Fetal and Neonatal Stress Research Group
| Directors: | |
| Vivette Glover | Professor of Perinatal Psychobiology |
| NM Fisk | Professor of Fetal Medicine |
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| Natalya Igosheva | Post-doctoral Research Associate |
| Diana Adams | Laboratory Manager |
| Kristin Bergman BSc | PhD Student |
Research registrars: |
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| Nichola Jackson MD | Doppler studies- Maternal anxiety, uterine blood flow and pre-eclampsia |
| Richard Smith MD | Studies of fetal responses to invasive procedures |
Visitors: |
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| Alexei Medvedev MD, PhD, DSc | Royal Society Research Fellow from Moscow Basic studies of stress |
| Professor Gyula Telegdy | British Council exchange from Hungary Basic studies of stress |
| Agnes Adamik | British Council exchange from Hungary Basic studies of stress |
Associated members: |
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| Ian St James Roberts PhD | Reader, Institute of Education Fetal movements and infant crying |
| Jane Hamilton MD and Ian Kerr MD | Consultant psychiatrists, St Mary’s Effects of maternal antenatal anxiety and depression on the fetus |
| Tom O’Connor | Institute of Psychiatry, London Effect of antenatal anxiety on child development (ALSPAC study) |
The aim is to carry out research to improve the care of babies before and after birth. This is for the immediate welfare of the baby, and for the best long term outcome for the future child and adult. The emphasis is particularly on the development of the baby’s brain, with implications for childhood behavioural problems and adult mental illness. This is a new field of study, one which involves linking obstetrics, paediatrics, psychology and psychiatry. The Group is now flourishing, with its own personnel, and several collaborations at home and abroad. We have raised several independent grants for research, and there is considerable public interest in the work that we are doing.
Of our research so far, of particular interest are a study showing that maternal antenatal anxiety doubles the risk for hyperactivity in boys; studies showing possible mechanisms by which maternal anxiety may affect the development of the fetus; a study showing that babies born by different methods (elective caesarean, normal vaginal, assisted ) have different stress and crying responses at 8 weeks; and the first trial of analgesia in the fetus.
Progress of Research
An article on our work appeared in the Daily Mail under "Stress in pregnancy lowers a child's IQ" and they highlight the point that stress during pregnancy should be treated as a major public health issue. We have previously shown that maternal anxiety in pregnancy (being in the top 15% of a normal population) doubles the risk of behavioural problems in the child. Click on the title to see the article.
Mechanisms by which maternal mood may affect the fetus
It is known that maternal stress or anxiety can affect the development of the baby in the womb. We are studying the mechanisms by which this occurs. We have found that there is a highly significant correlation between maternal and fetal cortisol levels, although the maternal levels are ten times higher. This suggests that enough of the maternal stress hormone cortisol crosses the placenta to affect the development of the fetus.
We have shown, using Doppler ultrasound, that the most anxious mothers have impaired blood flow through the uterine arteries. This could help to explain why mothers who are very anxious while pregnant tend to have smaller babies.
Fetal stress responses
We have now completed our first trial of giving the opiate fentanyl to the fetus. These are the first experiments to determine how to give pain relief to the fetus in a safe and effective way. At the doses used it ablated the blood flow redistribution to the brain, and the endorphin response but not the cortisol response.
We are continuing to characterise how the fetus responds to therapeutic but possibly painful invasive procedures, such as a blood transfusion. It can mount a rapid noradrenaline response from 18 weeks gestation and a slower cortisol and ß-endorphin response at least from 20 weeks. It also responds by increasing blood flow to the brain. This has been demonstrated from 16 weeks.
Delivery and links with later stress response
We have shown, by examining cord cortisol levels, that forceps/ventouse deliveries were the most stressful, normal vaginal intermediate, and caesarean section, the least stressful.
The babies stress response at 8 weeks was studied by measuring saliva cortisol levels before and 20 minutes after their inoculation jab. Those delivered by forceps/ventouse had the largest response, followed by those by normal vaginal delivery and those born by caesarean were the least responsive. This suggests that type of delivery may be one cause of long term stress responses. As this in turn has been linked with a predisposition to anxiety and depression, this has major implications for later health.
Massage and mother baby interaction with depressed mothers
Mothers with postnatal depression are known to have a worse relationship with their babies. The aim of this study was to find whether a program of attending mother baby massage classes which are on offer at Queen Charlotte’s would be beneficial. A group who attended 5 massage classes were compared with a similar group who attended a support group. At the end of the test period the massage group had significantly less depression and very significantly better interaction with their babies, than the control group. This is the first time that a method has been found for improving the relationship between a depressed mother and her baby.
Skin to skin study
This study is now well underway. The aim is to see whether a program of encouraging skin to skin contact between mothers and their preterm babies will help attachment and reduce stress and depression in both mother and baby. The babies will be scanned by magnetic resonance imaging as an additional way of determining their development.
Long term effects of maternal antenatal anxiety on the development of the child (in collaboration with T.O’Connor and Jean Golding).
