1. Prenatal Stress and Fetal Hemodynamics: a Systematic Review
Terri Levine
Professor Fiona Alderdice
Professor Ruth Grunau
Professor Fionnuala McAuliffe

2. Prenatal Stress Psychological distress experienced during pregnancy
Distinct from anxiety experienced at other times
Influenced by many factors
life events, ethnicity, social support, income level, educational background, attitudes towards pregnancy, partner relationship
Gurung et al Psychosocial predictors of prenatal anxiety. Journal of Social and Clinical Psychology.

3. Prenatal Stress
Assessed with self-reports and biomarkers in saliva, plasma, urine, hair
Associated with
stillbirth, preterm birth, lower fetal weight
delayed neurodevelopment
altered innate and adaptive immune responses
“difficult” infant temperament
emotional and behavioural problems
lower academic achievement
Dole et al Maternal stress and preterm birth. American Journal of Epidemiology
Rondo et al Maternal psychological stress and distress as predictors of low birth weight, prematurity, and intrauterine growth restriction. European Journal of Clinical Nutrition
Sandman et al Exposure to prenatal psychobiological stress exerts programming influences on the mother and her fetus. Neuroendocrinology

4. Pregnancy-Specific Stress
Fears and concerns related to pregnancy
Fetal health, diet, weight gain, appearance, labour, delivery
May be more sensitive predictor of outcomes than general prenatal stress
fetal behaviour, infant cognitive/motor development, emotional regulation
Associated with shorter gestation, preterm birth, delayed neurodevelopment, decreased grey matter, delayed executive function
Alderdice and Lynn Factor structure of the prenatal distress questionnaire. Midwifery
Davis and Sandman The timing of prenatal exposure to maternal cortisol and psychosocial stress is associated with human infant cognitive development. Child Development

5. Prenatal Stress and Fetal Hemodynamics
Relationship between maternal psychological state and fetal blood flow relatively unexplored
Significant hemodynamic changes occur during pregnancy to meet the needs of the developing fetus

6. Doppler Ultrasound Non-invasive measurement of placental blood flow
Gathers information about maternal and fetal blood flow
Insonates:
Maternal uterine arteries
Fetal umbilical artery
Fetal middle cerebral artery
Fetal venous circulation
Transabdominal Fetal Ultrasound
Ultrasound Transducer
Sound waves
Fetus
Placenta
Uterus

7. Doppler Ultrasound
Poor placentation results in resistance to blood flow
Decreased uterine artery blood flow linked to pre-eclampsia and fetal growth restriction
Decreased umbilical artery blood flow linked to fetal growth restriction, fetal distress, NICU admission, worse neurodevelopmental outcomes

8. Aims
Studies assessing link between prenatal stress and fetal well-being have not been systematically reviewed
Examine relationship between prenatal stress and abnormal fetal hemodynamics measured by Doppler ultrasound

9. Methods: Study Criteria
Eligibility criteria:
measured resistance, pulsatility index, and/or systolic/diastolic ratio in the uterine, umbilical, and/or fetal middle cerebral artery using Doppler ultrasound
measured prenatal stress with ≥1 standardised measure
Ineligibility criteria:
study participants not human
study methodology inadequately described
full English text not available

10. Methods: Search Strategy
Dates:
All studies published through April 2014
Databases:
Medline
Embase
PsycINFO
Maternity and Infant Care
CINAHL
Search terms:
pregnancy; stress; blood; fetus; Doppler; ultrasound

11. Methods: Data Extraction
Specifically designed data-extraction form
Authors
Year of publication
Location of study
Gestational age(s) at assessment
Exclusion criteria
Measures used
Results
Limitations

12. Methods: Quality Analysis
Standardised outline for assessing evidence quality
6 areas of potential bias:
Study participation
Attrition
Prognostic factor measurement
Outcome measurement
Confounding factor analysis
Data analysis

13. Results: Included Studies
2101 records identified in database search
1733 records screened after duplicate removal
1609 studies excluded by title
124 abstracts screened
112 studies excluded by abstract
11 full-text studies assessed for eligibility
11 studies included

14. Results: Uterine Artery Blood Flow
9 studies
2 with significant results
Significant association between state and trait anxiety scores and reduced blood flow (Teixeira et al. 1999)
Prenatal stress linked with reduced blood flow (Vythilingum et al. 2010)
7 without significant results
Harville et al. 2008, Helbig et al. 2011, 2013, Maina et al. 2008, Mendelson et al. 2011, Monk et al. 2011, Kent et al. 2002

15. Results: Umbilical Artery Blood Flow
9 studies
2 with significant results
Reduced blood flow linked with prenatal stress and state anxiety scores (Caliskan et al. 2009)
Women with high trait anxiety scores had reduced blood flow (Sjostrom et al. 1997)
7 without significant results
Harville et al. 2008, Helbig et al. 2011, 2013, Maina et al. 2008, Mendelson et al. 2011, Monk et al. 2011, Vythilingum et al. 2010
Normal
Abnormal

16. Fetal Middle Cerebral Artery
Measure of “brain-sparing” phenomenon
2 studies
1 with significant results
Fetal brain circulation was favoured in women with high trait anxiety (Sjostrom et al. 1997)
Indicates a pathological redistribution of blood flow
1 without significant results
Vythilingum et al. 2010

17. Strengths of Included Studies
Thoroughly described population groups
Adequately described prognostic factors and outcome measurement
Standardised outcome measures
decrease measurement bias
simplify study comparisons

18. Limitations of Included Studies
Small sample sizes
6 cross-sectional
acute v. chronic stress
changes in blood flow over time
Choice of stress measure(s) varied
Only 1 measured pregnancy-specific stress

19. Limitations of Included Studies
None adequately explained study attrition
5 excluded participants with psychiatric diagnoses, 6 did not
Specific exclusion criteria differed
Only one measured stress biomarkers

20. Sample Study Largest sample size: 872 Two assessment periods
~17 and ~27 weeks
Biomarker analysis
Cortisol in saliva and CRH in blood
Good attention to confounding factors
Age, education, marital status, etc.
Staggered Doppler ultrasound, biomarker analysis, stress measures

21. Future Studies Larger sample sizes
Repeated assessments across gestation
Biomarker analysis
Better control for confounding factors
Better accounting for psychiatric illness and medication use
Measures of pregnancy-specific stress

22. Conclusions
High levels of stress during pregnancy pose a risk to maternal and infant health
Underlying mechanisms remain unclear
Relationship between prenatal stress and fetal hemodynamics merits additional investigation
Systematic review findings inconclusive but interesting
Attention to mental health during pregnancy essential
Lobel and Dunkel Schetter Pregnancy and prenatal stress. Encyclopedia of Mental Health, Second Edition, in press.

23. Thank you!