Functional Magnetic Resonance Imaging, or fMRI, is today a well established tool used to assess both resting state connectivity and task activation in neuroscience. It has also been used for the study of brain development in neonates and there are a small number of pilot studies that seek to use fMRI in utero. However, there are formidable challenges in this application as the fetus lies within the mother and is moved by her respiration as well as performing its own sporadic and unpredictable motion. Thus motion is a core issue for any fetal fMRI study. The first chapter of the thesis discusses a pipeline that was developed to analyse fetal fMRI data acquired with standard sequences. The approach addresses motion correction as a primary requirement, both to stabilise anatomical content for each voxel in a fMRI time series, but also to correct the data from other sources of image artefacts that can be modulated by movement, such as bias eld, spin history and distortions. From the results of this study, it emerges that functional MRI is feasible in the developing fetus. The magnetic properties of fetal and infant brain tissue are very different from adults, leading to a longer T2* relaxation time. This would suggest the use of longer echo times to optimise the BOLD eect, with the downside of decreasing imaging speed. Therefore, the second chapter explores the use of an echo shifted EPI (es-EPI) sequence that achieves an improved signal sensitivity while maintaining ecient sampling. The sequence has been extensively tested on phantom experiments and an improved signal detection is demonstrated on a series of fMRI experiments run on preterm and term-equivalent babies. The long T2* and the lack of air-tissue boundaries between the fetal head and the womb encourages the use of EVI as favourable tool for fetal fMRI. A main benefit of an EVI sequence could indeed be imaging speed and robustness to motion. In a third chapter, EVI fetal imaging is explored and the methods developed allowed the fetal brain to be imaged in full 3D. Despite the challenges of making this work robustly, we speculate that further refinements of the sequence could constitute the ground work with which to perform fetal fMRI in the near future.

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Intrauterine growth restriction (IUGR) occurs in 5-8% of pregnancies and is associated with neonatal and paediatric morbidity and mortality. The aims of this follow-up study were to 1) determine whether pregnancy-specific stress (PSS) is associated with fetoplacental hemodynamics or neonatal outcomes in women with small for gestational age (SGA) pregnancies, and 2) examine differences in health-related quality of life (HRQoL), behavioural problems, and visual-motor integration (VMI)' in SGA three-year-olds. Measures used included the Prenatal Distress Questionnaire, the Pediatric Quality of Life Inventory, the Child Behavior Checklist, and the Beery-Buktenica Developmental Test of Visual-Motor Integration. PSS was associated with decreased UA PI and MCA PI, increased odds of AEDF, decreased CPR, birth weight <2500 g, prematurity, and decreased odds of NICU admission. IUGR children had poorer HRQoL, more affective and withdrawn behavioural problems, and poorer VMI than SGA children. Children who had been exposed to AEDF had more somatic complaints, withdrawn, attention, and internalising behavioural problems, and children who had been exposed to abnormal CPR had more withdrawn and attention behavioural problems. Term IUGR children had poorer physical functioning than preterm SGA children. Preterm IUGR children had more attention problems and poorer VMI than term SGA children, and more oppositional defiant, withdrawn, aggressive, and externalising behavioural problems than preterm SGA children. Male IUGR children had poorer HRQoL, more behavioural problems, and poorer VMI. This multicentre prospective observational study provided a unique opportunity to comprehensively assess PSS and early childhood development in a large cohort of women and SGA children in Ireland and Northern Ireland. This study provides the first available evidence of associations between PSS and fetoplacental hemodynamics and neonatal outcomes in SGA pregnancy. This study also provides novel insights into the developmental differences between SGA and IUGR children, and into the specific developmental vulnerabilities of premature or male IUGR children.

Background: Increasing physical activity (PA) may help to reduce the risk of obesity related pregnancy complications. However little is known about the amount, type and intensity of PA obese pregnant women engage in, or the most appropriate measurement method. Previous research suggests that obese pregnant women receive limited advice concerning PA from midwives. Objectives: To investigate the amount of PA carried out by this population and how this changes during pregnancy, to compare measurement methods, and to describe the knowledge, attitudes and practice of midwives surrounding PA. Methods: 1. 130 pregnant women, BMI≥25kg/m2, consented to PA measurement at 2 or 3 time points using the Actigraph accelerometer and Recent Physical Activity Questionnaire. 2. Questionnaires were designed and distributed to midwives within 3 NHS Trusts on Tyneside (n=365) with the aim of identifying barriers to discussing and advising PA with obese pregnant women. The design used the Theoretical Domains Framework approach which uses behavioural determinants to investigate implementation difficulties. Results: 1. At 12-16 weeks gestation over half of the participants achieved 30 minutes of moderate or vigorous PA, decreasing by 36 weeks to 24%. Women who were more active at baseline decreased their PA during pregnancy; those who were less active remained so. Self-reported PA also fell but did not correlate with objectively measured PA. 2. Midwives scored highest on knowledge and social-professional role and lowest on skills, capabilities and environment/context/resources domains. Regression analysis indicated that skills and memory/attention/decision domains had a significant influence on discussing PA. Conclusion: Research is needed to find methods to encourage obese women to increase and maintain PA levels before and during pregnancy, and to find the most appropriate PA measurement methods. Midwives feel knowledgeable and believe giving PA advice to be part of their role, but lack skills, capabilities and resources. Strategies to remove such barriers are needed.

In England and Wales, about 2-5% of pregnancies are complicated with diabetes each year. Diabetes is a particular problem in the South Asian (SA) ethnic group with the prevalence of Type 2 Diabetes and GDM being about 6 times and 11 times higher respectively as compared to White British (WB) women. My PhD project was undertaken to study the influence of ethnicity and maternal hyperglycaemia during pregnancy on neonatal outcomes. This project consists of two retrospective studies and one prospective pilot study. The first retrospective study was undertaken to compare the neonatal outcomes in WB and SA infants born to mothers with gestational or pre-gestational diabetes (Type 1 and Type 2 diabetes). The second retrospective study was undertaken to compare the risk of morbidity and mortality between large for gestational age infants with a birthweight ≥ 97th centile and appropriate for gestational age infants with birthweight between 10th – 90th centile, both born to mothers without diabetes. Maternal hyperglycaemia during pregnancy leads fetal exposure to high blood glucose levels, which in turn leads to fetal hyperinsulinism. The neonatal complications seen in infants of diabetic mothers are due to persistent fetal hyperinsulinism after birth. Currently there is no clinical or biochemical test to identify, at birth, the infants who are at risk of neonatal complications. A prospective pilot study was undertaken to evaluate the feasibility of using cord blood C-peptide (surrogate marker of insulin) to identify infants born to mothers with diabetes and LGA infants of non-diabetic mothers at risk of postnatal complications. Such a test would enable early implementation of interventions to avoid complications and at the same time free the vast majority of infants from unnecessary medicalisation of their postnatal care.

The current study aimed to investigate how attachment style and early maladaptive schemas of women might impact on the development of Post traumatic Stress Disorder symptoms after childbirth.

The current study aimed to investigate how attachment style and early maladaptive schemas of women might impact on the development of Post traumatic Stress Disorder symptoms after childbirth.

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