Hypoxia can result in brain injury. Hypoxic brain injury can also result in excess stress hormones and activated immune responses. In this study, we examined multiple spontaneous motor behaviors, concentrations of stress hormones, and gene expression of immune responses in rats after perinatal hypoxia. Hypoxic animals exhibited impaired spontaneous motor behaviors in several tests. Perinatal hypoxia also caused increased levels of stress hormones and altered expression of genes associated with adaptive and innate immunity at different time points after hypoxia exposure. Findings demonstrate stress hormones and immune responses are available to play an important role in perinatal brain injury and can impact delayed behavioral development.

The incidence of preterm labor has risen over recent decades and preventative antibiotic treatment is ineffective. Associated with a 40% increased risk of preterm birth, bacterial vaginosis is characterized by a decrease in lactobacilli and increase in pathogenic bacteria in the vaginal flora. Ascent of bacterial products to the intrauterine environment stimulates cytokine and prostaglandin secretion from invading immune cells and gestational tissues. Probiotic lactobacilli modulate the immune responses in mouse macrophages and human placental trophoblast cells. The focus of this thesis was to determine the influence of Lactobacillus rhamnosus GR-1 (GR-1) on cytokines and prostaglandins which are part of the activated pathway in infection and/or inflammation mediated preterm labour. GR-1 increased amnion chemokine and reduced pro-inflammatory cytokine release. GR-1 elevated prostaglandin E2 release that was paralleled by an increase in mPGES2 expression. It is possible that t that GR-1 may enhance the host defense barriers of the amnion to pathogenic bacteria.

The incidence of preterm labor has risen over recent decades and preventative antibiotic treatment is ineffective. Associated with a 40% increased risk of preterm birth, bacterial vaginosis is characterized by a decrease in lactobacilli and increase in pathogenic bacteria in the vaginal flora. Ascent of bacterial products to the intrauterine environment stimulates cytokine and prostaglandin secretion from invading immune cells and gestational tissues. Probiotic lactobacilli modulate the immune responses in mouse macrophages and human placental trophoblast cells. The focus of this thesis was to determine the influence of Lactobacillus rhamnosus GR-1 (GR-1) on cytokines and prostaglandins which are part of the activated pathway in infection and/or inflammation mediated preterm labour. GR-1 increased amnion chemokine and reduced pro-inflammatory cytokine release. GR-1 elevated prostaglandin E2 release that was paralleled by an increase in mPGES2 expression. It is possible that t that GR-1 may enhance the host defense barriers of the amnion to pathogenic bacteria.

