Professor Vivette Glover

Fetal and Neonatal Stress Research Group

Background

There is now good evidence that experience in the fetal and neonatal period can have long term consequences, and be a major cause of vulnerability to later disease (Talge et al 2007). Our group is interested in the long term effects of early stress on child emotional, behavioural and cognitive development, and in possible ways to improve outcome. We are studying the role of the major stress system, the hypothalamic-pituitary-adrenal axis, and cortisol, in mediating fetal and neonatal programming.

 
We have already shown both in large population studies (O’Connor et al 2002, 2003), and in smaller observer rated cohorts (Bergman et al 2007), that if the mother is stressed or anxious while she is pregnant the child is more likely to be anxious, have symptoms of attention deficit/hyperactivity and have lower scores on the Bayley’s Mental Developmental index. These effects are independent of the mother’s postnatal emotional state and the child’s postnatal experience.  We have also shown that the stress of delivery, (Miller et al 2005) and the early stress experienced by a preterm baby (Glover et al 2005) can have effects, of at least several months, on the baby’s own cortisol stress response.  If the mother is anxious while pregnant, the child at 10 years old, is more likely to have increased cortisol levels (O’Connor et al 2005).

We are also studying the mechanisms by which these effects may occur. We have demonstrated that there is a strong correlation between maternal and fetal cortisol levels (Gitau et al 1998, 2001), and that if the mother is anxious there is less blood flow to the baby (Teixeira et al 1999).  We recently have found that if the mother is very anxious the association between maternal and fetal cortisol is much higher (Glover et al 2009). This suggests that the maternal emotional state can affect the function of the placenta.

Aims

Our aims are:

• to further characterise the long term effects of maternal antenatal and early postnatal stress, anxiety and depression on child development and hormonal function
• to characterise the type of stress that is most damaging,
• study critical periods of sensitivity
• to study possible mediating hormonal and other mechanisms
• to examine gene environment interactions
• and to evaluate the efficacy of different interventions

Current and Future projects

1. (a) Further characterisation of effects of antenatal stress/life events on
   child cognitive and behavioural development
   (b) Examination of hormonal profile of amniotic fluid and maternal plasma to determine mediating mechanisms
2. Study of function of the hypothalamic-pituitary-adrenal axis in pregnancy and postpartum: links with antenatal and postnatal stress/ anxiety and depression.
3. Use of ALSPAC population cohort to determine long term effects of prenatal anxiety/stress on
   (a) diagnostic measures of psychopathology
   (b) on saliva cortisol –diurnal variation and stress test (n=1,000)
   (c) examine mediating mechanisms-postnatal psychosocial risk and protective factors
   (d) examine gene polymorphisms/prenatal stress interaction starting with the glucocorticoid receptor
4. An intervention trial. A study to evaluate cognitive analytic therapy in the treatment of anxiety and depression, and reduction of cortisol in stressed pregnant women

