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

David Barker

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