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Prenatal Anxiety and Stress Studies (in the UK)

ALSPAC-based studies ​

For about two decades, we (with collaborators Vivette Glover, Kieran O’Donnell, Jean Golding and others) have had the good fortune with work with the ALSPAC study, based at the University of Bristol in the UK. The study provided an unparalleled opportunity to examine the early-emerging and long-term effects of prenatal maternal anxiety on children’s behavioral, cognitive, and biological health.  Key findings from this study include: a) the earliest large-scale demonstration of a robust link between prenatal maternal anxiety and children’s behavioral and emotional health; b) evidence that stress physiology in mid-adolescence was predicted from maternal prenatal anxiety; c) modest but notable genetic moderation of prenatal maternal anxiety on child/adolescent behavioral, emotional, and neuro-developmental outcomes.  In addition to our work on prenatal maternal anxiety, our work on the ALSPAC cohort includes studies of parenting and family changes, stress and gene expression changes, and paternal health in the perinatal period.

Support for our work on that project has been supported by the National Institute of Mental Health and the Wynne Center for Family Research.

Representative Publications

O’Connor, T.G., Heron, J., Golding, J., Beveridge, M., & Glover, V. (2002). Maternal antenatal anxiety and children’s behavioural/emotional problems at 4 years. British Journal of Psychiatry, 180, 502-508. PMID: 12042228

Ramchandani, P., Stein, A., Evans, J., O’Connor, TG, and the ALSPAC study team. (2005). Paternal Postnatal Depressive Symptoms Predict Behavioral Problems in Children Independent of Maternal Postnatal Depression. The Lancet, 365, 2201-2205. PMID: 15978928

O'Donnell, K.J. Glover, V., Jenkins, J., Browne, D., Ben-Shlomo, Y., Golding, J., & O'Connor, T.G. (2013). Prenatal maternal mood is associated with altered diurnal cortisol in adolescence. Psychoneuroendocrinology, 38, 1630-1638. PMID 23433748.

O’Donnell, K.J., Glover, V., Holbrook, J.D., & O’Connor, T.G. (2014). Maternal prenatal anxiety and child brain-derived neurotrophic factor (BDNF) genotype: Effects on internalizing symptoms from 4 to 15 years of age. Development and Psychopathology, 26, 1255-1266. PMID 25422959

Capron, L.E., Glover, V. Pearson, R., Evans, J., Lewis, G., O'Connor, T.G., Stein, A., Murphy, S., Ramchandani, P. (2015). Associations of maternal and paternal antenatal mood with offspring anxiety disorder at age 18 years. Journal of Affective Disorders, 187, 20-26. PMID 26301478

O’Donnell, K.J., Glover, V., Lahti, J., Lahti, M., Edgar, R.D., Raikkonen, K., & O’Connor, T.G. (2017). Maternal prenatal anxiety and child COMT genotype predict working memory and symptoms of ADHD. PLOS One 12(6) e0177506. PMID 28614354

Amiel Castro, R.T., Glover, V., Ehlert, U., & O’Connor, T.G. (2017). Antenatal psychological and socioeconomic predictors of breastfeeding in a large community sample. Early Human Development, 110, 50-56.PMID 28595128

Barker, E.D., Cecil, C.A.M., Walton, E., Houtepen, L.C., O’Connor, T.G., Danese, A., Jaffee, S.R., Jensen, S.K.G., Pariente, C., McArdle, W., Gaunt, T.R., Relton, C.L., & Roberts, S. (2018). Inflammation-related epigenetic risk and child and adolescent mental health: A prospective study from pregnancy to middle adolescence. Development and Psychopathology, 30, 1145-1156. PMID 30068408

Imperial College Studies of Prenatal Anxiety and Stress

Studies of prenatal influences on child development are quite limited in measuring direct exposures to the fetus. Many years ago, we capitalized on the use of amniocentesis for clinical purposes to conduct a study of amniotic fluid, which provides a more direct index of fetal exposure; we targeted cortisol, a stress hormone, and testosterone, a sex steroid, in amniotic fluid. We followed up a subset of these children with behavioral, cognitive, and neuroimaging assessments through middle childhood.  A separate study, also based at Imperial College London, examined prenatal maternal anxiety and placental gene expression.  Key findings from the studies include a) there are reliable associations between prenatal maternal cortisol and anxiety and fetal exposure to cortisol; b) the demonstration that parent-child relationship quality moderates prenatal cortisol exposure on cognitive development; c) evidence that prenatal exposures to cortisol and testosterone predict behavioral and emotional development; d) demonstration that prenatal maternal anxiety is associated with down-regulation of a key placental enzyme in the stress exposure pathway. 

Funding for our work on this project was provided by the March of Dimes.

The group of investigators includes Drs. Vivette Glover, Tom O’Connor, and Kieran O’Donnell.

Representative Publications

Sarkar, P., Bergman, K., Fisk, N.M., O’Connor, T.G., & Glover, V. (2007). Ontogeny of foetal exposure to maternal cortisol using midtrimester amniotic fluid as a biomarker. Clinical Endocrinology, 66, 636-640. PMID: 17492950

Bergman, K., Sarkar, P., Glover, V., & O’Connor, T.G. (2008). Quality of child-parent attachment moderates the impact of antenatal stress on child fearfulness. Journal of Child Psychology and Psychiatry, 49, 1089-1098. PMID: 19017025

Bergman, K., Glover, V., Sarkar, P., Abbott, D.H., & O’Connor, T.G. (2010). In utero cortisol and testosterone exposure and fear reactivity in infancy. Hormones and Behavior, 57, 306-312. PMID: 20060000

O'Donnell, K.J., Bugge Jensen, A., Freeman, L., Khalife, N., O'Connor, T.G., & Glover, V. (2012). Maternal prenatal anxiety and downregulation of placental 11b-HSD2. Psychoneuroendocrinology, 37, 818-826. PMID 22001010.

Sarkar, S., Craig, M.C., Dell’Acqua, F., O’Connor, T.G., Catani, M., Deeley, Q., Glover, V., Murphy, D.G.M. (2014). Prenatal stress and limbic-prefrontal white matter microstructure in children aged 6-9 years: a preliminary diffusion tensor imaging study. World Journal of Biological Psychiatry, 15, 346-352. PMID 24815522.

Spencer, D., Pasterski, V., Neufeld, S., Glover, V., O’Connor, T.G., Hindmarsh, P.C., Hughes, I.A., Acerini, C.L., & Hines, M. (2017). Prenatal androgen exposure and children’s aggressive behavior and activity level. Hormones and Behavior, 96, 156-165. PMID 28939371

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