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Title: Maternal prenatal stress and fetal programming : long term biobehavioural outcomes in the child and potential placental mechanisms
Author: O'Donnell, Kieran J.
ISNI:       0000 0004 2695 6879
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2011
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Mounting evidence suggests prenatal stress can affect child development. Clinical studies of this concept, termed fetal programming, focus predominantly on early childhood. Also, little is known about the mechanisms underlying how maternal stress is transmitted to the fetus. This thesis will test if maternal anxiety during pregnancy is associated with (1) behavioural outcomes from childhood to early adolescence, (2) cortisol output in adolescence and (3) an altered placental phenotype. For Studies 1 and 2 participants were drawn from the Avon Longitudinal Study of Parents and Children (ALSPAC). Psychometric data from 9,871 mother child pairs (5,098 males, 4,773 females) were analysed using latent growth curve analysis. A subsample of the ALSPAC children aged 15 years (n = 899) provided saliva samples on three days at waking, +35mins, after school and before bed, for later cortisol analysis. For Study 3 a new cohort of women (n= 73) was recruited. Maternal psychometric data was collected one day prior to elective caesarean section, and the placenta collected after delivery. Study 1 showed that maternal prenatal anxiety was associated with conduct and emotional problems, and symptoms of ADHD at age 13 years, after allowing for a range of confounders, including postnatal anxiety. There were marked sex differences in the developing patterns. Saliva cortisol demonstrated a marked diurnal profile with a clear sex difference at age 15. Higher maternal prenatal anxiety was associated with a reduced cortisol awakening response. High levels of maternal prenatal anxiety were associated with reduced placental expression and activity of the cortisol metabolising enzyme 11β-Hydroxy steroid dehydrogenase 2 (11β-HSD2) and also with reduced placental weight. This thesis provides evidence that maternal prenatal anxiety can affect behavioural and neuroendocrine outcomes in adolescence. It also provides preliminary evidence that maternal anxiety is associated with alterations in the function of the placenta, which may underlie some aspects of fetal programming. These findings have public health implications. Increasing awareness about the lasting effects of prenatal anxiety may ultimately benefit mothers, the care they receive and their families.
Supervisor: Glover, Vivette ; O'Connor, Thomas Sponsor: National Institute of Health; Medical Research Council ; Genesis Research Trust
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral