Glover, V. and Barlow, J (2014), Psychological adversity in pregnancy: what works to

improve outcomes? Journal of Children's Services 9.2 (2014): 96-108.

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Psychological adversity in pregnancy: what works to improve outcomes?

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Psychological adversity in pregnancy: what works to improve outcomes? Vivette Glover and Jane Barlow

Abstract

Purpose – Foetal programming is one of the key mechanisms by which physical and social adversity is

biologically embedded during pregnancy. While early interest in such programming focused on the long-

term impact of the mother’s nutritional state on the child’s later physical health, more recent research has

identified an increased risk of psychopathology in children of women who have experienced stress, anxiety

and depression during pregnancy. The purpose of this paper is to examine the literature addressing the

impact of stress in pregnancy and the implications for practice.

Design/methodology/approach – An overview of the literature has been provided.

Findings – Both anxiety and depression in pregnancy are common, with a prevalence in the region of 20

per cent. Exposure in pregnancy to anxiety, depression and stress from a range of sources (e.g.

bereavement, relationship problems, external disasters and war), is associated with a range of physical

(e.g. congenital malformations, reduced birthweight and gestational age), neurodevelopmental, cognitive,

and emotional and behavioural (e.g. ADHD, conduct disorder) problems. The magnitude is significant, with the

attributable risk of childhood behaviour problems due to prenatal stress being between 10 and 15 per cent,

and the variance in cognitive development due to prenatal stress being around 17 per cent. A range of

methods of intervening are effective in improving both maternal anxiety and depression, and in the longer

term should improve outcomes for the infant and child.

Research limitations/implications – This research highlights the importance of intervening to support

the psychological wellbeing of pregnant women to improve outcomes for infants and children, and points to

the need for further research into innovative ways of working, particularly with high-risk groups of pregnant

women.

Keywords – Interventions, Stress, Depression, Anxiety, Prenatal, Foetus, Reflective Function

Introduction

The phenomenon of foetal programming, which refers to changes in the environment in utero during

specific critical periods and the consequential long-term effect on the child, has until recently focused on

the consequences of the mother’s physical health (mostly her nutritional state) in terms of the vulnerability

of the child to cardiovascular and related diseases (Barker, 1991, 2003). More recent research, however, has

highlighted the role of the mother’s psychological wellbeing during pregnancy (e.g. stress) in terms not only of

the physical development of the foetus (e.g. birthweight for gestational age, earlier delivery and pregnancy

induced hypertension) (Cardwell, 2013), and physical outcomes, such as an increased risk of asthma (Khashan

et al., 2012), but also later psychopathology. For example, there is now considerable evidence from

prospective studies that the children of women who are depressed, anxious or stressed during pregnancy

are more likely to experience a range of adverse neurodevelopmental, emotional, behavioural, and cognitive

outcomes compared with children of mothers who do not experience such problems (e.g. Van den Bergh et

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al., 2005; Talge et al.,2007; Glover, 2011).

In the first part of this overview of the literature we examine the research highlighting the ways in which a

number of aspects of maternal psychological functioning during pregnancy, focusing specifically on stress,

anxiety and depression, can adversely impact on the foetus/infant and later development of the child. This

section will also examine the impact of other aspects of psychological functioning in pregnancy such as

maternal reflective function. The second part of the paper examines a number of evidence-based methods

of working to support women during pregnancy to improve outcomes for both mother and infant.

Maternal mental health in pregnancy

The prevalence of depression in the antenatal period is similar to postpartum levels and ranges from 12 to

20 per cent (Marcus et al., 2003). Antenatal anxiety is also common, with as many as 21.9 per cent of

women experiencing anxiety in pregnancy (Heron et al., 2004). Both anxiety and depression in pregnancy are

associated with postnatal depression (Heron et al., 2004).

Many women also experience other problems in pregnancy that are strongly associated with both anxiety

and depression. For example, around 30 per cent of domestic abuse starts during pregnancy (Department of

Health, 2010), and around 9 per cent of women are being abused during pregnancy or after giving birth (Taft,

2002). Around 1 per cent of pregnancies in the UK (20,000 women per year) involve a drug dependant

mother (Home Office, 2003), and such drug dependency co-exists with a range of other problems including

psychiatric disorder (Frischer et al., 2005) and psychopathology (Hans et al., 1999), particularly disorders of

affect regulation (Taylor et al., 1997).

Types of psychological functioning associated with altered child outcome

A wide range of psychological exposures have been associated with altered child outcomes and can all be

subsumed under the generic term “stress”. This is a complex term, which can be defined in terms of

physiological responses such as activation of the cortisol producing hypothalamic-putuitary-adrenal axis, but

is here used to cover a range of maternal experiences. Those that have been shown to be associated with

altered child outcome vary from very severe stress, such as that caused by the death of an older child, to

quite mild stresses, such that as caused by daily hassles. They include symptoms of maternal anxiety

(O’Connor et al., 2002; Austin, 2004; Obel et al., 2003; Mennes et al., 2006; McMahon et al., 2013), and

depression (O’Connor et al., 2002; Pawlby et al., 2011), pregnancy-specific anxiety and daily hassles (Huizink et

al., 2003), bereavement (Khashan et al., 2008) and stress due to a relationship problems with the partner

(Bergman et al., 2007). They also include exposure to acute external disasters (Laplante et al., 2008),

9/11(Yehuda et al., 2005), Chernobyl (Huizink et al., 2008) a Louisiana hurricane (Kinney et al., 2008), and war

(van Os and Selten, 1998).

Impact of adverse mental health

Adverse prenatal mental health has been shown to be associated with a wide range of outcomes both in the

short (i.e. immediately following birth) and longer term (i.e. through to adolescence and adulthood). Very

severe stress in the first trimester such as the death of an older child has been shown to be associated with

an increase in congenital malformations (Hansen et al., 2000), while less severe forms of stress is associated

with somewhat lower birthweight and reduced gestational age (Rice et al., 2010; Wadhwa et al., 1993); and

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an altered sex ratio, with fewer males to females being born than in an unstressed population (Obel et al.,

2007; Peterka et al., 2004).

A number of studies have also identified an impact on neurodevelopmental functioning of newborns (e.g.

functioning on the Neontatal Behavioural Assessment Scale, Diego et al., 2004); and psychopathological

outcomes of infants and toddlers (e.g. difficult temperament; Austin et al., 2005; Buitelaar et al., 2003, sleep

problems; O’Connor et al., 2007), and lower cognitive performance and increased fearfulness (Bergman et

al., 2007).

Studies that have examined the association between prenatal stress and neurodevelopmental outcomes in

children age three to 16 years, show an increased risk of child emotional problems, especially anxiety and

depression, and symptoms of ADHD and conduct disorder (O’Connor et al.,2002, 2003; Kleinhaus et al., 2013;

Rice et al., 2010; Van Den Bergh and Marcoen, 2004; Rodriguez and Bohlin, 2005; Beversdorf et al., 2005). Other

studies have shown a reduction in cognitive performance (Laplante et al., 2008; Mennes et al., 2006)

associated with prenatal stress.

Some studies have found an association between prenatal stress in mid to late gestation and increased risk

of autism (Kinney et al., 2008; Beversdorf et al., 2005) although a large population study has failed to confirm

this finding (Li et al., 2009). Two studies have found an increased risk of schizophrenia in adults born to

mothers who experienced stress during pregnancy. Both showed associations with severe stress (i.e. the

death of a relative, Khashan et al., 2008, and exposure to the invasion of the Netherlands in 1940 (van Os

and Selten, 1998) during the first trimester.

A further set of studies have shown associations between prenatal stress and a range of altered physical and

physiological outcomes. These include specific regional reductions in brain grey matter density (Buss et al.,

2010), which may be associated with neurodevelopmental and psychiatric disorders as well as cognitive and

intellectual impairment. Several studies have shown that prenatal stress is associated with an altered diurnal

pattern or altered function of the HPA axis, although the pattern of alteration is quite complex (Glover et al.,

2010).

There is little consistency in the literature regarding the most sensitive time in gestation for the influence of

prenatal stress, and it is likely that there are different times of sensitivity dependent on the outcome

studied, and the stage of development of the relevant brain or other structures. The two studies of

schizophrenia (Khashan et al., 2008; van Os and Selten, 1998), for example, found the most sensitive period

was in the first trimester, which is when neuronal cells are migrating to their eventual site in the brain, a

process previously suggested to be disrupted in schizophrenia. In contrast two studies of conduct disorder,

or antisocial behaviour, found the greatest associations with stress in later pregnancy (Rice et al., 2010;

O’Connor et al., 2003).

Recent research has also begun to identify the importance of other aspects of psychological functioning in

pregnancy (the impact of which appears to be transmitted via the mothers parenting postnatally rather than

biologically or physically during pregnancy) such as the mother’s capacity for reflective functioning (RF). RF in

pregnancy is defined as the mother’s imagined relationship with her baby (Slade and Patterson, 2005).

Women who are described as “Balanced”, for example, can provide “richly detailed, coherent stories about

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their experiences of their pregnancies and their positive and negative thoughts and feelings about their

fetuses”. Women who are “Disengaged”, however, appear to be uninterested in the foetus per se or their

relationship with it, and demonstrate “few thoughts about the babies” future traits and behaviours or

themselves as mothers’; women described as “Distorted” tend to be “tangential or express intrusive

thoughts about their own experiences as children, often viewing their foetuses primarily as an extension of

themselves or their partners” (Levendosky et al., 2011, p. 214).

The importance of such representations is that they are stable over time such that women with distorted or

disengaged prenatal representations still have them at one year postpartum (Theran et al., 2005), and they

predict observed parenting behaviours and child attachment at age one (Levendosky et al., 2011).

The mechanisms involved

Although we do not currently fully understood the mechanisms that may underlie foetal programming by

prenatal stress in humans, a number of potential pathways have been identified. One early suggestion was

a decrease in blood flow to the foetus (Teixeira et al., 1999) (i.e. elevated/chronic sysmpathetic nervous

system stimulation caused increased release of catecholamines and vasoconstriction, altering utero-

placental blood flow reducing oxygen and calorie intake influencing foetal CNS development). However, it is

not clear if the decrease observed in this study would be clinically significant, and others have failed to

replicate the original finding (Mendelson et al., 2011).

A second mechanism identified in animal models involves the foetus being overexposed to glucocorticoids

as a result of maternal cortisol crossing the placenta, and high CRH levels in the foetus influencing the brain

development and HPA-axis regulation, and autonomic and endocrine functioning of the foetus, and later the

infant and child. However, the human HPA axis functions differently in pregnancy from most animal models,

because of the placental production of CRH, which in turn causes an increase in maternal cortisol. The

maternal HPA axis becomes gradually less responsive to stress as pregnancy progresses (Kammerer et al.,

2002), and there is only a weak, if any, association between maternal mood and her cortisol level, especially

later in pregnancy (O’Donnell et al., 2009). It thus seems unlikely that an increase in maternal cortisol is the

mediating mechanism between prenatal maternal stress, anxiety or depression in later pregnancy and

altered foetal outcome.

However, another mechanism by which the foetus could become overexposed to glucocorticoids that

has been demonstrated in both rats (Mairesse et al., 2007) and humans (O’Donnell et al., 2012) in the

absence of increases in maternal cortisol levels, is the impact of stress on transplacental transfer, through

changes in placental function, especially the enzyme 11b-hydroxysteroid dehydrogenase type II the barrier

enzyme which converts cortisol to the inactive cortisone.

Serotonin is another possible mediator of prenatal stress induced programming effects on offspring

neurocognitive and behavioural development. During gestation serotonin regulates cell division, differentiation

and synaptogenesis (Oberlander et al., 2009). Animal studies have shown that increased serotonin exposure

during gestation is associated with alterations in many neuronal processes and subsequent changes in

offspring behaviour. Recent work has identified an endogenous serotonin biosynthetic pathway in the human

placenta (Bonnin et al., 2011), suggesting a possible role for alterations in placental serotonin in human foetal

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programming.

Epigenetic changes, which can be induced by the environment and involve reversible changes to the

structure of DNA (i.e. such as the addition of a methyl group, control the amount of mRNA and protein

produced, may underlie many of the processes of) foetal programming. Prenatal stress has been shown to

cause epigenetic changes to the rodent brain, in the DNA that codes for the receptor that binds the stress

hormone cortisol (Mueller and Bale, 2008). In humans, stress during pregnancy caused by violence from the

partner, has been shown to cause epigenetic changes in the DNA for this same receptor, in the blood of their

adolescent children (Radtke et al., 2011).

Clinical magnitude of the effects of prenatal stress The magnitude of many of the effects described above are not just statistically significant but also clinically

significant. In the large ALSPAC population study it was found that if the mother was in the top 15 per cent

for anxiety, her child was at double the risk for emotional/behavioural problems at ages four and seven

(O’Connor et al., 2002, 2003) after controlling for a wide range of possible confounders including postnatal

maternal mood. The risk was raised from about 5 per cent in the general population to about 10 per cent in

the children of the high anxiety group. Most children were not affected, and those that were, were affected in

different ways. It is possible to calculate from this that the attributable risk of childhood behavioural problems

due to prenatal stress is about 10-15 per cent (Talge et al., 2007). Similar results have been obtained for older

children (i.e. 13 years old – unpublished observations).

The effects of prenatal stress on cognitive development also appear to be clinically significant. In a study

correlating prenatal life events with child cognitive development at 17 months, Bergman et al. (2007) found

that prenatal stress accounted for 17 per cent of the variance in cognitive ability, after controlling for a range

of confounders, including postnatal maternal mood. Prenatal partner relationship strain accounted for most

(73 per cent) of the life event stress related variance in cognitive ability. If the woman said she had suffered

from three or more prenatal partner related life events (e.g “your partner was emotionally cruel to you”) her

infant had a mean Bayley Mental Developmental index of 89, compared with 98 for the rest of the group (the

general population norm being 100). King and Laplante (2005) found even greater effects on cognitive ability,

when they examined two-year-old children of mothers who had been exposed to a Canadian Ice storm during

pregnancy, and compared the outcome for those who had been exposed to high or low stress. For

children of mothers exposed to high stress in the first or second trimesters the Bayleys’ scores were 14

and 19 points, respectively, lower than the children of the low stress mothers.

What works to improve maternal psychological wellbeing in pregnancy

This research provides an indication not only of the importance of intervening during pregnancy to reduce

the risk of adverse maternal mental health impacting child development as a result of foetal programming,

but also suggests what the focus of such interventions should be.

The Healthy Child Programme (Department of Health (DH), 2009) provides the policy context for the delivery of

a range of Universal (i.e. delivered to all pregnancy women), Universal Plus (i.e. delivered to women with

moderate level need) and Universal Partnership Plus (i.e. delivered to women with high level need) level

interventions, which are described below in more detail.

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Universal

Universal provision during pregnancy provides key opportunities to support wellbeing and to identify women

who may be in need of additional support. The NICE Guidelines on mental health in pregnancy and the

postnatal period (NICE, 2007) recommend that midwives are trained to detect depression and offer

support, and that they undertake screening to identify common mental health problems at booking-in and

subsequent visits using simple tools such as the Whooley questions. Midwife led care in the community

during the antenatal and postnatal period using evidence-based guidelines can also be effective in

improving maternal mental health (MacArthur et al., 2003)

Similarly, the Healthy Child Programme recommends the delivery of an Antenatal Promotional Interview by

the health visitor at 28 weeks (DH, 2009). The Promotional Interview is conducted using the Antenatal

Promotional Guide, which consists of a flexible and semi-structured framework of questions that is

conducted with both parents. The interview provides the health visitor with the opportunity to both support

wellbeing and to identify women who may be experiencing high levels of stress, anxiety or depression, or who

are not showing a good level of bonding with the foetus, in order to provide additional support.

Although antenatal education classes have long been used as a universal method of supporting wellbeing and

improving birth outcomes, a recent review found no evidence that participation in standard antenatal

education programmes prevented the onset of anxiety or depression or was effective in its treatment

(Schrader McMillan et al., 2009). There was some evidence to suggest that that group-based social support

including antenatal preparation for parenthood classes can be effective in supporting women with sub-

threshold symptoms of depression and anxiety, particularly where it involves adjuncts such as massage and

music therapy (Schrader McMillan et al., 2009). This review also found some evidence to suggest that some

of the new transition to parenthood programmes, which are replacing the delivery of antenatal classes in

many places and that have a more explicit focus on the emotional transition to parenthood, are promising

models of working in terms of promoting maternal psychological wellbeing, parental confidence, and

satisfaction with the couple and parent-infant relationship in the postnatal period (Schrader McMillan et al.,

2009).

Listening to music, has been found to decrease maternal plasma cortisol and self-reported state anxiety

score, in pregnant women awaiting amniocentesis (Ventura et al., 2012). Maternal relaxation has also been

shown to improve indices of foetal neurobehaviour, such as heart rate variability (DiPietro et al., 2008). One

study that compared active (directed by a therapist) and passive (sitting in a chair) relaxation found that

while both active and passive relaxation significantly reduced State Anxiety and maternal heart rate, the effect

was significantly greater with the active relaxation (Teixeira et al., 2005). In contrast, the passive relaxation

significantly reduced noradrenaline levels whereas active did not. Both methods significantly reduced

cortisol. This study showed that there can be a lack of correlation between psychological and biological

measures. This implies that interventions that reduce maternal psychological symptoms will not necessarily

change the relevant biological factors for foetal programming, and each intervention will need to be tested for

its effect on child outcome.

Other effective psychosocial and psychological interventions for preventing postnatal depression for

pregnant and new (up to six weeks postpartum) mothers, including both women with no known risk and

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those with risk of postpartum depression, include professional and lay support – home visiting, peer support

and interpersonal psychotherapy (Dennis and Dowswell, 2013).

A number of new approaches to working now focus on the provision of group-based support to high risk

groups of women during pregnancy aimed at building maternal reflective function to promote bonding and

help the mother to reflect on what this baby might be like, with the long-term aim of improving infant

attachment security (Jenkins and Williams, 2008).

Universal Plus

Universal Plus interventions are targeted at women who have been identified as having mild to moderate

problems and who need additional support. The NICE guidelines (NICE, 2007) recommend that women who

require psychological treatment should receive an appointment within one month of the initial assessment

(and no more than three months). Treatments that are recommended for mild to moderate problems

include self-help strategies (e.g. guided self-help; computerised cognitive-behavioural therapy (CBT) or

exercise); non-directive counseling delivered at home (e.g. listening visits); brief CBT or interpersonal

psychotherapy.

A recent systematic review of mind-body interventions during pregnancy for preventing or treating women’s

anxiety identified eight RCTs evaluating hypnotherapy (one trial), imagery (five trials), autogenic training (one

trial) and yoga (one trial), and found some evidence of effectiveness for the use of imagery and autogenic

training on anxiety during delivery and the immediate postpartum period only (Marc et al., 2011).

There is also emerging evidence to suggest that mindfulness-based stress reduction and a modified form

based on CBT called mindfulness-based cognitive therapy can be effective in improving mood states when

delivered during pregnancy (Vieten and Astin, 2008). The Nurse Family Partnership intensive home visiting

programme is effective in improving health behaviours in pregnancy of teenage mothers, including reducing

alcohol use (Olds et al., 1986).

Universal Partnership Plus

Women experiencing severe anxiety or depression during pregnancy should be referred to their GP who will

discuss with them the potential risks and benefits associated with the use of ante-depressants (NICE,

2007). Psychosocial and psychological interventions that have been shown to reduce anxiety and stress

include applied relaxation training (Bastani et al., 2005), and massage therapy, which can improve depression

and other outcomes (e.g. prematurity and low birthweight; Field et al., 2004). Interpersonal psychotherapy

has also been shown to be effective for pregnant women meeting DSM-IV criteria for major depression

(Spinelli and Endicott, 2003).

A range of interventions have been shown to reduce PTSD associated with interpartner violence including

individual trauma-focused cognitive-behavioural therapy (TFCBT), eye movement desensitisation and

reprocessing, stress management and group TFCBT (Pisson, 2009). Counselling (NICE, 2013) and forgiveness

therapy (NICE, 2013) have also been shown to reduce symptoms of depression and PTSD.

Brief behavioural counseling (Whitlock et al., 2004) and contingency management (Terplan and Lui, 2007) are

two of the few evidence-based interventions that have been shown to help improve the dependency of

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alcohol/substance dependence women but with no evidence about their benefits in terms of anxiety and

depression.

Clear care pathways should be established for women experiencing substance dependency, interpartner

violence or severe mental health problems, and should involve referral to social services for a prebirth

assessment and additional support including the input of specialist practitioners.

Summary

There is extensive evidence showing that the psychological wellbeing of women in pregnancy can have long-

term effects on the child, especially in terms of their later emotional and behavioural adjustment. This evidence

points to the importance of intervening during pregnancy to provide support that is aimed at reducing stress,

anxiety and depression, and promoting reflective function. Although a number of evidence-based methods

of working to promote the mental wellbeing of women during pregnancy are currently available, innovative

ways of working are still being developed, and further research is needed to identify effective treatments

for women experiencing severe problems such as substance dependency and interpartner violence. Much

more still needs to be done to ensure that the treatment of common mental health problems in pregnancy

is routinely addressed. This will help the women themselves and in the long-term should help their children

also.

Summary of implications for policy and practice:

The psychological wellbeing of women in pregnancy can have long-term effects on the child, especially

in terms of their later emotional and behavioural adjustment.

This evidence points to the importance of intervening during pregnancy to provide support that is

aimed at reducing stress, anxiety and depression, and promoting reflective function.

A number of evidence-based methods of working to promote the mental wellbeing of women during

pregnancy are currently available, and should be implemented.

More still needs to be done to ensure that the treatment of common mental health problems in

pregnancy is routinely addressed.

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About the authors

Vivette Glover is a Professor of Perinatal Psychobiology at the Imperial College London. Her first degree was in

Biochemistry at the Oxford University, and she did her PhD in Neurochemistry at the University College London.

In more recent years she has applied her expertise in biological psychiatry to the problems of mothers and

babies. The effects of the emotional state of the mother, both on the developing foetus and longer term on

the child are being studied. Her group are also studying the biological mechanisms that may underlie such

foetal programming. She has published over 400 papers. She has been awarded the International Marce

Society Medal given biennially for research into perinatal mental health, and has been a Special Advisor to the

Department of Health on the Family Nurse Partnership and Preparation for Pregnancy, Birth and Beyond.

Professor Vivette Glover is the corresponding author and can be contacted at: v.glover@imperial.ac.uk

Jane Barlow was appointed the Professor of Public Health in the Early Years at the University of Warwick in

October 2007. Her main research interest is the role of early parenting in the aetiology of mental health

problems, and in particular the evaluation of early interventions aimed at supporting the parent-infant

relationship during pregnancy and the postnatal period. She is the Director of the newly established

Warwick Infant and Family Wellbeing Unit (WIFWu), which provides training and research in innovative

evidence-based methods of supporting parenting during pregnancy and the early years to a wide range of

early years and primary care practitioners. She has also researched extensively on the effectiveness of

interventions aimed at preventing and treating abuse and is a strong advocate of a public health approach

to child protection. She is leading the evaluation of A Better Start.