Gestational diabetes mellitus (GDM) is the most common complication of pregnancy that affects 1-14% of all pregnancies. If not properly managed, GDM can be a devastating disease, leading to birth complications such as shoulder dystocia and neonatal hypoglycemia. GDM has many long-term implications as well, such as increased risk of obesity and type 2 diabetes mellitus (T2DM) in both the mother and the offspring. Additionally, women with a history of GDM are at increased risk of recurrent GDM in a subsequent pregnancy and multiple episodes of GDM further increases a woman’s risk for these short and long-term consequences. For this reason, a diagnosis of GDM provides an opportunity to target GDM and T2DM risk factors to prevent recurrence of GDM and halt the diabetes disease course. Research has shown that diet and physical activity interventions provided after a pregnancy complicated by GDM can delay or prevent the onset of T2DM yet literature on prevention of recurrent GDM is lacking. This thesis will propose a new intervention applied to the inter-pregnancy interval (IPI), designed to reduce incidence of recurrent GDM. The study will examine the effect of a diet and physical activity intervention for women with a recent pregnancy complicated by GDM on recurrence in a subsequent pregnancy and weight gain in the IPI. We hypothesize that our intervention will reduce incidence of GDM recurrence compared to the control group and that women in the intervention group will lose more weight compared to women in the control group. The results of this study will provide a background for further study on the prevention of GDM recurrence with the hope that prevention of recurrent GDM will prevent the short and long-term sequela of GDM.

Trisomies 18 and 13 are rare genetic conditions (occurring around 1 in 6,000 and 10,000 newborns respectively) which are caused by an extra copy of either chromosome 18 or 13, similar to trisomy 21 (Down syndrome). The only known risk factor for these syndromes is maternal age, however previous cluster analyses have linked trisomy risk to a number of alternate factors, including radiation exposure and infection. Cases of trisomies 18 and 13 from the National Down Syndrome Cytogenetic Register (NDSCR) were scanned for temporal and spatial clusters throughout England and Wales between 2004 and 2010. No temporal clusters were detected, however there were multiple significant spatial clusters detected for both trisomies in London. These clusters were likely caused by advanced maternal age in the region, and it is also possible that regional differences in gestational age at the time of prenatal screening could have contributed to these clusters. In order to account for maternal age and gestational age at diagnosis, a novel method was developed in R to directly weight cases based on these factors. Applying weights to cases directly allowed both factors to be simultaneously accounted for by multiplying weights together. This method was evaluated using synthetic data and compared with an alternate method in the widely used program SaTScan. Both programs returned similar results when the weighting method was mild, but when extreme weights were applied at random significant clusters were observed in SaTScan but not in R. The NDSCR data was weighted and then rescanned for spatial clusters in both programs. No evidence of clustering was detected using the novel method, while SaTScan returned multiple highly significant clusters. These findings, combined with those obtained using the synthetic data, indicate that the novel method produces more reliable results than SaTScan when extreme adjustment is applied.

Gestational diabetes mellitus can have devastating effects in the health of the mother and child. While pregnancy rates are decreasing, prevalence of GDM is increasing, and it is estimated that up to 9% of pregnancies are complicated by diabetes in the United States. Traditional treatment and monitoring of gestational diabetes mellitus relies on patient’s compliance to document glycemic levels. This proposed study will evaluate the effectiveness of telemedicine using a wireless glucose meter that transmits information to the providers in real time. The prospective open cohort randomized clinical trial will take place in medical centers around Boston. Two hundred participants diagnosed with gestational diabetes will be recruited over a period of 24 months from these centers and randomly placed into two groups. One group will follow traditional treatment, and the intervention group will be asked to use iGlucose meter system. Glycemic levels and frequency of prenatal visits will be evaluated and analyzed. If telemedicine proves to be efficacious in treating GDM, this would give providers a new treatment plan to consider to effectively manage blood glucose levels and reduce poor perinatal outcomes related to gestational diabetes mellitus.

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.

No description available.

