Preterm birth is a public health problem affecting almost 15 million newborns each year, with almost one million cases annually being fatal. Despite many decades of research, identifying high-risk pregnancies remains difficult. Even with the therapies currently available to clinicians, 95% of preterm births are seemingly intractable. We see a great opportunity for engineers to collaborate with clinicians to help reduce the adverse health impact of this phenomenon. This work is a multi-faceted contribution to the study of the biomechanical problem of preterm birth. We portray the successful, full-term, pregnancy as a delicate balance of organ geometry, tissue deformation behavior, and the physical interaction between the uterus, cervix, and fetal membranes. The cervix is our focus, as its preterm ripening and dilation are the final pathway to premature delivery. We consider a selection of geometric and material factors, studying their impact on the loading that occurs in the cervix. We also study the mechanical implications of the use of a cervical pessary on the mechanical environment of pregnancy. Our mechanical analyses use a custom parameterized model of the pregnant anatomy, coupled with Finite Element Analysis techniques, to allow for rapid model development. In addition, we present a push towards the in-vivo measurement of cervical material properties by way of a phantom study using modern MRI techniques.

LabPasteur / Objetivos deste estudo: identificar a prevalÃncia e os fatores de risco da colonizaÃÃo materna e infecÃÃo neonatal por streptococcus do grupo B (SGB), em mulheres com trabalho de parto prematuro (TPP) e/ou ruptura prematura de membranas (RPM); medir e comparar taxas de colonizaÃÃo vaginal e anorretal por SGB, comparar taxas de detecÃÃo do SGB em meio de cultura seletivo (Todd-Hewitt) e nÃo seletivo (Stuart) e com cultivo em Ãgar-sangue e Ãgar- CPS. Estudo transversal de 112 mulheres e 220 recÃm-nascidos realizou-se na Maternidade Escola Assis Chateaubriand da Universidade federal do Cearà (MEAC-UFC), de maio de 2008 a julho de 2009. Amostras vaginais e anorretais foram colhidas de cada mulher, usando swabs estÃreis. Em 71 mulheres, 2 swabs (vaginal e anorretal), colocaram-se separadamente em meio de transporte Stuart e 2 swabs (vaginal e anorretal), inocularam-se separadamente em meio seletivo Todd-Hewitt, todos subcultivados em placas de Ãgar-sangue. Outras gestantes do grupo, 41 mulheres, foram investigadas somente em meio seletivo com subcultivo em placas de Ãgar-CPS. Colheu-se hemocultura de cada recÃm-nascido pretermo com algum sinal de infecÃÃo. A taxa de colonizaÃÃo materna de 71 mulheres foi de 4,2% e do grupo de 41, de 17%. Meio seletivo Todd-Hewitt detectou 4,4% e meio nÃo seletivo, 7,2% das culturas positivas para SGB no grupo de 71 mulheres, resultados sem diferenÃa significativa. Amostras vaginais tiveram taxas de detecÃÃo de 10,7% e anorretais de 7,1%, nÃo alcanÃando significÃncia estatÃstica. Houve diferenÃa significativa no isolamento de SGB, entre o meio Ãgar-CPS e o Ãgar-sangue. InfecÃÃo urinÃria mostrou ser importante fator de risco (P < 0,01) e a profissÃo Do lar tambÃm associou-se significativamente com a colonizaÃÃo por SGB Dos RNs incluÃdos no estudo, nenhuma hemocultura teve resultado positivo para SGB, embora apresentassem sinais de infecÃÃo e hemogramas alterados. à possÃvel que o resultado tenha ocorrido pelo fato de que as mÃes tomaram antibiÃticos antes ou durante o trabalho de parto. As taxas de colonizaÃÃo por SGB, em nosso meio, sÃo semelhantes Ãs encontradas em outras regiÃes do Brasil, podendo ser tambÃm, aqui, agente de relevÃncia na sepse neonatal que requer, sÃrias medidas de prevenÃÃo. / The objectives of this study: to identify the prevalence and the risk factors from maternal colonization and neonatal infection from group B Streptococcus in women with preterm labor and/or premature rupture membranes. It measures and compare vaginal and anorectal colonization rates. It compare detection rates with selective and non-selective culture media and it compare detection rates with blood Ãgar and CPS Ãgar. A transversal study of 112 women and 220 newborns was performed at Maternidade Escola Assis Chateaubriand from Universidade Federal do Cearà (MEAC-UFC) from may /2008 to july/2009. Vaginal and anorectal samples from each woman were collected using sterile swabs. In 71 women two swabs (vaginal and anorectal) were placed separately in Stuart transport medium and two swabs (vaginal and anorectal) were inoculated separately in Todd-Hewitt selective medium. All subcultered in blood agar plates. The other pregnancies 41 women were investigated only in selective medium and subcultered in a CPS agar plates. A blood culture was collected from each preterm newborn that with any sign of infection. The maternal colonization rate from 71 women was of 4,2% and from the 41 women group was of 17%. Todd-Hewitt selective medium detected 4,4% and non-selective medium 7,2% GBS positive culture (not statistical relevant âNSR). Vaginal samples had a detection rate of 10,7% and anorectal samples had detection rate of 7,1% ( NSR). Urinary infection and be a housewife showed to be meaningful risk factors (p < 0,05). From the newborns studied none of them had GBS positive blood culture due to the sign of infection and altered hemogram. It,s possible that the result had occurred for the fact that the mothers had taken antibiotic before or during the labor. The GBS women colonization in our environment is similar to the other regions of Brazil. The GBS could be to here an important agent for neonatal infection disease and its necessary to take serious prevent measures.

