Neuroscience and Biobehavioral Reviews 35 (2010) 1722

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Neuroscience and Biobehavioral Reviews

journal homepage: www.elsevier.com/locate/neubiorev

Review

Prenatal stress and the programming of the HPA axis

Vivette Glover a,*, T.G. OConnor b, Kieran ODonnell a
a
Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, United Kingdom
b
Department of Psychiatry, University of Rochester Medical Center, 300 Crittenden Blvd, Rochester, NY 14642, USA

A R T I C L E I N F O A B S T R A C T

Keywords: There are several independent prospective studies showing that a wide variety of forms of prenatal stress
Prenatal stress can have long-term effects on the behavioural and cognitive outcome for the child. Animal studies have
Programming shown that prenatal stress, as well as affecting behaviour, can also reprogram the function of the HPA
HPA axis
axis in the offspring. However, the effects on the HPA axis are very variable depending on the nature of
Cortisol
the stress, its timing in gestation, the genetic strain of the animal, the sex and age of the offspring and
whether basal or stimulated HPA axis responses are studied. There are also several recent studies
showing long-term effects of prenatal stress on basal cortisol levels, or cortisol responses to stress, in
humans. The designs of these studies differ considerably, many are small, and the effects on outcome are
also varied. There is little evidence, so far, that altered function of the HPA axis in the child mediates the
behavioural or cognitive alterations observed to be associated with prenatal stress.
2009 Elsevier Ltd. All rights reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
2. Prenatal stress and programming the HPA axis-animal studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
3. Prenatal stress: human studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
4. Prenatal stress and the function of the HPA axis-humans. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
5. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

1. Introduction has been suggested that these fetal adaptations may have been of
evolutionary value, in order to confer characteristics in the
Fetal programming describes the process whereby the devel- offspring that were adaptive in the context of the stressful
opment of a fetus is altered because of changes in its immediate environments in which they were developing and presumably
environment. The effects can vary at different sensitive periods and would subsequently live in (Viltart and Vanbesien-Mailliot, 2007).
can shape the structure and function of the brain and peripheral However, for humans in the modern world, there may often be a
organ systems, with long-term or permanent effects on subse- mismatch between characteristics of the early environment during
quent child and adult physiology, behaviour and health. Many development and subsequent environment during later stages of
studies in animals have shown that prenatal stress can have such life. This, in turn, may result in maladaptive properties in the
programming effects on both neurodevelopment and the function context of a different environment, with direct implications for
of the hypothalamic-pituitary-adrenal (HPA) axis. In humans also increasing vulnerability for pathophysiological health outcomes
there is an increasing number of prospective studies showing that (Gluckman et al., 2005).
various forms of prenatal stress are associated with a range of later
behavioural and cognitive alterations in the child, and some 2. Prenatal stress and programming the HPA axis-animal
limited evidence for associations with alterations in the HPA axis. It studies

It has been known for over ve decades from animal studies

* Corresponding author. Tel.: +44 207 594 2136; fax: +44 207 594 2138. that maternal stress during pregnancy can have a range of long-
E-mail address: v.glover@imperial.ac.uk (V. Glover). term effect on the offspring (Weinstock, 2001). These include

0149-7634/$ see front matter 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.neubiorev.2009.11.008
18 V. Glover et al. / Neuroscience and Biobehavioral Reviews 35 (2010) 1722
learning decits, more anxious behaviour, reduced attention,
altered immune function, as well as altered cardiovascular
responses to stress (Igosheva et al., 2007) and glucose intolerance
(Lesage et al., 2004). These effects are clearly different in male and
female offspring (Darnaudery and Maccari, 2008). With animals it
is possible to cross-foster the prenatally stressed pups to control
mothers after birth, or nursery rear in the case of monkeys
(Schneider et al., 2002), and thus establish that the origin of these
effects are prenatal rather than postnatal.
In the animal work much research has shown how prenatal
stress can alter the function of the HPA axis in the offspring. These
effects have been found in a range of species. Variation in the
responsiveness of the HPA axis plays an adaptive role, and it is
plausible that the prenatal reprogramming has evolutionary
signicance and is part of the predictive adaptive response (Love
and Williams, 2008). Weinstock (2005, 2008) has reviewed this
comprehensively for the rodent. She discusses the variability in
results and the many parameters that may affect this: the nature
and the timing of the stress exposure during pregnancy, the age of
testing of the offspring, the genetic strain of rat or mouse used, the
sex of the offspring, the time of day of testing the offspring HPA
axis, and whether basal or stress-induced corticosterone levels
were measured. Despite the variability many of the studies have
found that prenatal stress did cause both an increase in basal levels
and an increase in corticosterone response in the offspring.
However, several others showed a decrease in the corticosterone
stress response, and others still showed no change. She concludes
that to have an effect the prenatal stress needs to be of sufcient
intensity, be administered daily in the last week of gestation, and
that female offspring are more sensitive than males. Different rat
strains appear to respond in different ways. There has been little
study of whether the changes in the function of the HPA axis
underlie the behavioural changes induced by prenatal stress,
although both have been shown to occur in the same model (Abe et
al., 2007).
Animal studies have also identied brain structures altered by
prenatal stress. For example, Coe et al. (2003), studying non-
human primates, have shown that exposure to unpredictable
noise, either early or late in pregnancy, resulted in reduced volume
of the hippocampus in the offspring. This is a part of the brain that
is important both for memory and the control of the HPA axis. In
rodents prenatal stress has been shown to reduce the number of
both glucocorticoid and mineralocorticoid receptors in the
hippocampus (Henry et al., 1994). This could explain why the
corticosterone response to a new stressor is both increased and
prolonged: there is less feedback inhibition via corticosterone
acting on its receptors.
Another nding in the animal research is that programming
effects can last until the grandchild generation. In one experiment
in which the pregnant female was treated with dexamethasone,
reduced birthweight and glucose intolerance were transmitted to
the second generation by both the rst generation female and male
offspring (Drake et al., 2005). This suggests the possibility that
epigenetic changes can affect both oocyte and sperm.
Rodent experiments have shown that the effects of prenatal
stress may be moderated and even reversed by positive postnatal
rearing (Maccari et al., 1995). This indicates that although there
can be persisting effects of prenatal stress, it is not inevitable, and
that the period of sensitivity or programming extends beyond the
prenatal period. Meaney and his group have shown how variation
in the nature of maternal care can have long lasting effects on both
the behaviour and function of the HPA axis of the offspring.
Offspring of mothers showing more maternal care are both less
anxious and have a less pronounced corticosterone response to a
new stressor (Liu et al., 1997). This group is also uncovering some
of the epigenetic changes in the brain, altered methylation in the
promoter region of the glucocorticoid receptor in the hippocam-
pus, which underlie this (Weaver et al., 2004).
Although many of the same mechanisms may well occur in
humans we need to be aware that there are obviously many
physiological and other differences between humans and animal
models. For example, rodents are born at a much less developed
stage than humans. There are differences in the nature and
regulation of maternalplacentalfetal neuroendocrine processes
underlying development and birth across mammals, even between
non-human primates and humans (Smith and Nicholson, 2007).
Nevertheless, and despite the caveats about the animal ndings
cited above, animal experiments have provided strong evidence
that prenatal stress can have long lasting and varied effects on the
offspring, including the function of the HPA axis.
3. Prenatal stress: human studies
An immediate link between prenatal maternal mood and fetal
behaviour is well established from 27 to 28 weeks of pregnancy
onwards (Van Den Bergh et al., 2005). The mechanisms underlying
this link are not known.
In the last 10 years several independent prospective studies
