Exploring the relationship between maternal prenatal stress and neonatal brain development using MRI

Student thesis: Doctoral ThesisDoctor of Philosophy


Prenatal stress exposure represents a global public health problem and has been associated with a range of adverse outcomes in the offspring. These include obstetric outcomes (such as premature birth and low birth weight), early behavioural outcomes (such as more fussing and crying) and an increased risk of neurodevelopmental, psychiatric, and behavioural disorders later in life.

A proposed mechanism of risk transmission is through the disruption of brain morphology and function during critical periods of in utero development. Recent advances in neuroimaging have enabled in vivo investigations of neonatal brains, offering novel insights into the relationship between prenatal stress and early brain development in the absence of postnatal influences. A better understanding of prenatal stress and associated offspring neuroanatomy is essential, as it can help inform further research and clinical decision-making. For example, it can be used to develop biomarkers to predict vulnerability to adverse outcomes and neurodevelopmental trajectories, as well as early interventions, leading to more positive outcomes for the family unit.

This thesis is focused on maternal depression, anxiety and life stress, and its over-arching scope is to investigate how these may impact in utero brain development. To establish the context in which this work takes place, Chapter 1 presents a general overview of essential concepts including prenatal stress, the developing brain, and magnetic resonance imaging. Chapter 2 includes a published narrative review of the effects of prenatal stress on fetal and child development (published in International Review of Neurobiology). The research presented in this review forms the basis for the motivation behind conducting the empirical studies presented in this thesis. Chapter 3 includes the overall methodology for the included studies.

Chapters 4 and 5 include two empirical peer-reviewed studies based on data from the evaluation of Preterm Imaging Study (ePRIME). Chapter 4 is focused on investigating whether maternal anxiety and stress may impact limbic-prefrontal white matter microstructure in infants born prematurely. We show that maternal prenatal stressful life events are associated with altered uncinate fasciculus microstructure (published in Biological Psychiatry). In an overlapping sample, in a study presented in Chapter 5, we find no evidence for an association between maternal prenatal stress or trait anxiety, and volumes in frontal, temporal, and limbic regions (published in PLOS ONE).

Chapters 6 and 7 are based on data from the developing Human Connectome Project (dHCP) and the Prenatal Stress Study (PSS), in which the Edinburgh Postnatal Depression Scale (EPDS) was used as a self-report measure of maternal depression. Firstly, given the high comorbidity between depression and anxiety and their potentially distinctive effects on the developing brain, it was essential to better understand the structure and utility of the EPDS. With this in mind, Chapter 6 presents a factor analysis of the EPDS in prenatal and postnatal samples including women at high-risk of depression and women from a community sample (published in Archives of Women’s Mental Health). Our results suggest that a subset of questions from the EPDS (EPDS-3A) could be used to provide screening information for anxiety. In Chapter 7, we build upon the work described in previous chapters, and use advanced neuroimaging to explore the relationship between maternal depressive symptoms, neonatal white matter, and toddler social-emotional development in a large community sample of neonates (part of the dHCP). We show that maternal depressive symptoms are positively associated with fibre density in the uncinate fasciculus in neonates; this is then associated with social-emotional abilities in toddlerhood.

Taken together, the results of this series of studies provide meaningful contributions to our understanding of maternal prenatal mental health, and its impact on early brain development and behavioural outcomes. Suggested future directions for research and overall conclusions are presented in Chapter 8.
Date of Award1 Feb 2022
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorMichael Craig (Supervisor), Suresh Victor (Supervisor) & Serena Counsell (Supervisor)

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