Effects of Antenatal Stress on Fetal and Child Neurodevelopment

Question 1

How can the mother affect the development of the foetus?

Answer 1

Mother’s emotional state in pregnancy and in the early postnatal period
can have a long lasting effect on her child

Question 2

How do ante-natal depression and post-natal depression vary?

Answer 2

Just as many women experience ante-natal anxiety / depression as post-natally

Question 3

Where does a child’s environment begin?

Answer 3

In the womb - mother’s emotional well-being affects child’s development

Question 4

What is fetal programming?

Answer 4

Environment in womb = long-lasting affect on fetus

Environment in the womb, during different sensitive periods for specific outcomes, can alter the development of the fetus, with a long lasting effect on the child

Question 5

What can counteract some of the negative fetal programming?

Answer 5

Sensitive motherhood = Sensitive early mothering helps attachment, and can counteract some of what happens in the womb

Question 6

How does the fetal brain form in the womb?

Answer 6

Signals it receives from the mother

Neurons proliferate from 5 weeks gestation through 18 months after birth
Then neural pruning continues til puberty

Question 7

What are the long term effects of prenatal stress on neurodevelopment?

Answer 7

Increase risk of changes in cognitive development and behaviour in the child

Question 8

What are the different maternal antenatal stresses associated with increased risk of changes in cognitive development and behaviour in the child?

Answer 8

Maternal anxiety and depression
Maternal daily hassles
Pregnancy specific anxiety - is my baby alright? am I alright?
Domestic abuse = upped during COVID; partner or family discord
Distress caused by war
Experience of acute disasters e.g. freezing ice storm, hurricane or 9/11

It’s not just extreme or toxic stress, or diagnosed mental illness

Question 9

What are the possible associated cognitive risks / outcomes of antenatal stress?

Answer 9

Anxiety and Depression
Behavioural problems-ADHD, conduct disorder
Impaired cognitive development
Neonatal behaviour
More difficult infant temperament
Victimisation in childhood 
Schizophrenia ( stress in first trimester)
Autism spectrum
Personality disorder

More likely to be bullied - unknown cause but deemed to be due to increased risk of the other things

Question 10

What medical conditions are associated with increased risk in the child due to antenatal stresses?

Answer 10

Increased risk for:
Reduced birthweight and gestational age
Preterm delivery
Mixed handedness
Decreased telomere length
Asthma
Altered immune function
Altered microbiome (in meconium)

Question 11

Are associations causal, rather than genetic of postnatal?

Answer 11

Yes - many pieces of supporting evidence from:
Animal studies
Effects of natural disasters
Studies which allow for confounders
Underlying mechanisms

Question 12

What is the ALSPAC?

Answer 12

Avon Longitudinal Study of Parents and Children -

Large prospective birth cohort ~14,000 pregnant women recruited around Bristol in 1990-1991

Question 13

What did ALSPAC collect data on?

Answer 13

Lots of data collected on:
Maternal Postnatal anxiety and depression
Paternal pre and postnatal anxiety
Parenting
Maternal age
Birthweight
Gestational age
Smoking
Alcohol
Psychosocial factors: crowding (SES)
Maternal education

n= 7,363 with complete data

Question 14

What did the ALSPAC reveal?

Answer 14

If the mother is in the top 15% of those with anxiety, the child had double the risk of a probable mental disorder

The combined effects of raised anxiety doubled from 6% to 12% at age 13 (similar results with depression)

Attributable load of probable mental disorder in whole population due to prenatal anxiety/depression~10%

Question 15

Why are some children affected and not others, and why in varying amounts?

Answer 15

Gene-environment interactions e.g. COMT gene is different in most people, switching it on and off is therefore different in most people

Question 16

What is the significance of the COMT gene?

Answer 16

COMT inactivates catecholamines – dopamine, adrenaline and noradrenaline

Gene variants are associated with working memory and ADHD

Question 17

There are 2 working memory genes, A and G - giving rise to the genotypes GG, AA and AG

How dot hey affect working memory at aged 8 and child ADHD at age 15?

Answer 17

AG and AA = normal working memory and risk of ADHD development despite maternal anxiety at 32 weeks gestation

GG gene = declining working memory and increased risk of ADHD with maternal anxiety at 32 weeks gestation

Birthweight, gestational age, maternal education, maternalage, household crowding, maternal smoking, alcohol consumption, postnatal mood and parenting controlled for

Question 18

What are the undrlying mechanisms to how mother’s stress during pregnancy affects the child?