have examined the longer lasting effects of prenatal stress, anxiety
or depression on the behavioural, emotional and cognitive
outcomes during childhood. Even though these studies used a
wide range of different methods, both for measuring prenatal
stress or anxiety, and for assessing the child, they all support a link
between prenatal mood and changes in outcome that suggest
changes in neurodevelopment (Van Den Bergh et al., 2005).
Different studies have examined the child at different ages, from
newborn to adolescence. The newborn studies show effects that
must be independent of postnatal experience; those with
adolescents show the persistence of impairment (Van Den Bergh
et al., 2005). In several studies these ndings have been shown to
be independent of potential confounding factors such as smoking
or poverty, and also maternal postnatal depression and anxiety.
This adds support to the effect being due to the prenatal
environment, rather than genetic transmissionalthough no
evidence directly testing the genetic mediation hypothesis has
yet been presented. The studies are mainly from European and
North America; none are from developing countries or countries at
war, where one might predict that the effects would be even more
marked.
A wide range of different outcomes have been found to be
affected by prenatal stress. The most consistent adverse outcome is
in symptoms of attention decit hyperactivity disorder (ADHD)
(Rodriguez and Bohlin, 2005; Van Den Bergh and Marcoen, 2004)
but an increase in anxiety is also often observed (Van Den Bergh
and Marcoen, 2004). Other studies have shown an effect of
prenatal stress or anxiety on the cognitive development of the
child, as assessed by scores on the Bayley Mental developmental
Index (MDI) (Huizink et al., 2003) or language development
(Laplante et al., 2004).
A recent study has shown that prenatal maternal stress, due to
exposure to a Canadian Ice storm, during the fetal period of
ngerprint development, in the second trimester, resulted in
greater dermatoglyphic asymmetry in their children, especially in
the face of greater maternal distress (King et al., 2009). This
asymmetric pattern is also found in subjects with schizophrenia.
The nding is of particular interest as the ngerprint pattern
develops at the same time as the hippocampus, and may be a
physical marker for altered development of this region, which is
important in both cognition, and feedback control of the function
of the HPA axis (Cottrell and Seckl, 2009).
A recent MRI study has shown that high pregnancy-specic
anxiety in mid-gestation, but not later, is associated with
 V. Glover et al. / Neuroscience and Biobehavioral Reviews 35 (2010) 1722
decreased gray matter in children in specic brain areas, including
the prefrontal cortex, which are also involved in both cognition and
stress hormone regulation (Buss et al., in press). It has also been
shown that women whose mothers had been exposed to a severe
life event during pregnancy had longer reaction times in a working
memory test, after cortisol administration (Entringer et al., 2009a).
This may also reect an impairment in prefrontal cortical
functioning. These three studies provide indirect evidence that
prenatal stress can affect brain development in a way that may also
affect regulation of the HPA axis.
More needs to be understood about the periods of gestation
which are most sensitive for all the effects described here. Different
studies have found different periods of vulnerability. In the study
of OConnor et al. (2002) anxiety was measured at 18 and 32 weeks
gestation, and the associations with behavioural/emotional
problems in the child were stronger with the latter time point
(OConnor et al., 2002). However, in the study showing that a life
event, the death of a relative, was associated with an increased risk
of schizophrenia, the risk was conned to the rst trimester
(Khashan et al., 2008). It is likely that the gestational age of
vulnerability is different for different outcomes. Brain systems
underlying different aspects of cognition or behaviour mature at
different stages. We still do not know why some children are
affected but not others. Possible explanations include specic
genetic vulnerabilities in both mother and child, timing of the
prenatal exposures, and the nature of the postnatal care.
These studies show that the nature of the risk can be quite
varied, and that many neurodevelopmental effects can be observed
with non-clinical levels of anxiety or stress (OConnor et al., 2002).
There is evidence from one study that the effect on the child
derives more from prenatal anxiety than depression (OConnor et
al., 2002); another study found that the life events most closely
linked with both low scores on the Bayley Mental Developmental
Index and increased fear reactivity were separation/divorce and
cruelty by the partner (Bergman et al., 2007). Nevertheless, as
noted, the nature of the risk phenotype is unclear and most
studies have focused on non-diagnostic levels of anxiety and
depression or life events.
In contrast to most of the ndings, two studies report enhanced
development following exposure to prenatal stress. In a cohort of
nancially and stable middle to upper class sample of women,
there was a small but signicant positive association between
prenatal stress and both the mental and physical development of
the child (Dipietro et al., 2006). A similar trend was observed by
