Placental programming of infant neurodevelopment in the context of maternal care

Providing a biological explanation for the relationship between the mother's mental health and her child's neurodevelopmental outcomes represents one of the greatest challenges of perinatal medicine. Maternal stress, anxiety and depression have all been shown to increase the risk of psychopathology in children while poor maternal care has similarly adverse outcomes. In an experimental model, we have shown that placental endocrine dysfunction programs both poor maternal care and adverse offspring behaviour. These observations lead us to the novel hypothesis that placental endocrine dysfunction underlies the co-occurrence of maternal mood disorders, impaired maternal care and adverse infant neurodevelopmental outcomes frequently reported in human pregnancies. Our recently published research (Psychological Medicine 2016) supports the relationship between placental endocrine dysfunction and prenatal depression. We now have a unique and timely opportunity to further test our hypothesis captilising on a current MRC funded human study cohort called Grown in Wales, to examine the role of placental endocrine dysfunction in the programming of maternal care and abnormal infant behaviour. Analysing infant neurodevelopment and parenting behaviour in this cohort will build on our current MRC study adding value and significantly enriching our understanding of the consequence of placental endocrine dysfunction. Importantly, the inclusion of similar measurements of parenting behaviour and infant outcomes in the ALSPAC-G2 study will substantially increase the wider impact of the proposed work. Added value: Existing data on maternal mood, maternal biological characteristics and lifestyles, maternal blood and saliva, cord blood, placenta, RNAseq of placenta from mothers with highest and lowest scores, follow-on maternal data at 2 and 12 months, infant assessment data at 12 months and access to data from the ALSPAC-G2 study. Aim 1. To assess infant cognitive, emotional and behavioural development alongside maternal care in a cohort of mother-infant pairs with well characterised pre and postnatal maternal mood data. Aim 2. To establish whether placental endocrine dysfunction and aberrant imprinting correlate with a) quality of maternal care and/or b) infant neurodevelopmental outcomes Aim 3. To determine the wider relevance of these findings within ALSPAC-G2. Aim 4. Where exposure-characterstic-outcome is established, apply a causal analysis framework to strengthen causal inference. Research training: Next generation sequencing, bioinformatics, theoretical, methodological and advanced data analytic skills (recognised as an area of significant skills deficiency in UK social science), multivariate statistics and analysis of longitudinal data (through formal courses and supervision by the applicants), user engagement and dissemination. Multidisciplinary: developmental epigenetics, infant neurodevelopment, epidemiology and social science.
Supporting Documentation.