A Dissertation that is being submitted for an MMed in Obstetrics and Gynaecology in partial fulfilment of the FCOG (SA) Part II 07 April 2015 / Objectives: The main objective of this study was to characterise women who presented at Chris Hani Baragwanath Academic Hospital (CHBAH) between 12 and 20 weeks for termination of pregnancy (TOP). Secondary objectives were to determine time to abortion, compare sonar gestational age to gestational age by dates and reasons for late presentation. Method: This was a prospective cohort study of women over the age of 18 who were referred to CHBAH for second trimester TOP between August 2012 and May 2013. The exclusion criteria were pregnancies more advanced than 20 weeks gestation. Data was collected from the medical file and by interview. Demographics and reasons to terminate were extracted from the files. Outcome variables included bleeding, pain, and time to abortion. Results: One hundred and ninety one women (91.39%) aborted. The median age of women was 25.00 (IQR=21.00-31.00), range (18-43). Women older than 25 years were 33% less likely to abort than women less than 25 years of age. Ninety nine women (47.14%) bled severely. One woman had a uterine perforation following evacuation of the uterus. The median gestational age by sonar was14.71 (IQR=13.86-16.14), range (13.00-20.00). The median gestational age by dates was13.57 (IQR=12.29-15.00), range (4.14-26.28). One hundred and thirty five women (63.98%) had an MVA for RPOC using analgesia following medical induction. Two women (0.95%) needed hysterotomy following failed TOP. The median time to abortion was 11.50(IQR=8.67-17.92), range (3.50-69.33) and incidence rate of 0.5 per hour or 1 per 2hours. Conclusion: The majority of women (91%) aborted within 72 hours following medical induction with less complication rate and short induction to abortion time. This affirm misoprostol efficacy as the suitable drug for conducting second trimester medical TOP. / MT2016

O Diabetes mellitus gestacional (DMG) é uma séria condição que afeta muitas gestantes e traz muitos riscos tanto para a gestante, como para o feto. A recomendação é que se faça o rastreamento com teste oral de tolerância à glicose (TOTG) entre 24 e 28 semanas de gestação. O objetivo desse estudo é determinar a utilidade do teste de hemoglobina glicada (A1c) como teste diagnóstico de DMG, comparado com os critérios baseados na medida de glicemia. Métodos: este é um estudo de acurácia de teste diagnóstico. Nós avaliamos o metabolismo dos carboidratos através dos testes de TOTG e A1c em mulheres grávidas brasileiras atendidas nas visitas de pré-natal do Hospital de Clínicas de Porto Alegre (HCPA). Além dos testes de TOTG e A1c, foi analisada a história clínica das pacientes. O DMG foi definido de acordo com critério da American Diabetes Association (ADA) - um ou mais pontos alterados, glicemia de jejum, 1h ou 2h com concentrações de glicose plasmática ≥5.1, 10.0, ou 8.5 mmol/L, respectivamente-, ou de acordo com os critérios da Organização Mundial da Saúde (OMS) - glicemia de jejum ou 2h com concentrações de glicose plasmática ≥7.0mmol/L ou ≥7.8mmol/L, respectivamente. Presença de anemia, hemoglobinas variantes e doença renal crônica foram excluídas. Para avaliar o desempenho do teste de A1c foi utilizada a curva ROC (receiver operating characteristic curve). Resultados: um total de 262 mulheres grávidas (média de idade de 30 anos, média de idade gestacional de 26 semanas) foram avaliadas e 82 (31,3%) tiveram diagnóstico positivo (40 pelo critério da ADA e 42 pelo critério da OMS). Baseado na análise da curva ROC, considerando os critérios da ADA e OMS juntos e o TOTG como teste de referência, o ponto de corte para obter o melhor equilíbrio entre sensibilidade e especificidade (diagonal 100% a 100%) foi o valor de A1c de 31mmol/mol (5,3%). A sensibilidade e especificidade para este ponto de corte foi de 69,9% e 65,9%, respectivamente. Os pontos de corte de 40 mmol/mol (5.8%), 41 mmol⁄mol (5.9%) e 42 mmol⁄mol (6.0%) representaram especificidades de 96,1%, 96,6% e 98,3%, respectivamente. Conclusões: o teste de A1c apresenta baixa sensibilidade e alta especificidade para o diagnóstico de DMG, quando comparado com o critério tradicional. Nossos resultados mostraram que 39% dos casos de DMG foram diagnosticados usando o ponto de corte de A1c≥ 40 mmol/mol (5.8%). O teste de A1c, sozinho ou em combinação com o TOTG, talvez seja bastante útil no diagnóstico de DMG. / BACKGROUND: Gestational diabetes mellitus (GDM) is a potentially serious condition that affects many pregnancies and it carries risk for the mother and neonate. The current recommendation is to perform screening before 24 - 28 weeks of gestation by an oral glucose tolerance test (OGTT). The aim of this study is to determine the usefulness of glycated hemoglobin (A1c) as a diagnostic tool for GDM compared with the traditional criteria based on glycemia measurements. METHODS: This is a study of diagnostic test accuracy. We evaluated the status of carbohydrate metabolism by performing OGTT and A1c in Brazilian pregnant women attending prenatal visits at Hospital de Clínicas de Porto Alegre (HCPA). A1c, OGTT, and clinical history were analyzed. GDM was defined according to the American Diabetes Association (ADA) criteria (one or more fasting, 1-h, or 2-h plasma glucose concentrations ≥5.1, 10.0, or 8.5 mmol/L; respectively) or World Health Organization (WHO) criteria (fasting or 2-h plasma glucose ≥7.0mmol/L or ≥7.8mmol/L, respectively). Presence of anemia, variant hemoglobins and chronic renal disease were excluded. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of A1c. RESULTS: A total of 262 pregnant women (mean age 30 years, mean gestational duration 26 weeks) were enrolled and 82 (31.3%) were diagnosed with diabetes (40 by ADA criteria and 42 by WHO criteria). Based on ROC curve analysis, and considering OGTT as the reference criterion, the cut-off point obtained by the point with the best equilibrium between sensitivity and specificity (100%-to-100% diagonal) was A1c value of 31 mmol⁄mol (5.3%). The sensitivity and specificity for this cut-off 27 point were 69.9 % and 65.9 %, respectively. The cut-off points of A1c of 40 mmol/mol (5.8%), 41 mmol⁄mol (5.9%) and 42 mmol⁄mol (6.0%) presented specificities of 96,1%, 96,6% and 98,3%, respectively. CONCLUSIONS: A1c test presented low sensitivity and very high specificity for GDM diagnosis when compared with traditional criteria. Our results show that 39% of GDM cases would be diagnosed by using the cut-off point A1c≥ 40 mmol/mol (5.8%) alone. A1c test, alone or in combination with OGTT, may be a very useful diagnostic tool in GDM.

