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Title: Exploring the relationship between perinatal risk factors and brain development in preterm infants using MRI
Author: Barnett, Madeleine Lucy
ISNI:       0000 0004 7969 9845
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2018
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Preterm birth is a leading cause of perinatal mortality and morbidity, and creates significant personal, social and health care costs. Around 15 million infants are born preterm each year, more than 1 in 10 of all births, and this incidence is increasing (WHO, 2013). While survival rates following preterm birth have improved, the incidence of neuromotor and neurocognitive deficits remains stable, with around 25% of extreme preterm infants displaying moderate or severe impairment in early childhood (Saigal and Doyle, 2008). A significant proportion of preterm birth follows multiple pregnancies. More than half of twin pregnancies end in preterm birth, with 10% delivering at less than 32 weeks or below 1500 grams (Chauhan et al., 2010). The birth rate of twins and multiples has risen sharply since the advent of artificial reproductive technologies (Bodeau-Livinec et al., 2013; Gnanendran et al., 2014) and the trend for an increase in maternal age, with multiple pregnancy rates of 9.8 per 1000 in 1976 having increased to 16.1 in 2011 (Office for National Statistics, 2013). It has, therefore, become increasingly important to determine their suitability for inclusion in neuroimaging studies exploring the relationship between clinical risk factors and brain development in infants born preterm. Structural and diffusion magnetic resonance imaging have improved the detection rate of focal lesions in preterm infants, facilitated quantitative assessment of regional brain volumes, and assessment of the properties of the white matter tracts of the brain (Ajayi-Obe et al., 2000; Ball et al., 2013b, 2012; Boardman et al., 2006; Dubois et al., 2008). Aberrant brain development identified using these techniques has been linked to neurodevelopmental outcome assessed in early childhood (Ball et al., 2015; Counsell et al., 2008; Van Kooij et al., 2012). Additionally a number of perinatal risk factors known to be associated with preterm birth appear to be associated with white matter injury (Ball et al., 2010; Counsell et al., 2008; Kuypers et al., 2012; Rose et al., 2009; Tan et al., 2008). This thesis aimed to determine whether preterm twins were suitable for inclusion in preterm imaging studies assessing brain development in the preterm population as a whole. In Chapter 4 I assessed lesions frequency, regional brain volumes, white matter injury determined by diffusion magnetic resonance imaging and neurodevelopmental outcome in a large cohort of preterm twins and singletons. Brain development in preterm twins and neurodevelopmental outcome was similar to preterm singletons, and so these infants are suitable for inclusion in general preterm studies. I then tested the hypothesis that white matter injury is related to preterm birth and specific perinatal risk factors using diffusion magnetic resonance imaging assessed with tract-based-spatial-statistics (Chapter 5). Gestational age, sex, fetal growth restriction, days on mechanical ventilation, days of parenteral nutrition and necrotising enterocolitis were associated with diffusion magnetic resonance imaging defined white matter damage at term-equivalent age. When these risk factors were combined to produce a cumulative risk factor score, a linear relationship between the number of risk factors and white matter damage was demonstrated. These findings are consistent with the multiple-hit hypothesis. To further explore the suitability of high-risk twins in preterm imaging studies in Chapter 6 I examined perinatal risk factors and brain injury in twin-to-twin-transfusion syndrome. This subgroup of the twin population is at risk of significant morbidity and mortality despite the current gold standard treatment (Rossi et al., 2011; Simpson, 2013) . Perinatal risk factors and brain abnormalities seen on postnatal MRI are described in 3 groups including monochorionic diamniotic twins born following pregnancies complicated by twin-to-twin-transfusion syndrome, monochorionic diamniotic twins without a history of twin-to-twin-transfusion syndrome and dichorionic diamniotic twins. Robust statistical analysis in this group was not possible due to heterogeneity of the sample and small sample size. Data collection for this study is on-going.
Supervisor: Counsell, Serena Jane ; Edwards, Anthony David ; Rutherford, Mary Ann Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available