Uterine smooth muscle contraction is determined by the state of myosin (MYL) phosphorylation which is regulated by the calcium dependent myosin light chain kinase (MYLK) and a protein phosphatase called myosin phosphatase. Agonist induced increases in intracellular calcium ([Ca²?]i)activates MYLK which phosphorylates MYL enabling it to bind to actin to cause contraction. Myosin phosphatase is a protein phosphatase that dephosphorylates phosphorylated MYL to induce relaxation. The state of MYL phosphorylation and contraction is therefore determined the equilibrium between MYLK and myosin phosphatase. The mechanisms that regulate these two enzymes in the human uterus remain poorly understood.

Preterm labour is a major reproductive health problem. In this thesis, I started with an epidemiological investigation of preterm birth risk factors in the local hospital population. Smoking, social problems, premature rupture of the membranes, vaginal bleeding, previous history of preterm birth and threatened preterm-Iabour were significantly associated with preterm delivery. However, women who stopped smoking in early pregnancy had no increased risk of preterm birth compared to non- smokers. Medically indicated preterm deliveries were associated with hypertension and fetal growth restriction. The second part of this thesis is a proteomics study of placental blood with the aim to understand the basic mechanisms of human parturition. By comparing five different types of delivery, 33 genes were found to have significantly alte4red expression profiles. The major pathways changed in labour correspond to "immune and defence responses". Although the signal transduction and regulation of these pathways varied among modes of delivery, hepatocyte nuclear factor 1 homeobox A (HNF1A) emerged as a shared protein in the mechanism of labour. Moreover, several apolipoproteins such as APOA4 and APOE were found to change with labour and these changes were also confirmed in maternal plasma. APOA 1 and APOB were negatively and positively correlated, respectively, with gestational age. Changes in alpha-fetoprotein (AFP) in placental blood levels were also replicated in maternal peripheral plasma, whereas the change in alpha 1 B-glycoprotein (A 1 BG) was limited to placental plasma. The last part of the thesis is a systematic review of the literature and meta- analysis AFP and apolipoproteins in order to obtain observational evidence to assess their possible roles in human parturition. The meta-analysis has demonstrated that AP01 and APOB levels are significantly associated with increasing gestational age, and could potentially be used as labour onset biomarkers. The meta-analysis also found a strong association between elevated maternal circulating AFP levels and preterm birth, but the association may be confounded by abnormalities in other biomarkers and pregnancy complications.

Background. Due to the increase in the rate of premature birth in the U.K., research into investigating psychological distress in parents of premature infants is clinically important. It has been identified that there is an absence of research in the area of psychological distress (anxiety, depression and trauma) in parents, particularly in fathers' of premature infants. Attachment theory states that templates of personal attachment are repeated from parents to children. Parents who have difficulty in forming an attachment with their newborn may be more likely to be psychologically distressed. Aims. The principle aim of the study was to understand the relationship between personal attachment style, psychological distress and trauma and the process of attachment in the postnatal period in the parents of premature infants. It aimed (1) to examine the most common personal attachment style of parents of premature infants, (2) to investigate, changes in psychological distress (anxiety, depression and trauma) for parents post birth and 3-4 months later, (3) to investigate the relationship between psychological distress (anxiety, depression and trauma) and parents own personal attachment style, (4) to investigate any changes in parents attachment to their infant post birth and 3-4 months later, and (5) to investigate the relationship between parental attachment to their infant and psychological distress (anxiety, depression and trauma). Method. Thirty-Two mothers and twenty-one fathers were recruited through neonatal intensive care units in two regional hospitals after the birth of their premature infant. Participants were also contacted 3-4 months later, twenty-two mothers and thirteen fathers completing and returning postal questionnaires. Findings. The participant group reported low scores on both the anxious and avoidant subscales of the Experience of Close Relationship-Revised (ECR-R) Questionnaire. Therefore, indicating that the participant group are securely attached. Results revealed that overall; parents of premature infants had lower levels of anxiety and depression at Time 2 (3-4 months post-partum) in relation to Time 1 (after the birth of the infant). However, parents reported higher levels of posttraumatic stress symptoms at Time 2 in comparison to Time 1. Additionally, mothers of premature infants reported higher levels of psychological distress (anxiety, depression and posttraumatic stress symptoms) at both Time periods in comparison to fathers. Mothers' anxiety scores (as measured by the HADS) reached caseness at Time 1. However, mothers' scores reduced significantly at Time 2. In relation to personal attachment style and changes in level of psychological distress, findings indicated a relationship. Mothers with lower avoidant scores reported a decrease in scores on the EPDS from Time 2 to Time 1. With respect to the relationship between changes in parental post-natal attachment and psychological distress, the overall findings suggest lower scores in three components of the Parental Post-Natal Attachment Scale (Tolerance, Pleasure in Proximity and Acceptance) at Time 2 in comparison to Time 1. However, the findings suggest higher scores on the Competence component of the Parental Post-Natal Attachment Scale at Time 2 in comparison to Time 1. Additionally, the findings highlighted a significant relationship between differences in both mothers' Competence scores and HADS depression scores. The findings also propose a significant relationship between changes in both Pleasure in Proximity scores and HADS anxiety and depression scores Conclusion. The findings highlight the importance of assessing parents' levels of psychological distress after the birth of their infant. Additionally, the findings highlight the importance of including fathers' of premature infants in the post-care of their infants to encourage positive interactions with their infant and thereby enabling them to gain from being in close proximity to their infant. Therefore, the findings highlight the importance of continued care for parents post-discharge as the findings indicate that the parents experience difficulties at both follow-up and in NICU.