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Presentation from the International Congress of the Royal College of Psychiatrists 24-27 June 2014, London
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The impact of prenatal depression, stress and anxiety on the emotional, behavioural and
cognitive development of the child; implications for perinatal psychiatry
Vivette Glover
Imperial College London
Royal College of Psychiatrists June 2014
1 2 3 4 5 6 7 8 9 10
Birthweight (Deciles)
127
128
129
130
Systolicblood
pressure(mm Hg)
p<0.001
The relation between systolic blood pressure and birthweight in 149,378 Swedish men aged 18
Fetal programming
Environment in the womb, during different sensitive periods for specific outcomes, can alter the development of the fetus, with a permanent effect on the child.
Relative increase in brain size
0
10
20
fetus20-40weeks
childbirth-5 years
fold
in
cre
ase
20 week fetus birth 5 years
17 4
The Fetal Brain is “Under Construction”
The mother’s emotional state in pregnancy can have a long lasting effect on her child
• Women have as many symptoms of depression and anxiety during pregnancy as postnatally
• 10-15% have major or minor depression both during pregnancy and postnatally
• Pregnancy can also be a time of domestic abuse and relationship strain
Maternal Depression (EPDS) n=8398
88.2% 11.8%
80.6% 5.7% 6.1%
77.2% 3.4% 5.7% 1.9% 4.6% 1.1% 3.4% 2.7%
18
weeks
AN
32
weeks
AN
8 weeks PN
13+
7.5%
Heron et al 2004
From fetus
To child
From fetus
To child
Animal studies. Wide range of effects
on offspring with prenatal stress
• More anxiety • Reduced attention • Learning deficits • Reduced laterality • Altered sexual behaviour • Effects different on male and female
offspring
• Mediated by HPA axis and cortisol/corticosterone in both mother and offspring
Anxiety and Depression
Behavioural problems-ADHD, conduct disorder
Impaired cognitive development
Sleep problems in infants
Neonatal behaviour
More difficult infant temperament
Victimisation in childhood
Schizophrenia?
Autism?
Prenatal stress is associated with increased levels in child :
Prenatal stress associated with increased :
Reduced birthweight and gestational age
Mixed handedness
Altered finger print pattern
Decreased telomere length
Asthma
Altered immune function
Examples of prenatal stress reported to be
associated with changes in development and
behavior
Maternal anxiety and depression
Maternal daily hassles
Pregnancy specific anxiety
Partner or family discord
Distress caused by 6 day war in Israel, 1967
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
ALSPAC Avon Longitudinal Study of Parents and Children
• Large prospective birth cohort
~14,000 pregnant women
recruited around Bristol in
1990-1991
• Detailed information on children at 4, 7, 11 and 13 years
Maternal anxiety-at 18 and 32 weeks of pregnancy Compared 15% most anxious mothers both pre and 33 months postnatally with the rest Child behaviour –maternal report at from 4 to 13 years old. Strengths and Difficulties questionnaire (SDQ). Attention deficit/hyperactivity; anxiety and depression; conduct disorder
ALSPAC study
Multivariate Analysis Cohort with complete data
n = 7, 363
• Maternal Postnatal anxiety and depression
• Paternal pre and postnatal anxiety
• Parenting
• Maternal age
• Birthweight
• Gestational age
• Smoking
• Alcohol
• Psychosocial factors: crowding (SES)
• Maternal education
0
2
4
6
8
10
12
14
Low prenatal anxiety (n=6,731)
High prenatal anxiety (n=1,213)
4 7 9 1311.5
Age (yrs)
To
tal S
DQ
sco
re
Total SDQ scores and maternal anxiety at 32 weeks -allowing for BW, GA, maternal age, maternal education, postnatal depression , postnatal anxiety, SES, maternal
substance use, parenting, paternal anxiety etc Results similar with prenatal depression
O’Donnell et al 2014
The combined effects of raised anxiety (or depression) both antenatally (32 weeks) and postnatally
(33months) on child outcome up to 13 years
O’Donnell et al 2014
ALSPAC. Predicted population prevalence of a probable mental
health disorder in children born to high (top 15%: open bars) and
low prenatal anxiety (full bars) mothers. Based on SDQ scores.
Results similar with prenatal depression
0.0
2.5
5.0
7.5
10.0
12.5
15.0Low prenatal anxiety (n=6,731)
High prenatal anxiety (n=1,213)
4 7 9 11.5 13
Age (yrs)
Po
pu
lati
on
pre
vale
nce %
(O’Donnell et al 2014)
• Why are some children affected and not others?
• Why are they affected in different ways?
• Gene-environment interactions?
COMTC
COMT
COMT
COMT breaks down catecholamines
–dopamine, adrenaline and noradrenaline- gene variants associated with working memory and ADHD
Maternal prenatal anxiety, child ADHD and working memory,
and child COMT rs4680 genotype using ALSPAC data
Co-variates birthweight, gestational age, maternal education, maternal age, household crowding,
maternal smoking, alcohol consumption, postnatal mood and parenting
were controlled for.
O’Donnell et al in prepn
Working memory at age 8
GG: N=1126
AG: N=2310 AA: N=1259
P<0.01
Maternal anxiety at 32 weeks gestation ( Crown Crisp)
COMT rs4680
Child ADHD symptoms (DAWBA) at age 15
GG: N=761
AG: N=1543 AA: N=857
P<0.05
Maternal anxiety at 32 weeks gestation ( Crown Crisp)
COMT rs4680
BDNF modifies synaptic plasticity through multiple
mechanisms. Lower in depression.; raised by antidepressants
BDNF
Maternal prenatal anxiety, child internalising symptoms (SDQ),
and child BDNF rs7124442 and rs 11030121 genotypes
using ALSPAC data Co-variates birthweight, gestational age, maternal
education, maternal age, household crowding, maternal smoking, alcohol consumption, postnatal
mood and parenting were controlled for.
O’Donnell et al in press 2014
Interaction between maternal prenatal anxiety (32weeks) and BDNF SNPs (n=8584)
Maternal prenatal anxiety
TT
TC/CC
CC
TT/TC
BDNF rs7124442 BDNF rs 11030121
P=0.029 P=0.018
Child emotional problems (depression and anxiety) at 4 years-SDQ subscale
• Why?
Predictive adaptive value of changes due to prenatal stress
in a stressful environment (predators)in the wild?
• Anxiety/fear reactivity-
beneficial effects of more vigilance
• ADHD- shifting attention helps if
predators about
Evolutionary benefit of changes caused by prenatal stress
•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 • Asberger’s understands things in a different way
Other findings explained by evolutionary perspective
Sex differences – females stay to look after offspring- more anxiety/vigilance -- males explore and fight, more conduct disorder, aggression, ADHD Effects of stress across the range - dose response effect to respond to the degree of stress in the environment Children not all affected in the same way - genetic variation basis for natural selection
Implications
Maybe characteristics of Anxiety or ADHD in child prenatally exposed to stress are different?
Mennes et al 2006,2009 Harvison et al 2009
www.beginbeforebirth.org
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