Thesis (Ph.D.) - Carleton University, 2007. / Includes bibliographical references (p. 240-252). Also available in electronic format on the Internet.

Premature births, which are among the leading causes of neonatal mortality and morbidity in South Africa, often result not only in adverse effects on the infant due to the poorly developed organs and systems, but also affect the mother. Much literature exists about the causes of premature birth, clinical manifestations and management of premature infants; but healthcare practitioners, researchers and authors have not reported much on the mothers’ thoughts and feelings while going through the experience of premature labour and birth. This study deals with the experiences of mothers relating to live premature birth and the premature infant at a private hospital in the Nelson Mandela Metropolitan Municipality, an urban area within the Eastern Cape Province. The objectives of the study were to explore and describe the experiences of mothers relating to live premature birth and the premature infant at a private hospital in the Eastern Cape Province and to make recommendations based on the research findings which could be utilised by midwives when caring for mothers who had experienced a premature birth. This study, which is qualitative in nature, utilised an explorative, descriptive and contextual design. The population of the study was mothers between the ages of 18 and 38 years who had had a premature birth and were of a gestational age ranging from 28 to 34 weeks. Data collection took place at a private hospital in the Eastern Cape Province over a period of five months. A private room that was designated for the data collection and was not far from the unit where the neonate was kept, proved to be suitable for data-collection purposes. Semi-structured one-on-one interviews were conducted and recorded with an audio digital taperecorder, with a purposefully selected sample of 12 mothers including the pilot study. Data analysis followed formally after data saturation and the data collected was transcribed verbatim and analysed as recommended by Tesch, namely, data coding. An independent coder was used to verify and finalise the results. Two main themes with three sub-themes each and several categories emerged from the data analysis. The two main themes were that: 1. participants had experienced premature birth as an unexpected and traumatic occurrence; and 2. participants had experienced positive support as a coping mechanism throughout the premature birth. Direct quotations were used from the raw data collected to support the description of experiences and findings of this study. Trustworthiness of the study was maintained by using the criteria of credibility, transferability, dependability and confirmability. Ethical principles such as autonomy, beneficence, non-maleficence and justice were used to ensure that the research was conducted in an ethical manner. A summary of the study including limitations, recommendations and conclusions was provided.

The purpose of this study was to investigate the relationship between antenatal care (ANC) adequacy and preterm births. The researcher used the quantitative, descriptive, correlational, retrospective, case control design on a sample size of 40 cases and 80 controls. A checklist was used to collect data at one state hospital in Windhoek. When the Adequacy of Prenatal Care Use (APNCU) index was applied, premature birth was found to be less likely for women in the higher categories of care (OR 0.121; 95% CI 0.124–0.613) as compared to those in the lower categories. Similarly when the Content and Timing of care in Pregnancy (CTP) tool was used; women in the higher categories of care, were less likely (OR 0.114; 95% CI 0.012–1.056) to give birth prematurely as compared to those in the lower categories / Health Studies / M.A. (Health Studies)

