Stress hormones during pregnancy:
How a natural rise in hormone levels may benefit babies and re-program mothers' brains
Copyright © 2008 by Gwen Dewar
Natural changes in stress hormones during pregnancy
Prolonged, severe stress is bad for pregnancy. And stress
hormones are to blame. When stress hormone levels run very high, women
are less likely to conceive and more likely to miscarry (Sapolsky 2004;
Nepomaschy et al 2006). Babies are more likely to be born prematurely
and underweight. They are also more likely to experience developmental
delays and metabolic diseases later in life (Sapolsky 2004; Poggi-Davis
and Sandman 2006).
But this doesn’t mean that a healthy pregnancy is a pregnancy
without elevated stress hormone levels. In this article, I review the
normal hormonal changes that take place during pregnancy. I also
• How stress hormones help the fetus develop
• How stress hormones may prime the maternal brain
• The negative effects of hormonal changes on mom's mood
The negative effects of stress
When you perceive a crisis—-or think a stressful thought—-your brain
secretes corticotrophin-releasing hormone (CRH). This master stress
hormone triggers the release of glucocorticoid stress hormones, such as
cortisol. Stimulated by glucocorticoids and other stress hormones (like
adrenaline), the brain and body shift into crisis mode. Your breathing
and pulse quicken, making more oxygen available to your muscles. Blood
sugar levels rise. Physiological processes that are non-essential in the
short term—like digestion, growth, and repair—are temporarily shut
down. You are in emergency mode. Mind alert, muscles ready for action
When the crisis is over, your stress hormones are supposed to
slip back to their previous, lower, baseline levels. But what if your
baseline levels are pretty high? Elevated basal cortisol is usually bad
news. It’s a sign that your body is on perpetual red alert. The body
suffers more wear and tear (Sapolsky 2004).
For a pregnant woman and her fetus, high cortisol levels pose
special risks. Elevated cortisol is associated with an increased risk of
early miscarriage (Nepomaschy et al 2006). It can also cause
preeclampsia (pregnancy-induced hypertension), fetal growth retardation,
premature birth, and postnatal developmental delays (Reis et al 1999;
Poggi-Davis and Sandman 2006).
Given these risks, we might expect healthy pregnancies to be
characterized by low baseline cortisol levels. Surprisingly, this isn’t
the case. Stress hormone levels rise.
The normal pattern
During the second trimester of pregnancy, circulating levels of
corticotrophin-releasing hormone (CRH) increase exponentially
(Mastorakos and Ilias 2003). Ordinarily, such a surge would stimulate an
overproduction of glucocorticoids in the mother. But messages are
ineffective if nobody receives them, and hormonal messages are no
exception. To do its work, CRH must attach to special receptors in the
brain (Dieterich et al 1999).
Pregnant women produce large quantities of a CRH-binding protein
(“CRH-BP") that prevent CRH from being recognized and used by receptors.
As a result, most of the extra CRH is rendered biologically inactive
(McLean and Smith 2001).
But the situation changes in the last weeks of pregnancy. In the
last three weeks of gestation, CRH levels climb even higher. At the same
time, CRH-binding proteins diminish. Suddenly, large quantities of CRH
become available and biologically active (McLean and Smith 2001). This
rise in biologically-active CRH coincides with a major spike in cortisol
Cortisol levels begin to climb during the second trimester (Carr
et al 1981), but they don’t reach their peak until in late pregnancy. In
the last weeks before birth, cortisol levels are two to three times
higher than normal (Dorr et al 1989). These levels are high (Kammerer et
al 2006)—in the same range as cortisol levels found in people with
major melancholic depression and Cushing’s syndrome (a hormonal disorder
associated with a variety of health problems and psychological
What triggers the hormonal surge?
Elevated, prenatal stress hormones have been found in a number of
mammals, including sheep (Keller-Wood 1998), rodents (Atkinson and
Waddell 1995; Robinson et al 1989), and primates (Power and Schulkin
2006). Species may differ in the details, but one group—the anthropoids
(human, monkeys and apes)—share a peculiar feature.
Ordinarily, CRH is secreted by the brain. But in pregnant
anthropoids, the mother’s steep rise in circulating stress hormones is
driven by the placenta—an organ controlled by fetal DNA. Genes from the
fetus direct the placenta to secrete its own supply of hormones. And
these hormones make their way into the mother’s bloodstream.
It’s not yet clear why the anthropoid placenta shows this
distinction (Power and Shulkin 2006). But if the placenta is secreting
all that extra CRH, one thing seems pretty certain. CRH must benefit the
How stress hormones help the fetus
What exactly are those prenatal stress hormones doing for the fetus? Researchers have uncovered several key functions.
In the first days of pregnancy, CRH suppresses the mother’s
immune system, preventing the mother’s body from attacking the fetus
(Makrigiannakis et al 2001). Later, CRH helps regulate the blow flow
between the placenta and the fetus (McLean and Smith 1999). CRH may also
help the fetal organs mature (Majzoub and Karalis 1999), and it appears
influence the timing of birth (McLean and Smith 2001).