Answer 18

Maternal stress / anxiety / mental illness = increase in cortisol, pro-inflammatory cytokines etc. in maternal blood = too much for placenta to filter out completely = cortisol passes through to foetus and affects growing foetus

Question 19

What is the role of the placenta?

Answer 19

Interface between mother and fetus

Filters what comes in from the mothers blood and enters the fetus

Question 20

How is the foetus exposed to more cortisol?

Answer 20

Increase in maternal cortisol in response to stress

Normally 1/11Beta-HSDS2 enzyme found in placenta = an enzyme that breaks down cortisol into cortisone before it enters the foetus, so cortisol itself cannot enter the foetus

In more anxious mothers, lower expression of this enzyme

Mothers is stressed - down-regulation of enzyme

Allows more cortisol to pass from mother to foetus

Question 21

What is the significance of the increased amniotic cortisol and so increased exposure of cortisol to the foetus?

Answer 21

Strong negative correlation between amniotic cortisol and IQ in children who are insecurely attached to their mothers

Those who were securely attached - this acted as a buffer. No correlation

Question 22

What are the Bayley Scalesof Infant Development (BSID-II)?

Answer 22

A scale used to study child’s cognitive development - especially to look for developmental delays and aid in intervention planning

Question 23

What patterns are observed with increased utero exposure to cortisol?

Answer 23

Associated with lower cognitive function, reduced attention and increased anxiety = can be reversed with sensitive early mothering

Similar to those observed in children with early maltreatment

Question 24

What did the Sarkar et Al study show?

Answer 24

fMRI study with 32 children contacted at ages 6-9 asked to do tasks that assessed sustained attention and the effects of reward

Results correlated with amniotic fluid cortisol and antenatal life events

Question 25

What do MRI studies show of antenatal stress on the child’s brain?

Answer 25

Structural MRIs show:
Thinner cortex (associated with depression and cognitive problems)
Enlarged amygdala (associated with increased anxiety)

Diffusion MRIs show:
Alterations in uncinate fasciculus which connects the amygdala with frontal cortex (associated with mood disorders and antisocial behaviour)

Question 26

What are epigenetic modifications as a basis for foetal programming?

Answer 26

Functionally relevant modifications
to the genome that do not involve a change in nucleotide sequence.
Can persist to grandchild generation

Question 27

What is the adaptive value of changes to child’s brain due to prenatal stress?

Answer 27

Evolution -
Predictive adaptive value of changes due to prenatal stress in a stressful environment e.g. predators in the wild?

Anxiety/fear reactivity-beneficial effects of more vigilance

ADHD - shifting attention helps if predators about

Question 28

What are the evolutionary benefits of other changes caused by prenatal stress?

Answer 28

Impulsive - more willing to explore new environments

Conduct disorder - more willing to break rules

Aggressive - fight predators or other tribes

Cognitive deficit - side effect of ADHD or autism spectrum

Autism spectrum - understand things in different ways

Question 29

What is the role of professionals?

Answer 29

Detect and treat anxiety and depression both in pregnancy and postnatally

Help with relationship problems or domestic abuse

Help to create more social support

Practical help with housing etc

Help to teach sensitive mothering

Question 30

What can help reduce antenatal stress?

Answer 30

Yoga
Gardening
Music

Question 31

What can help after the baby is born?

Answer 31

Sensitive mothering e.g.

Stroking babies - can help reverse some of the effects of antenatal anxiety e.g. reduce number of emotional and behavioural problems as the child grows up

Breastfeeding can help with IQ and hyperactivity - but not emotional problems and conduct disorder

Question 32

Does breastfeeding reverse the effects of antenatal stress on the child’s neurodevelopment?

Answer 32

No
Breastfeeding did not moderate the associations between prenatal depression and anxiety and child neurodevelopment, suggesting separate mechanisms of action.

Question 33

Is it the effects of nursing or contents of breast milk that aids IQ?

Answer 33

Babies bottle fed breast milk did better on cognitive and memory tests than those fed formula milk

Shows it is the contents of breast milk help that cognition

Question 34

What are the public health implications of reducing stress/anxiety/depression in pregnancy?

Answer 34

More than one million children in UK suffer from neurodevelopmental disorders

Attributable load of neurodevelopmental problems due to prenatal stress 10-15%

Potential to reduce number of affected children in the UK by 100,000-150,000