Preterm birth is a leading cause of both maternal and neonatal morbidity and mortality. It occurs in roughly one in every ten pregnancies, and at an even higher rate among Black Americans and residents of underdeveloped nations. Preterm birth can be initiated in response to a maternal or neonatal indication, or can occur spontaneously. Though indications for the former may vary, the most frequent indication for indicated preterm birth is preeclampsia, a disorder of pregnancy marked by high blood pressure and systemic organ damage. While spontaneous preterm birth and preeclampsia account for a substantial fraction of the burden of prematurity, our understanding of the triggers for and pathogenesis of both diseases are lacking. As a result, we are not able to accurately identify women early in pregnancy who are at high risk of having a spontaneous preterm birth or of developing preeclampsia. There is mounting evidence that local and systemic inflammation, infection, and environmental exposures impact the vaginal ecosystem and may be triggers of spontaneous preterm birth and preeclampsia. In this thesis, I explore the role of vaginal microbes, metabolites, and immune factors in spontaneous preterm birth and preeclampsia. After reviewing what is known about the vaginal ecosystem in spontaneous preterm birth and preeclampsia, I present a paired study of the vaginal microbiome and metabolome in a cohort of 232 women, 80 of whom delivered spontaneously preterm, and whose vaginal ecosystems were profiled during the second trimester of pregnancy. In this study I identify several metabolites strongly associated with spontaneous preterm birth, and suggest that many of these may be exogenous in origin. I also use metabolic models to investigate tyramine, a metabolite found to be associated with lower risk of spontaneous preterm birth. Finally, using predictive models I show that vaginal metabolite levels can be used to identify women at risk of spontaneous preterm birth months in advance. I then present a second study of the vaginal microbiome and immune factors in a cohort of 124 women, 62 of whom developed severe preeclampsia, and whose vaginal ecosystems were profiled at the end of the first trimester. In this study, I demonstrate for the first time that the levels of vaginal microbes early in pregnancy as well as genomic variation in the vaginal microbiome are associated with the risk of developing preeclampsia. I also identify that many vaginal immune factors are significantly depleted in the vaginal ecosystem of women who develop severe preeclampsia. I then use predictive models to show that the levels of vaginal microbes are modestly predictive of preeclampsia risk, and that features from the vaginal ecosystem can be used to improve current methods for the identification of women at risk for severe preeclampsia. Finally, I show that the microbiome signature associated with severe preeclampsia replicates in an independent cohort, suggesting that the early pregnancy vaginal microbiome is robustly associated with the diagnosis of preeclampsia months later in pregnancy. Overall, the microbial and molecular signatures that I identify in these studies contribute novel insight to our understanding of the signs and pathogenesis of both spontaneous preterm birth and preeclampsia, and in doing so, suggest novel approaches to intervention and diagnosis.

All human lives start with pregnancy. A pathological pregnancy can be physically, mentally, and financially detrimental to newborns and families. Preterm labor and birth (PTB) is one of the most serious pathological conditions associated with pregnancy. PTB affects 10% of global births and is the leading cause of death in children under five years of age. Multiple etiologies are identified for causing PTB and three major reproductive tissues are involved: the uterus, the cervix, and the feto–maternal interface. Throughout pregnancy, these reproductive tissues change in response to various signals, a process called remodeling. Timely and appropriate remodeling of these tissues is needed for a healthy pregnancy. One central element of remodeling is a change in tissues’ mechanical properties, the focus of this work. This dissertation investigates the mechanical environment of pregnancy by characterizing the remodeling of three reproductive tissues of primates (humans and Rhesus macaque monkeys) and computationally simulating pregnancy physiology. I combine comprehensive mechanical testing with digital image correlation (DIC) to capture the material behavior of reproductive tissues, characterize the architecture of these tissues’ fiber networks by optical coherence tomography (OCT), implement a microstructurally-inspired constitutive mate- rial model, conduct inverse finite element analysis (IFEA) to quantify observed remodeling, and finally use finite element analysis (FEA) to simulate pregnancy anatomy and physiology. Results presented here demonstrate that the non-human primate (NHP) cervix, human uterus, and NHP feto–maternal interface all undergo remodeling during pregnancy and experience com- plex stress conditions. In general, the NHP cervix becomes softer and more extensible, with distinct stages. While the ground substance compressibility stays approximately the same throughout gestation, the fiber network steadily becomes more extensible, though rapidly becomes less stiff and more dispersed during the second trimester. The human uterus late in gestation is softer and more extensible compared to its NP state; most of its remodeling involves changes to fiber network extensibility and architecture. The NHP feto–maternal interface adhesion strength reaches a peak early in the third trimester. Lastly, I generated preliminary subject-specific finite element models of NHP by using a workflow developed for human data. By doing this, the complex stress and stretch conditions that reproductive tissues undergo during pregnancy can be visualized. Future work advancing our understanding of pregnancy and women’s health should include the characterization of the time-dependent properties of reproductive tissues, investigation of the relationship between quantitative ultrasound measurements and tissues’ mechanical properties, and improvements to the current FEA workflow.