Laplante et al. (2008) on child IQ. The authors suggest that a small
to moderate amount of prenatal stress may actually promote an
accelerated rate of brain development, although this remains to be
conrmed.
4. Prenatal stress and the function of the HPA axis-humans
Our review of the literature revealed 11 studies published in the
last 10 years, that have examined in humans the association
between prenatal maternal mood or stress and the function of the
HPA axis (see Table 1). They all have different designs and are
mostly small in terms of their sample sizes. Most are from Europe,
one is from Canada, one from Australia, and three from the USA.
The type of prenatal stress studied varies from self-rated anxiety
(OConnor et al., 2005; Van Den Bergh et al., 2008), anxiety
diagnosed by a clinical interview (Grant et al., 2009), daily hassles
and fear of bearing a handicapped child (Gutteling et al., 2004,
2005), depression (Brennan et al., 2008; Oberlander et al., 2008), to
severe life events (Entringer et al., 2009b) or experience of an acute
disaster, Chernobyl (Huizink et al., 2008) or 9/11 (Yehuda et al.,
2005). The method of measuring outcome also varies from diurnal
saliva cortisol to single basal samples, or saliva or plasma cortisol
19
and ACTH response to a stressor. The age at which the offspring
was assessed varied from 1 week to young adults.
All the studies found that there were associations between
prenatal stress and some aspect of HPA axis function in the child.
However, perhaps unsurprisingly, the nature of this association
varied and we do not yet have any solid replications. As in the case
of the studies of cognitive and behavioural outcomes, the studies
on the effects on the HPA axis are not specic to one type of stress
or anxiety. Further confounding the HPA axis ndings is that
different forms of anxiety generalized anxiety, panic, specic
phobia, and posttraumatic stress may involve quite different, or
even opposite, physiological processes. Whereas anxiety in general
is associated with raised cortisol, PTSD is associated with reduced
cortisol (Tsigos and Chrousos, 2002). It is notable that whereas
prenatal maternal anxiety and depression have in general been
found to be associated with raised cortisol in the child (Table 1), the
infants of mothers exposed to the trauma of 9/11, who themselves
developed symptoms of PTSD, had lower cortisol levels (Yehuda et
al., 2005). The fact that the effect was particularly apparent in the
children of mothers exposed in the third, rather than earlier
trimesters, supports the possibility of fetal programming, rather
than a shared genetic vulnerability.
OConnor et al. (2005) and Van Den Bergh et al. (2008) both
examined diurnal cortisol levels and found increased basal levels in
the child associated with prenatal anxiety. OConnor et al. (2005)
found raised morning and afternoon levels, whereas Van Den
Bergh et al. (2008) found raised evening levels and a atter curve.
Gutteling et al. (2004) studying children of mothers reporting more
daily hassles and Huizink et al. (2008) studying children born to
mothers exposed to Chernobyl, had raised baseline cortisol levels.
Gutteling et al. (2005) also showed that prenatal fear of bearing a
handicapped child was associated with raised diurnal cortisol in
the 4-year-old child. Entringer et al. (2009b) carried out the most
comprehensive study to date. They retrospectively identied
pregnant women who had been exposed to a severe life event such
as the death of someone close or had experienced severe
relationship problems, and recruited the young adult offspring
of these mothers for their study (prenatal stress group) and a
matched non-exposed comparison group. They examined both the
diurnal cortisol pattern and the response to the Trier Social Stress
Test and to a pharmacological challenge of ACTH124 stimulation in
the young adult offspring. They found no differences in the diurnal
patterns. However, the exposed group had a lower plasma cortisol
pre-stress test level and, perhaps relatedly, a lower cortisol but
higher ACTH stress response. Exposed subjects also showed
signicantly lower cortisol levels during the ACTH challenge. A
recent study by Grant et al. (2009) found that prenatal anxiety was
associated with an increased cortisol after the stressor of the still
face procedure in 7-month-old infants. Interestingly they also
found that this was moderated by the sensitivity of the mother
infant interaction. This was a small study, with quite complex
analyses, and certainly warrants replication.
Our group is currently carrying out the largest study in this area
to date (ODonnell, OConnor and Glover in preparation). We are
examining the diurnal cortisol pattern in approximately 1000 15
year olds from the ALSPAC cohort for whom we have prospective
maternal self-report data on depression and anxiety at both 18 and
32 weeks gestation. We will later be able to investigate any
association with current psychopathology, and also with different
genetic vulnerabilities such as polymorphisms in the glucocorti-
coid receptor gene.
Van Den Bergh et al. (2008) have provided the only evidence
that an altered cortisol diurnal prole associated with prenatal
anxiety was also associated with an altered behavioural pheno-
type, depressive symptoms in adolescent girls. It is unlikely that
alterations in the function of the HPA axis underlie all, or even
 20
Table 1
Prenatal stress and effects on the HPA axis of the child.