BACKGROUND: Despite decades of research aimed at prevention, preterm birth remains an enormous leading cause of infant mortality in the United States and worldwide. Of concern, racial disparities in preterm birth remain an intractable public health issue. In an effort to reduce preterm birth, organizations such as the American Congress of Obstetricians and Gynecologists (ACOG) released policy statements in 2009 aimed at reducing early elective deliveries. Subsequently, the incidence of preterm birth in the United States has decreased, but whether this decrease is due to a reduction in iatrogenic or "medically-indicated" preterm birth is unknown. Further, the effect of the reduction in early elective deliveries on racial disparities is unknown. Our hypotheses were that 1) after 2009, preterm births would be less likely to be medically-indicated than due to spontaneous causes and 2) black-white differences in preterm births would be unchanged. OBJECTIVES: 1) Determine the proportion of preterm deliveries at Beth Israel Deaconess Medical Center (BIDMC) from 2004-2013 that were medically-indicated versus spontaneous. 2) Due to persistent disparities, determine if shifts in type of preterm delivery varied by race/ethnicity. METHODS: We reviewed the first 87 deliveries in 2013 and randomly selected 15% of the records for each year from 2004-2013. Additionally, we reviewed 69 charts to oversample black women's deliveries. We manually abstracted data from BIDMC's online medical record and designated each delivery as either medically-indicated (preeclampsia, poor fetal growth, hypertension, or other fetal/maternal condition) or spontaneous (preterm labor, preterm premature rupture of membranes or cervical incompetence). Two reviewers independently reviewed 18 records for concordance of medically-indicated versus spontaneous preterm birth typing. If the first reviewer could not phenotype the delivery, then a neonatologist and obstetrician were consulted. We reviewed 971 out of the 5,566 preterm deliveries and included 930 that were confirmed preterm and had a clear medically-indicated or spontaneous phenotype. We dichotomized the time period into early (2004-2009) and late (2010-2013). Statistical methods included comparisons of early versus late using Chi-Square tests, logistic regression models to adjust for potential confounding variables, and stratified analyses (singletons and black versus white). RESULTS: There were 46,981 deliveries at our institution during the study period, 5,566 of which were preterm. Among the 930 preterm deliveries sampled from the 10-year period, 45.6% were medically-indicated with a non-significant, subtle difference between the early (48.3%) and late (41.9%) (P=0.05) time periods. The odds ratios of medically-indicated versus spontaneous preterm birth in late versus early were 0.77 (P=0.05) and 0.73 (P=0.03) for all participants, unadjusted and adjusted, respectively. While not statistically significant, a higher proportion of preterm deliveries among black women were medically-indicated in the early (50.4%) versus late (40.6%) periods (P=0.19). There was a similar trend among white women between the early (50.0%) and late (46.9%) periods (P=0.48). The odds ratios of medically-indicated versus spontaneous preterm birth from late versus early were 0.67 (P=0.19) and 0.63 (P=0.14) for black participants, unadjusted and adjusted, respectively. For white participants, the odds ratios were 0.88 (P=0.48) for unadjusted and 0.80 for adjusted (P=0.20). Overall at BIDMC, the preterm delivery rate was significantly higher in the early period (12.3%) compared to the later period (11.2%) (P=0.0003). While we observed a reduction of preterm birth among all women, black women experienced a 20.8% decrease (from 16.2% in the early period to 12.8% in the late) in preterm birth, while white women experienced just a 4.9% decrease (from 12.4% to 11.7%), resulting in a narrowing of the racial disparity of preterm birth in our institution. CONCLUSION: At a Massachusetts birth hospital we found a reduction in the incidence of preterm deliveries over a 10-year period that coincided with policy efforts to reduce early elective deliveries. There was a reduction in the proportion of preterm births that were medically-indicated from 48.3% to 41.9%. The reduction in medically-indicated preterm birth was most evident among black women at BIDMC with concurrent decrease in the overall preterm birth rate among black women resulting in a near elimination of the racial disparity in preterm birth at BIDMC. Future work includes statistical analysis to account for the oversampling of deliveries in 2013 as well as oversampling of black women's deliveries using inverse probability weighting. We also plan to analyze which underlying conditions (preeclampsia, intrauterine growth restriction, fetal distress, etc.) were responsible for the reduction of the medically-indicated deliveries.

Abstract The aim of this study was to examine the effect of preterm birth on the development of the dentition. The spesific aims were to examine the effect on deciduous and permanent tooth crown dimensions, the eruption of permanent teeth and the sagittal occlusal relationships within the dentition. The subjects consisted of 328 prematurely born (< 37 gestational weeks ) white and black children and 1804 control children, who participated in the cross-sectional study of the Collaborative Perinatal Project (USA) in the 1960's and 1970's. Dental examinations, including dental casts were performed at the age of 6–12 years. Tooth crown size measurements, recording of the sagittal occlusal relationships and tooth eruption stages were performed by examining the dental casts. In general larger permanent tooth crown dimensions were found in preterm white boys and black girls and smaller permanent tooth crown dimensions in preterm white girls and black boys. There were both increased and decreased deciduous tooth crown dimensions in preterm children compared to controls, but no significant differences were found. Boys had larger tooth crown sizes than girls within all preterm and control groups showing sexual dimorphism. The results showed earlier eruption of permanent incisors and first molars in all preterm children compared to controls and also according to sex and race. Concerning the sagittal occlusal relationships, the results showed greater prevalence of prenormal canine relationships in preterm group than in the controls. When the molar relationships were concerned, the prevalence of mesial molar occlusion was greater in the preterm group. The incidence of bilateral symmetrical canine relationship was the same in both preterm and control groups, but inside the preterm group the girls had better symmetry than the boys. The findings of this research suggest that short gestation is not associated with reduced permanent and deciduous tooth crown dimensions in prematurely born children and also confirm the presence of the sexual dimorphism in tooth crown size. The studies also indicate that the clinical tooth eruption is accelerated in all observable permanent teeth in prematurely born children. The findings of occlusal morphology indicated that premature birth may effect the sagittal occlusal development. General health condition, neonatal and postnatal factors like intubation, postnatal molding of head shape and the importance of catch-up growth and early functional activity should be considered as possible influencing factors. Preterm birth may also interfere with the development of symmetry and lateralization.