Thesis (MSc)--Stellenbosch University, 2003. / ENGLISH ABSTRACT: Introduction Worldwide, up to 25% of women are assaulted during pregnancy, with estimates varying between populations. Violence has been associated with adverse pregnancy outcome, including preterm birth, abruptio placentae and low birth weight. Among the Coloured population of the Western Cape the incidence of spontaneous preterm birth is 20%, compared to the global figure of 10%. Overall, the rate of preterm labour has not dropped over the past 40 years and no clearer answer as to a specific cause has been found. The objective of this study was to determine whether patients who deliver preterm experience more domestic violence than those who deliver at term. Methods Two groups of patients were assessed. Firstly, patients who spontaneously delivered between 24 and 33 weeks (24wOd - 33w6d), who were admitted for suppression of active labour after 24 weeks, or who experienced placental abruption before 34 weeks, were screened for domestic violence using the "Abuse Assessment Screen". A second group of women, attending a local Midwife Obstetric Unit with uncomplicated pregnancies, completed the same questionnaire. The questionnaires were all administered by the same person (J.S.) after written informed consent was given. Results A total of 229 patients were interviewed, 99 in the low risk (LR) and 130 in the preterm labour (PTL) group, which included 23 women with abruptio placentae. The PTL group experienced significantly more violence throughout their lives than the LR group (59.7% vs. 40.4%, p = 0.038). Experiences of violence within the last year or during the pregnancy did not reach statistical significance between the two groups, although the numbers were higher for the PTL group. The PTL group smoked significantly more cigarettes per day (p = 0.009), used more alcohol (p < 0.001) and had a higher incidence of syphilis than the LR group (p = 0.005). These differences remained the same when the abruptio's were analyzed as a separate group. Conclusions: Women who delivered preterm did experience more violence at some point in their lives and were also more likely to engage in high-risk behaviour. Violence alone does not seem to cause PTL directly, but is part of a low socioeconomic lifestyle. The fact that the alcohol use is so high among these women is a problem that needs to be addressed, but once again, it is possibly the result of deeper social problems. The need for education on values and respect, family planning use and low risk sexual behaviour is once again challenged. / AFRIKAANSE OPSOMMING: GEWELD TEEN VROUE -IMPAK OP REPRODUKTIEWE GESONDHEID EN UITKOMS VAN SWANGERSKAP Inleiding Daar word beraam dat tot 25% van alle swanger vroue aangerand word, maar die insidensie wissel tussen verskillende populasies. Ervarings van geweld kan 'n direkte of indirekte oorsaak wees van swak verloskundige uitkoms wat voortydse kraam, abruptio placentae en lae geboortegewig insluit. In die Wes- Kaap, onder die Kleurlingbevolking, is die insidensie van voortydse kraam 20%, wat swak vergelyk met die wêreldwye insidensie van 10%. Gedurende die laaste 40 jaar het die voorkoms van voortydse kraam nie verminder nie en geen deurbrake is gemaak t.o.v die oorsaak van die probleem nie. Die doel van hierdie studie was om te bepaal of vroue wat prematuur verlos moontlik meer geweld ervaar as vroue wat op normale swangerskapsduur verlos. Metodes Twee groepe vroue is bestudeer. Die eerste groep het vroue ingesluit wat spontaan verlos het tussen 24 en 33 weke (24wOd - 33w6d) of vroue wat na 24 weke swangerskapsduur toegelaat is vir onderdrukking van kraam. Vroue met plasentale loslating (abruptio placentae) voor 34 weke, sonder onderliggende hipertensiewe toestande, was ook ingesluit in die groep. Daar is m.b.v. 'n vraelys ("Abuse Assessment Screen") bepaal watter van die vroue gesinsgeweld ervaar het. Die tweede groep het vroue ingesluit met ongekompliseerde swangerskappe en wat by 'n nabygeleë kliniek voorgeboortesorg ontvang het. Hulle is ook gevra om die vraelys te voltooi en is opgevolg om die uitkoms van hulle swangerskappe te noteer. Die vraelyste is almal deur een persoon (J.S.) aan die vroue voorgelê nadat hulle ingeligte, skriftelike toestemming gegee het. Resultate 'n Totaal van 229 vroue was ingesluit, 99 in die lae risiko (LR) groep en 130 in die voortydse kraam (VK) groep, waarvan 23 abruptio placentae gehad het. In vergelyking met die LR groep, het die VK groep het betekenisvol meer geweld in hulle leeftyd ervaar (59.7% teenoor 40.4%, p = 0.038). Geweld wat tydens die afgelope jaar of tydens die swangerskap ervaar is, het nie betekenisvol verskil tussen die twee groepe nie, alhoewel die getalle hoër was vir die VK groep. Die VK groep het betekenisvol meer sigarette per dag gerook (p = 0.009), meer alkohol gebruik (p < 0.001) en het 'n hoër insidensie van sifilis gehad as die LR groep (p = 0.005). Hierdie verskille was steeds beduidend nadat dié met abruptio placentae as 'n aparte groep geanaliseer is. Gevolgtrekking Die vroue wat prematuur verlos het, het meer emosionele en fisiese geweld in hulle leeftyd ervaar en is meer geneig om 'n ongesonde leefstyl te handhaaf. Geweld blyk nie 'n direkte oorsaak van voortydse kraam te wees nie, maar gaan gepaard met 'n lae sosio-ekonomiese lewensstyl. Die hoë insidensie van alkoholgebruik onder swanger vroue is 'n probleem wat aangespreek moet word, maar dit is waarskynlik die manifestasie van dieper emosionele probleme. Opvoeding in terme van waardes en respek, gesinsbeplanning en veilige seksuele gedrag is gevolglik 'n noodsaaklikheid.

