Title Promoter Affiliations Abstract "Advanced Solutions for Neonatal Sleep Analysis and the Effects of Maturation" "Sabine Van Huffel" "Woman and Child, ESAT - STADIUS, Stadius Centre for Dynamical Systems, Signal Processing and Data Analytics" "Worldwide approximately 11% of the babies are born before 37 weeks of gestation. The survival rates of these prematurely born infants have steadily increased during the last decades as a result of the technical and medical progress in the neonatal intensive care units (NICUs). The focus of the NICUs has therefore gradually evolvedfrom increasing life chances to improving quality of life. In this respect, promoting and supporting optimal brain development is crucial.Because these neonates are born during a period of rapid growth and development of the brain, they are susceptible to brain damage and therefore vulnerable to adverse neurodevelopmental outcome. In order to identify patients at risk of long-term disabilities, close monitoring of the neurological function during the first critical weeks is a primary concern in the current NICUs. Electroencephalography (EEG) is a valuable tool for continuous noninvasive brain monitoring at the bedside. The brain waves and patterns in the neonatal EEG provide interesting information about the newborn brain function. However, visual interpretation is a time-consuming and tedious task requiring expert knowledge. This indicates a need for automated analysis of the neonatal EEG characteristics. The work presented in this thesis aims at contributing to this.The first part of this thesis focuses on the development of algorithms to automatically classify sleep stages in preterm babies. In total three different strategies are proposed. In the first method, the problem is traditionally approached and a new set of EEG complexity features is combined with a classification algorithm. This analysis demonstrates that the complexity of the EEG signal is fundamentally different dependent on the vigilance state of the infant. Building on this finding, a novel tensor-based approach that detects quiet sleep in an unsupervised manner is presented.Finally, a deep convolutional neural network to classify neonatal sleep stages is implemented. This end-to-end model optimizes the feature extraction and classification model simultaneously, avoiding the challenging task of feature engineering.   The second part concentrates on the quantification of functional brain maturation in preterm infants. We establish that the complexity of the EEG time series is significantly positively correlated with the postmenstrual age of the neonate. Moreover, these promising biomarkers of brain maturity are used to develop a brain-age model. This model can accurately estimate the infant's age and thereby assess the functional brain maturation. In addition, the relationship between the early functional and structural brain development is investigated based on two complementary neuromonitoring modalities, EEG and MRI. Regression models show that the brain activity during the first postnatal days is related to the size and growth of the cerebellum in the subsequent weeks.At last, the influence of the thyroid function on the developing brain is examined in extremely premature infants. No significant association was observed between the change in free thyroxine concentrations during the first week of life and maturational features extracted from the EEG at term equivalent age. To shed more light on the precise relationship between thyroid function and brain maturation, prospective studies with a more homogeneous dataset are needed in the future." "Advances in the management of Obstetric Fistulae" "Dirk De Ridder" "Woman and Child" "In this thesis research on obstetric fistula is being presented. Obstetric fistula are complications of obstructive labour, where the foetal head compresses tissues against the bony pelvis. This induces ischaemia and necrosis of these tissues and subsequent fistulisation. The high prevalence of obstetric fistula in certain regions of developing countries is a hallmark of poor perinatal careEpidemiological studies have shown that the incidence in central Africa is about 4, 09 fistulae for 1000 deliveries. The prevalence is estimated at 0-81 fistulae per thousand women. Stillbirths are often the consequence. Up to 90% of the babies will be born dead. The most important risk factors are: young age at first marriage, short stature, not attending prenatal clinics, low socio-economic status, unemployment and illiteracy. Obstructive labour is one of the five most important causes of maternal deaths. This study is situated in the West of the Democratic Republic of the Congo, namely Kisantu in the province of Bas-Congo. Since 2007 an integrated fistula program has been implemented in collaboration with SOLFA, LUMOS and the local doctors and nurses. A database was kept on all patients that were seen within the Programme. In our first study we evaluated the aetiology of obstetric fistulae in the West of Congo, in comparison with those in other African regions. The study was conducted in 146 women with vesicovaginal fistula. Strikingly 63.4% of these women underwent a caesarean section, but this was carried out too late to save the life of the baby and to prevent the formation of the fistula. Being able to decide early to attend the hospital, being able to access the hospital and once arrived in the hospital being able to get adequate care were the most important interfering factors. In our first series 63% of the fish globe are successfully closed and 63% of the patients were confident after the surgery. This is in line with findings in the literature. Persisting incontinence despite the successfully close fistula remains a challenge. Secondly we looked at potential predictive factors for successful closure of the fistula and restoration of continence. For this study we evaluated 166 patients. The most prevalent fistula localisation was peri-cervical. 