The late-term cortisol surge seems to play a role in brain
development and the maturation of the lungs (Crowley 2000; Matthews et
al 2004). When babies are born prematurely (before the late-term
cortisol surge), they are more likely to experience respiratory problems
and interventricular hemorrhage (bleeding in the brain). For this
reason, the National Institutes of Health has recommended that women at
risk for premature delivery be given synthetic cortisol (NIH Consensus
Development Conference 1995).
CRH and cortisol may also make pregnant women less responsive to
acute stressors (Kammerer et al 2002). According to this idea, the
stress response system adjusts to high basal cortisol levels by “tuning
out" subsequent signals of stress. In support of this hypothesis, women
in the last stages of pregnancy showed no rise in cortisol after
immersing their hands in ice cold water (Kammerer et al 2002).
Priming the brain for motherhood
One of the most interesting functions of stress hormones concerns
maternal behavior. CRH-—or the hormones stimulated by CRH—-might help
prepare the pregnant brain for motherhood.
For example, prenatal cortisol levels have been linked to more
attentive mothering in baboons. In one study, the mothers who spent more
time watching, grooming, and manipulating infants were the ones who had
experienced higher cortisol levels during pregnancy (Bardi et al 2004).
Research on humans shows similar results. One study measured
cortisol levels within 24-48 hours of giving birth—-a time period when
women are still under the influence of prenatal hormones. Researchers
asked women to listen to the recorded cries of an infant, and they
measured cortisol levels before and after the cries. The mothers who
showed more sympathy to infant cries had higher baseline cortisol
levels. Moreover, higher-sympathy mothers had higher heart rates—both
before and after hearing the infant cries (Stallings et al 2001).
Other research has reported that postpartum women with higher cortisol levels show
• more positive maternal behavior towards infants (Fleming et al 1987)
• an increased liking for their infants’ body odors (Fleming et al 1997), and
• an enhanced ability to distinguish their babies’ odors from those of other infants (Fleming et al 1997).
How do stress hormones influence maternal behavior? It’s still
not clear. Possibly, the hormones have a direct effect on the mother’s
brain, making women more vigilant and emotionally aroused (Stallings et
al 2001). Alternatively, higher cortisol levels may serve merely as a
marker of other hormonal changes (Mastripieri 1999). Placental CRH, and
the cortisol it stimulates, triggers the production of estrogen (Power
and Shulkin 2006). Estrogen, in turn, may make women more responsive to
oxytocin and endorphins--the “feel good" brain chemistry that promotes
bonding between mother and infant (Keverne 1996).
Unpleasant side effects
It seems that prenatal stress hormones have many beneficial effects.
But is there a downside? Ordinarily, high basal cortisol is diagnostic
of Cushing’s syndrome, a condition associated with a variety of health
problems and mood disorders, like anxiety, irritability, mood swings,
and insomnia (Sonino and Fava 2001). High basal cortisol is also linked
with melancholic depression (Kammerer et al 2006; Carroll et al 2007).
Patients with melancholic depression lose their ability to experience
pleasure or positive moods. They experience physical agitation,
insomnia, and a reduced appetite.
Given these associations, it seems plausible that elevated stress
hormones could contribute to mood changes in pregnant women (Kammerer
et al 2006). And the psychological effects might extend to the
postpartum period as well.
Some studies report that basal cortisol levels decline within a
few days after childbirth (e.g., McLean and Smith 1999). However, basal
cortisol levels remain high in some postpartum women, and basal cortisol
may not return to pre-pregnant levels until after 8 weeks postpartum
(Kammerer et al 2002). This suggests that some postnatal mood disorders
could be caused by elevated cortisol. Interestingly, when postpartum
rats were injected with the rat equivalent of cortisol, they showed
signs of depressed behavior (Brummelte et al 2006).
But more research is needed to make a compelling case. Pregnancy
and childbirth are associated with changes in many hormones, not just
stress hormones. To identify cortisol as a cause of maternal mood
disorders, the possible effects of other hormones must be teased out.
Moreover, there is also the possibility that reduced cortisol causes
mood problems. When postpartum women experience a rapid withdrawal of
cortisol shortly after birth, they may be at greater risk for developing
“atypical" depression (Kammerer et al 2006). Despite its name, atypical
depression is more common than melancholic depression (described
above). Patients with atypical depression retain the ability feel
pleasure, and they eat and sleep more than healthy people do (Kammerer
et al 2006).
Does motherhood buffer the effects of stress?
Finally, it’s not clear if pregnant and postpartum women feel
stressors in the same way that other people do. As noted above, elevated
stress hormones may actually dampen the stress response system, making
mothers less reactive—not more reactive—to stressful situations
(Kammerer et al 2002). In addition, postpartum mothers who breastfeed
may enjoy special protective effects against stress. After they are
exposed to a stressor, women who breastfeed have lower levels of
cortisol than do non-breastfeeding controls (Heinrichs et al 2002).
Click here for references cited in this article about stress hormones during pregnancy.
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