L’accouchement prématuré est un problème de santé publique dans le monde et notamment dans les pays économiquement développés avec un taux variant entre 7 et 12 % des naissances. Le diagnostic du risque d’accouchement prématuré est difficile à faire et les outils à notre disposition ont peu évolué ces dernières années. La contraction utérine est la conséquence directe de l’activité électrique au niveau du myomètre. Le type de contraction est lié à l’importance de l’excitabilité cellulaire et de sa diffusion à l’ensemble du myomètre. Le recueil et l’analyse de cette activité électrique par des électrodes de surface est aujourd’hui le seul moyen non invasif d’étudier, pendant la grossesse, les mécanismes qui sont à l’origine de la contraction. L’enregistrement de l’électromyogramme utérin ou électrohystérogramme (EHG) est donc prometteur pour réaliser un diagnostic et une surveillance des femmes à risque d’accouchement prématuré. Dans ce travail de thèse 3 études cliniques ont été réalisées. Dans la première, j’ai étudié différentes électrodes de surface permettant d’enregistrer les signaux électriques. Je propose à la fin de cette première partie un système d’électrodes pour permettre à la fois un enregistrement de qualité et une pose aisée compatible avec une application clinique. Dans la deuxième étude j’ai étudié la détection automatique des contractions par l’EHG avec des résultats encourageants pour l’application clinique et notamment en ambulatoire. Enfin dans la troisième étude j’ai étudié la prédiction du risque d’accouchement prématuré par l’analyse de paramètres électriques issus de l’EHG. Les résultats obtenus permettent d’améliorer la prédiction du risque d’accouchement prématuré par rapport aux outils utilisés en routine. / Premature birth is a public health problem in the world, particularly in economically developed countries with a rate varying between 7% and 12% of births. The diagnosis of the risk of premature labor is difficult to make and the tools at our disposal have changed little in recent years. Uterine contraction is a direct consequence of electrical activity at the level of the myometrium. The type of contraction is related to the importance of cell excitability and its diffusion to the entire myometrium. The analysis of this electrical activity by surface electrodes is currently the only non-invasive way to study the mechanisms that are at the origin of the contraction. The recording of the uterine electromyogram or electrohysterogram (EHG) is therefore promising for the diagnosis and surveillance of women at risk of preterm birth. In this thesis work 3 clinical studies have been carried out. In the first clinical study, different surface electrodes to record electrical signals were tested. I propose at the end of this first part a system of electrodes to allow at the same time a recording of quality and an easy pose compatible with a clinical application. In the second study , the automatic detection of contractions by the El-IG was studied with encouraging results for the clinical application and especially in ambulatory. Finally, in the third clinical experiment, I studied the prediction of the risk of premature delivery by the analysis of electrical parameters extracted from the EHG. The results obtained make it possible to improve the prediction of the risk of premature delivery compared to the tools used routinely.

The doctoral dissertacion is focused on the role of inflammation in the pathogenesis of preterm labor. In the first part, we describe the current view on pathophysiology of preterm labor. In the second part, we evaluated the relationship of specific markers of inflammation and endothelial dysfunction to preterm birth and fetal inflammatory response. The most important findings of our study was that we found decreased levels of MMP-2 and decreased levels of sRAGE in women with preterm labor in comparison with the control group of pregnant women. Similarly, we found decreased levels of MMP-2 in women with subsequent diagnosed fetal inflammatory response. sRAGE is currently ranked among patttern recognition receptors. In the case of sRAGE we followed the results of our pilot project, it can be assumed that the its low level are connected with tissue damage. We confirmed that it can play an important role in the pathogenesis of preterm labor. We assume abnormal regulatory mechanisms of the production of MMP-2. In both cases, however, further studies are required to elucidate the functional significance of our results.