Abstract Chlamydiae are obligatory intracellular gram-negative bacteria with a unique growth cycle. They are very successful pathogens and responsible for a wide variety infections in humans and different animal species. In addition, they have a tendency to cause recurrent, persistent or chronic infections with potentially severe sequelae years or decades later. The general purpose of this work was to study the possible serological associations between chronic chlamydial infection, systemic inflammation and reproductive health in a general population. The chlamydial heat shock proteins 60 and 10 (Hs10 and Hsp60) have been suggested to contribute to the pathogenesis of chronic chlamydial infections. Thus, the antibodies to chlamydial Hsp10 and Hsp60 were also investigated in complications of pregnancy. The present study was a longitudinal population-based birth cohort study, and all of the original papers of this dissertation are based on a nested case - control design. Our results confirmed the serological association between C. trachomatis infections and subfertility and the rather high incidence of undiagnosed C. trachomatis infections in the male partners of subfertile couples. We further demonstrated a serological association between previous C. trachomatis infections, immunity to chlamydial Hsps and female subfertility. We also showed that serological markers of chronic chlamydial infection present as early as the first trimester are associated with preterm delivery among nulliparous women. When elevated levels of C. trachomatis IgG and hsCRP were present, the estimated risk for preterm delivery was over 4-fold. According to our study, nulliparous women who subsequently developed preeclampsia leading to preterm delivery, which was used as a marker of more serious illness, had significantly more often serum IgG antibodies to C. pneumoniae during the first trimester of pregnancy compared to the preeclamptic women who delivered at term. In conclusion, chronic C. trachomatis infection was found to associate with subfertility both in men and in women. In addition, a subclinical chronic inflammatory process associated at least partly with chronic C. trachomatis infection and present in the first trimester already may be important in the development of preterm delivery. Chronic C. pneumoniae infection and systemic low-grade inflammation were found to associate with pregnancies that lead to preeclampsia and preterm delivery.

Structured summary Aim of the study: To compare the diagnostic reliability, accuracy, and safety of amniocentesis and amniotic fluid Interleukin-6 testing in the diagnosis of intrauterine inflammation of patients with preterm premature rupture of membranes. Type of study: Prospective cohort study Name and location of study site: Department of Gynaecology and Obstetrics, Faculty of Medicine, Charles University in Pilsen Set and methodology: We prospectively examined patients with pPROM between the 23rd and 34th week of gestation in 2014 - 2017. All of them underwent amniocentesis and determination of IL-6 levels in amniotic fluid, leukocytes and bacteria in amniotic fluid as well as maternal blood examination for inflammation parameters. The results were compared to histological examination of the placenta after delivery for the presence of chorioamnionitis. Based on the values mentioned above the sensitivity, specificity, negative and positive predictive value, false positive and negative predictive value and accuracy of the test were determined together with an assessment of statistical significance. Furthermore, the feasibility and incidence of perioperative complications as well as the risk of secondary infection when pregnancy continued were evaluated by serial aniocenteses at weekly intervals. The...