Country Type of stress N Age tested Outcome measure Results Comments Reference

Germany Severe prenatal life events N = 31 prenatal stress Young adults Venous cortisol after Prenatal stress predicted lower cortisol Mainly females Entringer et al. (2009b)
N = 30 controls ACTH124 challenge pre-TSST and lower cortisol but higher studied
and TSST ACTH response to TSST. Cortisol
Diurnal saliva cortisols response to ACTH was lower in PS
subjects. No difference in diurnal levels
Finland Effect of Chernobyl N = 121 twins exposed 14 years Baseline salivas Cortisol raised in those exposed from Stress not Huizink et al. (2008)
N = 157 not exposed second trimester onwards measured directly
The Netherlands Self-rated maternal anxiety N = 58 1415 years Diurnal saliva cortisol Maternal trait anxiety at 1222 weeks Van Den Bergh

V. Glover et al. / Neuroscience and Biobehavioral Reviews 35 (2010) 1722

at 1222, 2332, 3240 associated with attened diurnal prole et al. (2008)
weeks gestation (lower in morning/higher in evening).
This prole was associated with
depressive symptoms in girls
UK Self-rated anxiety 18 and N = 74 10 years Diurnal salivas Basal waking and afternoon cortisol Co-varied alcohol, OConnor et al. (2005)
32 weeks gestation raised in children of mothers in top smoking, etc. and
15% anxiety at 32 weeks postnatal anxiety
The Netherlands Daily hassles, pregnancy N = 24 46 years Saliva cortisol pre- Maternal daily hassles and fear of bearing No cortisol response Gutteling et al. (2004)
related anxiety, perceived and post-inoculation a handicapped child predicted to the inoculation
stress at 16 weeks gestation raised cortisol in the child
The Netherlands Range of prenatal stress N = 29 4 years Diurnal salivas Prenatal fear of bearing a handicapped Maternal prenatal Gutteling et al. (2005)
indices on rst day of school predicted raised diurnal cortisol cortisol also showed
and weekend an association with
child cortisol
USA Exposure to 9/11 N = 38 9 months Saliva cortisol Low infant cortisol in mothers with Yehuda et al. (2005)
awakening and PTSD. Effect greatest with exposure
at bedtime in the third trimester
Australia Anxiety (diagnostic clinical N = 104 7 months Saliva cortisol Prenatal anxiety group showed higher Shows moderating Grant et al. (2009)
interview) pre- and post-still face cortisol at 40 min post-procedure effect of caregiving
procedure
USA Depression and anxiety N = 189 6 months Saliva cortisol at Maternal perinatal depression associated Maternal medication Brennan et al. (2008)
(Lifetime diagnostic baseline and following with raised baseline cortisol; comorbid during pregnancy offset
interview) stress tests anxiety associated with increased reactivity. effects of perinatal
No clear distinction of prenatal as mood on infant cortisol
opposed to postnatal effects
Canada Depression N = 82 (33 depressed 3 months Saliva cortisol Prenatal depressed mood predicted No direct analysis of Oberlander et al. (2008)
and treated with SSRI, pre- and post-infant methylation status of the promoter relationship between
13 depressed untreated, stress test region of GR (NR3C1) in the newborn. prenatal mood and
and 36 non-depressed) This methylation status predicted infant cortisol stress reactivity
cortisol stress response
USA Depression 26 weeks N = 71 1 week Urine cortisol Perinatal depression associated with Diego et al. (2004)
gestational age raised newborn cortisol
 V. Glover et al. / Neuroscience and Biobehavioral Reviews 35 (2010) 1722
most, of the neurodevelopmental outcomes found to be affected by
prenatal stress, but more studies of this type are needed. It is
important to note that studies have often found little correlation
between various psychological measures and cortisol levels (e.g.,
Teixeira et al., 2005).
Oberlander et al. (2008) have conducted the only prospective
prenatal study exploring a possible underlying epigenetic mecha-