No description available.

Environmental xenoestrogens (EEs) are chemicals that when they enter the body, the body responds to them as it would to endogenous estrogens. Humans are exposed to these chemicals on a daily basis via natural components, additives and contaminants in food and water, through the use of pharmaceuticals and personal care products such as sunscreens, lotions and toothpaste. Exposure to EEs is thought to result in adverse effects on humans such as decreased fertility, increased susceptibility to hormone-sensitive cancers, deformities of the male genitalia and precocious puberty in females. The critical window of exposure is thought to be early fetal development, when tissues are rapidly differentiating under the control of endogenous estrogens. However, there is limited data in the literature on human fetal exposure to EEs. The first objective of this study was to assess human fetal exposure to a suite of 35 EEs by analysis of paired samples of amniotic fluid and maternal urine were collected from 32 New Zealand women between 14 and 20 weeks gestation. The analytical chemistry methods required for this study were developed and validated. The results demonstrate that fetal exposure is highly correlated with maternal exposure. This study is the first to report maternal urine levels of two UV filters and amniotic fluid levels of parabens, UV filters and triclosan. A model based on simple additivity of effect was developed that combined the measured concentrations with literature data on relative estrogenic potency to assess the magnitude of the estrogen signal that may be attributed to the EEs. This model suggests that the fetus may experience an estrogen signal due to the measured EEs that could be as large as the endogenous estrogen signal. A second objective was to use computational docking to study the interactions of the EEs with the human estrogen receptor (hER) protein. The docking studies show that the rigid endogenous ligand, 17β-estradiol (E2) interacts with the hER to produce a single, well-defined complex with the receptor and the flexible EEs produce multiple, distinct energy-equivalent complexes. EEs are not able to interact with the binding cavity to stabilise the rigid hER-E2-like topology of the complex. As a result, the hER-EE complexes can be thought of as more pliable or ‘floppy’ and thus able to respond to the cell context in multiple ways, leading to variations in gene expression in different target tissues. These multiple pathways may explain the range of physiological responses attributed to exposure that depend on the timing of exposure and the sex of the individual exposed.

Thesis (Ph. D.)--University of Texas at Austin, 2007. / Vita. Includes bibliographical references.