MCur / Department of Advanced Nursing Science / Introduction: During the provision of care to preterm babies, midwives encounter many problems and challenges which may vary according to the gestational age of the women, condition of the foetus, availability of equipment and resources, and experience of the midwives. In addition, poor working conditions, feelings of insecurity, staff shortage, and lack of support from the management and having to deal with parents who do not comply with the hospital management plan for their babies; all contribute to the problems faced by midwives. The purpose of this study was to determine challenges encountered by midwives when providing care to preterm neonates at selected hospitals in the Mopani District of Limpopo Province, South Africa. Methods: Qualitative research in this study was conducted in a natural setting at the selected hospitals. The target population was the midwives who have been working in maternity wards for at least two years and were on duty during the period of data collection. Non-random purposive sampling was used to select the participants. Data were collected using unstructured interviews, which were tape recorded and transcribed. The six steps as described by Creswell were used for data analysis. Trustworthiness was ensured by using the model of Lincoln & Guba that included credibility, dependability, confirmability and transferability. Ethical principles, namely, permission to conduct the study, informed consent from participants, privacy, confidentiality, autonomy, anonymity and respect were observed. Results: When midwives provide care to preterm babies they often encounter multiple challenges which can be human or material resource related. In his study, midwives were found to perform their duties in the face of multiple challenges, including staff vi shortages, which resulted in exhaustion of the available midwives. Nursing a preterm baby is a challenge on its own as these babies are likely to develop clinical problems related to immaturity, e.g., hypoglycaemia, hypothermia, jaundice, sepsis and respiratory distress. Mothers may be traumatised and find it difficult to accept their babies as they are, this leads to lack of cooperation in the care of the neonate and it becomes a problem for the midwives who are directly providing such care. The aforementioned challenges are related to all the four major concepts of human caring as described by Jean Watson which are health, human being, nursing and environment. Recommendations: It is recommended that further research be conducted on the same topic, but in a different setting to generate more knowledge. Policy makers should work together with health care professionals who are directly involved in the care of preterm babies to improve the practice of the contents in the policies. / NRF

Preterm birth (PTB) is defined as birth before the 37th week of pregnancy and affects 15 million infants per year. Presently, there is no clinical test to determine PTB risk. A 3D printed microfluidic device is being developed as a clinical test for PTB risk via detection of a panel of biomarkers. A significant step is extraction of the PTB biomarkers from blood serum. In this work, I developed 3D printed microfluidic devices in which monoliths can be polymerized. Using the monolith as a solid support to attach antibody, I show that ferritin, one of the PTB biomarkers, can be selectively extracted from human blood serum. This is the first study where a monolith has been formed in a 3D printed microfluidic device and used to perform an immunoaffinity extraction. This work is an important step in developing a clinical test for PTB risk. The realization of this work also demonstrates that 3D printing can be used to fabricate functional microfluidic devices.

Background: Adolescent female depressive symptomatology is an unrecognized mood disorder that impairs health in adolescence or adulthood. However, the long-term effects of pre-pregnancy depressive symptoms on birth outcomes in adulthood have not been given adequate empirical assessments. Method: In this study, we assessed the relationship between the life time duration of depressive symptoms over a 14-year period and birth outcomes (LBW and PTB) among a sample of 6023 female respondents who took part in the National Longitudinal Study of Adolescent to Adult Health (Add Health). We used the generalized estimating equation (GEE) models to assess these relationships. Results: Exposure to elevated depressive symptoms in late adolescence, but not in adulthood, was associated with increased odds of LBW by more than 2-fold in early and young adulthoods (adjusted odds ratio [aOR] = 2.19; 95% confidence interval, CI: 1.56, 3.08). Depressive symptoms in early adulthood were independently associated with increased odds of PTB and were higher for black mothers. Maternal race modified the relationship between consistent reporting of depressive symptoms in adolescence and LBW or PTB in adulthood. Conclusion: This study provides compelling evidence that effects of elevated depressive symptomatology on LBW or PTB appear to be linked to a specific development period in adolescence. National policies to address social inequalities and stratification particularly in health at all stages of human development, will provide an important step in reducing depressive symptoms prior to early adulthood and in pregnancy and childbirth.