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 explain:

• 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 (Sapolsky 2004).

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 levels.

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 disturbances—-see below).

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 fetus.

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).



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