20% of the patients had severe vaginal fibrosis as a consequence of the fistula formation. Patients with severe fibrosis were 68% less likely to be dry postoperatively. Also a urethral localisation of the fistula was an important negative predictive factor. In that case the likelihood of being dry after the surgery was 73% less. These findings are in line with recent publications. They also lead to the fact that on an international level the Goh classification is now being recommended as classification system. In this  fistula classification, fibrosis is used as a prognostic factor, while in other classifications like the Waaldijk classification, this is not the case. It has been shown in the meantime that classification system of Goh has a higher predictive value for outcome than that of Waaldijk. An important challenge in the research on obstetric fistula is the estimation of the quality of life of the patients. Language barriers and cultural barriers between the often illiterate patients and foreign fistula teams, lead to difficult communication. To improve this situation we validated two internationally accepted questionnaires in Lingala and Kikongo, two important languages in Congo. The UDI-6 or Urogenital distress Inventory assesses the presence of urogenital symptoms, while the IIQ-7 or the Incontinence Impact Questionnaire assesses the impact of incontinence on the daily life of the patients. After translation into both languages, the questionnaires were first tested in a normal population. The test-retest variability was checked as well as the internal consistency. The values that we obtained were comparable to those of other translations in other languages. Next we evaluated the internal consistency and test-retest variability in an obstetric fistula population. Also in this population the results were comparable to those in other international reports. Therefore we concluded that the translations in both languages were valid. We also measured the responsiveness of the questionnaire in a patient population in Lingala. This measures the responsiveness to change of the questionnaire. The values we obtained where impressively high in comparison with those that are found in stress incontinence literature or mixed incontinence studies. This shows that cure of a fistula has an enormous positive impact on the quality of life of these patients. The impact of a holistic integrated fistula program has been measured by correlating the data from our database to the official hospital activity reports from the St. Luc hospital in Kisantu. Over the course of the years we noted a steady decline of new fistula from the own health district. After three years of implementation no new fistula were found in health region of Kisantu. In the same time the obstetric activity in the hospital increased considerably. This could mean that the hospital was more able to act as a reference centre for complex obstetrical care. It also showed that the surrounding health centres and dispensaries referred their patients in a more efficient and proactive way then they did before. We also noted that the distance, that patients had to travel to reach the centre for fistula repair, increased over time. This was a sign that surrounding regions were now referring fistula patients to the fistula centre in Kisantu. This evolution shows that not only a curative intent but also of preventive plan is needed to tackle the fistula problem and to improve the perinatal care.Our understanding of the aetiological mechanisms of obstetric fistula could improve by developing an animal model. When a fistula is formed, this does not happen from one day to the other. After the ischaemia, a period of time passes where the tissues become necrotic. If one could find a way to improve the vascularisation and to reduce the inflammation during that time, fistula formation could eventually be prevented or at least the size of the fistula could eventually be reduced. The use of stem cells or a cocktail of chemokines and cytokines could be useful. To achieve this, we tried to establish a fistula model in rats. Despite several attempts with several methodologies, no durable fistula formation could be established. With this work we have contributed to the knowledge of obstetric fistula. We could show that getting a caesarean section on time remains a challenge in the Congolese society. It is a task for the government that should put education of the population, installing good road infrastructure and offering decent hospital infrastructures high on the agenda. We also contributed to the understanding of predictive factors for success and failure of the fistula repair. We made large progress in measuring quality of life in African women who underwent fistula repair. We sincerely hope that in the near future this will offer us a better view on the real impact of incontinence in this population. The fact that an integrated holistic fistula program was able to eliminate fistula formation in this region, can be an example for other organisations and other regions within Africa.  "