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.