nism. They showed that prenatal depressed mood predicted the
methylation status of the promoter region of the glucocorticoid
receptor (NR3C1) in lymphocytes in the newborn. This methyla-
tion status in turn predicted infant cortisol stress response. The
nding is indeed intriguing. However, there are a number of
conceptual and methodological questions about assessing epige-
netics in peripheral tissue as markers of CNS processes that need to
be resolved before it is possible to interpret this nding. More
recently Meaney and colleagues have translated their work in
rodents and report epigenetic changes in brain samples from
adults exposed to childhood abuse (McGowan et al., 2009). This
study suggests that early adversity may have a lasting effect on
gene expression.
Most studies did not examine mode of delivery as a co-variate,
although there is some evidence that a more stressful delivery is
associated with an altered cortisol response to the stress of
inoculation, at least for the rst 2 months (Miller et al., 2005). This
effect of delivery on infant cortisol level was also found by Brennan
et al. (2008). Other evidence that early exposure to stress can have
an effect on the cortisol response of the infant later comes from
examining stress responses of babies born preterm, who have
much higher levels of cortisol than a fetus of similar gestational age
(Glover et al., 2005). This study showed that the magnitude of
glucocorticoid exposure, both endogenous and exogenous, was
associated with the magnitude of the later cortisol response to
inoculation. Another factor which should be taken into account is
birth weight. Low birth weight, an index of impaired fetal growth,
which can have a variety of causes including increased in utero
exposure to cortisol, has been shown to be associated with altered
function of the HPA axis (Seckl, 2004). In 79 year old children,
birth weight has been reported to be inversely related to the saliva
cortisol response to stress in boys, but not morning diurnal cortisol
levels. In girls birth weight was inversely correlated with morning
peak cortisol (Jones et al., 2006), but not to the stress response.
There is starting to be some evidence that the nature of the stress
response can be modied by sensitive early mothering (Grant et al.,
2009), as in the animal literature. There is also evidence that early
exposure to childhood abuse or trauma can be associated with later
alterations in both stimulated and basal diurnal cortisol patterns
(Heim et al., 2009).
The biological mechanisms which underlie the association
between prenatal stress and the reprogramming of the function
of the HPA axis remain to be determined. One possibility is that there
is an alteration in the function of the placenta, which allows a greater
passage of cortisol from mother to fetus (ODonnell et al., 2009).
5. Conclusion
The animal literature shows convincingly that prenatal stress
can have a long-term effect on the function of the HPA axis in the
offspring; but it also shows the variability and complexity of the
possible effects. Equivalent work in humans is only just starting,
but there is suggestive evidence that there may be equivalent
reprogramming effects. These are also very variable, but mostly
suggest that prenatal stress or anxiety is associated with raised
basal cortisol or raised cortisol reactivity in the offspring. Future
work needs to take account of many more potentially relevant
variables including timing and nature of the prenatal exposure,
method of delivery, birth weight, genetic vulnerabilities in mother
21
and offspring, sex of offspring, age at testing and nature of the
postnatal care; as well as trying to understand more about the
underlying mechanisms, such as the epigenetic changes in relevant
genes.
Acknowledgement
Thanks to Dr Pathik Wadhwa for helpful comments and
suggestions.
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