In a new study we have been able to test the hypothesis that antenatal maternal anxiety has a long term effect on the behaviour of the child. We have had access to the data obtained in the prospective ALSPAC cohort of mothers and children in the Bristol region; this includes self reports of maternal anxiety both in the antenatal and postnatal period and the child’s behaviour at 4 years of age. Complete data was available for 7,447 mothers and children. We have found that if the mother is very anxious in pregnancy, this doubles the risk for hyperactivity/inattention in her 4 year old boy. There was also an increased risk for emotional problems in both boys and girls. This is after allowing for postnatal anxiety, obstetric and social factors, smoking, drinking etc. This confirms some suggestive previous studies, and results with animals. However it is the first definitive study in humans and is of great interest. It suggests that there is a direct effect of maternal mood on fetal brain development, which affects the behavioural development of the child. It also raises the possibility that a program of anxiety reduction in the most anxious pregnant women could have a major beneficial effect on the behaviour of their children.
Selected publications
Miller NM, Fisk NM, Modi N, Glover V: Stress responses at birth: determinants of cord arterial cortisol and links with cortisol response in infancy. Bjog 2005; 112(7): 921-6.
Taylor A, Atkins R, Kumar R, Adams D, Glover V: A new Mother-to-Infant Bonding Scale: links with early maternal mood. Arch Women Ment Health 2005; 8(1): 45-51.
Van den Bergh BR, Mulder EJ, Mennes M, Glover V: Antenatal maternal anxiety and stress and the neurobehavioural development of the fetus and child: links and possible mechanisms. A review. Neurosci Biobehav Rev 2005; 29(2): 237-58.
O'Connor TG, Ben-Shlomo Y, Heron J, Golding J, Adams D, Glover V Prenatal Anxiety Predicts Individual Differences in Cortisol in Pre-Adolescent Children Biol Psychiatry 2005; 58:211-217.
Glover V, MilesR , Matta S, Modi N, Stevenson J. (2005) Glucocorticoid exposure in preterm babies predicts saliva cortisol response to immunisation at 4 months. Ped Res 2005; 58(6):1233-1237
Glover V. (1997) Maternal stress or anxiety in pregnancy and emotional development of the child. Brit J Psychiat 171, 105-106.
Mooncey S, Giannakoulopoulos X, Modi N, Acolet D, Glover V. (1997) The effect of mother-infant skin-to-skin contact on plasma cortisol and ß-endorphin concentrations in preterm neonates. Infant Behav Develop 20, 553-557.
Gitau R, Cameron A, Fisk NM, Glover V. (1998) Fetal exposure to maternal cortisol. Lancet 352, 707-708.
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.
Glover V. (1999) Maternal stress or anxiety during pregnancy. The Practising Midwife 2, 20-22.
Giannakoulopoulos X, Teixeira J, Fisk N, Glover V. (1999) Human fetal and maternal noradrenaline responses to invasive procedures. Ped Res 45, 494-499.
Glover V, Fisk NM. (1999) Fetal pain: implications for research and practice. Brit J Obstet Gynaecol. 106, 881-886
Smith R.P. Glover V, Fisk NM (1999) Do fetuses feel pain? Eur Soc Reg Anaes. 174-176
Glover V, Teixeira J, Gitau R, Fisk NM. (1999) Mechanisms by which maternal mood in pregnancy may affect the fetus. Contemp Rev Obstet Gynaecol. September 155-160
Teixeira JMA, Glover V, Fisk NM. (1999) Acute cerebral redistribution in response to invasive procedures in the human fetus. Am J Obstet Gynaecol. 1811018-25
Taylor,A., Fisk, N.M., Glover, V. (2000) Mode of delivery and subsequent stress response. Lancet 355 120
Smith R, Gitau R, Glover V, Fisk NM (2000) Pain and stress in the human fetus. Eur J Obstet Gynaecol Rep Biol 92 161-165
Modi N., Glover V. Fetal pain and stress In: "Pain in Neonates (2nd Edition) K.J.S. Anand,BJ Stevens, PJ McGrath ed.( Elsevier, Amsterdam).2000, 217-227
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
Gitau R, Menson E, Pickles V, Fisk NM, Glover V, l MacLachlan N. (2001)Cord cortisol levels as an indicator of the fetal stress response to assisted vaginal delivery." Eur J Obstet Gynaecol 39 18 1-4
Taniguchi K, Glover V, Adams D, Modi N, Kumar R. (2001)Infant massage improves mother-infant interaction for mothers with postnatal depression. J Affect Disord. 63 201-207
Gitau R, Fisk NM, Glover V (2001) Human fetal and maternal stress responses. In Stress. The role of catecholamines and other neurotransmitters. Ed R Kvetnansky, In press.
Fisk NM, Gitau R, Teixeira J, Giannakoulopoulos X, Cameron A, Glover V. (2001) Effect of direct fetal opiod analgesia on fetal hormonal and hemodynamic stress response to intrauterine needling. Anesthesiology. In press.
O’Connor T, Heron J, Golding J, Beveridge M, Glover V (2000) Maternal antenatal anxiety and behavioural problems in early childhood. Submitted for publication
