups are noticeably small, and we find that a reduced ratio of glycogen cells in the junctional zone of their placenta partly explains this. We next investigated the role of FGL2 in trophoblast function, using BeWo and HTR-8/SVneo cell lines. Inflammatory cytokines increase FGL2 expression in BeWo, and FGL2 overexpression promotes syncytialization. We show that it therefore rescues the deleterious effect of inflammation on syncytium formation. In a large cohort of PE and non-PE human placentas, FGL2 is high in a subtype with immune activation, and low in a canonical, anti-angiogenic subtype. Its expression correlates with incidence of chronic inflammatory histopathological lesions, likely driven by immune rejection gene sets. High FGL2 also associates with a high incidence of fibrin deposition in the placenta. Overall, we conclude that FGL2 is involved in several steps of maternal immune adaptation, both before and after pregnancy. Its absence and excess both contribute to mouse subfertility. In the developing and mature placenta, FGL2 is increased by inflammation in the trophoblast and immune compartment of the mature placenta, as a physiological attempt to re-establish immune equilibrium and protect the ongoing pregnancy.