References

1. Gitau R, Cameron A, Fisk NM, Glover V. (1998) Fetal exposure to maternal cortisol.  Lancet 352, 707-708.
2. Teixeira J, Fisk N, Glover V. (1999)  Association between maternal anxiety in pregnancy and increased uterine artery resistance index: cohort based study.BMJ 318, 153-157.
3. Taylor,A., Fisk, N.M., Glover, V. (2000)  Mode of delivery and subsequent stress response.Lancet  355, 120.
4. Gitau R, Fisk NM, Cameron A, Teixeira J, Glover V. (2001). Fetal HPA stress responses to invasive procedures are independent of maternal responses.J Clin End Met. 86, 104-109.
5. O’Connor TG, Heron J, Golding J, Beveridge M, Glover V (2002)  Maternal Antenatal Anxiety and Behavioural Problems in Early Childhood.   Brit J Psychiat 180, 502-508.
6. O’Connor, T.G., Heron, J., Golding, J., & Glover, V., and the ALSPAC study team (2003). Maternal Antenatal Anxiety and Behavioural/Emotional Problems in Children: A Test of a Programming Hypothesis.J Child Psychol Psychiat 44,1025-1036.
7. Miller NM, Fisk NM, Modi N, Glover V (2005) Stress responses at birth: determinants of cord arterial cortisol and links with cortisol response in infancy.Bjog; 112(7): 921-6.
8. Van den Bergh BR, Mulder EJ, Mennes M, Glover V (2005) Antenatal maternal anxiety and stress and the neurobehavioural development of the fetus and child: links and possible mechanisms. A review. Neurosci Biobehav Rev; 29(2): 237-58.
9. Gitau R, Adams D, Fisk NM, Glover V (2005) Fetal plasma testosterone correlates positively with cortisol. Arch Dis Child Fetal Neonatal Ed; 90(2): F166-9.
10. O'Connor TG, Ben-Shlomo Y, Heron J, Golding J, Adams D,  Glover V (2005) Prenatal Anxiety Predicts Individual  Differences in Cortisol in Pre-Adolescent ChildrenBiol Psychiatry ; 58:211-217.
11. Glover V, Miles R , Matta S, Modi N, Stevenson J.  (2005) Glucocorticoid exposure in preterm babies predicts saliva cortisol response to immunisation at  4 months. Ped Res ; 58(6):1233-1237.
12. Teixeira J, Martin D, Prendiville O , Glover V. (2005) The effects of acute relaxation on indices of anxiety  during pregnancy. J Psychosom Obstet Gynaecol. 26(4):271-6.
13. Kammerer M, Taylor A, Glover V. (2006) The HPA axis and perinatal depression: a hypothesis. Arch Womens Ment Health. 9 (4):187-96.
14. Sarker P, Bergman K, Fisk NM, Glover V. (2006) Maternal anxiety at amniocentesis and plasma cortisol. Prenat Diagn. 26(6):505-9.
15. Talge NM, Neal C, Glover V (2007) Antenatal maternal stress and long-term effects on child neurodevelopment: how and why? J Child Psychol Psychiatry. 48 :245-61
16. Sarkar P, Bergman K, Fisk NM, O'Connor TG, Glover V (2007) Ontogeny of foetal exposure to maternal cortisol using midtrimester amniotic fluid as a biomarker Clin Endocrinol 66(5) 636-40.
17. Igosheva N, Taylor PD, Poston L, Glover V. (2007) Prenatal stress in the rat results in increased blood pressure responsiveness to stress and enhanced arterial reactivity to neuropeptide Y in adulthood. J Physiol. 582 :665-74.
18. Sarkar P, Bergman K, Fisk N, O' Connor TG, Glover V (2007) Amniotic fluid testosterone: relationship with cortisol and gestational age Clin Endocrinol. 67(5) 636-40.
19. O'Connor TG, Capraiello P, Blackmore ER, Gregory AM, Glover V, Fleming P (2007) ALSPAC Study Team. Prenatal mood disturbance predicts sleep problems in infancy and toddlerhood. Early Hum Dev. l;83(7):451-8.
20. Bergman K, Sarkar P, O'Connor TG, Modi N, Glover V (2007) Maternal stress during pregnancy predicts cognitive ability and fearfulness in infancy.  J. Am. Acad. Child. Adolesc. Psychiatr   46: 1454-1463.
21. Sarker P, Bergman K, O'Connor TG, Glover V. (2008) Maternal antenatal anxiety and amniotic fluid cortisol and testosterone: possible implications for foetal programming. J Neuroendocrinol. ;20; :489-96.
22. O'Higgins M, St James Roberts I, Glover V. (2008) Postnatal depression and mother and infant outcomes after infant massage. J Affect Disord. 109(1-2): 189-92.
23. 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. J Child Psychol Psychiatry. 49:1089-109.
24. Glover V, Bergman K, Sarkar P, O'Connor TG.(2009) Association between maternal and amniotic fluid cortisol is moderated by maternal anxiety. Psychoneuroendocrinology.  34(3) 430-5.
25. Kammerer M, Marks MN, Pinard C, Taylor A, von Castelberg B, Künzli H, Glover V.(2009) Symptoms associated with the DSM IV diagnosis of depression in pregnancy and post partum. Arch Womens Ment Health. 12(3):135-41.
26. K O’Donnell K,  O’Connor TG , Glover V (2009) Prenatal stress and neurodevelopment of the child: focus on the HPA axis and the role of the placenta  Dev Neurosci.;31(4):285-292.

Team members

Scientific staff

Diana Adams

Research fellows

Martin Kammerer
Alyx Taylor

Graduate Students

Kieran O'Donnell
Laura Freeman
Benedicta Agbagwara

Associated members
Tom O' Connor
Natasha Khalife

Current Funding from the National Institutes of Health, MRC and Bailey Thomas Foundation.